JoVE   
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Biology

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Neuroscience

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Immunology and Infection

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Clinical and Translational Medicine

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Bioengineering

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Applied Physics

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Chemistry

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Behavior

  
You do not have subscription access to articles in this section. Learn more about access.

  JoVE Environment

|   

JoVE Science Education

General Laboratory Techniques

You do not have subscription access to videos in this collection. Learn more about access.

Basic Methods in Cellular and Molecular Biology

You do not have subscription access to videos in this collection. Learn more about access.

Model Organisms I

You do not have subscription access to videos in this collection. Learn more about access.

Model Organisms II

You do not have subscription access to videos in this collection. Learn more about access.

In JoVE (1)

Other Publications (199)

Articles by Julio C. Castillo in JoVE

 JoVE Biology

A Simple Protocol for Extracting Hemocytes from Wild Caterpillars

1Department of Biological Sciences, The George Washington University


JoVE 4173

Insect hemocytes carry out many important functions, both immune and non-immune, throughout all stages of insect development. Our present knowledge of hemocyte types and function comes from studies on insect genetic models. Here, we present a method for extracting, quantifying and visualizing hemocytes from wild caterpillars.

Other articles by Julio C. Castillo on PubMed

Opportunities in Global Health Education: a Survey of the Virtual Landscape

A new generation of medical students is seeking residency programs offering global health education (GHE), and there is growing awareness of the benefits this training provides. However, basic factors that have an impact on its implementation and its effect on the residency match are insufficiently understood. The purpose of this study was to explore the extent of online information on GHE available to potential US pediatric residency program applicants.

Effects of an Emergency Medical Services-based Resource Access Program on Frequent Users of Health Services

A small group of adults disproportionately and ineffectively use acute services including emergency medical services (EMS) and emergency departments (EDs). The resulting episodic, uncoordinated care is of lower quality and higher cost and simultaneously consumes valuable public safety and acute care resources.

A Protein Phosphatase 1 Gamma (PP1γ) of the Human Protozoan Parasite Trichomonas Vaginalis is Involved in Proliferation and Cell Attachment to the Host Cell

In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1γ) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor. Secondly, it was demonstrated that the enzyme activity of native and recombinant TvPP1γ proteins was inhibited by CA. Thirdly, reverse genetic studies confirmed that antisense oligonucleotides targeted to PP1γ but not PP1α or β inhibited proliferation and attachment of trichomonads CA-treated parasites underwent cytoskeletal modifications, including a lack of axostyle typical labelling, suggesting that cytoskeletal phosphorylation could be regulated by a CA-sensitive phosphatase where the role of PP1γ could not be ruled out. Analysis of subcellular distribution of TvPP1γ by cell fractionation and electron microscopy demonstrated the association between TvPP1γ and the cytoskeleton. The expression of adhesins, AP120 and AP65, at the cell surface was also inhibited by CA. The concomitant inhibition of expression of adhesins and changes in the cytoskeleton in CA-treated parasites suggest a specific role for PP1γ -dependent dephosphorylation in the early stages of the host-parasite interaction. Molecular modelling of TvPP1γ showed the conservation of residues critical for maintaining proper folding into the gross structure common to PP1 proteins. Taken together, these results suggest that TvPP1γ could be considered a potential novel drug target for treatment of trichomoniasis.

The Use of Native and Protonated Grapefruit Biomass (Citrus Paradisi L.) for Cadmium(II) Biosorption: Equilibrium and Kinetic Modelling

This paper describes the use of native and protonated grapefruit biomass, a by-product of the food industry, as an effective and low-cost biosorbent for cadmium removal from aqueous solutions. The biomass composition was analysed by high-performance liquid chromatography, scanning electron microscopy coupled with energy-dispersive X-ray analysis and Fourier transform infrared spectroscopy, showing that hydroxyl and carboxylic groups were the main functional groups implicated in Cd(II) biosorption. The effect of different parameters affecting the biosorption process were studied. The optimum removal of cadmium ions was at pH 4.5. Elution of alkaline-earth ions proved to be related with cadmium uptake, aiming for an ion-exchange mechanism. Protonated biomass showed higher adsorption affinity, binding strength and irreversibility for cadmium than native grapefruit, although the optimum metal uptake and high reaction rate was for the native form of grapefruit. Biosorption experimental data fitted Freundlich > Langmuir > Temkin equilibrium adsorption models. Data for both types of biomass were better fitted by a pseudo-second-order kinetic model, with an excellent correlation between calculated and experimental values. Because of these experimental results, and taking into account that both types of biomass displayed an exothermic and spontaneous physical adsorption process, native grapefruit can be proposed in further experiments as a cheap, effective, low-cost and environmentally friendly natural sorbent for the removal of cadmium from industrial wastewater effluents, avoiding chemical pretreatment before its use.

Human α-defensin 6 Promotes Mucosal Innate Immunity Through Self-assembled Peptide Nanonets

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

Iron and Vitamin Status Biomarkers and Its Association with Physical Fitness in Adolescents: the HELENA Study

There is a lack of studies that analyze the association between micronutrient-related biomarker status and physical fitness in adolescents. In the present study, biochemical parameters for iron and vitamin status were studied, along with objective measures of physical fitness in healthy male and female European adolescents. One thousand eighty-nine adolescents (580 girls, 12.5-17.5 yr) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were included. Hierarchical linear models were performed to determine the associations between micronutrient biomarkers and physical fitness. Age, seasonality, latitude, body mass index, menarche (in girls), and physical activity were used as covariates. For cardiorespiratory fitness, concentrations of hemoglobin, retinol, and vitamin C in male adolescents and β-carotene and 25(OH)D in female adolescents were associated with maximal oxygen consumption. For muscular fitness, concentrations of hemoglobin, β-carotene, retinol, and α-tocopherol in male adolescents and β-carotene and 25(OH)D in female adolescents were associated with better performance of the standing long jump test. In summary, concentrations of hemoglobin and most antioxidant vitamins in male adolescents and β-carotene and 25(OH)D in female adolescents were positively associated with cardiorespiratory and muscular fitness, after controlling for relevant confounders. The associations between physical fitness and iron or vitamin status observed in this cross-sectional study in adolescents should be followed up by a study specifically designed to evaluate causal relationships.

Synthetic Control to Achieve Lanthanide(III)/pyrimidine-4,6-dicarboxylate Compounds by Preventing Oxalate Formation: Structural, Magnetic, and Luminescent Properties

Control over the synthetic conditions in many metal/diazinedicarboxylato systems is crucial to prevent oxalate formation, since dicarboxylato ligands easily undergo degradation in the presence of metal salts. We report here an efficient route to obtain oxalato-free compounds for the lanthanide/pyrimidine-4,6-dicarboxylato (pmdc) system on the basis of the reaction temperature and nonacidic pH or oxygen free atmosphere. Two different crystal architectures have been obtained: {[Ln(μ-pmdc)(1.5)(H(2)O)(3)]·xH(2)O}(n) (1-Ln) and {[Ln(2)(μ(4)-pmdc)(2)(μ-pmdc)(H(2)O)(2)]·H(2)O}(n) (2-Ln) with Ln(III) = La-Yb, except Pm. Both crystal structures are built from distorted two-dimensional honeycomb networks based on the recurrent double chelating mode established by the pmdc. In compounds 1-Ln, the tricapped trigonal prismatic coordination environment of the lanthanides is completed by three water molecules, precluding a further increase in the dimensionality. Crystallization water molecules are arranged in the interlamellar space, giving rise to highly flexible supramolecular clusters that are responsible for the modulation found in compound 1-Gd. Two of the coordinated water molecules are replaced by nonchelating carboxylate oxygen atoms of pmdc ligands in compounds 2-Ln, joining the metal-organic layers together and thus providing a compact three-dimensional network. The crystal structure of the compounds is governed by the competition between two opposing factors: the ionic size and the reaction temperature. The lanthanide contraction rejects the sterically hindered coordination geometries whereas high-temperature entropy driven desolvation pathway favors the release of solvent molecules leading to more compact frameworks. The characteristic luminescence of the Nd, Eu, and Tb centers is improved when moving from 1-Ln to 2-Ln compounds as a consequence of the decrease of the O-H oscillators. The magnetic properties of the compounds are dominated by the spin-orbit coupling and the ligand field perturbation, the exchange coupling being almost negligible.

Conservative Surgical Treatment for Toxic Megacolon Due to Clostridium Difficile Infection in a Transplanted Pediatric Patient

Severe disease caused by Clostridium difficile is frequently encountered in transplant recipients and carries a high mortality. Numerous studies have been published on this subject in the adult population, but few in the pediatric setting. A 4-year-old boy who had undergone heart transplant 20 months earlier was admitted to the pediatric intensive care unit after humoral rejection. Seven days after admission, he developed septic shock, abdominal distension, and paralytic ileus without diarrhea. Pseudomembranous colitis due to C. difficile was confirmed by microbiological and radiological studies. Despite treatment with rectal vancomycin and intravenous metronidazole, the patient did not improve and required decompressive laparotomy; because of the poor subsequent clinical course, terminal ileostomy and cecostomy were performed in a second operation. Recovery was satisfactory, and surgical reconstruction of intestinal tract was performed 3 months later without complications. Although early surgery with total colectomy is indicated, when there is a poor response to medical treatment in cases of C. difficile toxic megacolon, the case we present responded favorably to a conservative surgical approach that enabled intestinal integrity to be restored 3 months later. In the pediatric population, less aggressive therapeutic options should be considered, as they have benefits on the subsequent quality of life of the patient.

A Retrospective Review of Early Gastrointestinal Symptoms in the Prediction of Crotaline Envenomation Severity

OBJECTIVES.-: Rattlesnake envenomations are cited to cause gastrointestinal (GI) symptoms, which may be indicators of systemic envenomation. We sought to identify whether the presence of early GI symptoms, defined as occurring within 4 hours of the bite, could be used to predict antivenom use or bite severity. METHODS.-: We performed a retrospective review of a statewide poison system's database for all cases of rattlesnake envenomation from January 2000 to December 2009. Data collected included presence of GI symptoms and antivenom use. The GI symptoms were further classified as early (within 4 hours) or late. Bite severity was determined using the minimal to moderate to severe scoring system from collected data. Data were then analyzed with a χ(2) test and Fisher's exact test to evaluate for association between early GI symptoms and either antivenom use or bite severity. RESULTS.-: There were 2570 reported rattlesnake exposures in the database. Sixty-one (2.4%) of these had GI symptoms reported. Of these, 36 (59%) had symptoms develop within 4 hours of envenomation. A total of 49 patients (80%) received antivenom. Early GI symptoms were seen in 31 (63%) of patients receiving antivenom versus 5 (42%) of patients not receiving antivenom (P = .20). Early GI symptoms were seen in 4 of 6 (66%) of the severe group, 19 of 29 (66%) of the moderate group, and 13 of 26 (50%) of the minimal group (P = .47). CONCLUSIONS.-: Gastrointestinal symptoms after rattlesnake envenomations were rarely reported in this poison center study, and the presence of early GI symptoms did not predict bite severity or the use of antivenom.

Histological Changes Due to Intravesical Instillation of Mitomycin C

Transurethral resection (TUR) is highly effective in the local control of superficial bladder cancer. However, the recurrence rate can reach 80% of the cases. Adjuvant intravesical chemotherapy may decrease significantly tumor recurrence. We describe a bladder adverse reaction to mitomycin C as adjuvant therapy for non-invasive bladder cancer

Structural, Spectroscopic, and Electrochemical Properties of Tri- and Tetradentate N3 and N3S Copper Complexes with Mixed Benzimidazole/thioether Donors

Cupric and cuprous complexes of bis(2-methylbenzimidazolyl)(2-methylthiophene)amine (L(1)), bis(2-methylbenzimidazolyl)benzylamine (L(2)), bis(2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (L(3)), bis(1-methyl-2-methylbenzimidazolyl)benzylamine (Me(2)L(2)), and bis(1-methyl-2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (Me(2)L(3)) have been spectroscopically, structurally, and electrochemically characterised. The thioether-containing ligands L(3) and Me(2)L(3) give rise to complexes with Cu-S bonds in solution and in the solid state, as evidenced by UV-vis spectroscopy and X-ray crystallography. The Cu(2+) complexes [L(1)CuCl(2)] (1), [L(2)CuCl(2)] (2) and [Me(2)L(3)CuCl]ClO(4) (3(Me,ClO4)) are monomeric in solution according to ESI mass spectrometry data, as well as in the solid state. Their Cu(+) analogues [L(1)Cu]ClO(4), [L(2)Cu]ClO(4), [L(3)Cu]ClO(4) (4-6), [BOC(2)L(1)Cu(NCCH(3))]ClO(4) (4(BOC)), [Me(2)L(2)Cu(NCCH(3))(2)]PF(6) (5(Me)) and [Me(2)L(3)Cu](2)(ClO(4))(2) (6(Me)) are also monomeric in acetonitrile solution, as confirmed crystallographically for 4(BOC) and 5(Me). In contrast, 6(Me) is dimeric in the solid state, with the thioether group of one of the ligands bound to a symmetry-related Cu(+) ion. Cyclic voltammetry studies revealed that the bis(2-methylbenzimidazolyl)amine-Cu(2+)/Cu(+) systems possess half-wave potentials in the range -0.16 to -0.08 V (referenced to the ferrocenium-ferrocene couple); these values are nearly 0.23 V less negative than those reported for related bis(picolyl)amine-derived ligands. Based on these observations, the N(3) or N(3)S donor set of the benzimidazole-derived ligands is analogous to previously reported chelating systems, but the electronic environment they provide is unique, and may have relevance to histidine and methionine-containing metalloenzymes. This is also reflected in the reactivity of [Me(2)L(2)Cu(NCCH(3))(2)](+) (5(Me)) and [Me(2)L(3)Cu](+) (6(Me)) towards dioxygen, which results in the production of the superoxide anion in both cases. The thioether-bound Cu(+) centre in 6(Me) appears to be more selective in the generation of O(2)Ë™(-) than 5(Me), lending evidence to the hypothesis of the modulating properties of thioether ligands in Cu-O(2) reactions.

Anterograde Flow Compromise of a Patent Left Internal Mammary Artery Graft from a Proximal Subclavian Artery Stenosis. Myocardial Ischemia Not Driven by the Coronary-subclavian Steal Syndrome Mechanism

A 54-year male with previous triple vessel coronary artery and aorto-bi-femoral bypass graft surgeries complained of crescent angina. Stress induced myocardial ischemia on echocardiography was demonstrated. We performed direct stenting of a saphenous vein graft to the right coronary artery, via right radial approach. Subsequently stenting of a severe left subclavian artery proximal stenosis was performed via right brachial approach in order to relieve an overt myocardial ischemia in the territory supplied by a patent left internal mammary artery graft originated distally to the left subclavian stenosis. The finding of a total left axillary artery occlusion complement the pathogenesis of myocardial ischemia produced by limited anterograde flow and not driven by the common flow reversal mechanism of a typical coronary-subclavian steal syndrome.

Recommendations for the Nomenclature of IgG4-related Disease and Its Individual Organ System Manifestations

New Perspectives in Occult Hepatitis C Virus Infection

Occult hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology. Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection. Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV. This occult infection has been reported also in healthy populations without evidence of liver disease. Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma. Thus, anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylated-interferon plus ribavirin. The persistence of very low levels of HCV RNA in serum and in PBMCs, along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C, indicate that occult HCV is a persistent infection that is not spontaneously eradicated. This is an updated report on diagnosis, epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases.

Dual Super-systolic Core for Real-time Reconstructive Algorithms of High-resolution Radar/SAR Imaging Systems

A high-speed dual super-systolic core for reconstructive signal processing (SP) operations consists of a double parallel systolic array (SA) machine in which each processing element of the array is also conceptualized as another SA in a bit-level fashion. In this study, we addressed the design of a high-speed dual super-systolic array (SSA) core for the enhancement/reconstruction of remote sensing (RS) imaging of radar/synthetic aperture radar (SAR) sensor systems. The selected reconstructive SP algorithms are efficiently transformed in their parallel representation and then, they are mapped into an efficient high performance embedded computing (HPEC) architecture in reconfigurable Xilinx field programmable gate array (FPGA) platforms. As an implementation test case, the proposed approach was aggregated in a HW/SW co-design scheme in order to solve the nonlinear ill-posed inverse problem of nonparametric estimation of the power spatial spectrum pattern (SSP) from a remotely sensed scene. We show how such dual SSA core, drastically reduces the computational load of complex RS regularization techniques achieving the required real-time operational mode.

Protected Graft Copolymer (PGC) in Imaging and Therapy: A Platform for the Delivery of Covalently and Non-Covalently Bound Drugs

Initially developed in 1992 as an MR imaging agent, the family of protected graft copolymers (PGC) is based on a conjugate of polylysine backbone to which methoxypoly(ethylene glycol) (MPEG) chains are covalently linked in a random fasion via N-ε-amino groups. While PGC is relatively simple in terms of its chemcial composition and structure, it has proved to be a versatile platform for in vivo drug delivery. The advantages of poly amino acid backbone grafting include multiple available linking sites for drug and adaptor molecules. The grafting of PEG chains to PGC does not compromise biodegradability and does not result in measurable toxicity or immunogenicity. In fact, the biocompatablility of PGC has resulted in its being one of the few 100% synthetic non-proteinaceous macromolecules that has suceeded in passing the initial safety phase of clinical trials. PGC is capable of long circulation times after injection into the blood stream and as such found use early on as a carrier system for delivery of paramagnetic imaging compounds for angiography. Other PGC types were later developed for use in nuclear medicine and optical imaging applications in vivo. Recent developments in PGC-based drug carrier formulations include the use of zinc as a bridge between the PGC carrier and zinc-binding proteins and re-engineering of the PGC carrier as a covalent amphiphile that is capabe of binding to hydrophobic residues of small proteins and peptides. At present, PGC-based formulations have been developed and tested in various disease models for: 1) MR imaging local blood circulation in stroke, cancer and diabetes; 2) MR and nuclear imaging of blood volume and vascular permeability in inflammation; 3) optical imaging of proteolytic activity in cancer and inflammation; 4) delivery of platinum(II) compounds for treating cancer; 5) delivery of small proteins and peptides for treating diabetes, obesity and myocardial infarction. This review summarizes the experience accumulated by various research groups that chose to use PGC as a drug delivery platform.

Recognizing Famous Faces

Hydrolysis of Phosphotriesters: a Theoretical Analysis of the Enzymatic and Solution Mechanisms

A theoretical study on the alkaline hydrolysis of paraoxon, one of the most popular organophosphorus pesticides, in aqueous solution and in the active site of Pseudomonas diminuta phosphotriesterase (PTE) is presented. Simulations by means of hybrid quantum mechanics/molecular mechanics (QM/MM) potentials show that the hydrolysis of paraoxon takes place through an A(N)D(N) or associative mechanism both in solution and in the active site of PTE. The results correctly reproduce the magnitude of the activation free energies and can be used to rationalize the observed kinetic isotope effects (KIEs) for the hydrolysis of paraoxon in both media. Enzymatic hydrolysis of O,O-diethyl p-chlorophenyl phosphate, a phosphotriester having a leaving group with higher pK(a) than paraoxon, was also simulated. Hydrolysis of this phosphotriester by PTE follows a A(N)+D(N) mechanism with a pentacoordinate intermediate. Moreover, the leaving group of this new substrate coordinates to one of the zinc ions of the bimetallic active site in order to stabilize the large negative charge developed on the oxygen atom of the leaving group when the P-O bond is broken in the products state. To accommodate this new ligand in the coordination shell, carbamylated Lys169 must be displaced from one zinc ion to the other, which in turn affects the acidity of Asp301, a residue originally bound to the second zinc ion. This ability to displace some of the ligands of the coordination shell of the zinc centers would explain the promiscuity of this enzyme, which is capable of catalyzing hydrolysis of different substrate by means of different mechanisms.

Fat Facets Deubiquitylation of Medea/Smad4 Modulates Interpretation of a Dpp Morphogen Gradient

The ability of secreted Transforming Growth Factor β (TGFβ) proteins to act as morphogens dictates that their influence be strictly regulated. Here, we report that maternally contributed fat facets (faf; a homolog of USP9X/FAM) is essential for proper interpretation of the zygotic Decapentaplegic (Dpp) morphogen gradient that patterns the embryonic dorsal-ventral axis. The data suggest that the loss of faf reduces the activity of Medea (a homolog of Smad4) below the minimum necessary for adequate Dpp signaling and that this is likely due to excessive ubiquitylation on a specific lysine. This study supports the hypothesis that the control of cellular responsiveness to TGFβ signals at the level of Smad4 ubiquitylation is a conserved mechanism required for proper implementation of a morphogen gradient.

Carotid Resistive Index in Treated Hypertensive Patients: Relationship with Target Organ Damage

Aim. The resistive index (RI) is a hemodynamic parameter that reflects local wall extensibility and related vascular resistance. We analyze the relationship between common carotid RI and target organ damage in treated hypertensive patients. Methods. We analyzed 265 consecutive hypertensive patients. Risk factors, cardiovascular history and treatments were collected; blood test, urinary albumin excretion (UAE), echocardiography to determine left ventricular mass index (LVMI), ankle-brachial index (ABI) and carotid echo-Doppler ultrasound to calculate the carotid intima-media thickness (IMT) and RI of both common carotids arteries were performed. Results. A positive correlation was found between carotid RI and age, systolic blood pressure, heart rate, carotid IMT, LVMI, UAE and a negative correlation was found with diastolic blood pressure and ABI. Subjects at the top quartile of carotid RI showed a higher prevalence of left ventricular hypertrophy and peripheral artery disease (increased IMT, carotid plaques and lower ABI) compared with those with low RI (p < 0.05). Multiple regression analysis demonstrated that age, systolic and diastolic blood pressure and LVMI independently influence carotid RI. Conclusion. Carotid RI is related with age, systolic-diastolic blood pressure and LVMI in hypertensive patient. This evaluation could predict the presence of early cardiovascular damage and provide an accurate estimation of overall risk in this population.

Seasonal Variation and Comparative Analysis of Non-specific Humoral Immune Substances in the Skin Mucus of Olive Flounder (Paralichthys Olivaceus)

The epidermal secretion of fish contains various non-specific immune substances that act as the first line of defense against invading pathogens. The present study investigated the level of mucosal antibodies, the activities of hemagglutinin and protease, and other enzymes in the skin mucus of farm reared olive flounder (Paralichthys olivaceus) for 1 year, in order to gain an insight into the relationship between these mucosal immune substances and their seasonal variation. These levels varied significantly during different months of sample collection. The present study showed a positive correlation between water temperature and the level of mucosal antibodies, and an inverse relationship between the level of mucosal antibodies and the activity of mucosal hemagglutinin and protease, but no relationship between lysozyme activity and other innate immune substances. This relationship is thought to be a compensatory response in olive flounder to protect itself against pathogenic microorganisms which are inherently present in the aquatic environment.

A Latent Class Analysis of Dissociation and Posttraumatic Stress Disorder: Evidence for a Dissociative Subtype

The nature of the relationship of dissociation to posttraumatic stress disorder (PTSD) is controversial and of considerable clinical and nosologic importance.

Synthesis of 2-monoacylglycerols and Structured Triacylglycerols Rich in Polyunsaturated Fatty Acids by Enzyme Catalyzed Reactions

This paper studies the synthesis of structured triacylglycerols (STAGs) by a four-step process: (i) obtaining 2-monoacylglycerols (2-MAGs) by alcoholysis of cod liver oil with several alcohols, catalyzed by lipases Novozym 435, from Candida antartica and DF, from Rhizopus oryzae, (ii) purification of 2-MAGs, (iii) formation of STAGs by esterification of 2-MAGs with caprylic acid catalyzed by lipase DF, from R. oryzae, and (iv) purification of these STAGs. For the alcoholysis of cod liver oil, absolute ethanol, ethanol 96% (v/v) and 1-butanol were compared; the conditions with ethanol 96% were then optimized and 2-MAG yields of around 54-57% were attained using Novozym 435. In these 2-MAGs, DHA accounted for 24-31% of total fatty acids. In the operational conditions this lipase maintained a stable level of activity over at least 11 uses. These results were compared with those obtained with lipase DF, which deactivated after only three uses. The alcoholysis of cod liver oil and ethanol 96% catalyzed by Novozym 435 was scaled up by multiplying the reactant amounts 100-fold and maintaining the intensity of treatment constant (IOT=3g lipase h/g oil). In these conditions, the 2-MAG yield attained was about 67%; these 2-MAGs contained 36.6% DHA. The synthesized 2-MAGs were separated and purified from the alcoholysis reaction products by solvent extraction using solvents of low toxicity (ethanol and hexane); 2-MAG recovery yield and purity of the target product were approximately 96.4% and 83.9%, respectively. These 2-MAGs were transformed to STAGs using the optimal conditions obtained in a previous work. After synthesis and purification, 93% pure STAGs were obtained, containing 38% DHA at sn-2 position and 60% caprylic acid (CA) at sn-1,3 positions (of total fatty acids at these positions), i.e. the major TAG is the STAG with the structure CA-DHA-CA.

Ecotoxicological Characterization of a Tropical Soil After Diazinon Spraying

The impact of diazinon spraying in an agricultural tropical soil through the evaluation of both the habitat and retention functions of the soil system was never reported. To fill this gap, five times the recommended dose of a commercial diazinon formulation was sprayed in an agricultural area of Costa Rica, and dilution gradients of the sprayed soil were prepared in the laboratory. Avoidance and reproduction tests with soil organisms (Eisenia andrei, Enchytraeus crypticus and Folsomia candida) to evaluate losses in terrestrial habitat function, and growth and reproduction tests with aquatic organisms (Chlorella vulgaris and Daphnia magna, respectively) to evaluate the retention function of soil were performed. Results demonstrated that regarding habitat function, F. candida reproduction was the most sensitive endpoint (EC(50) = 0.288 mg a.i./kg), followed by avoidance behaviour of E. andrei (EC(20) = 1.75 mg a.i./kg). F. candida avoidance and the reproduction of E. andrei and E. crypticus were not affected by diazinon. The toxicity tests with aquatic organisms showed that the soil retention function was insufficient to prevent effects of diazinon either on microalgae growth (EC(50) ≤ 0.742 mg/L and EC(20) ≤ 0.223 mg/L) and on the reproduction of the cladoceran (EC(50) ≤ 0.00771 mg/L and EC(20) ≤ 0.00646 mg/L). Results suggested that diazinon exerted toxic effects even at the dilution corresponding to the recommended dose, fact which makes its misuse an issue of environmental concern. Furthermore, the present study highlighted the importance and complementary nature of the assessment of both habitat and retention functions to an ecological risk assessment in tropical systems.

Delayed Cardiac Tamponade After Stent Fracture

Ceramide Mediates Nanovesicle Shedding and Cell Death in Response to Phosphatidylinositol Ether Lipid Analogs and Perifosine

Anticancer phospholipids that inhibit Akt such as the alkylphospholipid perifosine (Per) and phosphatidylinositol ether lipid analogs (PIAs) promote cellular detachment and apoptosis and have a similar cytotoxicity profile against cancer cell lines in the NCI60 panel. While investigating the mechanism of Akt inhibition, we found that short-term incubation with these compounds induced rapid shedding of cellular nanovesicles containing EGFR, IGFR and p-Akt that occurred in vitro and in vivo, while prolonged incubation led to cell detachment and death that depended on sphingomyelinase-mediated generation of ceramide. Pretreatment with sphingomyelinase inhibitors blocked ceramide generation, decreases in phospho-Akt, nanovesicle release and cell detachment in response to alkylphospholipids and PIAs in non-small cell lung cancer cell lines. Similarly, exogenous ceramide also decreased active Akt and induced nanovesicle release. Knockdown of neutral sphingomyelinase decreased, whereas overexpression of neutral or acid sphingomyelinase increased cell detachment and death in response to the compounds. When transferred in vitro, PIA or Per-induced nanovesicles increased ceramide levels and death in recipient cells. These results indicate ceramide generation underlies the Akt inhibition and cytotoxicity of this group of agents, and suggests nanovesicle shedding and uptake might potentially propagate their cytotoxicity in vivo.

Corporal Punishment and Youth Externalizing Behavior in Santiago, Chile

Corporal punishment is still widely practiced around the globe, despite the large body of child development research that substantiates its short- and long-term consequences. Within this context, this paper examined the relationship between parental use of corporal punishment and youth externalizing behavior with a Chilean sample to add to the growing empirical evidence concerning the potential relationship between increased corporal punishment and undesirable youth outcomes across cultures.

Inflammation and Apoptosis in Hypertension. Relevance of the Extent of Target Organ Damage

INTRODUCTION AND OBJECTIVES: To investigate the relationship between inflammatory and apoptotic parameters and the severity and extent of target organ damage in patients with essential hypertension. METHODS: We studied 159 consecutive patients with treated essential hypertension. An exhaustive evaluation of damage to heart, kidney, and blood vessels was performed and plasma levels of inflammatory (interleukin 6 and soluble receptor of tumor necrosis factor-alpha type 2) and apoptotic markers (soluble receptor of tumor necrosis factor-alpha type 1 and soluble Fas receptor) were determined. Patients were categorized into four groups: a) no organ damage (33 patients); b) 1 organ damaged (52 patients); c) 2 organs damaged (44 patients), and d) 3 organs damaged (30 patients). RESULTS: Serum levels of interleukin 6, soluble receptor of tumor necrosis factor-alpha type 1 and soluble receptor of tumor necrosis factor-alpha type 2 were higher in patients with target organ damage than in hypertensive patients without organ damage. Increasing levels of these molecules were progressively associated with an increase in the number of organs damaged, and the highest levels were observed in the group with damage to 3 organs (heart, kidney, and blood vessels). There were no differences in soluble Fas receptor levels between groups. Logistic regression analysis showed that age, smoking, diabetes mellitus, abdominal circumference, interleukin 6, and soluble receptor of tumor necrosis factor-alpha type 1 were independently related to the number of target organs damaged. CONCLUSIONS: Extensive hypertensive disease with involvement of more target organs was associated with greater inflammatory and apoptotic activation in these hypertensive patients. Full English text available from:www.revespcardiol.org.

Long Term Evolution of Multiple Outbreaks of Serratia Marcescens Bacteremia in a Neonatal Intensive Care Unit

The annual incidence of S. marcescens bacteremia in a neonatal intensive care unit increased significantly between 2002 and 2010. Molecular epidemiology studies revealed that 8 clones were responsible for 85.2% of cases. Given that these infections are potentially preventable, even the appearance of one case of bacteremia should be an indicator for outbreak management.

Postmortem Characterization of Patients With Clinical Diagnosis of Plasmodium Vivax Malaria: To What Extent Does This Parasite Kill?

Background. Severe disease attributable to Plasmodium vivax infection is already well described worldwide; however, autopsies in these patients are scarce. Methods. From 1996 to 2010, 19 patient deaths with a clinical diagnosis of P. vivax infection occurred in a tertiary care center in the Brazilian Amazon. Seventeen of these 19 deaths were fully autopsied. Clinical charts, macroscopic autopsy reports, and stored paraffinized tissue blocks were retrieved. Nested polymerase chain reaction was performed in paraffinized samples of spleen and lung to confirm P. vivax monoinfection. Immunohistofluorescence was used to detect P. vivax parasitized red blood cells (RBCs). Results. Of 17 autopsies, 13 revealed that death could be attributed to P. vivax infection; in the remaining 4, acute diseases other than malaria were found to be the cause of death. The primary complication in patients in which malaria contributed to death was acute respiratory distress syndrome (ARDS) and pulmonary edema associated with the accumulation of neutrophils in the interalveolar space (6 cases). Spleen rupture (3 cases) and multiorgan dysfunction syndrome (3 cases) were the second most common complications. One child evolving with coma was also characterized, but no parasite was detected in the brain tissue. In one patient who developed ARDS and presented negative peripheral parasitemia by the time of death, scattered parasitized red blood cells were seen inside pulmonary capillaries, suggesting some sequestration in the lung. Conclusions. In 13 of 17 deceased patients, P. vivax infection was the plausible cause of death. However, more studies are needed to understand pathogenesis related to severe disease.

Structure and Dynamics of 1-butyl-3-methylimidazolium Hexafluorophosphate Phases on Silica and Laponite Clay: from Liquid to Solid Behavior

Solid-state NMR experiments show that the behavior of supported 1-butyl-3-methylimidazolium hexafluorophosphate ionic liquid phases depends on the type of support and the phase thickness. A mobile nearly liquid phase is obtained on silica, on the basis of the line widths of the bands in (1)H, (31)P, and (13)C spectra. However, the mobility is somehow restricted, as shown by the possibility of using the cross-polarization technique, although with slow dynamics. On laponite clay, a layered material with a negatively charged surface, a truly solid phase is obtained at low coverage, whereas the increase in ionic liquid loading leads to a second liquid phase, as shown by the presence of two contributions with very different line widths. These two phases seem to coexist without exchange in the NMR time frame. Heteronuclear correlation experiments evidence different relative dispositions of the imidazolium-surface-PF(6) system, with only aromatic protons involved in all the interactions on silica but participation of the benzylic groups (N-CH(3) and/or N-CH(2)) in the case of laponite clay.

The Structural Diversity Triggered by Intermolecular Interactions Between Au(I)S2 Groups: Aurophilia and Beyond

The present study is aimed at elucidating the factors that direct the assembly of a specific family of Au(I) species. The assembly of Au(I) centers and dithiocarboxylato or xanthato ligands results in a surprising structural diversity observed by single-crystal X-ray diffraction. However, in solution, just evidences for discrete bimetallic [Au(2)L(2)] species have been observed. Interestingly, when dithiocarboxylato ligands have been used, a reversible supramolecular assembly has been observed forming the supramolecules of formulae [Au(2)L(2)](2) and [Au(2)L(2)](3). Initial studies on luminescent properties have been carried out at variable temperature. All the compounds show red emissions in the solid state at very similar energies, suggesting that the intramolecular interactions play a more relevant role in the luminescent properties than the intermolecular ones. The computational studies indicate that not only Au···Au interactions, but also Au···S and S···S ones play a role in the structure and energetic of the supramolecular species, as well as for the choice between supramolecular association or intramolecular oligomerization.

Boosting Your Brain, Part 2: The Hard Way

What's Up with the Cover?

Beating the Weekend Trend: Increased Mortality in Older Adult Traumatic Brain Injury (TBI) Patients Admitted on Weekends

Weekend admission is associated with mortality in cardiovascular emergencies and stroke but the effect of weekend admission for trauma is not well defined. We sought to determine whether differences in mortality outcomes existed for older adults with substantial head trauma admitted on a weekday versus over the weekend.

Regulating the Immune System Via IL-15 Transpresentation

Transpresentation has emerged as an important mechanism mediating IL-15 responses in a subset of lymphocytes during the steady state. In transpresentation, cell surface IL-15, bound to IL-15Rα is delivered to opposing lymphocytes during a cell-cell interaction. The events most dependent on IL-15 include the development and homeostasis of memory CD8 T cells, Natural Killer cells, invariant Natural Killer T cells, and intraepithelial lymphocytes. As lymphocyte development and homeostasis involve multiple steps and mechanisms, IL-15 transpresentation can have diverse roles throughout. Moreover, distinct stages of lymphocyte differentiation require IL-15 transpresented by different cells, which include both hematopoietic and non-hematopoietic cell types. Herein, we will describe the points where IL-15 transpresentation impacts these processes, the specific cells thought to drive IL-15 responses, as well as their role in the course of development and homeostasis.

Least Median of Squares Filtering of Locally Optimal Point Matches for Compressible Flow Image Registration

Compressible flow based image registration operates under the assumption that the mass of the imaged material is conserved from one image to the next. Depending on how the mass conservation assumption is modeled, the performance of existing compressible flow methods is limited by factors such as image quality, noise, large magnitude voxel displacements, and computational requirements. The Least Median of Squares Filtered Compressible Flow (LFC) method introduced here is based on a localized, nonlinear least squares, compressible flow model that describes the displacement of a single voxel that lends itself to a simple grid search (block matching) optimization strategy. Spatially inaccurate grid search point matches, corresponding to erroneous local minimizers of the nonlinear compressible flow model, are removed by a novel filtering approach based on least median of squares fitting and the forward search outlier detection method. The spatial accuracy of the method is measured using ten thoracic CT image sets and large samples of expert determined landmarks (available at www.dir-lab.com). The LFC method produces an average error within the intra-observer error on eight of the ten cases, indicating that the method is capable of achieving a high spatial accuracy for thoracic CT registration.

Should We Adjust Erythropoiesis-stimulating Agent Dosage to Postdialysis Hemoglobin Levels? A Pilot Study

Predialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE).

Effects of Feeding a High Omega-3 Fatty Acids Diet in Dogs with Naturally Occurring Osteoarthritis

The aim of this randomized, placebo-controlled and double-blinded trial was to compare the effect of a veterinary therapeutic diet (VTD) rich in omega-3 fatty acids (omega-3) from fish origin to a regular diet used as control (CTR) over a period of 13 weeks in dogs afflicted by naturally occurring osteoarthritis (OA). Thirty privately owned dogs were selected. Dogs had lameness confirmed by an orthopaedic examination, had stifle/hip OA and had locomotor disability based on the peak of the vertically oriented ground reaction force (PVF) measured using a force platform. At Baseline, all owners were asked to determine 2-5 activities of daily living that were the most impaired. Activities were scores (0-4) in accordance with severity using case-specific outcome measures (CSOM). The PVF was also measured. Dogs (15/group) were then randomly assigned to receive either the CTR or the VTD. The CSOM was completed twice weekly. The recording of PVF was repeated at Week 7 and 13. The VTD-fed dogs showed a significantly higher PVF at Week 7 (p < 0.001) and at Week 13 (p < 0.001) when compared to Baseline. From Baseline to Week 13, VTD-fed dogs had a mean (± SD) change in PVF recording of 3.5 ± 6.8% of body weight (%BW) compared with 0.5 ± 6.1%BW (p = 0.211) in CTR-fed dogs. This change in primary outcome was consistent with an effect size of 0.5. Conversely, dogs fed the CTR did not show significant change in PVF measurements. At the end of the study, the CSOM was significantly decreased (p = 0.047) only in VTD fed dogs. In lame OA dogs, a VTD that contains high level of omega-3 from fish origin improved the locomotor disability and the performance in activities of daily living. Such nutritional approach appears interesting for the management of OA.

Antibiotic Therapy in Necrotising External Otitis: Case Series of 32 Patients and Review of the Literature

Necrotising external otitis (NEO) is a rare but severe bone infection, usually due to Pseudomonas aeruginosa, the management of which is not standardised. Systemic antibiotic therapy is usually prescribed for at least 6 weeks, but no review has been published on this topic. We report our experience and have reviewed the literature regarding antibiotic therapy in NEO. Here we describe a case-series of consecutive NEO cases seen over an 8-year period (2004-2011) in a French tertiary-care teaching hospital. Since 2009 we have shortened the duration of antibiotic therapy to 6 weeks. We also present a review of the literature regarding antibiotic therapy in NEO. We include 32 NEO cases, with positive microbiological cultures in 30 cases. Among the 30 patients with suspected or proven P. aeruginosa infections, 27 received an initial combination therapy of ceftazidime and ciprofloxacin. The duration of antibiotic therapy and length of hospital stay were significantly reduced after 2009 (9.4 ± 3.2 weeks versus 5.8 ± 0.7, P < .0.001; and 18.2 ± 8.7 days versus 11.6 ± 6.9, P = .0.03, respectively). Patient outcomes were favorable in all cases, with a 14-month median duration of follow-up. Our literature review (30 case series) shows that initial combination therapy is associated with better outcomes as compared with single therapy (97 % versus 83 %, P < .0.001). We suggest 3 weeks of initial combination therapy (ceftazidime + ciprofloxacin, high doses) followed by 3 weeks single therapy with ciprofloxacin in susceptible P. aeruginosa NEO. A close collaboration between ear, nose and throat and infectious diseases specialists is needed.

Observational Studies in the Era of Randomized Trials: Finding the Balance

Randomized controlled trials (RCTs) constitute the gold standard for the generation of evidence-based medicine, but may not always be feasible. Furthermore, randomization alone does not guarantee the utility of the research, as evidenced by thousands of uninformative RCTs documented in the literature. Observational studies, including longitudinal, retrospective, and case-control designs, can contribute to the body of evidence in meaningful ways, provide useful information when an RCT is unethical or not feasible, generate hypotheses for RCTs, or provide preliminary work to better inform design of future RCTs. They can also be used to study rare outcomes, risk factors, and side effects, and to examine whether results from RCTs translate into effective treatment in routine practice. Use of modern statistical techniques, both in the study design and in the analysis stage, can improve the usefulness of the evidence obtained from observational studies.

Identification of the Spinal Pathways Involved in the Recovery of Baroreflex Control After Spinal Lesion in the Rat Using Pseudorabies Virus

Neurons in the rostroventrolateral medulla (RVLM) mediate baroreflex regulation (BR) of spinal sympathetic preganglionic neurons. Previously, our laboratory has shown that recovery of BR occurs in the rat after spinal hemisection. (Zahner MR, Kulikowicz E, and Schramm LP. Am J Physiol Regul Integr Comp Physiol 301: R1584-R1590, 2011). The goal of these experiments was to determine whether the observed recovery of BR is mediated by the reorganization of ipsilateral pathways or by compensation by spared contralateral pathways. To determine this, we infected the left kidney in rats with the retrograde transynaptic tracer, pseudorabies virus (PRV), either 1 or 8 wk after left spinal hemisection at either T(3) or T(8), or after a sham lesion. In sham-lesioned rats, PRV infection of RVLM neurons was bilateral. In all rats with a left hemisection, regardless of the location of the lesion (T(3) or T(8)) or postlesion recovery time (1 or 8 wk), PRV infection of left RVLM neurons was significantly reduced compared with sham-lesioned rats (P < 0.05). In a separate group of rats, we performed BR tests by measuring responses of left renal sympathetic nerve activity to pharmacologically induced decreases and increases in arterial pressure. In rats with T(8) left hemisection and 8-wk recovery, BR was robust, and acute right upper thoracic hemisection abolished all BR of left renal sympathetic nerve activity. Collectively, these data suggest that the recovery of BR is not mediated by reorganization of ipsilateral bulbospinal connections, but instead by improved efficacy of existing contralateral pathways.

Endothelial Progenitor Cells: a New Key for Endothelial Dysfunction in Migraine

We aimed to study endothelial function with biochemical and ultrasonographic markers and its relation with endothelial progenitor cells (EPCs) in patients with migraine.

Evaluation of Different Antiretroviral Drug Protocols on Naturally Infected Feline Immunodeficiency Virus (FIV) Cats in the Late Phase of the Asymptomatic Stage of Infection

The aim of this study was to evaluate the efficacy of the antiretrovirals: Zidovudine (ZDV) alone; ZDV + Recombinant Human Interferon-α (rHuIFN-α); ZDV + Lamivudine (3TC) and ZDV + valproic acid (Valp) on naturally feline immunodeficiency virus (FIV)-infected cats, in the late phase of the asymptomatic stage of infection. The follow-up was performed over one year, through clinical evaluation and the determination of viral loads and CD4+/CD8+ ratios. Neurological signs were studied by visual and auditory evoked potentials (VEP, AEP) and the responses were abnormal in 80% of the FIV-infected cats. After one year, an improvement in VEP and AEP was observed in the ZDV + Valp group and a worsening in the group receiving ZDV + rHuIFN-α. The CD4+/CD8+ ratio showed a significant increase (both intra and inter-groups) only in ZDV and ZDV + 3TC, between their pre-treatment and one year values, as well as among the other groups. Viral load only showed a significant decrease in ZDV and ZDV + 3TC groups, when comparing the values at one year of treatment vs. pre-treatment values and when the different groups were compared. In addition, the viral load decrease was significantly more pronounced in the ZDV + 3TC vs. ZDV group. We conclude that ZDV and ZDV + 3TC produce significant reductions in viral load and stimulate a recovery of the CD4+/CD8+ ratio, compared with the other protocols. It is clear that the addition of 3TC resulted in a greater reduction in viral load than use of ZDV as a single drug. Therefore, the combination ZDV + 3TC could be more effective than the sole use of ZDV.

[Hemodynamic Effects of Intravenous Omeprazole in Critically Ill Children.]

INTRODUCTION: Critical patients usually have hemodynamic disturbances which may become worse by the administration of some drugs. Omeprazole is a drug used in the prophylaxis of the gastrointestinal bleeding in these patients, but its cardiovascular effects are unknown. The objective was to study the hemodynamic changes produced by intravenous omeprazole in critically ill children and to find out if there are differences between two different doses of omeprazole. MATERIAL AND METHODS: A randomized prospective observational study was performed on 37 critically ill children aged from 1 month to 14 years of age who required prophylaxis for gastrointestinal bleeding. Of these, 19 received intravenous omeprazole 0.5mg/kg every 12hours, and 18 received intravenous omeprazole 1mg/kg every 12hours. Intravenous omeprazole was administered in 20minutes by continuous infusion pump. Heart rate, systolic, diastolic and mean arterial blood pressure, central venous pressure and ECG were recorded at baseline, and at 15, 30, 60 and 120minutes of the infusion. RESULTS: There were no significant changes in the electrocardiogram, heart rate, blood pressure and central venous pressure. No patients required inotropic therapy modification. There were no differences between the two doses of omeprazole. CONCLUSIONS: Intravenous omeprazole administration of 0.5mg/kg and 1mg/kg is a hemodynamically safe drug in critically ill children.

Excess of the Endocannabinoid Anandamide During Lactation Induces Overweight, Fat Accumulation and Insulin Resistance in Adult Mice

Environmental conditions in early life can induce permanent physiological changes, sometimes increasing the risk of chronic diseases during adulthood. Neural and peripheral circuits controlling energy balance may be modulated during such a critical period. Since type 1 cannabinoid receptors (CB1R) have recently emerged as targets for modulating energy balance, their premature chronic activation during early life may result in long-term metabolic consequences associated to overweight/obesity. Endogenous activation of CB1R mainly occurs after binding to the endocannabinoid Anandamide (AEA).

Risk Factors for In-hospital Mortality Among Children with Tuberculosis: the 25-year Experience in Peru

We examined factors associated with in-hospital death among children with tuberculosis (TB). We hypothesized that a negative response to tuberculin skin testing (TST) would predict decreased survival.

Associations Among Physician Advice, Physical Activity, and Socio-demographic Groups in Older Spanish Adults

This study examined the relationship between medical advice to engage in physical activity with type of demand required by physical activity and demographic variables. A cross-sectional study was developed, featuring a questionnaire on physicians' advice, and type of demand. The questionnaire was completed by a probability and nationwide sample of older adults in Spain (n = 933, M = 74.1, range 65-93), randomly selected using multistage sampling. More physically active older adults have, more often than the less active, received physicians' advice to engage in physical activity. There is a significant relationship between medical advice and type of demand (p < .01) and age (p < .05). However, no relationship was found between physician medical advice and gender, social class, or income. Physicians can effectively promote physical activity among sedentary older adults through appropriate advice. Consequently, health authorities should promote physicians' advising older patients to pursue physical activity.

Construction of Coffee Transcriptome Networks Based on Gene Annotation Semantics

Gene annotation is a process that encompasses multiple approaches on the analysis of nucleic acids or protein sequences in order to assign structural and functional characteristics to gene models. When thousands of gene models are being described in an organism genome, construction and visualization of gene networks impose novel challenges in the understanding of complex expression patterns and the generation of new knowledge in genomics research. In order to take advantage of accumulated text data after conventional gene sequence analysis, this work applied semantics in combination with visualization tools to build transcriptome networks from a set of coffee gene annotations. A set of selected coffee transcriptome sequences, chosen by the quality of the sequence comparison reported by Basic Local Alignment Search Tool (BLAST) and Interproscan, were filtered out by coverage, identity, length of the query, and e-values. Meanwhile, term descriptors for molecular biology and biochemistry were obtained along the Wordnet dictionary in order to construct a Resource Description Framework (RDF) using Ruby scripts and Methontology to find associations between concepts. Relationships between sequence annotations and semantic concepts were graphically represented through a total of 6845 oriented vectors, which were reduced to 745 non-redundant associations. A large gene network connecting transcripts by way of relational concepts was created where detailed connections remain to be validated for biological significance based on current biochemical and genetics frameworks. Besides reusing text information in the generation of gene connections and for data mining purposes, this tool development opens the possibility to visualize complex and abundant transcriptome data, and triggers the formulation of new hypotheses in metabolic pathways analysis.

Adolescent Metabolic Syndrome Risk Is Increased with Higher Infancy Weight Gain and Decreased with Longer Breast Feeding

Background. Prevalence of the metabolic syndrome is increasing in pediatric age groups worldwide. Meeting the criteria for the metabolic syndrome puts children at risk for later cardiovascular and metabolic disease. Methods. Using linear regression, we examined the association between infant weight gain from birth to 3 months and risk for the metabolic syndrome among 16- to 17-year-old Chilean adolescents (n = 357), accounting for the extent of breastfeeding in infancy and known covariates including gender, birth weight, and socioeconomic status. Results. Participants were approximately half male (51%), born at 40 weeks of gestation weighing 3.5 kg, and 48% were exclusively breastfed for ≥90 days. Factors independently associated with increased risk of metabolic syndrome in adolescence were faster weight gain in the first 3 months of life (B = 0.16, P < 0.05) and male gender (B = 0.24, P < 0.05). Breastfeeding as the sole source of milk for ≥90 days was associated with significantly decreased risk of metabolic syndrome (B = -0.16). Conclusion. This study adds to current knowledge about early infant growth and breastfeeding and their long-term health effects.

The Effects of Essential Oils Carvacrol and Thymol on Growth of Penicillium Digitatum and P. Italicum Involved in Lemon Decay

In this work the antifungal efficacy of thymol, carvacrol and the mixture of both pure essential oils has been proved against Penicillium digitatum and Penicillium italicum, by using in vitro (liquid media, PDA plates and disk growth) and in vivo (lemon) tests. Results indicated that both essential oils were effective in inhibiting fungal growth in all in vitro tests, with the highest efficacy displayed by thymol. In addition, the application of wax with thymol and carvacrol to lemons inoculated with P. digitatum demonstrated the reduction of decay (expressed as percentage of infected fruit surface) in a concentration dependent manner, as well as reduced respiration rate, ethylene production and total acidity losses. Thus, the application of these essential oils together with wax in the citrus packing lines could be considered as good alternatives to reduce the use of synthetic fungicides.

Bladder Hemangioma: Case Report

Bladder hemangioma is a benign rare lesion. There are no pathognomonic clinical signs and management is controversial due to the bleeding risk. We report a bladder cavernous hemangioma resolved using bipolar transurethral resection.

The SOX Family of Genes in Cancer Development: Biological Relevance and Opportunities for Therapy

INTRODUCTION: It has been more that 20 years since the first SOX genes were discovered. Twenty SOX genes have now been identified in mammals and classified into groups with respect to protein identity. SOX family genes code for transcription factors that either activate or repress lineage-specific genes during embryonic development. Furthermore, SOX genes are altered in human genetic syndromes and malignancies, highlighting their involvement in development. AREAS COVERED: This paper reviews the role of SOX genes in embryonic development and human diseases, and describe their involvement in human cancers and possible use in cancer therapeutics. EXPERT OPINION: Since most SOX genes behave as oncogenes in many human cancers, their targeting has great therapeutic potential. However, novel specific therapies such as those recently developed against growth factor receptors based on monoclonal antibodies, small inhibitors and even small interfering RNA strategies are difficult to implement for transcriptional factors. Novel strategies are being developed to overcome some of these obstacles. Alternative approaches could indirectly tackle altered SOX genes by exploiting the related molecular networks.

Aqueous Extract of Ocimum Tenuiflorum Decreases Levels of Blood Glucose in Induced Hyperglycemic Tilapia (Oreochromis Niloticus)

To evaluate, in hyperglycemic tilapia [Oreochromis niloticus (O. niloticus)], the effect of this aqueous extract on blood glucose levels.

Pre-hospital Electrocardiography by Emergency Medical Personnel: Effects on Scene and Transport Times for Chest Pain and ST-segment Elevation Myocardial Infarction Patients

This study sought to measure the impact of pre-hospital (PH) electrocardiography (ECG) on scene-to-hospital time for patients with chest pain of cardiac origin and those with ST-segment elevation myocardial infarction (STEMI).

Late Arterial Switch, Without Previous Preparation or Extracorporeal Membrane Oxygenation Back-up

Age Estimation Through Histological Study of Trabecular Volume and Cortical Bone Width of the Iliac Crest

There have been many methods proposed to estimate the age of human bones in forensic medicine or in forensic anthropology, including those that assess histological structures. In this study, age was evaluated through the histomorphometric study of trabecular volume and cortical width of the right iliac crest. A total of 25 samples A total of 66 samples (42 male and 24 female) were obtained from necropsies of judicial cases, with ages ranging from 13 to 58years, who had died a sudden or violent death. The samples were obtained using Bordier's trocar for bone biopsy, in a period not exceeding 24h after death. The samples were examined without decalcification, with 96° alcohol dehydration, embedding in methyl methacrylate, and sectioned with a microtome Reichert (3μm). The sections were fixed on microscope slides and stained using toluidine blue, Goldner trichrome and hematoxylin-eosin methods. The samples were studied under a Leica DM LB microscope and the images were digitally captured. The digital images were processed using an image analysis program and data were analyzed using the SPSS statistical package. The results demonstrated that the combination of the trabecular volume and cortical width acted as predictors of the age in subjects which did not suffer from any deterioration of bone and/or mineral metabolism.

Hyperoxia, Hypocapnia and Hypercapnia As Outcome Factors After Cardiac Arrest in Children

PURPOSE: Arterial hyperoxia after resuscitation has been associated with increased mortality in adults. The aim of this study was to test the hypothesis that post-resuscitation hyperoxia and hypocapnia are associated with increased mortality after resuscitation in pediatric patients. METHODS: We performed a prospective observational multicenter hospital-based study including 223 children aged between 1 month and 18 years who achieved return of spontaneous circulation after in-hospital cardiac arrest and for whom arterial blood gas analysis data were available. RESULTS: After return of spontaneous circulation, 8.5% of patients had hyperoxia (defined as PaO(2)>300mmHg) and 26.5% hypoxia (defined as PaO(2)<60mmHg). No statistical differences in mortality were observed when patients with hyperoxia (52.6%), hypoxia (42.4%), or normoxia (40.7%) (p=0.61). Hypocapnia (defined as PaCO(2)<30mmHg) was observed in 13.5% of patients and hypercapnia (defined as PaCO(2)>50mmHg) in 27.6%. Patients with hypercapnia or hypocapnia had significantly higher mortality (59.0% and 50.0%, respectively) than patients with normocapnia (33.1%) (p=0.002). At 24h after return of spontaneous circulation, neither PaO(2) nor PaCO(2) values were associated with mortality. Multiple logistic regression analysis showed that hypercapnia (OR, 3.27; 95% CI, 1.62-6.61; p=0.001) and hypocapnia (OR, 2.71; 95% CI, 1.04-7.05; p=0.04) after return of spontaneous circulation were significant mortality factors. CONCLUSIONS: In children resuscitated from cardiac arrest, hyperoxemia after return of spontaneous circulation or 24h later was not associated with mortality. On the other hand, hypercapnia and hypocapnia were associated with higher mortality than normocapnia.

Replacing Xylene with N-heptane for Paraffin Embedding

In standard histological technique, aromatic solvents such as xylene and toluene are used as clearing agents between ethanol dehydration and paraffin embedding. In addition, these solvents are used for de-waxing paraffin sections. Unfortunately, these solvents are harmful and therefore adequate substitutes would be useful. We suggest the use of n-heptane as a convenient substitute for xylene. Paraffin sections of rat tissues processed with n-heptane and stained with hematoxylin-eosin or Masson's trichrome showed proper embedment, well preserved morphology and excellent staining.

Clues for Diagnosing Primary Pancreatic Lymphoma

Primary pancreatic lymphoma (PPL), a localized lymphoma in the pancreas, accounts for <0.5% of all pancreatic masses and presents with symptoms favoring the more common adenocarcinoma. It is important to differentiate PPL from adenocarcinoma since treatment and prognosis differ considerably. PPL is potentially curable with chemotherapy, especially if it is diagnosed at early stages. A definitive diagnosis can only be based on histopathological findings. Endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) is a reliable, minimally invasive and cost-effective method for this purpose. Even though there are neither typical clinical features nor specific biomarker for the diagnosis of PPL, certain common presentations have been observed which may indicate PPL. We herein present the case of a 43-year-old man who was successfully diagnosed with PPL by EUS-guided FNA. His clinical, laboratory and radiographic findings supported PPL over adenocarcinoma as well. This case demonstrates that high clinical suspicion based on clinical, laboratory and imaging features is critical in PPL diagnosis and management.

Hormesis: Protecting Neurons Against Cellular Stress in Parkinson Disease

Protein folding stress is a salient feature of the most frequent neurodegenerative diseases. Although the accumulation of abnormally folded proteins is a well-characterized event underlying the pathology, the way cells respond to this phenomenon is not well understood. Signs of endoplasmic reticulum (ER) stress are a common marker of neurodegeneration in many diseases, which may represent two contrasting processes: cell protection events due to activation of adaptive programs, or a chronic stress state that culminates in apoptosis to eliminate irreversibly injured cells. Autophagy has been proposed as a protective mechanism to overcome neurodegeneration that is also modulated by ER stress. In this issue of autophagy Bertrand Mollereau's group provides novel evidence indicating that engagement of nonharmful levels of ER stress protects against experimental Parkinson disease. At the mechanistic level, a homeostatic crosstalk between ER stress signaling and the autophagy pathway was proposed to mediate the therapeutic effects. This study, together with recent findings, supports the involvement of a "hormesis mechanism" to handle degeneration through preconditioning mediated by a dynamic balance between ER stress and autophagy. The implications for aging and future therapeutic development are discussed.

Oxidative Stress Markers Are Associated to Vascular Recurrence in Non-cardioembolic Stroke Patients Non-treated with Statins

ABSTRACT: BACKGROUND: Since atherogenesis is related to oxidative stress, our objective was to study the association of oxidative stress markers with the vascular recurrence in non-cardioembolic stroke. METHODS: Atherosclerotic and oxidative stress markers were evaluated on admission, in 477 patients suffering from a first non-cardioembolic stroke. Patients were followed at 6 and 12 months after inclusion, recording cardiovascular events. As markers of endothelial oxidative stress we used oxidized LDL, Cu/Zn superoxide dismutase and 8-OH deoxiguanosine. 136 patients were being treated with statins at the moment of serum samples acquisition. RESULTS: Patients who suffered vascular recurrence or vascular-origin death had higher levels of 8-OHDG (40.06±24.70vs33.11±15.18;p=0.003). We also found associations between vascular recurrence or vascular origin death and Cu/ZnSOD (OR,1.02; 95%CI,1.00-1.03;p=0.0001) and 8-OHDG (OR,1.12;95%CI,1.08-1.16;p<0.0001) in a subgroup of 333 patients that were not in treatment with statins on admission. We also found associations between 8-OHDG and intima media thickness (IMT) (OR,1.13;95%CI,1.09-1.16;p<0.0001), presence of ipsilatieral stenosis≥50% (OR,1.03;95%CI1.00-1.05;p=0.007) and other atherosclerotic plaque characteristics. CONCLUSIONS: Specific oxidative stress markers were found to be markers of atherosclerosis plaque types and vascular recurrence in non-statins treated patients at admission.

Prognostic Impact of Baseline Low Blood Pressure in Hypertensive Patients with Stable Coronary Artery Disease of Daily Clinical Practice

The authors' aim was to investigate the prognostic value of first-visit systolic and diastolic blood pressure (SBP/DBP) in hypertensive patients with stable coronary artery disease (sCAD) in conditions of contemporary daily clinical practice. From February 1, 2000, to January 31, 2004, 690 consecutive hypertensive patients with sCAD (mean age 68 ± 10 years, 65% male) were prospectively followed in the outpatient cardiology clinic for major events (acute coronary syndrome, revascularization, stroke, heart failure, or death) and associations with baseline SBP/DBP were investigated. At first visit, median SBP/SDP were 130/75 mm Hg (interquartile range, 25-75; 120-140/70-80 mm Hg). After 25 months of follow-up (median), 19 patients died (2.8%); 10 from cardiovascular causes (1.5%), 87 patients experienced a coronary event (13%), and 130 patients (19%) a major event. After adjusting for baseline variables, DBP <75 mm Hg or SBP <130 mm Hg resulted in independent predictors of major events (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.07-2.16, P=.02; HR, 1.68; 95% CI, 1.18-2.40, P=.004, respectively), coronary events (HR, 1.78; 95% CI, 1.15-2.75, P=.009; HR, 1.84; 95% CI, 1.20-2.83, P=.005, respectively), and cardiovascular mortality (HR, 7.02; 95% CI, 1.26-39.04, P=.03; HR, 9.26; 95% CI, 1.33-64.32, P=.02, respectively). In this study, a low first-visit SBP or DBP was associated with an adverse prognosis in hypertensive patients with sCAD of contemporary daily clinical practice.

Evaluation of a Nationally Funded State-based Programme to Reduce Fatal Occupational Injuries

The Fatality Assessment and Control Evaluation (FACE) programme was established by the National Institute for Occupational Safety and Health to help prevent occupational traumatic fatalities by funding states to conduct targeted fatality investigations within cause-specific focus areas and associated prevention efforts.

Measurement of Functional Outcomes in the Major Extremity Trauma Research Consortium (METRC)

Measurement of functional outcome is a central tool in the assessment of the human and economic consequences of trauma. As such, functional outcome is the ideal basis against which to judge the efficacy of surgical approaches, drugs, and devices in the context of evidence-based medicine. A well-designed outcome measurement plan improves the validity of clinical research, facilitates the optimal use of limited research resources, and maximizes opportunities for future secondary data analyses. However, a key challenge in the development of a study measurement plan is the identification of appropriate, practical, well-validated measures. The Major Extremity Trauma Research Consortium (METRC) is a large 5-year research effort to develop and conduct multicenter clinical studies relevant to the treatment and outcomes of orthopaedic trauma. METRC is funded to conduct nine clinical studies. One of the main goals is to benefit from the consortium approach by standardizing data collection across these studies. METRC investigators have developed a standard set of measurement instruments designed to examine outcomes across a defined set of key domains: complications, depression, posttraumatic stress disorder, pain, activity and participation, health-related quality of life, patient satisfaction, and healthcare utilization. In addition, METRC investigators have developed a standard set of sociodemographic and clinical covariates to be collected across all studies.

Longitudinal Stent Compression is Not Always a Bad Event: a Case Report

Ostial left anterior descending artery stent implantation was performed, while trying to cross another stent through the left main coronary artery into the left circumflex artery the stent was detached from the delivery balloon, subsequently jamming the stent of the ostial left anterior descending artery stent. Removing the detached stent was possible, but longitudinal compression of the ostial left anterior descending artery stent occurred. We finally took advantage of the longitudinal compression to advance the equipment into the left circumflex artery with good final result.

Highly Potent Aminopyridines As Syk Kinase Inhibitors

A novel class of potent Syk inhibitors has been developed from rational design. Highly potent aminopyridine derivatives bearing a 4-trifluoromethyl-2-pyridyl motif and represented by compound 13b IC(50): 0.6 nM were identified. Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the central core provided diverse potent non-cytotoxic Syk inhibitors showing nanomolar activity inhibiting human mast cell line LAD2 degranulation.

CASE Plots for the Chemotype-Based Activity and Selectivity Analysis: A CASE Study of Cyclooxygenase Inhibitors

Structure-activity characterization of molecular databases plays a central role in drug discovery. However, the characterization of large databases containing structurally diverse molecules with several end-points represents a major challenge. For this purpose, the use of chemoinformatic methods plays an important role to elucidate structure-activity relationships. Herein, a general methodology, namely Chemotype Activity and Selectivity Enrichment plots, is presented. Chemotype Activity and Selectivity Enrichment plots provide graphical information concerning the activity and selectivity patterns of particular chemotypes contained in structurally diverse databases. As a case study, we analyzed a set of 658 compounds screened against cyclooxygenase-1 and cyclooxygenase-2. Chemotype Activity and Selectivity Enrichment plots analysis highlighted chemotypes enriched with active and selective molecules against cyclooxygenase-2; all this in a simple 2D graphical representation. Additionally, the most active and selective chemotypes detected in Chemotype Activity and Selectivity Enrichment plots were analyzed separately using the previously reported dual activity-difference maps. These findings indicate that Chemotype Activity and Selectivity Enrichment plots and dual activity-difference maps are complementary chemoinformatic tools to explore the structure-activity relationships of structurally diverse databases screened against two biological end-points.

The Pollen Dispersal Kernel and Mating System of an Insect-pollinated Tropical Palm, Oenocarpus Bataua

Pollen dispersal shapes the local genetic structure of plant populations and determines the opportunity for local selection and genetic drift, but has been well studied in few animal-pollinated plants in tropical rainforests. Here, we characterise pollen movement for an insect-pollinated Neotropical canopy palm, Oenocarpus bataua, and relate these data to adult mating system and population genetic structure. The study covers a 130-ha parcel in which all adult trees (n=185) were mapped and genotyped at 12 microsatellite loci, allowing us to positively identify the source tree for 90% of pollination events (n=287 of 318 events). Mating system analysis showed O. bataua was effectively outcrossed (t(m)=1.02) with little biparental inbreeding (t(m)-t(s)=-0.005) and an average of 5.4 effective pollen donors (N(ep)) per female. Dispersal distances were relatively large for an insect-pollinated species (mean=303 m, max=1263 m), and far exceeded nearest-neighbour distances. Dispersal kernel modelling indicated a thin-tailed Weibull distribution offered the best fit to the genetic data, which contrasts with the fat-tailed kernels typically reported for pollen dispersal in trees. Preliminary analyses suggest that our findings may be explained, at least in part, by a relatively diffuse spatial and temporal distribution of flowering trees. Comparison with previously reported estimates of seed movement for O. bataua suggests that pollen and seed dispersal distances may be similar. These findings add to the growing body of information on dispersal in insect-pollinated trees, but underscore the need for continued research on tropical systems in general, and palms in particular.

Survival of Patients with Marginal Zone Lymphoma: Analysis of the Surveillance, Epidemiology, and End Results Database

BACKGROUND.: Prognostic factors and outcomes in patients with marginal zone lymphoma (MZL) have been studied in small cohort studies, which may not reflect the population at large. METHODS.: Clinical characteristics and survival outcomes of adult patients with MZL who were diagnosed between 1995 and 2009 were evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. The authors generated clinical prognostic models for subtypes of MZL and compared survival during the periods of 1995 through 2000, 2001 through 2004, and 2005 through 2009. RESULTS.: The prognosis was significantly better for patients with mucosa-associated lymphoid tissue (MALT) lymphoma (5-year relative survival rate of 88.7%; P < .0001) compared with those with the splenic MZL (SMLZ)or nodal MZL (NMZL) subtypes (5-year relative survival rates of 79.7% and 76.5%, respectively). There was evidence of improved outcomes in patients with NMZL and MALT lymphomas between 1995 and 2009 (P < .0001), with no difference noted in patients with SMZL (P = .56). Advancing age and the presence of B symptoms had prognostic significance in all MZL subtypes. Male sex and stage of disease were significant only for the NMZL and MALT categories. Survival in patients with MALT lymphomas varied depending on the site of origin, with a worse prognosis noted in those with gastrointestinal and pulmonary locations of origin (5-year incidence rate of lymphoma-related death, 9.5%-14.3%) compared with ocular, cutaneous, and endocrine sites (4.5%-7.8%; P < .0001). CONCLUSIONS.: The survival for patients with SMZL is similar to that for those with NMZL, and unlike the NMZL and MALT subtypes, it has not improved over the past decade. The prognosis of patients with MALT lymphoma varies according to the anatomical site of origin. Cancer 2012. © 2012 American Cancer Society.

Confirmation of TNIP1 but Not RHOB and PSORS1C1 As Systemic Sclerosis Risk Factors in a Large Independent Replication Study

INTRODUCTION: A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. METHODS: 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. RESULTS: Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 p(MH)=1.94×10(-4), OR 1.19; rs4958881 p(MH)=3.26×10(-5), OR 1.19; rs3792783 p(MH)=2.16×10(-4), OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. CONCLUSIONS: These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.

Intraductal Papillary Mucinous Neoplasms: Does a Family History of Pancreatic Cancer Matter?

The purpose of this study is to compare surgically resected intraductal papillary mucinous neoplasms (IPMNs) in patients with and without a family history of pancreatic cancer to gain insight into differences that may suggest the need for differential management.

Objective Evaluation of Acute Adverse Events and Image Quality of Gadolinium-based Contrast Agents (gadobutrol and Gadobenate Dimeglumine) by Blinded Evaluation. Pilot Study

PURPOSE: The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. METHODS: Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. RESULTS: No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. CONCLUSIONS: Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events.

New Concepts and Best Practices for Management of Pre- and Post-transplantation Cancer

Solid-organ transplant recipients are at increased risk of developing cancer compared with the general population. Tumours can arise de novo, as a recurrence of a preexisting malignancy, or from the donated organ. The ATOS (Aula sobre Trasplantes de Órganos Sólidos; the Solid-Organ Transplantation Working Group) group, integrated by Spanish transplant experts, meets annually to discuss current advances in the field. In 2011, the 11th edition covered a range of new topics on cancer and transplantation. In this review we have highlighted the new concepts and best practices for managing cancer in the pre-transplant and post-transplant settings that were presented at the ATOS meeting. Immunosuppression plays a major role in oncogenesis in the transplant recipient, both through impaired immunosurveillance and through direct oncogenic activity. It is possible to transplant organs obtained from donors with a history of cancer as long as an effective minimization of malignancy transmission strategy is followed. Tumour-specific wait-periods have been proposed for the increased number of transplantation candidates with a history of malignancy; however, the patient's individual risk of death from organ failure must be taken into consideration. It is important to actively prevent tumour recurrence, especially the recurrence of hepatocellular carcinoma in liver transplant recipients. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients, with long-term intensive screening programs showing a reduced incidence of cancer post-transplantation. Proposed management strategies for post-transplantation malignancies include viral monitoring and prophylaxis to decrease infection-related cancer, immunosuppression modulation with lower doses of calcineurin inhibitors, and addition of or conversion to inhibitors of the mammalian target of rapamycin.

Immune Gene Transcription in Drosophila Adult Flies Infected by Entomopathogenic Nematodes and Their Mutualistic Bacteria

Despite impressive advances in the broad field of insect innate immunity, our understanding of the molecular basis of insect immune responses to nematode infections remains incomplete. Here we have investigated the transcriptional induction of immune pathway genes in the fruit fly Drosophila melanogaster upon infection with the entomopathogenic (or insect pathogenic) nematodes Heterorhabditis bacteriophora and their mutualistic bacteria Photorhabdus luminescens, either collectively or separately. We show that in most cases, infection of wild-type adult flies with Heterorhabditis nematodes carrying or lacking mutualistic Photorhabdus bacteria results in the up-regulation of genes in the Toll, Imd, JAK/STAT, JNK and TGF-beta pathways. We also find that direct injection of Photorhabdus bacteria into flies fails to induce the transcription of antimicrobial peptide genes and stress-related genes in Drosophila. These results suggest that Heterorhabditis nematodes and their associated Photorhabdus bacteria employ distinct strategies to evade the Drosophila immune response and establish infection.

Active Relatives and Health-related Physical Fitness in European Adolescents: The HELENA Study

Abstract High physical fitness in childhood and adolescence is positively associated with favourable health-related outcomes. Our aim was to examine the relationship between relatives' (father, mother, brother, sister, and best friend) physical activity engagement and encouragement on adolescents' physical fitness. Adolescents were part of the HELENA study, a multi-centre study conducted in 10 cities from nine European countries in 2006-2008. Participants were 3288 adolescents (48% boys, 52% girls) aged 12.5-17.5 years with valid data on at least one of the three fitness variables studied: muscular strength (standing long jump), speed/agility (4×10 m shuttle run), and cardiorespiratory fitness (20 m shuttle run). The adolescents reported their relatives' physical activity engagement and encouragement. Analysis of covariance showed that relatives' physical activity engagement (father, mother, brother, and best friend) was positively related to cardiorespiratory fitness (P < 0.05); and mother's and sisters' physical activity engagement were positively associated with higher muscular strength in adolescents (P < 0.05). Furthermore, father's physical activity encouragement was positively linked to physical fitness (all fitness components) in adolescents (P < 0.05). Interventions aimed at improving physical fitness in young people might be more successful when family members, particularly mothers and fathers, are encouraged to engage in physical activity and support adolescents' physical activity.

On the Mechanism Behind the Instability of Isoreticular Metal-organic Frameworks (IRMOFs) in Humid Environments

Increasing the resistance to humid environments is mandatory for the implementation of isoreticular metal-organic frameworks (IRMOFs) in industry. To date, the causes behind the sensitivity of [Zn(4)(μ(4)-O)(μ-bdc)(3)](8)(IRMOF-1; bdc=1,4-benzenedicarboxylate) to water remain still open. A multiscale scheme that combines Monte Carlo simulations, density functional theory and first-principles Born-Oppenheimer molecular dynamics on IRMOF-1 was employed to unravel the underlying atomistic mechanism responsible for lattice disruption. At very low water contents, H(2)O molecules are isolated in the lattice but provoke a dynamic opening of the terephthalic acid, and the lattice collapse occurs at about 6% water weight at room temperature. The ability of Zn to form fivefold coordination spheres and the increasing basicity of water when forming clusters are responsible for the displacement of the organic linker. The present results pave the way for synthetic challenges with new target linkers that might provide more robust IRMOF structures.

Successful Public Health Response to Four Cases of Imported Measles in Panama

In Panama, the last endemic cases of measles occurred in 1995. In this paper, we report four cases of imported measles in three girls and one boy after they returned from a trip to Poland and Israel between 28 April and 11 May 2011. The etiologic diagnosis of the four cases was confirmed by detection of IgM antibodies against measles virus and positive polymerase chain reaction using measles-specific primers. All cases had genotype D4 with close genetic similarity to virus reported from Poland. Public health interventions included isolation of the cases in their homes and an extensive search for and vaccination of contacts of the four cases, regardless of their vaccination status. A nationwide vaccination campaign was also implemented after the first case was identified. A total of 70,950 measles vaccine doses were administered in Panama in the two months following the identification of these cases. In addition, 94,179 persons were confirmed to have their immunization schedule up-to-date and did not receive the vaccine. No secondary cases were detected in Panama in the following six months.

Toward a Formal Synthesis of Laureatin: Unexpected Rearrangements Involving Cyclic Ether Nucleophiles

Laureatin, a metabolite of the red algae Laurencia nipponica, has shown potent activity as a mosquito larvicide. The two previously published syntheses of laureatin involved an initial preparation of the 8-membered cyclic ether, followed by formation of the oxetane ring. Our strategy was the reverse, i.e., to utilize an oxetane as the framework to construct the larger ring. During this work, attempted N-bromosuccinimide (NBS)-mediated cyclization of oxetane alcohol 17, prepared from readily accessible 2-methyleneoxetane 12, yielded epoxytetrahydrofuran 19 rather than the expected laureatin core. Further derivatization of 19 yielded trans fused bis-tetrahydrofuran 32. The synthesis of 19 and 32, as well as structural and stereochemical elucidation studies, are described.

Overwhelmed by Choices

Do Not Brainstorm!

Conserved Transcriptional Unit Organization of the Cag Pathogenicity Island Among Helicobacter Pylori Strains

The Helicobacter pyloricag pathogenicity island (cag PAI) encodes a type IV secretion system that is more commonly found in strains isolated from patients with gastroduodenal disease than from those with asymptomatic gastritis. Genome-wide organization of the transcriptional units in H. pylori strain 26695 was recently established using RNA sequence analysis (Sharma et al., 2010). Here we used quantitative reverse-transcription polymerase chain reaction of open reading frames and intergenic regions to identify putative cag PAI operons in H. pylori; these operons were analyzed further by transcript profiling after deletion of selected promoter regions. Additionally, we used a promoter-trap system to identify functional cag PAI promoters. The results demonstrated that expression of genes on the H. pyloricag PAI varies by nearly five orders of magnitude and that the organization of cag PAI genes into transcriptional units is conserved among several H. pylori strains, including, 26695, J99, G27, and J166. We found evidence for 20 transcripts within the cag PAI, many of which likely overlap. Our data suggests that there are at least 11 operons: cag1-4, cag3-4, cag10-9, cag8-7, cag6-5, cag11-12, cag16-17, cag19-18, cag21-20, cag23-22, and cag25-24, as well as five monocistronic genes (cag4, cag13, cag14, cag15, and cag26). Additionally, the location of four of our functionally identified promoters suggests they are directing expression of, in one case, a truncated version of cag26 and in the other three, transcripts that are antisense to cag7, cag17, and cag23. We verified expression of two of these antisense transcripts, those antisense to cag17 and cag23, by reverse-transcription polymerase chain reaction. Taken together, our results suggest that the cag PAI transcriptional profile is generally conserved among H. pylori strains, 26695, J99, G27, and J166, and is likely complex.

MRI of Cervical Spinal Cord Infarction in a Patient with Sickle Cell Disease

We report a patient with sickle cell disease who developed spinal cord ischemia. Initial conventional magnetic resonance imaging (MRI) was unremarkable, but diffusion-weighted imaging showed restricted diffusion in the cervical spinal cord. Follow-up MRI performed 3 days later showed development of findings on conventional images that confirmed the infarction.

Case Report of Systemic IgG-related Disease Affecting the Pancreas and Orbit

The purpose was to describe the magnetic resonance imaging appearance of the brain and spine in a patient.

Subtype Specificity Interaction of Bactridines with Mammalian, Insect and Bacterial Sodium Channels Under Voltage Clamp Conditions

The present work demonstrates that bactridines (Bacts) possess different selectivities for neuronal and muscular voltage-dependent sodium (Na(V) ) channels, with subtle differences on channel isoforms. Bacts 2, 3, 4, 5 and 6 (100 nm) reduced the peak current of several skeletal and neuronal channel isoforms selectively. Bacts 2 and 3 were more potent on Na(V) 1.4, Bacts 4 and 6 on Na(V) 1.3 and Bact 5 on Na(V) 1.7. Bactridines (except Bacts 1 and 5) caused a hyperpolarizing shift in the V(1/2) of activation and inactivation of Na(V) 1.3, Na(V) 1.4 and Na(V) 1.6. Voltage shifts of Boltzmann curves fitted to activation and inactivation occurred with a decrease in κ. Since the slope is proportional to κ = RT/zF, changes in κ probably express changes in z, the valence, in a voltage-dependent manner. Changes in z may express toxin-induced changes in the channel ionic environment, perhaps due to surface charges of the molecules. Bact 2 induced a Na(V) 1.2 voltage shift of the activation curves but no shift of the mutant Na(V) 1.2 IFM/QQQ; peak I(N) (a) was reduced in both channel forms, suggesting that channel blockage resulted from toxin binding to a site partially distinct from the α subunit binding site 4. Bactridines emerge as potential research tools to understand sodium channel isoform structure-function relationships and also as pharmacologically interesting peptides.

Not All Aggressive Adult T-cell Leukemia/lymphoma Subtypes Are Created Equal

Bronchoesophageal Fistula Secondary to Broncholith

Is Psycho-physical Stress a Risk Factor for Stroke? A Case-control Study

Chronic stress is associated with cardiovascular diseases, but the link with stroke has not been well established. Stress is influenced by life-style habits, personality type and anxiety levels. We sought to evaluate psycho-physical stress as a risk factor for stroke, while assessing gender influences.

Familial Hemiplegic Migraine with Prolonged Global Aura: Follow-up Findings of Subtraction Ictal SPECT Co-registered to MRI (SISCOM)

All authors contributed equally to this work. Susana Arias-Rivas wrote the main paper. Manuel Rodriguez-Yáñez investigated the supplementary data. Julia Cortés and Pablo Aguiar performed the nuclear image studies and analysed and described the neuroimaging results. María Pardo, Rogelio Leira and Jose Castillo jointly conceived the study, followed the patient and prepared the manuscript. Miguel Blanco discussed the results. All authors discussed the results and implications and commented on the manuscript at all stages.

SIGLEC1 and SIGLEC7 Expression in Circulating Monocytes of Patients with Multiple Sclerosis

BACKGROUND: Sialic acid binding immunoglobulin-like lectins (Siglecs) are cell surface receptors that recognize sialic acids and may attenuate immune responses and reduce inflammation. OBJECTIVE: The purpose of this study was to investigate the role of two members of the Siglec family, SIGLEC1 and SIGLEC7, in the clinical course and disease activity of patients with multiple sclerosis (MS). METHODS: SIGLEC1 and SIGLEC7 expression was determined by flow cytometry in the blood monocytes of 16 healthy controls and 55 untreated MS patients (13 primary progressive MS (PPMS) patients, 13 secondary progressive MS (SPMS) patients and 29 relapsing-remitting MS (RRMS) patients (18 during clinical remission and 11 during relapse)). RESULTS: SIGLEC1 expression by CD14+ monocytes was significantly increased in MS patients compared with controls (p=0.025 for percentage of positive cells; p=0.007 for mean fluorescence intensity (MFI)). Stratification of patients into different clinical forms revealed increased SIGLEC1 expression in patients with progressive forms of the disease, particularly in those with PPMS (p=0.003 for percentage of positive cells and p=0.001 for MFI when compared with controls; p=0.031 for percentage of positive cells when compared with RRMS patients). Both inflammatory and resident monocytes contributed to the increase in SIGLEC1 expression observed in PPMS patients. SIGLEC7 expression was significantly up-regulated in blood monocytes from RRMS during relapse compared with patients during clinical remission (p=0.001 for MFI). CONCLUSIONS: These findings suggest roles for SIGLEC1 in the chronic progressive phases of MS and for SIGLEC7 in acute disease activity.

A Direct Reaction Approach for the Synthesis of Zeolitic Imidazolate Frameworks: Template and Temperature Mediated Control on Network Topology and Crystal Size

The direct acid-base reaction between ZnO/CoO/Co(OH)(2) and imidazolic ligands under moderate heating (100-160 °C), in a closed vessel, leads to the generation of the corresponding zinc/cobalt-imidazolates in a high yield (87-97%) in which network topology is controlled by the addition of small amounts of structure directing agents. Moreover, the fine tuning of the thermal process at the synthetic stage permits us to increase the crystal size, and even to grow X-ray quality single crystals.

Phosphodiesterase III Inhibition Increases CAMP Levels and Augments the Infarct Size Limiting Effect of a DPP-4 Inhibitor in Mice with Type-2 Diabetes Mellitus

PURPOSE: We assessed whether phosphodiesterase-III inhibition with cilostazol (Cil) augments the infarct size (IS)-limiting effects of MK0626 (MK), a dipeptidyl-peptidase-4 (DPP4) inhibitor, by increasing intracellular cAMP in mice with type-2 diabetes. METHODS: Db/Db mice received 3-day MK (0, 1, 2 or 3 mg/kg/d) with or without Cil (15 mg/kg/d) by oral gavage and were subjected to 30 min coronary artery occlusion and 24 h reperfusion. RESULTS: Cil and MK at 2 and 3 mg/kg/d significantly reduced IS. Cil and MK had additive effects at all three MK doses. IS was the smallest in the MK-3+Cil. MK in a dose dependent manner and Cil increased cAMP levels (p < 0.001). cAMP levels were higher in the combination groups at all MK doses. MK-2 and Cil increased PKA activity when given alone; however, PKA activity was significantly higher in the MK-2+Cil group than in the other groups. Both MK-2 and Cil increased myocardial levels of Ser(133) P-CREB, Ser(523) P-5-lipoxygenase, Ser(473)P-Akt and Ser(633) P-eNOS. These levels were significantly higher in the MK-2+Cil group. Myocardial PTEN (Phosphatase and tensin homolog on chromosome ten) levels were significantly higher in the Db/Db mice compared to nondiabetic mice. MK-2 and Cil normalized PTEN levels. PTEN levels tended to be lower in the combination group than in the MK and Cil alone groups. CONCLUSION: MK and Cil have additive IS-limiting effects in diabetic mice. The additive effects are associated with an increase in myocardial cAMP levels and PKA activity with downstream phosphorylation of Akt, eNOS, 5-lipoxygenase and CREB and downregulation of PTEN expression.

MicroRNA 16 Modulates Epithelial Sodium Channel in Human Alveolar Epithelial Cells

Acute lung injury (ALI) is a devastating disease characterized by pulmonary edema. Removal of edema from the air spaces of lung is a critical function of the epithelial sodium channel (ENaC) in ALI. The molecular mechanisms behind resolution of pulmonary edema are incompletely understood. MicroRNA's (miRNA) are crucial gene regulators and are dysregulated in various diseases including ALI. Recent studies suggest that microRNA-16 (miR-16) targets serotonin transporter (SERT) involved in the serotonin (5-HT) transmitter system. Alterations in serotonin levels have been reported in various pulmonary diseases. However, the role of miR-16 on its target SERT, and ENaC, a key ion channel involved in the resolution of pulmonary edema, have not been studied. In the present study, the expression patterns of miR-16, SERT, ENaC and serotonin were investigated in mice exposed to room air and hyperoxia. The effects of miR-16 overexpression on ENaC, SERT, TGF-β and Nedd4 in human alveolar epithelial cells were analyzed. miR-16 and ENaC were downregulated in mice exposed to hyperoxia. miR-16 downregulation in mouse lung was correlated with an increase in SERT expression and pulmonary edema. Overexpression of miR-16 in human alveolar epithelial cells (A549) suppressed SERT and increased ENaCβ levels when compared to control-vector transfected cells. In addition, miR-16 over expression suppressed TGFβ release, a critical inhibitor of ENaC. Interestingly Nedd4, a negative regulator of ENaC remained unaltered in miR-16 over expressed A549 cells when compared to controls. Taken together, our data suggests that miR-16 upregulates ENaC, a major sodium channel involved in resolution of pulmonary edema in ALI.

Regioselective Glucosylation of Inositols Catalyzed by Thermoanaerobacter Sp. CGTase

Monoglucosylated products of L-chiro-, D-chiro-, muco-, and allo-inositol were synthesized by regioselective α-D-glucosylation with cyclodextrin glucosyl transferase from Thermoanaerobacter sp. after hydrolysis of by products with Aspergillus niger glucoamylase. While the reactions carried out with D-chiro-, muco-, and allo-inositol resulted in the regioselective formation of monoglucosylated products, two products were obtained in the reaction with L-chiro-inositol. Through the structural characterization of the glucosylated inositols here we demonstrated that the selectivity observed in the glucosylation of several inositols by Thermoanaerobacter sp. CGTase, is analogous to the specificity observed for the glucosylation of β-D-glucopyranose and equivalent glucosides.

Hope Predicts Positive Functional Role Outcomes in Acute Rehabilitation Populations

The purpose of this study was to examine the association between facilitating psychological variables and functional rehabilitation outcomes following acute medical rehabilitation. RESEARCH METHOD/DESIGN: Using a longitudinal design and correlational and regression analyses, we studied 174 adults who were participating in inpatient rehabilitation for acute spinal cord dysfunction, stroke, amputation, or orthopedic surgery recovery. All participants completed the Hope Scale, Positive and Negative Affect Schedule, and Functional Independence Measure (FIM) during the first days of their inpatient stay, and then were contacted 3 months after discharge to complete the Craig Hospital Assessment and Reporting Technique (CHART) and FIM.

Effects of Lactic Acid and Commercial Chilling Processes on Survival of Salmonella, Yersinia Enterocolitica, and Campylobacter Coli in Pork Variety Meats

Current industry chilling practices with and without the application of 2% L-lactic acid were compared for their effectiveness at reducing levels of Salmonella, Yersinia enterocolitica, and Campylobacter coli on pork variety meats. Pork variety meats (livers, intestines, hearts, and stomachs) were inoculated individually with one of the three pathogens and subjected to five different treatment combinations that included one or more of the following: water wash (25°C), lactic acid spray (2%, 40 to 50°C), chilling (4°C), and freezing (-15°C). Samples were analyzed before treatment, after each treatment step, and after 2, 4, and 6 months of frozen storage. Results showed that when a lactic acid spray was used in combination with water spray, immediate reductions were approximately 0.5 log CFU per sample of Salmonella, 0.8 log CFU per sample of Y. enterocolitica, and 1.1 log CFU per sample of C. coli. Chilling, both alone and in combination with spray treatments, had little effect on pathogens, while freezing resulted in additional 0.5-log CFU per sample reductions in levels of Salmonella and Y. enterocolitica, and an additional 1.0-log CFU per sample reduction in levels of C. coli. While reductions of at least 1 log CFU per sample were observed on variety meats treated with only a water wash and subsequently frozen, samples treated with lactic acid had greater additional reductions than those treated with only a water spray throughout frozen storage. The results of this study suggest that the use of lactic acid as a decontamination intervention, when used in combination with good manufacturing practices during processing, causes significant reductions in levels of Salmonella, Y. enterocolitica, and C. coli on pork variety meats.

Surviving a Rare Event: Left Main Coronary Artery Occlusion

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Herbicide Bentazon: Exploring Better Formulations

The knowledge of the host-guest complexes using cyclodextrins (CDs) has prompted an increase in the development of new formulations. The capacity of these organic host structures of including guest within their hydrophobic cavities, improves physicochemical properties of the guest. In the case of pesticides, several inclusion complexes with cyclodextrins have been reported. However, in order to explore rationally new pesticide formulations, it is essential to know the effect of cyclodextrins on the properties of guest molecules. In this study, the inclusion complexes of bentazon (Btz) with native βCD and two derivatives, 2-hydroxypropyl-β-cyclodextrin (HPCD) and sulfobutylether-β-cyclodextrin (SBECD), were prepared by two methods: kneading and freeze-drying, and their characterization was investigated with different analytical techniques including Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), X-ray diffractometry (XRD) and differential pulse voltammetry (DPV). All these approaches indicate that Btz forms inclusion complexes with CDs in solution and in solid state, with a stoichiometry of 1:1, although some of them are obtained in mixtures with free Btz. The calculated association constant of the Btz/HPCD complex by DPV was 244±19 M(-1) being an intermediate value compared with those obtained with βCD and SBECD. The use of CDs significantly increases Btz photostability, and depending on the CDs, decreases the surface tension. The results indicated that bentazon forms inclusion complexes with CDs showing improved physicochemical properties compared to free bentazon indicating that CDs may serve as excipient in herbicide formulations.

Glutamate Excitoxicity is the Key Molecular Mechanism Which is Influenced by Body Temperature During the Acute Phase of Brain Stroke

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the Literature

Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has the lowest incidence amongst the chronic myeloproliferative neoplasms and is characterized by a rather short median survival and a risk of progression to acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a terminal event. As observed with other chronic myeloproliferative neoplasms, the bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive in nature. In our paper, we present a 70-year-old Caucasian male who was diagnosed with primary myelofibrosis, and after 8 years of followup and therapy developed an AML. The small lymphoid aggregates noted in his bone marrow were neoplastic in nature and represented bone marrow involvement by a CD5-negative mantle cell lymphoma (MCL) that presented without any associated lymphadenopathy. We reviewed the English medical literature to identify a single case report of simultaneous association of AML and a MCL in the bone marrow. The unusual association presented here suggests an increase in observer awareness to apparently benign lymphoid aggregates in chronic myeloproliferative neoplasms.

Quantifying Bovine Insulin: Conversion of Units

The Power of Collateral Circulation: a Case of Asymptomatic Chronic Total Occlusion of the Left Main Coronary Artery

Total occlusion of the left main coronary artery predominantly presents with recurrent angina or myocardial infarction. Long-term survival and myocardial function depends on the well-developed right to left collaterals. We report a case of a 46-year-old man who was referred because of incidental finding of low ejection fraction during work-up for syncope 5 months prior. The patient denied any recurrence or any other symptom after that episode and claimed an unchanged exercise capacity. He had hypertension, hyperlipidemia, and history of 15-pack/year smoking. Except for class II morbid obesity, he had completely normal vital signs, physical examination, and lab tests on admission. The echocardiogram was suggestive of previous anterior wall myocardial infarction and demonstrated a low left ventricle ejection fraction with diffuse hypokinesis of the left ventricle. The patient underwent cardiac catheterization, which revealed total occlusion of the left main coronary artery, dominant right coronary artery with a 95% stenosis in the proximal segment, and collaterals from the right to the left coronary arteries. The patient was immediately referred for coronary artery bypass surgery. This case demonstrates the power of collateral circulation in protecting the patient from symptoms and death despite total occlusion of the left main coronary artery and severe stenosis of the proximal right coronary artery.

Diagnosis of Femoral Neck Fracture Associated with Femoral Shaft Fracture: Blinded Comparison of Computed Tomography and Plain Radiography

OBJECTIVE:: Femoral neck fractures that are associated with femoral shaft fractures have historically been associated with high rates of missed diagnosis. Despite the potentially serious consequences of a missed femoral neck fracture, little work has been conducted to rigorously evaluate the ability of commonly used imaging studies to detect such fractures. Our hypothesis was that axial view computed tomography is superior to plain radiography at detecting femoral neck fractures. DESIGN:: Blinded assessment of a randomized image set that included axial view computed tomographic scans of the pelvis, anteroposterior view radiographs of the pelvis, and anteroposterior view radiographs of the femur. SETTING:: Academic trauma center. PATIENTS:: Twenty-eight patients who had femoral shaft fractures with femoral neck fractures and 60 patients who had femoral shaft fractures without femoral neck fractures. INTERVENTION:: Images that were stripped of demographic data were independently viewed in random order on computer workstations by 5 trauma fellowship-trained orthopaedic surgeons who were blinded to treatment and diagnosis. MAIN OUTCOME MEASUREMENTS:: Sensitivity, specificity, post-test positive probability, and 1 minus post-test negative probability were calculated for diagnosing femoral neck fracture based on each image type. RESULTS:: Inter-observer reliability showed "substantial agreement" (kappa > 0.65) for all imaging modalities, indicating that the surgeons had a high level of agreement. All 3 imaging sets had high specificity (>94%) and 1 minus post-test negative probability (>95%) but had poor sensitivity (<65%) and post-test positive probability (<58%). False positives and false negatives were equally likely for all imaging modalities (P > 0.2). CONCLUSIONS:: Plain radiography and computed tomography have rates of missed femoral neck fractures that are similar and substantial, with a sensitivity of only 56% to 64%. Our data emphasize the importance of intraoperative and postoperative imaging in detecting non-displaced femoral neck fractures in association with femoral shaft fractures.

Impact of Cadmium Exposure During Pregnancy on Hepatic Glucocorticoid Receptor Methylation and Expression in Rat Fetus

Adverse fetal environment due to maternal undernutrition or exposure to environmental chemicals alters glucocorticoid (GC) metabolism increasing the risk of metabolic disorders in adulthood. In this study, we investigated the effects of maternal exposure to cadmium (Cd, 50 ppm) during pregnancy in the methylation of fetal hepatic glucocorticoid receptor promoter (GR) and the correlation with its expression and that of the DNA methyltransferases (DNMT1a and 3a). We also studied the expression of liver phosphoenolpyruvate carboxykinase (PEPCK) and acyl-CoA oxidase (AOX), two enzymes involved in the metabolism of carbohydrates and lipids respectively. The methylation of the rat GR gene exon 1(10) (GR1(10)) in nucleotides -2536 to -2361 was analyzed by pyrosequencing. Quantitative real time PCR was used to assess hepatic GR, PEPCK and AOX mRNA, and their protein levels using Western blotting analysis. Differential methylation was noted across groups at all CpG sites in the GR exon 1(10) in a sex-dependent manner. In males, CpG were more methylated than the controls (185 ± 21%, p<0.001) but only CpG sites 1,6,7 and 9 showed a significantly different extent of methylation. In addition, a lower expression of GR (mRNA and protein) was found. On the contrary, in females, CpG were less methylated than the controls (62 ± 11%, p<0.05) and overexpressed, affecting PEPCK and AOX expression, which did not change in males. The GR methylation profile correlates with DNMT3a expression which may explain epigenetic sex-dependent changes on GR1(10) promoter induced by Cd treatment. In conclusion, Cd exposure during pregnancy affects fetal liver DNMT3a resulting in sex-dependent changes in methylation and expression of GR1(10). Although these effects do not seem to be directly involved in the low birth weight and height, they may have relevant implications for long-term health.

Main Characteristics and Participation Rate of European Adolescents Included in the HELENA Study

Participation rate and response rate are key issues in a cross sectional large-scale epidemiological study. The objective of this paper is to describe the study population and to evaluate participation and response rate as well as the key nutritional status variables in male and female adolescents involved in the HELENA study.

REST-dependent Epigenetic Remodeling Promotes the Developmental Switch in Synaptic NMDA Receptors

NMDA receptors (NMDARs) are critical to synaptogenesis, neural circuitry and higher cognitive functions. A hallmark feature of NMDARs is an early postnatal developmental switch from those containing primarily GluN2B to primarily GluN2A subunits. Although the switch in phenotype has been an area of intense interest for two decades, the mechanisms that trigger it and the link between experience and the switch are unclear. Here we show a new role for the transcriptional repressor REST in the developmental switch of synaptic NMDARs. REST is activated at a critical window of time and acts via epigenetic remodeling to repress Grin2b expression and alter NMDAR properties at rat hippocampal synapses. Knockdown of REST in vivo prevented the decline in GluN2B and developmental switch in NMDARs. Maternal deprivation impaired REST activation and acquisition of the mature NMDAR phenotype. Thus, REST is essential for experience-dependent fine-tuning of genes involved in synaptic plasticity.

Ototopical Neomycin Exposure in Children with Nonintact Tympanic Membranes

Although contraindicated, neomycin otic preparations may be administered to children with nonintact tympanic membranes (TMs), such as tympanostomy tubes or TM perforations. The goal of this study was to assess the magnitude of neomycin exposure in children with nonintact TMs.

Intracellular Delivery of SiRNA by Polycationic Superparamagnetic Nanoparticles

The siRNA transfection efficiency of nanoparticles (NPs), composed of a superparamagnetic iron oxide core modified with polycationic polymers (poly(hexamethylene biguanide) or branched polyethyleneimine), were studied in CHO-K1 and HeLa cell lines. Both NPs demonstrated to be good siRNA transfection vehicles, but unmodified branched polyethyleneimine (25 kD) was superior on both cell lines. However, application of an external magnetic field during transfection (magnetofection) increased the efficiency of the superparamagnetic NPs. Furthermore, our results reveal that these NPs are less toxic towards CHO-K1 cell lines than the unmodified polycationic-branched polyethyleneimine (PEI). In general, the external magnetic field did not alter the cell's viability nor it disrupted the cell membranes, except for the poly(hexamethylene biguanide)-modified NP, where it was observed that in CHO-K1 cells application of the external magnetic field promoted membrane damage. This paper presents new polycationic superparamagnetic NPs as promising transfection vehicles for siRNA and demonstrates the advantages of magnetofection.

Mixed Epithelial and Stromal Tumor of the Kidney (MEST)

To report an unusual case of renal tumor and review the literature.

Andalusian Registry of Heart Transplantation: First Official Adult Heart Transplant Report 2010

This is the first official report of the Andalusian Registry of Heart Transplantation. Since 1986, two centers in the community have been authorized to perform adult heart transplantation. Until 2010, 854 adult heart transplantation procedures were performed, which constitute the basis of the present report. Clinical features and survival are analyzed. The leading reason for heart transplantation was ischemic cardiomyopathy (34%) and nonischemic dilated cardiomyopathy (34%). The mean age of the recipients was 46 ± 16 years and the mean age of the donors was 29 ± 13 years. After a median follow-up of 106 months, the mean survival was 13.4 ± 0.6 years.

Neuroprotection Afforded by Antagonists of Endothelin-1 Receptors in Experimental Stroke

Endothelin-1 (ET-1) is involved on the development of cerebral edema in acute ischemic stroke. As edema is a therapeutic target in cerebral ischemia, our aim was to study the effect of antagonists for ET-1 receptors (Clazosentan(®) and BQ-788, specific antagonists for receptors A and B, respectively) on the development of edema, infarct volume and sensorial-motor deficits in rats subjected to ischemia by occlusion of the middle cerebral artery (MCAO). We used Wistar rats (280-320 g) submitted to ischemia by intraluminal transient (90 min) MCAO. After ischemia, rats were randomized into 4 groups (n = 6) treated with; 1) control group (saline), 2) Clazosentan(®) group (10 mg/kg iv), 3) BQ-788 group (3 mg/kg iv), and 4) combined treatment (Clazosentan(®) 10 mg/kg plus BQ-788 3 mg/kg iv). We observed that rats treated with Clazosentan(®) showed a reduction of edema, measured by MRI, at 72 h (hours) and at day 7 (both p < 0.0001), and a decrease in the serum levels of ET-1 at 72 h (p < 0.0001) and at day 7 (p = 0.009). The combined treatment also induced a reduction of edema at 24 h (p = 0.004), 72 h (p < 0.0001) and at day 7 (p < 0.0001), a reduction on infarct volume, measured by MRI, at 24 and 72 h, and at day 7 (all p < 0.01), and a better sensorimotor recovery at 24 and 72 h, and at day 7 (all p < 0.01). Moreover, Clazosentan(®) induced a decrease in AQP4 expression, while BQ-788 induced an increase in AQP9 expression. These results suggest that antagonists for ET-1 receptors may be a good therapeutic target for cerebral ischemia.

Changes in Chemical Composition and Antioxidative Properties of Rye Ginger Cakes During Their Shelf-life

Changes in chemical composition and antioxidative properties of rye ginger cakes during their shelf-life were investigated in this study. In particular, the changes in antioxidants content, antioxidative and reducing capacity, and Maillard reaction development in rye ginger cakes after long-term storage were addressed. Ginger cakes produced according to the traditional and current recipe were stored for 5 years at room temperature in a dark place. The total phenolic compounds (TPC), inositol hexaphosphate (IP6), reduced (GSH) and oxidised glutathione (GSSG) contents, antioxidant and reducing capacity and Maillard reaction products (MRPs) were determined in ginger cakes after storage and then compared to those measured after baking. After long-term storage a decrease in TPC and IP6 contents in cakes was noted. In contrast, an increase in antioxidative and reducing capacity of stored cakes was observed. Long-term storage induced formation of furosine, advanced and final Maillard reaction products and caused changes in both reduced and oxidised forms of glutathione. After long-term storage the modest changes in furosine, FAST index and browning in ginger cake formulated with dark rye flour may suggest that this product is the healthiest among others. Therefore, traditional rye ginger cakes can be considered as an example of a healthy food that is also relatively stable during long term storage as noted by the small chemical changes observed in its composition.

Usefulness of a Large Field of View Sensor for Physicochemical, Textural, and Yield Predictions Under Industrial Goat Cheese (Murcia Al Vino) Manufacturing Conditions

The applicability of a light backscatter sensor with a large field of view was tested for on-line monitoring of coagulation and syneresis in a goat cheese (Murcia al Vino) manufactured under industrial conditions. Cheesemaking was carried out concurrently in a 12-L pilot vat and a 10,000-L industrial vat following the normal cheesemaking protocol. Cheese moisture, whey fat content, hardness, springiness, and adhesiveness were measured during syneresis. The results obtained show that cutting time is best predicted by considering the coagulation ratio at the inflection point and the percentage increase in the ratio during coagulation, with no need for the first derivative. The large field of view reflectance ratio provided good results for the prediction of moisture content, yield, hardness, springiness, and adhesiveness of the final cheese.

Electrical and Mechanical Recovery of Cardiac Function Following Out-of-hospital Cardiac Arrest

BACKGROUND: Compression pauses may be particularly harmful following the electrical recovery but prior to the mechanical recovery from cardiopulmonary arrest. METHODS AND RESULTS: A convenience sample of patients with out-of-hospital cardiac arrest (OOHCA) were identified. Data were exported from defibrillators to define compression pauses, electrocardiogram rhythm, PetCO2, and the presence of palpable pulses. Pulse-check episodes were randomly assigned to a derivation set (one-third) and a validation set (two-thirds). Both an unweighted and a weighted receiver-operator curve (ROC) analysis were performed on the derivation set to identify optimal thresholds to predict ROSC using heart rate and PetCO2. A sequential decision guideline was generated to predict the presence of ROSC during compressions and confirm perfusion once compressions were stopped. The ability of this decision guideline to correctly identify pauses in which pulses were and were not palpated was then evaluated. A total of 145 patients with 349 compression pauses were included. The ROC analyses on the derivation set identified an optimal pre-pause heart rate threshold of >40beatsmin(-1) and an optimal PetCO2 threshold of >20mmHg to predict ROSC. A sequential decision guideline was developed using pre-pause heart rate and PetCO2 as well as the PetCO2 pattern during compression pauses to predict and rapidly confirm ROSC. This decision guideline demonstrated excellent predictive ability to identifying compression pauses with and without palpable pulses (positive predictive value 95%, negative predictive value 99%). The mean latency period between recovery of electrical and mechanical cardiac function was 78s (95% CI 36-120s). CONCLUSIONS: Heart rate and PetCO2 can predict ROSC without stopping compressions, and the PetCO2 pattern during compression pauses can rapidly confirm ROSC. Use of a sequential decision guideline using heart rate and PetCO2 may reduce unnecessary compression pauses during critical moments during recovery from cardiopulmonary arrest.

Supramolecular Assembly of Diplatinum Species Through Weak Pt(II) â‹…â‹…â‹…Pt(II) Intermolecular Interactions: A Combined Experimental and Computational Study

The present study elucidates the factors that govern the spontaneous self-assembly of a family of dimetal [Pt(2) L(4) ] (L=dithiocarboxylato ligand) complexes. Experimental data show that variables such as temperature, concentration, solvent and the nature of the ligand L have a critical effect on the reversible self-assembly of supramolecular [Pt(2) L(4) ](n) entities. In solution, new UV/Vis spectroscopic features emerge at low temperatures and/or high concentrations, which are attributed to the formation of oligomeric [Pt(2) L(4) ](n) species. The description of intermolecular Ptâ‹…â‹…â‹…Pt interactions, the main driving force for the association, was addressed from a computational perspective. The contributions from intermolecular Ptâ‹…â‹…â‹…S and Sâ‹…â‹…â‹…S interactions to these supramolecular assemblies were found to be repulsive. Experimental UV/Vis data have been interpreted by means of computational spectroscopy.

The Niemann-Pick C1 Gene Is Downregulated in Livers of C57BL/6J Mice by Dietary Fatty Acids, but Not Dietary Cholesterol, Through Feedback Inhibition of the SREBP Pathway

The Niemann-Pick C1 (NPC1) gene is associated with human obesity. Mouse models with decreased Npc1 gene dosage are susceptible to weight gain when fed a high-fat diet, but not a low-fat diet, consistent with an Npc1 gene-diet interaction. The objectives of this study were to define regulation of the Npc1 gene and to investigate the Npc1 gene-diet interaction responsible for weight gain. The experimental design involved feeding C57BL/6J male mice a low-fat diet (with 0.00, 0.10, or 1.00% cholesterol) or a high-fat diet (with 0.02% cholesterol) until 30 wk to determine regulation of the Npc1 gene in liver. The key results showed that the Npc1 gene was downregulated by dietary fatty acids (54%, P = 0.022), but not by dietary cholesterol, through feedback inhibition of the sterol regulatory element-binding protein (SREBP) pathway. However, the dietary fatty acids secondarily increased liver cholesterol, which also inhibits the SREBP pathway. Similarly, the Npc1 gene was downregulated in peritoneal fibroblasts isolated from C57BL/6J weanling male mice not exposed to the experimental diets and incubated in media supplemented with purified oleic acid (37%, P = 0.038) but not in media supplemented with purified cholesterol. These results are important because they suggest a novel mechanism for the interaction of fatty acids with the Npc1 gene to influence energy balance and to promote weight gain. Moreover, the responsiveness of the Npc1 gene to fatty acids is consistent with studies that suggest that the encoded NPC1 protein has a physiologic role in regulating both cholesterol and fatty acid metabolism.

The Costs of Stroke in Spain by Aetiology: the CONOCES Study Protocol

INTRODUCTION: Patients with stroke associated with non-valvular atrial fibrillation (NVAF) are a specific group, and their disease has a considerable social and economic impact. The primary objective of the CONOCES study, the protocol of which is presented here, is to compare the costs of stroke in NVAF patients to those of patients without NVAF in Spanish stroke units from a social perspective. MATERIALS AND METHODS: CONOCES is an epidemiological, observational, naturalistic, prospective, multicentre study of the cost of the illness in a sample of patients who have suffered a stroke and were admitted to a Spanish stroke unit. During a 12-month of follow-up period, we record sociodemographic and clinical variables, score on the NIH stroke scale, level of disability, degree of functional dependency according to the modified Rankin scale, and use of healthcare resources (hospitalisation at the time of the first episode, readmissions, outpatient rehabilitation, orthotic and/or prosthetic material, medication for secondary prevention, medical check-ups, nursing care and formal social care services). Estimated monthly income, lost work productivity and health-related quality of life with the generic EQ-5D questionnaire are also recorded. We also administer a direct interview to the caregiver to determine loss of productivity, informal care, and caregiver burden. RESULTS AND CONCLUSIONS: The contribution of the CONOCES study will help to set the economic and clinical impact of stroke on the basis of its association with NVAF.

Draft Whole Genome Sequence of the Cyanide-degrading Bacterium Pseudomonas Pseudoalcaligenes CECT5344

Pseudomonas pseudoalcaligenes CECT5344 is a Gram-negative bacterium able to tolerate cyanide and to use it as the sole nitrogen source. We report here the first draft of the whole genome sequence of a P. pseudoalcaligenes strain that assimilates cyanide. Three aspects are specially emphasized in this manuscript. First, some generalities of the genome are shown and discussed in the context of other Pseudomonadaceae genomes, including genome size, G + C content, core genome and singletons among other features. Second, the genome is analysed in the context of cyanide metabolism, describing genes probably involved in cyanide assimilation, like those encoding nitrilases, and genes related to cyanide resistance, like the cio genes encoding the cyanide insensitive oxidases. Finally, the presence of genes probably involved in other processes with a great biotechnological potential like production of bioplastics and biodegradation of pollutants also is discussed.

Hyperpolarized (3)He Magnetic Resonance Imaging: Comparison with Four-dimensional X-ray Computed Tomography Imaging in Lung Cancer

Pulmonary functional imaging using four-dimensional x-ray computed tomographic (4DCT) imaging and hyperpolarized (3)He magnetic resonance imaging (MRI) provides regional lung function estimates in patients with lung cancer in whom pulmonary function measurements are typically dominated by tumor burden. The aim of this study was to evaluate the quantitative spatial relationship between 4DCT and hyperpolarized (3)He MRI ventilation maps.

Cathepsins in the Kidney of Olive Flounder, Paralichthys Olivaceus, and Their Responses to Bacterial Infection

Cathepsin activities are responsible for mediating various pathways involved in immune response, including the apoptosis pathway, toll-like receptor (TLR) signaling, cytokine induction and activation of granule serine proteases. In the present study, we investigated cathepsin responses in the kidneys of olive flounder infected with Streptococcus parauberis, analyzing cathepsin expression using a label-free, quantitative proteomic approach in conjunction with quantitative real-time polymerase chain reaction (qRT-PCR). In proteomic analyses, we detected cathepsin B, D, L and S proteins, noting significant decreases and increases in cathepsins B and L, respectively, with infection. Taken together with an evaluation of cathepsin B, D, F, K, L, S and X gene expression in normal and infected kidneys by qRT-PCR, our results indicate that cathepsins B, D, L and S are the dominant lysosomal proteases in the immune system of the teleostei, olive flounder. Cathepsins F, K and X were regarded as minor cathepsins.

Fluctuations and Criticality of a Granular Solid-liquid-like Phase Transition

We present an experimental study of density and order fluctuations in the vicinity of the solid-liquid-like transition that occurs in a vibrated quasi-two-dimensional granular system. The two-dimensional projected static and dynamic correlation functions are studied. We show that density fluctuations, characterized through the structure factor, increase in size and intensity as the transition is approached, but they do not change significantly at the transition itself. The dense, metastable clusters, which present square symmetry, also increase their local order in the vicinity of the transition. This is characterized through the bond-orientational order parameter Q_{4}, which in Fourier space shows an Ornstein-Zernike-like behavior. Depending on the filling density and vertical height, the transition can be of first- or second-order type. In the latter case, the associated correlation length ξ_{4}, the relaxation time τ_{4}, the zero k limit of Q_{4} fluctuations (static susceptibility), the pair correlation function of Q_{4}, and the amplitude of the order parameter obey critical power laws, with saturations due to finite size effects. Their respective critical exponents are ν_{⊥}=1, ν_{∥}=2, γ=1, η=0.67, and β=1/2, whereas the dynamical critical exponent z=ν_{∥}/ν_{⊥}=2. These results are consistent with model C of dynamical critical phenomena, valid for a nonconserved critical order parameter (bond-orientation order) coupled to a conserved field (density).

Nutritional Status and Clinical Outcome of Children on Continuous Renal Replacement Therapy: a Prospective Observational Study

ABSTRACT: BACKGROUND: No studies on continuous renal replacement therapy (CRRT) have analyzed nutritional status in children. The objective of this study was to assess the association between mortality and nutritional status of children receiving CRRT. METHODS: Prospective observational study to analyze the nutritional status of children receiving CRRT and its association with mortality. The variables recorded were age, weight, sex, diagnosis, albumin, creatinine, urea, uric acid, severity of illness scores, CRRT-related complications, duration of admission to the pediatric intensive care unit, and mortality. RESULTS: The sample comprised 174 critically ill children on CRRT. The median weight of the patients was 10 kg, 35% were under percentile (P) 3, and 56% had a weight/P50 ratio of less than 0.85. Only two patients were above P95. The mean age for patients under P3 was significantly lower than that of the other patients (p = 0.03). The incidence of weight under P3 was greater in younger children (p = 0.007) and in cardiac patients and in those who had previous chronic renal insufficiency (p = 0.047). The mortality analysis did not include patients with pre-existing renal disease. Mortality was 38.9%. Mortality for patients with weight < P3 was greater than that of children with weight > P3 (51% vs 33%; p = 0.037). In the univariate and multivariate logistic regression analyses, the only factor associated with mortality was protein-energy wasting (malnutrition) (OR, 2.11; 95% CI, 1.067-4.173; p = 0.032). CONCLUSIONS: The frequency of protein-energy wasting in children who require CRRT is high, and the frequency of obesity is low. Protein-energy wasting is more frequent in children with previous end-stage renal disease and heart disease. Underweight children present a higher mortality rate than patients with normal body weight.

Value of a Short Four-joint Ultrasound Test for Gout Diagnosis: a Pilot Study

OBJECTIVES: The goal of this study was to investigate the usefulness of a short ultrasound (US) assessment in gout. METHODS: Patients with gout, confirmed by urate crystal identification, and having at least one symptomatic flare in the last three months were included. Standardised US examinations of sixteen joints and eight tendons in the lower limbs were carried out. Six lesions were studied: hyperechoic spots in the synovial fluid, hyperechoic cloudy areas (HCA), bright stippled aggregates (BSA), the double contour sign (DCS), erosions and the Doppler signal. For reliability, inter-reader analyses were performed by five rheumatologists. With the results, a short US assessment was created. RESULTS: Twenty-nine consecutive patients were included (93% men). The Doppler signal, HCAs and BSAs appeared in 100%, 97% and 93% of the patients, respectively. The DCS was found in 69% of patients. The locations that were most affected were the first metatarsophalangeal joint (MTP) and the knee joints, both of which are in 93% of patients. Reliability analyses showed consistent results for erosions, the Doppler signal, HCAs and the DCS in the 1st MTP (k=0.818, k=0.958, k=0.739 and k= 0.697, respectively) and for the DCS in the knees (k=0.779). A six-minute US examination of four joints (knees and the 1st MTPs) detected HCAs or DCS in 97% of cases. CONCLUSIONS: A US examination of four joints for two elemental lesions (the DCS and HCAs) is feasible, reliable and has face and content validity as a diagnostic test in patients with crystal-proven gout.

Ectopic Pyriform Sinus Parathyroid Adenoma

OBJECTIVE: To describe the diagnosis and treatment of ectopic pyriform sinus parathyroid adenoma. MATERIAL AND METHODS: A 44-year-old woman presented with persistent primary hyperparathyroidism after previous failed cervical exploratory surgery. RESULTS: Diagnosis of ectopic pyriform sinus parathyroid adenoma was suggested by computed tomography and technetium-99m sestamibi scintigraphy (99mTc-MIBI SPECT/CT). A submucosal tumor was identified under laryngoscopy and resected by endoscopic CO(2) laser. Histopathology confirmed the diagnosis of parathyroid adenoma. CONCLUSIONS: Ectopic pyriform sinus locations are rare in parathyroid adenoma. 99mTc-MIBI SPECT/CT facilitates diagnosis, especially in case of previous failed neck exploration. Endoscopic CO(2) laser resection is the treatment of choice.

Quantitative Assessment of the Efficacy of Spiral-wound Membrane Cleaning Procedures to Remove Biofilms

Cleaning of high pressure RO/NF membranes is an important operational tool to control biofouling. Quantitative information on the efficacy of cleaning agents and protocols to remove biomass is scarce. Therefore, a laboratory cleaning test to assess the efficiency of cleaning procedures to remove attached biomass was developed. The major components of the test are (i) production of uniform biofilm samples, (ii) the quantification of the biomass concentrations with robust parameters and (iii) a simple test procedure with optimal exposure of the biofilm samples to the chemicals. The results showed that PVC-P is a suitable substratum for the production of uniform biofilm samples. ATP and carbohydrates (CH) as major components of the biofilm matrix for nucleotides (living bacterial cells) and extracellular polymeric substances EPS, respectively, were selected as robust biomass parameters. The removal of ATP and CH with the NaOH/Sodium Dodecyl Sulfate (SDS) mixture, selected as a standard treatment at pH 12.0, was reproducible. The resistance of the EPS matrix against chemical cleaning was demonstrated by a low CH removal (32.8 ± 6.0%) compared to the ATP removal (70.5 ± 15.1%). The inverse relationship of biomass removal with the CH to ATP ratio (μg/ng) of the biofilms demonstrated the influence of the biomass characteristics on cleaning. None of the 27 chemicals tested (analytical-grade and commercial brands) in single step or in double-step treatments were significantly more effective than NaOH/SDS. Oxidizing agents NaOCl and H(2)O(2), the latter in combination with SDS, both tested as common agents in biofilm control, showed a significantly higher efficiency (70%) to remove biofilms. In the test, simultaneously, the efficiency of agents to remove precipitated minerals such as Fe can be assessed. Validation tests with Cleaning in Place (CIP) in 8 and 2.5-inch RO membrane pilot plant experiments showed similar ranking of the cleaning efficiency of cleaning protocols as determined in the laboratory tests. Further studies with the laboratory test are required to study the effect of cleaning conditions such as duration, temperature, shear forces as well as chemical conditions (concentrations, alternative agents or mixtures and sequence of application) on the efficiency to remove attached biomass.

Host Preference of the Arbovirus Vector Culex Erraticus (Diptera: Culicidae) at Sonso Lake, Cauca Valley Department, Colombia

Culex erraticus (Dyar & Knab) is a competent vector of Eastern equine encephalitis virus and subtype IC Venezuelan equine encephalitis virus, and both St. Louis encephalitis virus and West Nile virus have been isolated from field-collected specimens. Previous bloodmeal analysis studies have shown this species to be a generalist, feeding on a variety of mammals, birds, reptiles, and amphibians. This behavior can bridge arboviral transmission across different vertebrate groups. Our study examined the host preference of Cx. erraticus at Sonso Lake in Colombia. From July to August 2008, blood-engorged mosquitoes were collected from resting boxes, while vertebrate abundance was determined to calculate host preference. Based on mitochondrial DNA analysis of bloodmeals, birds were the predominant hosts (57.6%), followed by mammals (30.8%), and reptiles (6.7%); 9.5% of the bloodmeals were mixed. The most commonly fed upon species were: limpkin, black-crowned night-heron, striated heron, human, and capybara. Forage ratios showed the least bittern, limpkin, Cocoi heron, striated heron, capybara, and black-crowned night heron were preferred hosts across all vertebrates. Of the available avifauna, the least bittern, limpkin, striated heron, Cocoi heron, and black-crowned night heron were preferred, whereas the bare faced ibis, great egret, snowy egret, and cattle egret were under-used. This study shows that while Cx. erraticus is an opportunistic feeder, using diverse vertebrate hosts in the environment, certain avian species are targeted preferentially for bloodmeals.

Factors That Promote H3 Chromatin Integrity During Transcription Prevent Promiscuous Deposition of CENP-A(Cnp1) in Fission Yeast

Specialized chromatin containing CENP-A nucleosomes instead of H3 nucleosomes is found at all centromeres. However, the mechanisms that specify the locations at which CENP-A chromatin is assembled remain elusive in organisms with regional, epigenetically regulated centromeres. It is known that normal centromeric DNA is transcribed in several systems including the fission yeast, Schizosaccharomyces pombe. Here, we show that factors which preserve stable histone H3 chromatin during transcription also play a role in preventing promiscuous CENP-A(Cnp1) deposition in fission yeast. Mutations in the histone chaperone FACT impair the maintenance of H3 chromatin on transcribed regions and promote widespread CENP-A(Cnp1) incorporation at non-centromeric sites. FACT has little or no effect on CENP-A(Cnp1) assembly at endogenous centromeres where CENP-A(Cnp1) is normally assembled. In contrast, Clr6 complex II (Clr6-CII; equivalent to Rpd3S) histone deacetylase function has a more subtle impact on the stability of transcribed H3 chromatin and acts to prevent the ectopic accumulation of CENP-A(Cnp1) at specific loci, including subtelomeric regions, where CENP-A(Cnp1) is preferentially assembled. Moreover, defective Clr6-CII function allows the de novo assembly of CENP-A(Cnp1) chromatin on centromeric DNA, bypassing the normal requirement for heterochromatin. Thus, our analyses show that alterations in the process of chromatin assembly during transcription can destabilize H3 nucleosomes and thereby allow CENP-A(Cnp1) to assemble in its place. We propose that normal centromeres provide a specific chromatin context that limits reassembly of H3 chromatin during transcription and thereby promotes the establishment of CENP-A(Cnp1) chromatin and associated kinetochores. These findings have important implications for genetic and epigenetic processes involved in centromere specification.

Focal Adhesion Kinase Plays a Role in Osteoblast Mechanotransduction in Vitro but Does Not Affect Load-induced Bone Formation in Vivo

A healthy skeleton relies on bone's ability to respond to external mechanical forces. The molecular mechanisms by which bone cells sense and convert mechanical stimuli into biochemical signals, a process known as mechanotransduction, are unclear. Focal adhesions play a critical role in cell survival, migration and sensing physical force. Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that controls focal adhesion dynamics and can mediate reparative bone formation in vivo and osteoblast mechanotransduction in vitro. Based on these data, we hypothesized that FAK plays a role in load-induced bone formation. To test this hypothesis, we performed in vitro fluid flow experiments and in vivo bone loading studies in FAK-/- clonal lines and conditional FAK knockout mice, respectively. FAK-/- osteoblasts showed an ablated prostaglandin E(2) (PGE(2)) response to fluid flow shear. This effect was reversed with the re-expression of wild-type FAK. Re-expression of FAK containing site-specific mutations at Tyr-397 and Tyr-925 phosphorylation sites did not rescue the phenotype, suggesting that these sites are important in osteoblast mechanotransduction. Interestingly, mice in which FAK was conditionally deleted in osteoblasts and osteocytes did not exhibit altered load-induced periosteal bone formation. Together these data suggest that although FAK is important in mechanically-induced signaling in osteoblasts in vitro, it is not required for an adaptive response in vivo, possibly due to a compensatory mechanism that does not exist in the cell culture system.

Evaluation of Organic, Conventional and Intensive Beef Farm Systems: Health, Management and Animal Production

The overall aim of the present study was to analyse and compare organic beef cattle farming in Spain with intensive and conventional systems. An on-farm study comparing farm management practices and animal health was carried out. The study also focussed on a slaughterhouse analysis by comparing impacts on the safety and quality of the cattle products. Twenty-four organic and 26 conventional farms were inspected, and farmers responded to a questionnaire that covered all basic data on their husbandry practices, farm management, veterinary treatments and reproductive performance during 2007. Furthermore, data on the hygiene and quality of 244, 2596 and 3021 carcasses of calves from organic, intensive and conventional farms, respectively, were retrieved from the official yearbook (2007) of a slaughterhouse. Differences found between organic and conventional farms across the farm analysis did not substantially reflect differences between both farm types in the predominant diseases that usually occur on beef cattle farms. However, calves reared organically presented fewer condemnations at slaughter compared with intensive and to a lesser extent with conventionally reared calves. Carcass performance also reflected differences between farm type and breed and was not necessarily better in organic farms.

Downregulation of Mdr1 and Abcg2 Genes is a Mechanism of Inhibition of Efflux Pumps Mediated by Polymeric Amphiphiles

The ability of cells to acquire resistance to multiple pharmaceuticals, namely multidrug resistance (MDR), is often mediated by the over-expression of efflux transporters of the ATP-binding cassette (ABC) superfamily; for example P-glycoprotein (P-gp or MDR1), breast cancer resistance protein (BCRP or ABCG2), and multidrug resistance-associated protein MRP1. ABCs pump drug molecules out of cells against a concentration gradient, reducing their intracellular concentration. The ability of polymeric amphiphiles to inhibit ABCs as well as the cellular pathways involved in the inhibition has been extensively investigated. This work investigated for the first time the effect of branched poly(ethylene oxide)-poly(propylene oxide) block copolymers (poloxamines) on the levels of mRNA encoding for MDR1, BCRP and MRP1, in a human hepatoma cell line (Huh7). Copolymers with a broad range of molecular weights and hydrophilic-lipophilic balances were assayed. Results confirmed the down-regulation of mdr1 and abcg2 genes. Conversely, the mrp1 gene was not affected. These findings further support the versatility of these temperature- and pH-responsive copolymers to overcome drug resistance in cancer and infectious diseases.

Analysis of Prognostic Factors Associated with Longitudinally Extensive Transverse Myelitis

OBJECTIVE: The aim of this study is to report the clinical profile and outcome of longitudinally extensive transverse myelitis (LETM). METHODS: We prospectively studied adult patients who presented with LETM from January 2008 to December 2011. Information on demographic, clinical course, magnetic resonance imaging (MRI) and outcome was collected. HLA-DRB1 genotype was compared with those of 225 normal controls and patients with MS (228) and neuromyelitis optica (NMO) (22). RESULTS: In total, 23 patients (16 female) with a median age of 44.5 years (range: 20-77 years) were included. Most (74%) had moderate-severe disability at nadir (48% non-ambulatory), normal/non-multiple sclerosis (MS) brain MRI (96%) and a median MRI cord lesion of 5 vertebral segments (range: 3-19). Laboratory analysis showed cerebrospinal fluid pleocytosis (45%), NMO-IgG (9%), antinuclear antibodies (70%), and genotype HLA-DRB1*13 (57%). The frequency of DRB1*13 genotype was higher compared with controls (p=0.002), MS (p=0.001) and NMO (p= 0.003) patients. After a median follow-up of 32 months, one patient converted to MS, two had relapsing LETM with NMO-IgG, and 20 remained as idiopathic with recurrences in four (20%). Twelve (52%) patients recovered with minimal disability (Expanded Disability Status Scale (EDSS) <2.5) and three (13%) remained wheelchair dependent. Disability at nadir was associated with the final outcome and extension of the spinal cord lesion with risk of recurrence. Recurrence was not associated with worse outcome. CONCLUSIONS: Inflammatory LETM is mostly idiopathic with a good outcome. It includes a relatively homogenous group of patients with an overrepresentation of the HLA-DRB1*13 genotype. EDSS at nadir is a predictor of the final outcome and extension of the myelitis of the recurrence risk.

Endocannabinoid Signaling and Synaptic Function

Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can regulate several neural functions and behaviors. As experimental tools advance, the repertoire of known endocannabinoid-mediated effects at the synapse, and their underlying mechanism, continues to expand. Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a nonretrograde manner. In addition to mediating synaptic plasticity, the endocannabinoid system is itself subject to plastic changes. Multiple points of interaction with other neuromodulatory and signaling systems have now been identified. In this Review, we focus on new advances in synaptic endocannabinoid signaling in the mammalian brain. The emerging picture not only reinforces endocannabinoids as potent regulators of synaptic function but also reveals that endocannabinoid signaling is mechanistically more complex and diverse than originally thought.

Some Things Are Better Left Unsaid

Synthesis of Novel Quinoline-2-one Based Chalcones of Potential Anti-tumor Activity

Novel quinoline-2-one based chalcones were synthesized from a Claisen-Schmidt condensation by using the couple KOH/1,4-dioxane as reaction medium. A relatively stable aldol was isolated and identified as the intermediate species in the formation of the target chalcones. Nine of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines. Products 16c, 16d, 16h and 27 exhibited the highest activity, being compound 27 the most active, displaying remarkable activity against 50 human tumor cell lines, thirteen of them with GI(50) values ≤1.0 μM, being the HCT-116 (Colon, GI(50) = 0.131 μM) and LOX IMVI (Melanoma, GI(50) = 0.134 μM) the most sensitive strains. Compound 27 was referred to in vivo acute toxicity and hollow fiber assay by the Biological Evaluation Committee of the NCI. The acute toxicity study indicated that compound 27 was well tolerated intraperitoneally (150 mg/kg/dose) by athymic nude mice. This compound may possibly be used as lead compound for developing new anticancer agents.

Effect of Chemical Sanitizers on Salmonella Enterica Serovar Poona on the Surface of Cantaloupe and Pathogen Contamination of Internal Tissues As a Function of Cutting Procedure

Survival of Salmonella enterica subsp. enterica serovar Poona on surface and stem scar portions of inoculated cantaloupe following sanitizer application, transfer of pathogen from the rind to the flesh during cutting, and growth of Salmonella Poona on cantaloupe cubes over 15 days of refrigerated storage were investigated. Cantaloupes inoculated with a rifampin-resistant strain of Salmonella Poona (10(7) CFU/ml) for 3 min and dried for 12 h were washed with chlorine (200 mg free chlorine per liter, 3 min), lactic acid (2%, 2 min), or ozone (30 mg/liter, 5 min). Fresh-cut cantaloupe cubes were prepared by (i) cutting the cantaloupe and then removing the rind or by (ii) peeling the rind and then cutting the flesh into pieces. The numbers of Salmonella bacteria recovered were higher in the stem scar portion (6.3 ± 0.3 log CFU/cm(2)) than the surface (4.8 ± 0.2 log CFU/cm(2)). Surface treatment with tap water or chlorine did not reduce Salmonella numbers, while treatment with lactic acid or ozone reduced Salmonella by 2.5 or 2.3 log CFU/cm(2), respectively. The use of lactic acid to sanitize the cantaloupes resulted in less Salmonella transfer to flesh during cutting; Salmonella numbers decreased to below detectable levels over 9 days of refrigerated (4°C) storage. Cutting cantaloupes after peeling the rind was more effective at reducing transfer of Salmonella to the internal tissue than cutting of cantaloupes prior to rind removal. These data suggest that treatment of cantaloupe rinds with lactic acid or ozone may be effective at reducing Salmonella numbers, while lactic acid application resulted in reduction of Salmonella transfer to cantaloupe flesh.

Clinical Management Guidelines for Subarachnoid Haemorrhage. Diagnosis and Treatment

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Translation and Cross-cultural Adaptation of the Lower Extremity Functional Scale Into a Brazilian Portuguese Version and Validation on Patients With Knee Injuries

Clinical measurement.

Comparison of PCR/Electron Spray Ionization-Time-of-Flight-Mass Spectrometry Versus Traditional Clinical Microbiology for Active Surveillance of Organisms Contaminating High-use Surfaces in a Burn Intensive Care Unit, an Orthopedic Ward and Healthcare Workers

ABSTRACT: BACKGROUND: Understanding nosocomial pathogen transmission is restricted by culture limitations. Novel platforms, such as PCR-based electron spray ionization-time-of-flight-mass spectrometry (ESI-TOF-MS), may be useful as investigational tools. METHODS: Traditional clinical microbiology (TCM) and PCR/ESI-TOF-MS were used to recover and detect microorganisms from the hands and personal protective equipment of 10 burn intensive care unit (ICU) healthcare workers providing clinical care at a tertiary care military referral hospital. High-use environmental surfaces were assessed in 9 burn ICU and 10 orthopedic patient rooms. Clinical cultures during the study period were reviewed for pathogen comparison with investigational molecular diagnostic methods. RESULTS: From 158 samples, 142 organisms were identified by TCM and 718 by PCR/ESI-TOF-MS. The molecular diagnostic method detected more organisms (4.5 +/- 2.1 vs. 0.9 +/- 0.8, p < 0.01) from 99% vs. 67% of samples (p < 0.01). TCM detected S. aureus in 13 samples vs. 21 by PCR/ESI-TOF-MS. Gram-negative organisms were less commonly identified than gram-positive by both methods; especially by TCM. Among all detected bacterial species, similar percentages were typical nosocomial pathogens (18-19%) for TCM vs. PCR/ESI-TOF-MS. PCR/ESI-TOF-MS also detected mecA in 112 samples, vanA in 13, and KPC-3 in 2. MecA was associated (p < 0.01) with codetection of coagulase negative staphylococci but not S. aureus. No vanA was codetected with enterococci; one KPC-3 was detected without Klebsiella spp. CONCLUSIONS: In this pilot study, PCR/ESI-TOF-MS detected more organisms, especially gram-negatives, compared to TCM, but the current assay format is limited by the number of antibiotic resistance determinants it covers. Further large-scale assessments of PCR/ESI-TOF-MS for hospital surveillance are warranted.

Reactions of Ketones with Aromatics in Acid Media. The Effect of Trifluoromethyl Groups and the Acidity Media. A Theoretical Study

The reactions of acetone, 2,2,2-trifluoroacetone and hexafluoroacetone in methanesulfonic (MSA) and triflic acids (TFSA) with benzene have been studied at M06-2X/6-311+G(d,p) level using cluster-continuum model, where the carbonyl group is explicitly solvated by acid molecules. The introduction of a trifluoromethyl group into the ketone structure reduces the activation energy of the tetrahedral intermediates formation due to an increase of the electrophilicity of the carbonyl group and raises the activation and the reaction energies of the C-O bond cleavage in formed carbinol due to the destabilization of the corresponding carbocation. The introduction of the second trifluoromethyl group inhibits the hydroxyalkylation reaction due to a very strong increase of the reaction and activation energies of the C-O bond cleavage which becomes the rate determining step. The most important catalytic effect of TFSA compared to MSA is not the protonation of the ketone carbonyl, but the reduction of the activation and reaction energies of the carbinol C-O bond cleavage due to better protosolvation properties. Even for TFSA no complete proton transfer to carbonyl oxygen has been observed for free ketones. Therefore, the protonation energies of free ketones cannot be considered as a measure of ketone reactivity in the hydroxyalkylation reaction.

Smoking and Survival After Breast Cancer Diagnosis: a Prospective Observational Study and Systematic Review

The association of smoking with outcomes following breast cancer prognosis is not well understood. In a cohort study called Life After Cancer Epidemiology (LACE), 2,265 women diagnosed with breast cancer were followed for a median of 12 years. We used multivariable proportional-hazards models to determine whether smoking, assessed approximately two years post-diagnosis, was associated with risk of death among these women. We also undertook a systematic review of all cohort studies to date that have examined the association between smoking and breast cancer mortality. Compared with never smokers, women who were current smokers had a twofold higher rate of dying from breast cancer [hazard ratio (HR) = 2.01, 95 % confidence interval (CI) 1.27-3.18] and an approximately fourfold higher rate of dying from competing (non-breast cancer) causes (HR = 3.84, 95 % CI 2.50-5.89). Among seven studies that met the inclusion criteria in the systematic review, three studies and our own reported significantly increased risk of breast cancer death with current smoking. We found little evidence of an association between former smoking and breast cancer mortality (HR = 1.24, 95 % CI 0.94-1.64). Consistent with findings from our prospective observational study, the systematic review of seven additional studies indicates positive association of current smoking with breast cancer mortality, but weak association with former smoking. Women who smoke following breast cancer diagnosis and treatment are at higher risk of death both from breast cancer and other causes.

In Vivo Electrical Bioimpedance Characterization of Human Lung Tissue During the Bronchoscopy Procedure. A Feasibility Study

Lung biopsies form the basis for the diagnosis of lung cancer. However, in a significant number of cases bronchoscopic lung biopsies fail to provide useful information, especially in diffuse lung disease, so more aggressive procedures are required. Success could be improved using a guided electronic biopsy based on multisine electrical impedance spectroscopy (EIS), a technique which is evaluated in this paper. The theoretical basis of the measurement method and the instrument developed are described, characterized and calibrated while the performance of the instrument is assessed by experiments to evaluate the noise and nonlinear source of errors from measurements on phantoms. Additional preliminary results are included to demonstrate that it is both feasible and safe to monitor in vivo human lung tissue electrical bioimpedance (EBI) during the bronchoscopy procedure. The time required for performing bronchoscopy is not extended because the bioimpedance measurements, present no complications, tolerance problems or side effects among any of the patients measured.

Electrical Behaviour of Heterobimetallic [MM'(EtCS(2) )(4) ] (MM'=NiPd, NiPt, PdPt) and MM'X-Chain Polymers [PtM(EtCS(2) )(4) I] (M=Ni, Pd)

Herein, we report the isolation of new heterobimetallic complexes [Ni(0.6) Pd(1.4) (EtCS(2) )(4) ] (1), [NiPt(EtCS(2) )(4) ] (2) and [Pd(0.4) Pt(1.6) (EtCS(2) )(4) ] (3), which were constructed by using transmetallation procedures. Subsequent oxidation with iodine furnished the MM'X monodimensional chains [Ni(0.6) Pt(1.4) (EtCS(2) )(4) I] (4) and [Ni(0.1) Pd(0.3) Pt(1.6) (EtCS(2) )(4) I] (5). The physical properties of these systems were investigated and the chain structures 4 and 5 were found to be reminiscent of the parent [Pt(2) (EtCS(2) )(4) I] species. However, they were more sensitively dependent on the localised nature of the charge on the Ni ion, which caused spontaneous breaking of the conduction bands.

Coaches' Interpersonal Style, Basic Psychological Needs and the Well- and Ill-being of Young Soccer Players: A Longitudinal Analysis

Abstract This study entailed a longitudinal test of basic psychological needs theory, a sub-theory in the self-determination framework (Deci & Ryan, 2000), in young soccer players. We examined whether changes in soccer players' perceptions of the coaches' interpersonal style (autonomy supportive and controlling) predicted changes in the players' need satisfaction/need thwarting, and in turn, variability in their reported subjective vitality and burnout over the course of a season. Young male soccer players (M = 12.58 ± 0.54 years) completed a questionnaire at two time points in the season [n(T1) = 725; n(T2) = 597]. Changes in the players' perceptions of an autonomy supportive environment significantly predicted changes in psychological need satisfaction (positively) and in psychological need thwarting (negatively). Changes in psychological need satisfaction positively predicted changes in subjective vitality and negatively related to cross-time variation in global burnout scores. In contrast, changes in the players' perceptions of a controlling coach-created environment were positively associated with changes in psychological need thwarting that corresponded to increases in player burnout. Finally, results provided support for the assumed mediational roles of psychological need satisfaction and need thwarting in the social environment to well- and ill-being relationships.

The Endogenous Opioid Dynorphin is Required for Normal Bone Homeostasis in Mice

Chronic opiate usage, whether prescribed or illicit, has been associated with changes in bone mass and is a recognized risk factor for the development of osteoporosis; however, the mechanism behind this effect is unknown. Here we show that lack of dynorphin, an endogenous opioid, in mice (Dyn-/-), resulted in a significantly elevated cancellous bone volume associated with greater mineral apposition rate and increased resorption indices. A similar anabolic phenotype was evident in bone of mice lacking dynorphin's cognate receptor, the kappa opioid receptor. Lack of opioid receptor expression in primary osteoblastic cultures and no change in bone cell function after dynorphin agonist treatment in vitro indicates an indirect mode of action. Consistent with a hypothalamic action, central dynorphin signaling induces extracellular signal-regulated kinase (ERK) phosphorylation and c-fos activation of neurons in the arcuate nucleus of the hypothalamus (Arc). Importantly, this signaling also leads to an increase in Arc NPY mRNA expression, a change known to decrease bone formation. Further implicating NPY in the skeletal effects of dynorphin, Dyn-/-/NPY-/- double mutant mice showed comparable increases in bone formation to single mutant mice, suggesting that dynorphin acts upstream of NPY signaling to control bone formation. Thus the dynorphin system, acting via NPY, may represent a pathway by which higher processes including stress, reward/addiction and depression influence skeletal metabolism. Moreover, understanding of these unique interactions may enable modulation of the adverse effects of exogenous opioid treatment without directly affecting analgesic responses.

Evaluation of Organic Substrates to Enhance the Sulfate-reducing Activity in Phosphogypsum

Several experiments were conducted to evaluate the activity and growth of sulfate-reducing bacteria (SRB) in a metal-rich culture medium (approx. 250mg/L Fe, 75mg/L Zn and Cu, 10mg/L Cd) with phosphogypsum as bacterial inoculum. Phosphogypsum was collected from the stack covering the salt-marshes of the Tinto river (SW Spain). Three organic amendments were used as carbon sources, two low-cost wastes (horse manure and legume compost) and one sample of natural soil (vegetal cover). In the experiments, sulfate was reduced to sulfide during the growth of SRB populations, and concentrations were decreased in the solution. Metal concentrations also decreased to values below the detection limit. Metal removal took place by precipitation of newly-formed sulfides. Pyrite-S was the main sulfide component (approx. 200μmol/g and 80% of pyritization) and occurred mainly as framboidal grains and rarely as isolated polyhedral crystals. Horse manure was the most successful organic substrate to promote SRB activity (sulfate removal of 61%), followed by vegetal cover (49%) and legume compost (31%). These findings propose the possibility of using naturally-occurring SRB in the phosphogypsum for bioremediation strategies based on natural soil covers with organic amendments.

Linkage Between HPRTB STR Alleles and Lesch-Nyhan Syndrome Inside a Family: Implications in Forensic Casework

Efficacy of a 28-day Oral Cyanocobalamin Supplementation on Vitamin B Status in Spanish Institutionalized Elderly

Cobalamin deficiency is a common problem in the elderly. There is no consensus about adequate doses for supplementation.

Intrapericardial Pacemaker in a 2-kilogram Newborn

A 2-kilogram child had a pacemaker implanted by a subxyphoid approach with the generator located under the rectus sheath. Days later, the battery eroded the abdominal wall and the peritoneum. The whole system was removed and a new one was implanted inside the pericardium on an emergent basis.

Evaluation of Gel Electrophoresis Techniques and Laser Ablation-inductively Coupled Plasma-mass Spectrometry for Screening Analysis of Zn and Cu-binding Proteins in Plankton

The determination of metal-binding proteins in plankton is important because of their involvement in photosynthesis, which is fundamental to the biogeochemical cycle of the oceans and other ecosystems. We have elaborated a new strategy for screening of Cu and Zn-containing proteins in plankton on the basis of separation of proteins by use of Blue-Native PAGE (BN-PAGE), which entails use of a non-denaturing Tris-tricine system and detection of metals in the proteins by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). For comparison, denaturing PAGE based on Tris-glycine and Tris-tricine systems and Anodic-Native PAGE have also been investigated. A large number of protein bands with MW between 20 and 75 kDa were obtained by use of Tris-glycine PAGE but detection of metals by LA-ICP-MS was unsuccessful because of loss of metals from the proteins during the separation process. Different protein extraction, purification, and preconcentration methods were evaluated, focussing on both issues-achieving the best extraction and characterization of the proteins while maintaining the integrity of metal-protein binding in the plankton sample. Use of 25 mmol L(-1) Tris-HCl and a protease inhibitor as extraction buffer with subsequent ultrafiltration and acetone precipitation was the most efficient means of sample preparation. Two Cu and Zn proteins were detected, a protein band corresponding to a MW of 60 kDa and another poorly resolved band with a MW between 15 and 35 kDa.

Comparative Sequence Analysis of a Multi-drug Resistant Plasmid from Aeromonas Hydrophila

Aeromonas hydrophila is a pathogenic bacterium that has been implicated in fish, animal, and human disease. Recently, a multi-drug resistance (MDR) plasmid pR148 was isolated from A. hydrophila obtained from a tilapia (Oreochromis niloticus) farm in Thailand. pR148 is a 165,906 bp circular plasmid containing 147 coding regions showing highest similarity to pNDM-1_Dok1, an MDR plasmid isolated from a human pathogen. It was also very similar to other IncA/C plasmids isolated from humans, animals, food, and fish. pR148 contains a mercuric resistance operon and encodes the complete set of genes for the type 4 secretion system. pR148 encodes for a Tn21 type transposon. This contains the drug resistance genes qacH, bla(OXA-10), aadA1, and sul1 in a class 1 integron; tetA and tetR in a transposon Tn1721; and catA2 and a duplicate sul1 in a locus showing 100% similarity to IncU plasmids isolated from fish. The bla(OXA-10) and aadA1 genes showed 100% similarity with those from the Acinetobacter baumannii AYE chromosomal genome. The similarity of pR148 to a human pathogen-derived plasmid indicates that the plasmids were either transferred between them or that they are derived from a common origin. Previous studies have shown that IncA/C plasmids retain a conserved backbone, while the accessory region points to lateral gene transfer. These observations point out the dangers of indiscriminate use of antibiotics in humans and in animals and the necessity of understanding how drug resistance determinants are disseminated and transferred.

Infrared Spectroscopy As Alternative to Wet Chemical Analysis to Characterize Eucalyptus Globulus Pulps and Predict Their Ethanol Yield for a Simultaneous Saccharification and Fermentation Process

Bioethanol can be obtained from wood by simultaneous enzymatic saccharification and fermentation step (SSF). However, for enzymatic process to be effective, a pretreatment is needed to break the wood structure and to remove lignin to expose the carbohydrates components. Evaluation of these processes requires characterization of the materials generated in the different stages. The traditional analytical methods of wood, pretreated materials (pulps), monosaccharides in the hydrolyzated pulps, and ethanol involve laborious and destructive methodologies. This, together with the high cost of enzymes and the possibility to obtain low ethanol yields from some pulps, makes it suitable to have rapid, nondestructive, less expensive, and quantitative methods to monitoring the processes to obtain ethanol from wood. In this work, infrared spectroscopy (IR) accompanied with multivariate analysis is used to characterize chemically organosolv pretreated Eucalyptus globulus pulps (glucans, lignin, and hemicellulosic sugars), as well as to predict the ethanol yield after a SSF process. Mid (4,000-400 cm(-1)) and near-infrared (12,500-4,000 cm(-1)) spectra of pulps were used in order to obtain calibration models through of partial least squares regression (PLS). The obtained multivariate models were validated by cross validation and by external validation. Mid-infrared (mid-IR)/NIR PLS models to quantify ethanol concentration were also compared with a mathematical approach to predict ethanol yield estimated from the chemical composition of the pulps determined by wet chemical methods (discrete chemical data). Results show the high ability of the infrared spectra in both regions, mid-IR and NIR, to calibrate and predict the ethanol yield and the chemical components of pulps, with low values of standard calibration and validation errors (root mean square error of calibration, root mean square error of validation (RMSEV), and root mean square error of prediction), high correlation between predicted and measured by the reference methods values (R (2) between 0.789 and 0.997), and adequate values of the ratio between the standard deviation of the reference methods and the standard errors of infrared PLS models relative performance determinant (RPD) (greater than 3 for majority of the models). Use of IR for ethanol quantification showed similar and even better results to the obtained with the discrete chemical data, especially in the case of mid-IR models, where ethanol concentration can be estimated with a RMSEV equal to 1.9 g L(-1). These results could facilitate the analysis of high number of samples required in the evaluation and optimization of the processes.

The Girl with the Iron Tattoo

We describe a young woman with profound anemia whose serum iron studies were incongruous with what we expected from iron deficiency anemia. Her high serum iron was not fully explainable until we examined the patient and noticed a large black tattoo on her left flank area. Apparently iron oxide in the ink used for the tattoo was absorbed transcutaneously and led to high serum iron in the face of the other data, which suggested iron deficiency. She was slow in mobilizing her serum iron for erythropoiesis and we discovered that there was a concurrent acute B19 parvovirus infection, which impeded utilization of the iron for red blood cell production. We believe that this case report reinforces the imperative to always do a careful physical examination with any patient who has anemia, and also illustrates the potential toxicity of tattoo ink. The impairment of utilization of the serum iron because of the patient's acute B19 parvovirus infection demonstrates the many consequences of infection induced aplastic anemia.

Routine Habitat Change: a Source of Unrecognized Transient Alteration of Intestinal Microbiota in Laboratory Mice

The mammalian intestine harbors a vast, complex and dynamic microbial population, which has profound effects on host nutrition, intestinal function and immune response, as well as influence on physiology outside of the alimentary tract. Imbalance in the composition of the dense colonizing bacterial population can increase susceptibility to various acute and chronic diseases. Valuable insights on the association of the microbiota with disease critically depend on investigation of mouse models. Like in humans, the microbial community in the mouse intestine is relatively stable and resilient, yet can be influenced by environmental factors. An often-overlooked variable in research is basic animal husbandry, which can potentially alter mouse physiology and experimental outcomes. This study examined the effects of common husbandry practices, including food and bedding alterations, as well as facility and cage changes, on the gut microbiota over a short time course of five days using three culture-independent techniques, quantitative PCR, terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). This study detected a substantial transient alteration in microbiota after the common practice of a short cross-campus facility transfer, but found no comparable alterations in microbiota within 5 days of switches in common laboratory food or bedding, or following an isolated cage change in mice acclimated to their housing facility. Our results highlight the importance of an acclimation period following even simple transfer of mice between campus facilities, and highlights that occult changes in microbiota should be considered when imposing husbandry variables on laboratory animals.

Short- and Midterm Effects of Emotional Intelligence Training on Adolescent Mental Health

To analyze the effects that an emotional intelligence (EI) educational program based on the EI ability model had on adolescent mental health immediately and 6 months after completion of the training.

Homology Modeling, Docking and Molecular Dynamics of the Leishmania Mexicana Arginase: A Description of the Catalytic Site Useful for Drug Design

The crystallographic structure of the Leishmania mexicana arginase, an attractive target for the design of leishmanicidal agents, is still unknown. For this reason, we report a computer-assisted homology study conducted to build its three-dimensional structure based on the known sequence of amino acids of this enzyme. In this study, the amino acid sequence in the arginase of the parasite was compared with the sequence of the amino acids in the crystallographic structure of rat and human liver arginases. The best similarity was found with the rat liver arginase. The catalytic site of the three-dimensional arginase structure built for L. mexicana has important structural differences as compared with that of the human liver arginase with regard to reasonable design selective compounds against L. mexicana. With this information, a docking study was conducted to find the inhibitors of this enzyme. 1439 molecules were docked and 18 were selective to the L. mexicana arginase. Moreover, molecular dynamics were carried out to study the stability of the homologue protein (including manganeses) and the ligand-enzyme complex. The results indicated that the manganese remains inside the protein throughout the simulation. Besides, hydrogen bonds interactions between the ligand and the arginase were analyzed. These results provide important information for the design of new inhibitors.

Bactridine's Effects on DUM Cricket Neurons Under Voltage Clamp Conditions

We describe the effects of six bactridines (150nM) on cricket dorsal unpaired median (DUM) neurons. The addition of bactridine 2 to DUM neurons induced a large current component with a reversal potential more negative than -30mV, most evident at the end of the pulses. This current was completely suppressed when 1μM amiloride was applied before adding the bactridines. Since the amiloride sensitive current is able to distort the aim of our study, i.e. the effect of bactridines on sodium channels, all experiments were done in the presence of 1μM amiloride. Most bactridines induced voltage shifts of V(1/2) of the Boltzmann inactivation voltage dependency curves in the hyperpolarizing direction. Bactridines 1, 4 and 6 reduced Na current peak by 65, 80 and 24% of the control, respectively. The sodium conductance blockage by bactridines was voltage independent at potentials >20mV. Bactridines effect on cricket DUM neurons does not correspond to neither α- nor β-toxins. Most bactridines shifted the inactivation curves in the hyperpolarizing direction without any effects on the activation m(∞)-like curves. Also bactridines differ from other NaScpTx in that they increased an amiloride-sensitive conductance in DUM neurons. Our result suggest that the α/β classification of sodium scorpion toxins is not all encompassing. The present work shows that bactridines target more than one site: insect voltage dependent Na channels and an amiloride-sensitive ionic pathway which is under study.

Characterization of Interictal Epileptiform Discharges with Time-resolved Cortical Current Maps Using the Helmholtz-hodge Decomposition

Source estimates performed using a single equivalent current dipole (ECD) model for interictal epileptiform discharges (IEDs) which appear unifocal have proven highly accurate in neocortical epilepsies, falling within millimeters of that demonstrated by electrocorticography. Despite this success, the single ECD solution is limited, best describing sources which are temporally stable. Adapted from the field of optics, optical flow analysis of distributed source models of MEG or EEG data has been proposed as a means to estimate the current motion field of cortical activity, or "cortical flow." The motion field so defined can be used to identify dynamic features of interest such as patterns of directional flow, current sources, and sinks. The Helmholtz-Hodge Decomposition (HHD) is a technique frequently applied in fluid dynamics to separate a flow pattern into three components: (1) a non-rotational scalar potential U describing sinks and sources, (2) a non-diverging scalar potential A accounting for vortices, and (3) an harmonic vector field H. As IEDs seem likely to represent periods of highly correlated directional flow of cortical currents, the U component of the HHD suggests itself as a way to characterize spikes in terms of current sources and sinks. In a series of patients with refractory epilepsy who were studied with magnetoencephalography as part of their evaluation for possible resective surgery, spike localization with ECD was compared to HHD applied to an optical flow analysis of the same spike. Reasonable anatomic correlation between the two techniques was seen in the majority of patients, suggesting that this method may offer an additional means of characterization of epileptic discharges.

Design of a Trial to Evaluate the Impact of Clinical Pharmacists and Community Health Promoters Working with African-Americans and Latinos with Diabetes

ABSTRACT: BACKGROUND: Given the increasing prevalence of diabetes and the lack of patients reaching recommended therapeutic goals, novel models of team-based care are emerging. These teams typically include a combination of physicians, nurses, case managers, pharmacists, and community-based peer health promoters (HPs). Recent evidence supports the role of pharmacists in diabetes management to improve glycemic control, as they offer expertise in medication management with the ability to collaboratively intensify therapy. However, few studies of pharmacy-based models of care have focused on low income, minority populations that are most in need of intervention. Alternatively, HP interventions have focused largely upon low income minority groups, addressing their unique psychosocial and environmental challenges in diabetes self-care. This study will evaluate the impact of HPs as a complement to pharmacist management in a randomized controlled trial. METHODS: The primary aim of this randomized trial is to evaluate the effectiveness of clinical pharmacists and HPs on diabetes behaviors (including healthy eating, physical activity, and medication adherence), hemoglobin A1c, blood pressure, and LDL-cholesterol levels. A total of 300 minority patients with uncontrolled diabetes from the University of Illinois Medical Center ambulatory network in Chicago will be randomized to either pharmacist management alone, or pharmacist management plus HP support. After one year, the pharmacist-only group will be intensified by the addition of HP support and maintenance will be assessed by phasing out HP support from the pharmacist plus HP group (crossover design). Outcomes will be evaluated at baseline, 6, 12, and 24 months. In addition, program and healthcare utilization data will be incorporated into cost and cost-effectiveness evaluations of pharmacist management with and without HP support. DISCUSSION: The study will evaluate an innovative, integrated approach to chronic disease management in minorities with poorly controlled diabetes. The approach is comprised of clinic-based pharmacists and community-based health promoters collaborating together. They will target patient-level factors (e.g., lack of adherence to lifestyle modification and medications) and provider-level factors (e.g., clinical inertia) that contribute to poor clinical outcomes in diabetes. Importantly, the study design and analytic approach will help determine the differential and combined impact of adherence to lifestyle changes, medication, and intensification on clinical outcomes.Trial registrationClinicalTrials.gov identifier: NCT01498159.

The Impact of Post-discharge Patient Call Back on Patient Satisfaction in Two Academic Emergency Departments

BACKGROUND: Patients' satisfaction is a common parameter tracked by health care systems and Emergency Departments (EDs). OBJECTIVES: To determine whether telephone calls by health care providers to patients after discharge from the ED was associated with improved patient satisfaction. METHODS: Retrospective analysis of Press Ganey (PG; Press Ganey Associates, South Bend, IN) surveys from two EDs operated by the University of California San Diego Health System. Responses to the YES/NO question, "After discharge, did you receive a phone call from an ED staff member?" was compared to the responses to the question "likelihood of recommending this ED to others" (LR). This variable could be ranked with a score of 1 (very poor) to 5 (very good). Responses were dichotomized into two groups, 1-4 and 5. Chi-squared was performed to assess LR between those answering YES vs. NO to the call back question. Differences in proportion, 95% confidence interval (CI), and p-value are reported. Rankings for percentage of 5s across all EDs in the PG database were compared based upon YES/NO responses. RESULTS: In the 12-month study period, about 30,000 surveys were mailed and 2250 (7.5%) were returned. Three hundred forty-seven (15.4%) checked off YES for the call back question. Percentage of 5s for LR for NO call back was 51.1% and for YES call back was 70.6% (difference = 19.5; 95% CI 14.0-24.6; p < 0.001).These values correlated with an ED ranking of 14(th) and 85(th) percentile, respectively. CONCLUSION: This retrospective study demonstrated a strong association between post-visit patient call back and LR. Further prospective study with control for co-variables is warranted.

An Application of Reconfigurable Technologies for Non-invasive Fetal Heart Rate Extraction

This paper illustrates the use of a reconfigurable system for fetal electrocardiogram (FECG) estimation from mother's abdomen ECG measurements. The system is based on two different reconfigurable devices. Initially, a field-programmable analog array (FPAA) device implements the analog reconfigurable preprocessing for ECG signal acquisition. The signal processing chain continues onto a field-programmable gate array (FPGA) device, which contains all the communication and interfacing protocols along with specific digital signal processing blocks required for fundamental period extraction from FECG waveforms. The synergy between these devices provides the system the ability to change any necessary parameter during the acquisition process for enhancing the result. The use of a FPGA allows implementing different algorithms for FECG signal extraction, such as adaptive signal filtering. Preliminary works employ commercially available development platforms for test experiments, which suffice for the processing of real FECG signals from biomedical databases, as the presented results illustrate.

Fast and Accurate Procedure for the Determination of Cr(VI) in Solid Samples by Isotope Dilution Mass Spectrometry

We present here a new environmental measurement method for the rapid extraction and accurate quantification of Cr(VI) in solid samples. The quantitative extraction of Cr(VI) is achieved in 10 minutes by means of focused microwave assisted extraction using 50 mmol/L Ethylendiamintetraacetic acid (EDTA) at pH 10 as extractant. In addition, it enables the separation of Cr species by anion exchange chromatography using a mobile phase which is a 1:10 dilution of the extracting solution. Thus, neutralization or acidification steps which are prone to cause interconversion of Cr species are not needed. Another benefit of using EDTA is that it allows to measure Cr(III)-EDTA complex and Cr(VI) simultaneously in an alkaline extraction solution. The application of a 10 minutes focused microwave assisted extraction (5 min at 90 °C plus 5 min at 110 °C) has been shown to quantitatively extract all forms of hexavalent chromium from the standard reference materials (SRM) candidate NIST 2700 and NIST 2701. A double spike isotope dilution mass spectrometry (IDMS) procedure was employed to study chromium interconversion reactions. It was observed that the formation of a Cr(III)-EDTA complex avoided Cr(III) oxidation for these two reference materials. Thus, the use of a double spiking strategy for quantification is not required and a single spike IDMS procedure using isotopically enriched Cr(VI) provided accurate results.

Identifying Indoor Environmental Patterns from Bioaerosol Material Using HPLC

A substantial portion of the atmospheric particle budget is of biological origin (human and animal dander, plant and insect debris, etc.). These bioaerosols can be considered information-rich packets of biochemical data specific to the organism of origin. In this study, bioaerosol samples from various indoor environments were analyzed to create identifiable patterns attributable to a source level of occupation. Air samples were collected from environments representative of human high-traffic- and low-traffic indoor spaces along with direct human skin sampling. In all settings, total suspended particulate matter was collected and the total aerosol protein concentration ranged from 0.03 to 1.2 μg/m(3). High performance liquid chromatography was chosen as a standard analysis technique for the examination of aqueous aerosol extracts to distinguish signatures of occupation compared to environmental background. The results of this study suggest that bioaerosol "fingerprinting" is possible with the two test environments being distinguishable at a 97 % confidence interval.

Autophagy Protects Against Active Tuberculosis by Suppressing Bacterial Burden and Inflammation

Autophagy is a cell biological pathway affecting immune responses. In vitro, autophagy acts as a cell-autonomous defense against Mycobacterium tuberculosis, but its role in vivo is unknown. Here we show that autophagy plays a dual role against tuberculosis: antibacterial and anti-inflammatory. M. tuberculosis infection of Atg5(fl/fl) LysM-Cre(+) mice relative to autophagy-proficient littermates resulted in increased bacillary burden and excessive pulmonary inflammation characterized by neutrophil infiltration and IL-17 response with increased IL-1α levels. Macrophages from uninfected Atg5(fl/fl) LysM-Cre(+) mice displayed a cell-autonomous IL-1α hypersecretion phenotype, whereas T cells showed propensity toward IL-17 polarization during nonspecific activation or upon restimulation with mycobacterial antigens. Thus, autophagy acts in vivo by suppressing both M. tuberculosis growth and damaging inflammation.

[Epidemiological and Clinical Characteristics of Influenza A (H1N1) 2009 at San Felipe, Valparaiso Region, Chile: June-August 2009]

In order to understand the clinical and epidemiological aspects of infection with the AH1N1 influenza virus in Chile, a prospective study in the city of San Felipe was undertaken. It analyses the trends in consultations for respiratory causes in three primary care centers and hospital discharges by comparing data from years 2008 and 2009 until epidemiological week 37.It also includes a study of cases of ILI / SARI (influenza like disease/severe acute respiratory disease) in which viruses were detected by direct immunofluorescence (DIF) of nasopharyngeal aspirates and by real-time polymerase chain reaction in the case of influenza A (H1N1) 2009. A household survey was conducted in those cases with confirmed A (H1N1) infection, to identify contacts and history related to influenza virus transmission. The results indicate that the behavior of the pandemic was similar to that observed in the rest of the country, with an increase in emergency room visits for ILI. The most affected age group was from 5 to 14 years (26.5 per thousand inhabitants) and the least affected 60 years or older (1.2 per thousand). A 2.78% of the cases corresponded to SARI and the fatality rate was 0.11%.

Relationship Between Discordance in Parental Monitoring and Behavioral Problems Among Chilean Adolescents

This study investigated the role of discrepancies between parent and youth reports of perceived parental monitoring in adolescent problem behaviors with a Chilean sample (N= 850). Higher levels of discordance concerning parental monitoring predicted greater levels of maladaptive youth behaviors. A positive association between parent-youth discordance and externalizing problems indicated that large adult-youth disagreement in parental monitoring may impose a great risk, despite protective efforts of parental monitoring. Although the direct relationship between parental monitoring and youth internalizing behaviors was not significant, parent-youth incongruence in monitoring was associated with greater levels of internalizing behaviors. Therefore, differing assessments of parental behaviors, as an indicator of less optimal family functioning, may provide important information about youth maladjustment and may potentially provide a beginning point for family-focused intervention.

Endocrine and Metabolic Changes During Sepsis: An Update

Sepsis is associated with various metabolic and endocrine disorders that can be confusing. A cardinal manifestation is hyperglycemia. The glycemic goal has been somewhat relaxed based on evidence that very tight glucose control may be undesirable. Relative adrenal insufficiency has receded into the background, and the unconditional love for steroids is no longer justified. Instead, glucocorticoids need to be used in special cases, and testing for adrenal reserve is no longer necessary or justifiable. Thyroid dysfunction, and hypogonadism, both often noted with sepsis, do not require any treatment. Abnormalities in growth hormone, prolactin, and vasopressin secretion similarly require no treatment.

Phosphodiesterase-3 Inhibition Augments the Myocardial Infarct Size Limiting Effects of Exenatide in Mice with Type-2 Diabetes

Background: GLP1 receptor activation increases intracellular cAMP with downstream activation of protein kinase A (PKA). Cilostazol (CIL), a phosphodiesterase-3 inhibitor, prevents cAMP degradation. We assessed whether CIL amplifies the exenatide (EX)-induced increase in myocardial cAMP, PKA activity and augments the infarct size (IS)-limiting effects of EX in Db/Db mice. Methods: Mice fed a Western Diet received oral CIL (10mg/kg) or vehicle by oral gavage 24h before surgery. One hour before surgery mice received S.C. EX (1µg/kg) or vehicle. Additional mice received H89, a PKA inhibitor, alone or with CIL+EX. Mice underwent 30min coronary artery occlusion and 24h reperfusion. Results: Both EX and CIL increased myocardial cAMP levels and PKA activity. Levels were significantly higher in the EX+CIL group. Both EX and CIL reduced IS. IS was the smallest in the CIL+EX group. H89 completely blocked the IS-limiting effects of EX+CIL. EX+ CIL decreased PTEN upregulation and increased Akt and ERK 1/2 phosphorylation following ischemia-reperfusion. These effects were blocked by H89. Conclusions: EX and CIL have additive effects on IS limitation in diabetic mice. The additive effects are related to cAMP induced PKA activation, as H89 blocked the protective effect of CIL+EX.

Role of Matrix Metalloproteinases 2 and 9 in Ex vivo Trypanosoma Cruzi Infection of Human Placental Chorionic Villi

BACKGROUND: Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier. In the present study we analyzed the participation of matrix metalloproteases (MMPs) in the extracellular matrix (ECM) remodeling during T. cruzi ex vivo infection of human placental chorionic villi explants. METHODS: Chorionic villi from healthy woman placentas were incubated in the presence or absence of 10(5) or 10(6)T. cruzi trypomastigotes (Y strain) with or without the MMPs inhibitor doxycycline. Effective infection was tested measuring parasite DNA by real time PCR (qPCR). MMP-2 and MMP-9 expression were determined by western blotting and immunohistochemistry and their activities were measured by zymography. The effect of MMPs on ECM structure was analyzed histochemically. RESULTS: T. cruzi induces the expression and activity of MMP-2 and MMP-9 in chorionic villi. Inhibition of the MMPs prevents the tissue damage induced by T. cruzi and partially decreases the ex vivo infection of the chorionic villi. CONCLUSION: MMPs are partially responsible for the ECM changes observed in human chorionic villi during T. cruzi infection and participate in tissue invasion. On the other hand, MMPs may be part of a local placental antiparasitic mechanism.

Five Year Trends on Total and Abdominal Adiposity in Spanish Adolescents

Objective: To assess five years trends in total and abdominal fat in Spanish adolescents. Design: Two cross-sectional studies: adolescents from the city of Zaragoza (Spain) assessed during 2001-2002 and 2006-2007. Subjects: 399 adolescents in 2001-02 and 392 adolescents in 2006-07. Main outcome measurements: Socio-economic status was assessed using the education level of both parents. A complete anthropometric assessment was performed in both surveys using the same methodology: weight, height, skinfold thickness (biceps, triceps, subscapular, suprailiac, thigh and calf) and circumferences (waist and hip). The body mass index (BMI) and the sum of 6 skinfold thicknesses were calculated. Body fat percentage (BF%) was also calculated by the formulas described by Slaughter et al. Results: After adjusting for age and pubertal status, only females showed a significantly decrease in weight, BMI and waist circumference, and a significant increase in the sum of 6 skinfolds (all P < 0.05 and Cohen's d ≥ 0.25) in 2006-2007, when compared to values obtained in 2001-2002. Males did not show any significant change between the two surveys. Concerning centile values, a slight general reduction was observed in weight, BMI and waist circumference for both males and females. On the contrary, the sum of 6 skinfolds and the BF% were higher in 2006-2007 than in 2001-2002. Conclusion: According to these results, there might be a levelling-off in the trends of BMI, BF% and waist circumference in male adolescents from Zaragoza. In females, despite a trend towards higher body fat mass, there was a trend towards lower BMI and waist circumference values.

High Genetic Diversity and Predominance of Rhinovirus A and C from Panamanian Hospitalized Children Under Five Years with Respiratory Infections

ABSTRACT: BACKGROUND: Human Rhinoviruses (HRVs) have high genetic diversity and three species have been described: HRV-A, HRV-B, and the recently recognized HRV-C, which has been rapidly identified worldwide. FINDINGS: In the present study, we report the frequency and diversity of Human Rhinovirus (HRV) strains circulating in Panama from children hospitalized with respiratory infections. CONCLUSIONS: HRVs of species A, B and C have been identified with a predominance of HRV-A and HRV-C over HRV-B, and marked genetic diversity within each species.

Phospholipase C Gamma and ERK1/2 Mitogen Activated Kinase Pathways Are Differentially Modulated by Trypanosoma Cruzi During Tissue Invasion in Human Placenta

Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier, however studies about the physiopathology of this process are scarce. Different signal transduction pathways are involved during cell invasion of the parasite. However, the possible role of those processes during tissue infection has not been studied. In the present study we analyzed the modulation of two signal transduction pathways, PLC-γ and ERK1/2 MAPK, during ex vivo infection of human placental chorionic villi explants. Chorionic villi from healthy woman placentas were incubated in the presence or absence of 105 or 106 T. cruzi trypomastigotes (DM28c strain) with or without specific inhibitors for each pathway. Effective infection was tested determining parasite DNA by PCR. The activation of PLC-γ and ERK1/2 MAPK signaling pathways was determined by western blotting and immunofluorescence. The low concentration of T. cruzi trypomastigotes activates both signaling pathways; however, the high concentration of parasite induces a modest activation of the PLC-γ pathway and impairs the ERK1/2 MAPK pathway activation. Interestingly, inhibition of any of those signaling pathways did not prevent parasite infection, as it was previously shown in cell cultures. We conclude that both signal transduction pathways are modulated during ex vivo T. cruzi infection of human placental chorionic villi explants.

Ureteral Inverted Papilloma: Laparoscopic Distal Ureterectomy and Boari Flap

OBJECTIVE: To report a case of ureteral inverted papilloma (IP) with laparoscopic resolution. METHODS: We report the case of a 30-year-old male patient who consulted for asymptomatic hematuria with the radiological finding of a filling defect at the distal right ureter. Ureteroscopy biopsy was not diagnostic, so laparoscopic ureterectomy with a Boari flap technique was performed. The pathology report showed a ureteral inverted papilloma. CONCLUSION: Laparoscopic ureteral replacement by Boari flap is a safe surgical alternative for defects in the distal ureter with the advantages of a minimally invasive procedure.

Discontinuous Intrabdominal Splenogonadal Fusion with Germ Cell Tumor. Excision with Robotic Assistence. Adult Case Report

OBJECTIVE: Present the case of a patient with a discontinuous intrabdominal splenogonadal fusion with an associated germ cell tumor. METHODS: A case of a man of 29 years with bilateral cryptorchidism and left intra-abdominal discontinuous splenogonadal fusion associated with seminoma as an accidental finding in the context of a robotic pyeloplasty due to ipsilateral ureteropelvic junction stenosis. RESULTS: The total operative time was 80 minutes (atrophic gonad removal and pyeloplasty by the Anderson-Hynes technique) with an estimated blood loss less than 100 cc. The hospitalization time was less than 36 hrs. The pathology and immunohistochemical report was compatible with intratubular germ cell neoplasia (seminoma). CONCLUSION: The splenogonadal fusion is an uncommon pathology. While a high clinical suspicion may avoid unnecessary orchiectomy in young patients, its association with disorders such as cryptorchidism should make us suspect the possible presence of a concomitant germ cell neoplasia.

Intraurethral Foreign Body

The Epidemiology of Herpes Zoster in Patients with Newly Diagnosed Cancer

BACKGROUND: Given the limited literature, we conducted a study to examine the epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients. METHODS: We identified adult health plan members of Kaiser Permanente Northern California diagnosed with invasive cancer from 2001-2005. Electronic health records with inpatient and outpatient diagnoses, laboratory tests, and antiviral medications were used to identify HZ diagnoses from 2001-2006. HZ diagnoses and associated complications were confirmed by medical chart review. Treatment with chemotherapy and corticosteroids was used to classify patients by immunosuppression level. RESULTS: Among 14,670 cancer patients, 424 were diagnosed with HZ during follow-up (median 22 months). The incidence of HZ was 31/1,000 person-year (PY) in patients with hematologic malignancies and 12/1,000 PY in patients with solid tumors. The corresponding 2-year cumulative incidence of HZ was approximately 6% and 2%, respectively. Compared to incidence rates of HZ reported in a general US population, the age- and sex-standardized rates of HZ were 4.8 times higher (95% confidence interval (CI), 4.0-5.6) in patients with hematologic malignancies and 1.9 times higher (95% CI 1.7-2.1) in those with solid tumors. HZ risk increased with increasing level of immunosuppression. Among HZ cases, 19% with hematologic malignancies and 14% with solid tumors had HZ-associated pain for at least 30 days. The corresponding numbers for non-pain related complications were 30% and 18%, respectively. CONCLUSIONS: Cancer patients are at substantially increased risk of HZ and among those with HZ, complications are relatively common. IMPACT: Better HZ prevention and treatment options for cancer patients are needed.

Effects of Vitamin D Supplementation During the Induction and Progression of Osteoarthritis in a Rat Model

Epidemiological studies correlate low levels of vitamin D with the osteoarthritis (OA) progression. Cytokines and metalloproteases play a major role in OA promoting the inflammation and degradation of the cartilage and can be induced through the Toll-like receptor (TLR) pathway. The aim of this study was to evaluate the protective effect of vitamin D supplementation on the development of osteoarthritis (OA) through examining the genetic regulation of TLRs, cytokines, and metalloproteases in chondrocytes as well as the wideness of cartilage in rats with OA. Our results demonstrate that the signaling through TLR-4 is a proinflammatory mechanism in osteoarthritis that drives the upregulation of MMP-3, IL-1β, and TNF-α gene expression, leading to cartilage degradation and inflammation. Vitamin D supplementation had a protective effect during the onset but not during the chronic stage of OA in the rat model.

Mutations of the Gene Encoding Otogelin Are a Cause of Autosomal-recessive Nonsyndromic Moderate Hearing Impairment

Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screening of 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.

[Estimation of the "vascular Age" Based on Body Mass Index in a Population in Primary Prevention. Association with Subclinical Carotid Atherosclerosis.]

BACKGROUND AND OBJECTIVES: To know the relationship between "vascular age" (VA) and the diagnosis of subclinical atherosclerosis could improve cardiovascular risk stratification. Objectives: 1) to know the VA in a primary prevention population, and 2) to determine the relationship between VA and the presence of carotid atherosclerotic plaque (CAP). PATIENTS AND METHODS: We calculated VA based on body mass index (BMI). We obtained the difference between VA and chronological age (Delta). The screening of CAP was done by ultrasound. We analyzed the association between quintiles of VA and Delta with the presence of CAP. ROC analysis was performed. RESULTS: In total, 411 patients were included (age 47 [10] years, 54% men). The VA and Delta were 55 (15) and 7 (9) years respectively. In 75% of the patients VA was higher than the chronological age (50%≥6 years). Subjects with CAP had significantly higher VA (66 [11] versus 50 [14] years, P<.0001) and Delta (13 [9] versus 5 [7] years, P<.0001) than subjects without CAP. We observed a positive association of quintiles of VA and Delta with the prevalence of CAP. The area under de curve and the optimal cutoff point of VA for the detection of CAP were 0.813 and 60 years, respectively, and for Delta, 0,771 and 11 years, respectively. CONCLUSIONS: The VA based on BMI could be a simple tool to estimate the presence of CAP and improve cardiovascular risk stratification in patients in primary prevention.

Testing the Feasibility of a National Spina Bifida Patient Registry

BACKGROUND: The purpose of this study was to describe the development and early implementation of a national spina bifida (SB) patient registry, the goal of which is to monitor the health status, clinical care, and outcomes of people with SB by collecting and analyzing patient data from comprehensive SB clinics. METHODS: Using a web-based, SB-specific electronic medical record, 10 SB clinics collected health-related information for patients diagnosed with myelomeningocele, lipomyelomeningocele, fatty filum, or meningocele. This information was compiled and de-identified for transmission to the Centers for Disease Control and Prevention (CDC) for quality control and analysis. RESULTS: A total of 2070 patients were enrolled from 2009 through 2011: 84.9% were younger than 18 years of age; 1095 were women; 64.2% were non-Hispanic white; 6.5% were non-Hispanic black or African American; and 24.2% were Hispanic or Latino. Myelomeningocele was the most common diagnosis (81.5%). CONCLUSIONS: The creation of a National Spina Bifida Patient Registry partnership between the CDC and SB clinics has been feasible. Through planned longitudinal data collection and the inclusion of additional clinics, the data generated by the registry will become more robust and representative of the population of patients attending SB clinics in the United States and will allow for the investigation of patient outcomes. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.

Access to Mental Health Care in Rural Communities Among Women Diagnosed with Breast Cancer

Proton Therapy Radiation Pneumonitis Local Dose-response in Esophagus Cancer Patients

PURPOSE: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. MATERIALS/METHODS: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. RESULTS: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p=0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. CONCLUSIONS: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope.

Molecular Relationships and Classification of Several Tufted Capuchin Lineages ( Cebus Apella , Cebus Xanthosternos and Cebus Nigritus , Cebidae), by Means of Mitochondrial Cytochrome Oxidase II Gene Sequences

The morphological systematics of the tufted capuchins is confusing. In an attempt to clarify the complex systematics and phylogeography of this taxon, we provide a first molecular analysis. We obtained mitochondrial cytochrome oxidase II (mtCOII) gene sequences from 49 tufted capuchins that had exact geographic origins from diverse lineages in Colombia, Peru, Bolivia, French Guyana, Brazil, Argentina and Paraguay and that belonged to clearly recognized morphological taxa. This project had 4 main findings: (1) we determined 2 established and related taxa in the northern Amazon River area, which we named C. a. apella and C. a. fatuellus. C. a. apella is distributed from French Guyana until, at least, the Negro River in the northern Brazilian Amazon, whereas C. a. fatuellus is distributed throughout the Colombian Eastern Llanos and the northern Colombian Amazon. We also determined 2 other southern C. apella taxa, which we named C. a. macrodon and C. a. cay. C. a. macrodon has a western and southern Amazon distribution, while C. a. cay has a more southern distribution outside the Amazon basin. (2) In the upper Amazon basin, there is a unique lineage (C. a. macrocephalus) with 1 widely distributed haplotype. The 4 morphological subspecies (C. a. maranonis, C. a. macrocephalus, C. a. peruanus, C. a. pallidus), and maybe a fifth unknown subspecies, described in this area were molecularly undifferentiated at least for the mitochondrial gene analyzed. (3) Our molecular analysis determined that 1 individual of C. robustus fell into the lineage of C. a. macrocephalus. Therefore, this form does not receive any specific name. (4) The animals classified a priori as C. nigritus and C. xanthosternos (because of their morphological phenotypes and by their geographical origins) were clearly differentiated from the other specimens analyzed with the molecular marker employed. Therefore, we consider that these 2 lineages could be assigned the status of full species following the biological species definition. (5) In 2001, Groves described 4 tufted capuchin species (C. apella, C. libidinosus, C. nigritus and C. xanthosternos), while Silva Jr. determined 7 species (C. apella, C. macrocephalus, C. libidinosus, C. cay, C. nigritus, C. robustus and C. xanthosternos). The tests of Swofford-Olsen-Waddell-Hillis, of Shimodaira and Hasegawa and of Templeton did not fit with either of these two classificatory schemes, although Groves' scheme was better with regard to our data than that of Silva Jr. (6) All the temporal splits among the tufted capuchin taxa studied were estimated to have occurred during the last phase of the Pleistocene by using the ρ statistic applied to the median joining haplotype network.

[Alternative Therapies for Smoking Cessation: Clinical Practice Guidelines Review]

Antecedentes: el tabaquismo es una enfermedad crónica perteneciente al grupo de las adicciones y su tratamiento incluye dos componentes: psicosocial y farmacológico. Se han utilizado también terapias alternativas para el manejo de las cuales la acupuntura, hipnosis y homeopatía son las más utilizadas. Objetivo: revisar la evidencia disponible sobre el uso de terapias alternativas para cesación de la adicción al tabaco en población adulta a partir de las guías de práctica clínica (GPC) publicadas. Métodos: se realizó un proceso de adaptación de recomendaciones clínicas a partir de una revisión sistemática de GPC relacionadas con el uso de las terapias alternativas para la cesación de tabaco. Resultados: se encontraron 925 referencias, se preseleccionaron 9 GPC y se escogieron cinco para adaptación por su calidad. La acupuntura y sus técnicas relacionadas no mejoran las tasas de abstinencia en comparación con el efecto placebo. No existe suficiente evidencia para recomendar el uso de la hipnosis como terapia para dejar de fumar. No existe evidencia que justifique el uso de medicamentos homeopáticos para el tratamiento del tabaquismo. Conclusiones: las terapias alternativas no tienen eficacia demostrada en cesación. Se recomienda utilizar otras opciones terapéuticas con eficacia probada para dejar de fumar.

Effects of Potassium Apigenin and Verbena Extract on the Wound Healing Process of SKH-1 Mouse Skin

Tissue repair is a complex process, which may be favoured or inhibited by different factors. Potassium apigenin (AP) and other flavonoids present in verbena extract (PLX®) possess powerful anti-inflammatory properties. The aim of this study was to evaluate the effects of topical treatment with AP and PLX gels on wounds inflicted on SKH-1/CRL mice. Forty-eight SKH-1 mice were used (4 groups with 12 animals each), which were subjected to wound excision with a round scalpel, 4 mm in diameter, on the dorsal skin. Animals were divided into four groups: Group I received topical applications of apigenin gel; Group II received PLX gel; Group III received vehicle gel; Group IV acted as control. Wound contraction, re-epithelialisation, inflammation and neovascularisation (by means of immunohistochemical staining with anti-laminin) were recorded at study periods established at 2, 7 and 14 days. Re-epithelialisation was faster in Groups I and II at 7 days (56·25% grade 3 and 43·75% grade 4) compared with the other groups. The degree of inflammation showed improvement with a tendency towards statistical significance in Groups I and II at 2 and 7 days. Anti-laminin staining was more intense in the group treated with PLX at the 2- and 7-day periods. Topical treatment with PLX gel improved the degree of re-epithelialisation and inflammation and favoured neo-vascularisation of the wounds at 2 and 7 days following surgery.

Massive Plasmodium Falciparum Visceral Sequestration: a Cause of Maternal Death in Africa

Sequestration of Plasmodium falciparum-infected erythrocytes (PfIE) in the capillaries of the central nervous system (CNS) is the pathognomonic feature of cerebral malaria, a condition frequently leading to death. Sequestration of PfIE in the placental intervillous spaces is the characteristic feature of malaria in pregnancy and is associated with low birthweight and prematurity. Although both patterns of sequestration are thought to result from the expression of different parasite proteins involved in cytoadhesion to human receptors, scant information exists on whether both conditions can coexist and whether this can lead to death. We conducted a prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary-level referral hospital in Maputo, Mozambique, between October 2002 and December 2006. Extensive sampling of all major viscera was performed. All cases showing parasites in any of the viscera were included in the analysis. From 317 complete autopsies PfIEs were identified in ten women (3.2%). All cases showed massive accumulation of PfIE in small capillaries of the CNS but also in most visceral capillaries (heart, lung, kidney, uterus). Placental tissue, available in four cases, showed a massive accumulation of maternal PfIE in the intervillous space. Coma (six women) and dyspnoea (five women) were the most frequent presenting clinical symptoms. In conclusion, massive visceral sequestration of PfIE with significant involvement of the CNS is an infrequent but definite direct cause of maternal death in endemic areas of Africa. The PfIE sequestered in cerebral capillaries and the placenta coexist in these fatal cases.

Study of the Effect Exerted by Fructo-oligosaccharides from Yacon (Smallanthus Sonchifolius) Root Flour in an Intestinal Infection Model with Salmonella Typhimurium

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50-70 % of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can up-regulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immunomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45 d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1α+ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.

Proliferating Cell Nuclear Antigen (PCNA) Interactions in Solution Studied by NMR

PCNA is an essential factor for DNA replication and repair. It forms a ring shaped structure of 86 kDa by the symmetric association of three identical protomers. The ring encircles the DNA and acts as a docking platform for other proteins, most of them containing the PCNA Interaction Protein sequence (PIP-box). We have used NMR to characterize the interactions of PCNA with several other proteins and fragments in solution. The binding of the PIP-box peptide of the cell cycle inhibitor p21 to PCNA is consistent with the crystal structure of the complex. A shorter p21 peptide binds with reduced affinity but retains most of the molecular recognition determinants. However the binding of the corresponding peptide of the tumor suppressor ING1 is extremely weak, indicating that slight deviations from the consensus PIP-box sequence dramatically reduce the affinity for PCNA, in contrast with a proposed less stringent PIP-box sequence requirement. We could not detect any binding between PCNA and the MCL-1 or the CDK2 protein, reported to interact with PCNA in biochemical assays. This suggests that they do not bind directly to PCNA, or they do but very weakly, with additional unidentified factors stabilizing the interactions in the cell. Backbone dynamics measurements show three PCNA regions with high relative flexibility, including the interdomain connector loop (IDCL) and the C-terminus, both of them involved in the interaction with the PIP-box. Our work provides the basis for high resolution studies of direct ligand binding to PCNA in solution.

Narrow Irregular QRS Tachycardia with AV Dissociation: What Is the Mechanism?

Arrhythmia Rounds. A 39-year-old woman with no structural heart disease and frequent episodes of sudden onset palpitations was referred for the electrophysiological study. During the study, a slightly irregular narrow QRS tachycardia with AV dissociation was repeatedly induced and spontaneously terminated. Apparently, irregular cycles and termination of the tachycardia were related to the dissociated sinus rhythm: atrial depolarizations timed when the AV junction was refractory were able to reset the tachycardia, while early atrial depolarizations caused its termination. This observation was enough to diagnose the tachycardia mechanism in our case. (J Cardiovasc Electrophysiol, Vol. pp. 1-3).

The Role of Radiation Therapy in Pediatric Mucoepidermoid Carcinomas of the Salivary Glands

OBJECTIVE: To investigate the role of radiation therapy in rare salivary gland pediatric mucoepidermoid carcinoma (MEC). STUDY DESIGN: A French multicenter retrospective study (level of evidence 4) of children/adolescents treated for MEC between 1980 and 2010 was conducted. RESULTS: Median age of the 38 patients was 14 years. Parotid subsite, low-grade, and early primary stage tumors were encountered in 81%, 82%, and 68% of cases, respectively. All except 1 patient were treated by tumoral surgical excision, and 53% by neck dissection (80% of high grades). Postoperative radiation therapy and chemotherapy were performed in 29% and 11% of cases. With a median 62-month follow-up, overall survival and local control rates were 95% and 84%, respectively. There was 1 nodal relapse. Lower grade and early stage tumors had better survival. Postoperative radiation therapy and chemotherapy were associated with similar local rates. Patients with or without prior cancer had similar outcomes. CONCLUSIONS: Pediatric salivary gland MEC carries a good prognosis. Low-intermediate grade, early-stage tumors should be treated with surgery alone. Neck dissection should be performed in high-grade tumors. Radiation therapy should be proposed for high grade and/or advanced primary stage MEC. For high-grade tumors without massive neck involvement, irradiation volumes may be limited to the primary area, given the risk of long-term side effects of radiation therapy in children. Pediatric MEC as second cancers retain a similar prognosis. Long-term follow-up is needed to assess late side effects and second cancers.

Social Networks, Social Support, and Burden in Relationships, and Mortality After Breast Cancer Diagnosis in the Life After Breast Cancer Epidemiology (LACE) Study

Larger social networks have been associated with lower breast cancer mortality. The authors evaluated how levels of social support and burden influenced this association. We included 2,264 women from the Life After Cancer Epidemiology study who were diagnosed with early-stage, invasive breast cancer between 1997 and 2000, and provided data on social networks (spouse or intimate partner, religious/social ties, volunteering, time socializing with friends, and number of first-degree female relatives), social support, and caregiving. 401 died during a median follow-up of 10.8 years follow-up with 215 from breast cancer. We used delayed entry Cox proportional hazards regression to evaluate associations. In multivariate-adjusted analyses, social isolation was unrelated to recurrence or breast cancer-specific mortality. However, socially isolated women had higher all-cause mortality (HR = 1.34, 95 % CI: 1.03-1.73) and mortality from other causes (HR = 1.79, 95 % CI: 1.19-2.68). Levels of social support and burden modified associations. Among those with low, but not high, levels of social support from friends and family, lack of religious/social participation (HR = 1.58, 95 % CI: 1.07-2.36, p = 0.02, p interaction = 0.01) and lack of volunteering (HR = 1.78, 95 % CI: 1.15-2.77, p = 0.01, p interaction = 0.01) predicted higher all-cause mortality. In cross-classification analyses, only women with both small networks and low levels of support (HR = 1.61, 95 % CI: 1.10-2.38) had a significantly higher risk of mortality than women with large networks and high levels of support; women with small networks and high levels of support had no higher risk of mortality (HR = 1.13, 95 % CI: 0.74-1.72). Social networks were also more important for caregivers versus noncaregivers. Larger social networks predicted better prognosis after breast cancer, but associations depended on the quality and burden of family relationships.

[Evaluation of Psychometric Characteristics of the Argentinean Version of the Hare Psychopathy Checklist: Youth Version]

In spite of the relevance on diagnosis, therapeutic strategies and prevention of psychopathy of the accurate assessment of psychopathic traits in youngsters, in Argentina the internationally widespread specific instruments have not been validated. This research is aimed to the assessment of the reliability and aspects of the validity of the Argentinean version of the Hare Psychopathy Checklist: Youth Version. Thus, thirty institutionalized juvenile offenders were simultaneously assessed by two raters who produced independent and a consensus scores. The raters used information from the same multiple sources of information. The results support that the Argentinian version of the scale is a reliable, homogeneous instrument with high internal consistence. The Intraclass Correlation Coefficient for the total score was .98 and the Cronbach's Alpha Coefficient was 0.96. Findings also support concurrent and convergent validity of the scale using correlation measures with other criteria and measures relevant to the construct, such as the score of non-violent offenses (r = 0.55; p= 0.002), the score of violent-offenses (r = 0.48; p = 0.008); Impulsivity scale score (r = 0.44; p = 0.02) and the count of types of conduct problems.

Repeated Aspergillus Isolation in Respiratory Samples from Non-immunocompromised Patients Not Selected Based on Clinical Diagnoses: Colonisation or Infection?

ABSTRACT: BACKGROUND: Isolation of Aspergillus from lower respiratory samples is associated with colonisation in high percentage of cases, making it of unclear significance. This study explored factors associated with diagnosis (infection vs. colonisation), treatment (administration or not of antifungals) and prognosis (mortality) in non-transplant/non-neutropenic patients showing repeated isolation of Aspergillus from lower respiratory samples. METHODS: Records of adult patients (29 Spanish hospitals) presenting >=2 respiratory cultures yielding Aspergillus were retrospectively reviewed and categorised as proven (histopathological confirmation) or probable aspergillosis (new respiratory signs/symptoms with suggestive chest imaging) or colonisation (symptoms not attributable to Aspergillus without dyspnoea exacerbation, bronchospasm or new infiltrates). Logistic regression models (step--wise) were performed using Aspergillosis (probable + proven), antifungal treatment and mortality as dependent variables. Significant (p < 0.001) models showing the highest R2 were considered. RESULTS: A total of 245 patients were identified, 139 (56.7%) with Aspergillosis. Aspergillosis was associated (R2 = 0.291) with ICU admission (OR = 2.82), congestive heart failure (OR = 2.39) and steroids pre-admission (OR = 2.19) as well as with cavitations in X-ray/CT scan (OR = 10.68), radiological worsening (OR = 5.22) and COPD exacerbations/need for O2 interaction (OR = 3.52). Antifungals were administered to 79.1% patients with Aspergillosis (100% proven, 76.8% probable) and 29.2% colonised, with 69.5% patients receiving voriconazole alone or in combination. In colonised patients, administration of antifungals was associated with ICU admission at hospitalisation (OR = 12.38). In Aspergillosis patients its administration was positively associated (R2 = 0.312) with bronchospasm (OR = 9.21) and days in ICU (OR = 1.82) and negatively with Gold III + IV (OR = 0.26), stroke (OR = 0.024) and quinolone treatment (OR = 0.29). Mortality was 78.6% in proven, 41.6% in probable and 12.3% in colonised patients, and was positively associated in Aspergillosis patients (R2 = 0.290) with radiological worsening (OR = 3.04), APACHE-II (OR = 1.09) and number of antibiotics for treatment (OR = 1.51) and negatively with species other than A. fumigatus (OR = 0.14) and aspergillar tracheobronchitis (OR = 0.27). CONCLUSIONS: Administration of antifungals was not always closely linked to the diagnostic categorisation (colonisation vs. Aspergillosis), being negatively associated with severe COPD (GOLD III + IV) and concomitant treatment with quinolones in patients with Aspergillosis, probably due to the similarity of signs/symptoms between this entity and pulmonary bacterial infections.

Clinical Management of Small-Cell Carcinoma of the Urinary Tract: A 10-Year Single-Center's Experience

BACKGROUND: Small-cell carcinoma (SCC) comprises 1% of primary bladder tumors and approximately 2% of prostate neoplasms. Metastatic disease at diagnosis is common, and survival outcomes are extremely poor. There is controversy about the ideal clinical management of these patients. The neuron-specific enolase (NSE) serum levels have never been studied in patients with small-cell carcinoma of the urinary tract (SCCUT). PATIENTS AND METHODS: We report the clinical outcome of 12 consecutive SCCUT patients treated during the past 10 years. We also study the NSE levels at diagnosis and during treatment. RESULTS: Patients with limited disease (LD) experienced a non-significant longer progression-free survival (PFS) and overall survival (OS) compared with extensive disease (ED) subjects. Patients with bladder SCC showed a significantly higher median PFS compared with prostate SCCUT patients (22 vs. 6 months; P = .034), although that difference did not impact on a significant longer OS. NSE levels decreased during chemotherapy administration in all patients with ED and baseline high levels. CONCLUSIONS: Our patients showed a poor prognosis as described in previous studies. A better outcome for patients with bladder SCC compared with prostate SCC could be suggested. Serum NSE levels should be further evaluated to prove its potential use in early diagnosis and treatment monitoring during chemotherapy.

A Survey of Invasive Catheter Practices in U.s. Burn Centers

Burn-specific guidelines for optimal catheter rotation, catheter type, insertion methods, and catheter site care do not exist, and practices vary widely from one burn unit to another. The purpose of this study was to define current practices and identify areas of practice variation for future clinical investigation. An online survey was sent to the directors of 123 U.S. burn centers. The survey consisted of 23 questions related to specific practices in placement and maintenance of central venous catheters (CVCs), arterial catheters, and peripherally inserted central catheters (PICCs). The overall response rate was 36%; response rate from verified centers was 52%. Geographic representation was wide. CVC and arterial catheter replacement varied from every 3 days (24% of sites) to only for overt infection (24% of sites); 23% of sites did not use the femoral position for CVC placement. Nearly 60% of units used some kind of antiseptic catheter. Physicians inserted the majority of catheters, and 22% of sites used nonphysicians for at least some insertions. Ultrasound was routinely used by less than 50% of units. A wide variety of post-insertion dressing protocols were followed. PICCs were used in some critically injured patients in 37% of units; the majority of these users did not rotate PICCs. Thus, it can be surmised that wide practice variation exists among burn centers with regard to insertion and maintenance of invasive catheters. Areas with particular variability that would be appropriate targets of clinical investigation are line rotation protocols, catheter site care protocols, and use of PICCs in acute burns.

Identification of a New Cell Line Permissive to Porcine Reproductive and Respiratory Syndrome Virus Infection and Replication Which is Phenotypically Distinct from MARC-145 Cell Line

ABSTRACT: BACKGROUND: Airborne transmitted pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV), need to interact with host cells of the respiratory tract in order to be able to enter and disseminate in the host organism. Pulmonary alveolar macrophages (PAM) and MA104 derived monkey kidney MARC-145 cells are known to be permissive to PRRSV infection and replication and are the most studied cells in the literature. More recently, new cell lines developed to study PRRSV have been genetically modified to make them permissive to the virus. The SJPL cell line origin was initially reported to be epithelial cells of the respiratory tract of swine. Thus, the goal of this study was to determine if SJPL cells could support PRRSV infection and replication in vitro. RESULTS: The SJPL cell growth was significantly slower than MARC-145 cell growth. The SJPL cells were found to express the CD151 protein but not the CD163 and neither the sialoadhesin PRRSV receptors. During the course of the present study, the SJPL cells have been reported to be of monkey origin. Nevertheless, SJPL cells were found to be permissive to PRRSV infection and replication even if the development of the cytopathic effect was delayed compared to PRRSV-infected MARC-145 cells. Following PRRSV replication, the amount of infectious viral particles produced in SJPL and MARC-145 infected cells was similar. The SJPL cells allowed the replication of several PRRSV North-American strains and were almost efficient as MARC-145 cells for virus isolation. Interestingly, PRRSV is 8 to 16 times more sensitive to IFNalpha antiviral effect in SJPL cell in comparison to that in MARC-145 cells. PRRSV induced an increase in IFNbeta mRNA and no up regulation of IFNalpha mRNA in both infected cell types. In addition, PRRSV induced an up regulation of IFNgamma and TNF-alpha mRNAs only in infected MARC-145 cells. CONCLUSIONS: In conclusion, the SJPL cells are permissive to PRRSV. In addition, they are phenotypically different from MARC-145 cells and are an additional tool that could be used to study PRRSV pathogenesis mechanisms in vitro.

Collective Action in the Management of a Tropical Dry Forest Ecosystem: Effects of Mexico's Property Rights Regime

Dilemmas of natural resources governance have been a central concern for scholars, policy makers, and users. Major debates occur over the implications of property rights for common resources management. After the Mexican Revolution (1910-1917), land was distributed mainly as ejidos conceived as a hereditary but unalienable collective form of property. In 1992, a new Agrarian Law was decreed that allows individual ownership by removing various restrictions over the transfer of land. Scholars have examined the reform mainly focusing on land-tenure changes and environmental fragmentation. This study examines how the new ownership regime is affecting collective decision-making in ejidos located in a tropical dry forest (TDF) ecosystem. Information on decision-making processes before and after the 1992 reform was gathered through 52 interviews conducted in four ejidos selected along a gradient including agricultural, cattle-raising, and TDF use. The new individualized land property system reduced collective action in ejidos but did not trigger it. Collective action responses to the 1992 reform were buffered by self-organization each ejido already had. Heterogeneous users who shared a short history and showed little understanding of TDF and low dependence on its resources seemed to explain why ejidos have not been able to share a sense of community that would shape the construction of institutions for the collective management of forest resources. However, when a resource is scarce and highly valuable such as water the same users showed capacities for undertaking costly co-operative activities.

Detection of Cancer Cells Using a Peptide Nanotube-folic Acid Modified Graphene Electrode

This article describes the preparation of a graphene electrode modified with a new conjugate of peptide nanotubes and folic acid for the selective detection of human cervical cancer cells over-expressing folate receptors. The functionalization of peptide nanotubes with folic acid was confirmed by fluorescence microscopy and atomic force microscopy. The peptide nanotube-folic acid modified graphene electrode was characterized by scanning electron microscopy and cyclic voltammetry. The modification of the graphene electrode with peptide nanotube-folic acid led to an increase in the current signal. The human cervical cancer cells were bound to the modified electrode through the folic acid-folate receptor interaction. Cyclic voltammograms in the presence of [Fe(CN)(6)](3-/4-) as a redox species demonstrated that the binding of the folate receptor from human cervical cancer cells to the peptide nanotube-folic acid modified electrode lowered the electron transfer resulting in a decrease in the measured current. A detection limit of 250 human cervical cancer cells per mL was obtained. Control experiments confirmed that the peptide nanotube-folic acid electrode specifically recognized folate receptors. The modified electrode described here opens up new possibilities for future applications in early stage diagnoses of diseases where cells over-express folate receptors, such as in cancer or leishmaniasis disease.

Cardioprotection Against Ischaemia/reperfusion by Vitamins C and E Plus N-3 Fatty Acids: Molecular Mechanisms and Potential Clinical Applications

The role of oxidative stress in ischaemic heart disease has been thoroughly investigated in humans. Increased levels of ROS (reactive oxygen species) and RNS (reactive nitrogen species) have been demonstrated during ischaemia and post-ischaemic reperfusion in humans. Depending on their concentrations, these reactive species can act either as benevolent molecules that promote cell survival (at low-to-moderate concentrations) or can induce irreversible cellular damage and death (at high concentrations). Although high ROS levels can induce NF-κB (nuclear factor κB) activation, inflammation, apoptosis or necrosis, low-to-moderate levels can enhance the antioxidant response, via Nrf2 (nuclear factor-erythroid 2-related factor 2) activation. However, a clear definition of these concentration thresholds remains to be established. Although a number of experimental studies have demonstrated that oxidative stress plays a major role in heart ischaemia/reperfusion pathophysiology, controlled clinical trials have failed to prove the efficacy of antioxidants in acute or long-term treatments of ischaemic heart disease. Oral doses of vitamin C are not sufficient to promote ROS scavenging and only down-regulate their production via NADPH oxidase, a biological effect shared by vitamin E to abrogate oxidative stress. However, infusion of vitamin C at doses high enough to achieve plasma levels of 10 mmol/l should prevent superoxide production and the pathophysiological cascade of deleterious heart effects. In turn, n-3 PUFA (polyunsaturated fatty acid) exposure leads to enhanced activity of antioxidant enzymes. In the present review, we present evidence to support the molecular basis for a novel pharmacological strategy using these antioxidant vitamins plus n-3 PUFAs for cardioprotection in clinical settings, such as post-operative atrial fibrillation, percutaneous coronary intervention following acute myocardial infarction and other events that are associated with ischaemia/reperfusion.

Waiting
simple hit counter