The aim of the current study was to asses the effect of goat or cow milk-based diets, either normal or Fe-overloaded and folic acid supplement on some aspects of hepatic physiology, enzymatic antioxidant defence and lipid peroxidation in liver, brain and erythrocyte of control and anaemic rats after chronic Fe repletion. 160 male Wistar rats were placed on 40 d in two groups, a control group receiving normal-Fe diet and the Fe-deficient group receiving low Fe diet. Lately, the rats were fed with goat and cow milk-based diets during 30 d, with normal-Fe content or Fe-overload and either with normal folic or folic acid supplemented. Fe-overload increased plasma alanine transaminase and aspartate transaminase levels when cow milk was supplied. Dietary folate supplementation reduced plasma transaminases levels in animals fed goat milk with chronic Fe overload. A remarkable increase in the superoxide dismutase activity was observed in the animals fed cow milk. Dietary folate supplement lead to a decrease on the activity of this enzyme in all the tissues studied with both milk-based diets. A concomitant increment in catalase was also observed. The increase in lipid peroxidation products levels in rats fed cow milk with Fe-overload, suggest an imbalance in the functioning of the enzymatic antioxidant defence. In conclusion, dietary folate-supplemented goat milk reduces both plasma transaminases levels, suggesting a hepatoprotective effect and has beneficial effects in situation of Fe-overload, improving the antioxidant enzymes activities and reducing lipid peroxidation.
Background:There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy but there is little data on whether these differences impact effectiveness. Methods:This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to >50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health related quality of life (HRQOL) as measured by the SF-6D. Results:Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (p=0.02). Endobronchial obstruction and stent placement were associated with success while ASA >3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea while smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL while lobar obstruction was associated with smaller improvements. Conclusions:Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most.
Extracts of neem (Azadirachta indica A.) and mata-raton (Gliricidia sepium) leaves were used as insect repellent during organic cultivation of tomato plants (Solanum lycopersicum) and were compared with untreated plants or plants treated with lambda-cyhalothrin (chemical treatment). The best developed tomato plants were found in the Gliricidia treatment, while difference between other treatments were small. The number of different species of macrofauna found on tomato plants were similar in different treatments, except for corn rootworm (Diabrotica spp.) found in the Gliricidia treatment, but not in other treatments. It was found that leaf extract of G. sepium stimulated tomato growth and altered the leaf and fruit characteristics. This was most likely due to its action as a growth regulator and/or an inductor of changes in the tomato growth regulation, but not due to its action as an insect repellent. Consequently, leaf extract of G. sepium could be used to stimulate tomato development.
The development of digital imaging technology is creating extraordinary levels of accuracy that provide support for improved reliability in different aspects of the image analysis, such as content-based image retrieval, image segmentation, and classification. This has dramatically increased the volume and rate at which data are generated. Together these facts make querying and sharing non-trivial and render centralized solutions unfeasible. Moreover, in many cases this data is often distributed and must be shared across multiple institutions requiring decentralized solutions. In this context, a new generation of data/information driven applications must be developed to take advantage of the national advanced cyber-infrastructure (ACI) which enable investigators to seamlessly and securely interact with information/data which is distributed across geographically disparate resources. This paper presents the development and evaluation of a novel content-based image retrieval (CBIR) framework. The methods were tested extensively using both peripheral blood smears and renal glomeruli specimens. The datasets and performance were evaluated by two pathologists to determine the concordance.
DNA is constantly under attack by a number of both exogenous and endogenous agents that challenge its integrity. Among the mechanisms that have evolved to counteract this deleterious action, mismatch repair (MMR) has specialized in removing DNA biosynthetic errors that occur when replicating the genome. Malfunction or inactivation of this system results in an increase in spontaneous mutability and a strong predisposition to tumor development. Besides this key corrective role, MMR proteins are involved in other pathways of DNA metabolism such as mitotic and meiotic recombination and processing of oxidative damage. Surprisingly, MMR is also required for certain mutagenic processes. The mutagenic MMR has beneficial consequences contributing to the generation of a vast repertoire of antibodies through class switch recombination and somatic hypermutation processes. However, this non-canonical mutagenic MMR also has detrimental effects; it promotes repeat expansions associated with neuromuscular and neurodegenerative diseases and may contribute to cancer/disease-related aberrant mutations and translocations. The reaction responsible for replication error correction has been the most thoroughly studied and it is the subject to numerous reviews. This review describes briefly the biochemistry of MMR and focuses primarily on the non-canonical MMR activities described in mammals as well as emerging research implicating interplay of MMR and chromatin.
Bacillus thuringiensis (Bt) is a soil-dwelling bacterium of great interest for agronomical research because of its use as biological pesticide. There are some limitations regarding the subspecies classification. Phenotyping and genotyping studies are important to ascertain its variability. The diversity of 40 environmental strains, isolated from different regions in Mexico, was analyzed by ERIC-PCR and the ability of biofilm formation. Thirty-nine different fingerprinting patterns revealed enough data to discriminate among the 40 strains. A total of 24 polymorphic fragments with sizes between 139 and 1,468 bp were amplified. Almost all (95 %) strains showed biofilm formation after 96 h of incubation. At 96 h of incubation the biofilm-forming strains from the CINVESTAV collection showed a more heterogeneous ability as biofilms producers. Results showed a large intra-species genomic variability in Bt. However, some strains could be correlated as they were found within clusters depending on the location of isolation.
The surgical electronic logbook (surgical e-logbook) aims to: simplify registration of the training activities of surgical residents, and to obtain reliable and detailed reports about these activities for resident evaluation.
Clamping and cutting of the umbilical cord is the most prevalent of all operations, but the optimal timing of cord clamping is controversial, with different timings offering advantages and disadvantages. This study, for the first time, compares the influence of early and late cord clamping in correlation with oxidative stress and inflammation signaling, Because cord clamping timing may have a significant influence on placenta-to-infant blood transfer, thereby modifying oxygenation of maternal and fetal tissues, and on the transfer of inflammatory mediators throughout the placenta.
Total mesorectal excision (TME) is the standard treatment for rectal cancer, but complications are frequent and rates of morbidity, mortality and genitourinary alterations are high. Transanal endoscopic microsurgery (TEM) allows preservation of the anal sphincters and, via its vision system through a rectoscope, allows access to rectal tumors located as far as 20 cm from the anal verge. The capacity of local surgery to cure rectal cancer depends on the risk of lymph node invasion. This means that correct preoperative staging of the rectal tumor is necessary. Currently, local surgery is indicated for rectal adenomas and adenocarcinomas invading the submucosa, but not beyond (T1). Here we describe the standard technique for TEM, the different types of equipment used, and the technical limitations of this approach. TEM to remove rectal adenoma should be performed in the same way as if the lesion were an adenocarcinoma, due to the high percentage of infiltrating adenocarcinomas in these lesions. In spite of the generally good results with T1, some authors have published surprisingly high recurrence rates; this is due to the existence of two types of lesions, tumors with good and poor prognosis, divided according to histological and surgical factors. The standard treatment for rectal adenocarcinoma T2N0M0 is TME without adjuvant therapy. In this type of adenocarcinoma, local surgery obtains the best results when complete pathological response has been achieved with previous chemoradiotherapy. The results with chemoradiotherapy and TEM are encouraging, but the scientific evidence remains limited at present.
Members of the Crotalus triseriatus species group of montane rattlesnakes are widely distributed across the highlands of Mexico and southwestern USA. Although five species are currently recognized within the group, species limits remain to be tested. Genetic studies suggest that species may be paraphyletic and that at least one cryptic species may be present. We generate 3,346 base pairs of DNA sequence data from seven nuclear loci to test competing models of species delimitation in the C. triseriatus group using Bayes factor delimitation. We also examine museum specimens from the Trans-Mexican Volcanic Belt for evidence of cryptic species. We find strong support for a nine-species model and genetic and morphological evidence for recognizing two new species within the group, which we formally describe here. Our results suggest that the current taxonomy of the C. triseriatus species group does not reflect evolutionary history. We suggest several conservative taxonomic changes to the group, but future studies are needed to better clarify relationships among species and examine genetic patterns and structure within wide-ranging lineages.
In this article we review the most significant published papers on active surveillance in prostate cancer and present the results of our case series. We used as main response variables the percentage of patients remaining in surveillance and the oncological results presented as global, cancer specific and metastasis free survivals. Globally, in published series 71.2% of patients included in active surveillance programs, 10-year overall survival is 68% in the series with longer follow up, and cancer-specific survival varies from 97% to 100%. In our series of 144 patients with median follow up of 3.2 years, 76.3% of the patients continue on surveillance. 24 patients (15.9%) stopped surveillance due to histological progression. 5 patients (21.3%) out of the 23 undergoing surgery presented unfavorable pathological criteria on prostatectomy specimen. No patient has died or developed metastases.
Several types of large atypical epithelioid cells can mimic tumoral melanocytes and can therefore be a source of misdiagnosis of melanoma. Megakaryocytes are one of these types, and are not frequently mentioned in the literature. In the current report, we present the case of a 76-year-old man presenting with acute panmyelosis with myelofibrosis. The bone marrow biopsy contained atypical megakaryocytes that expressed S100 in the cytoplasm. We discuss how such aberrant expression could be a source of some diagnostic problems in dermatopathology, including cutaneous melanoma, metastasis of melanoma in bone marrow and metastasis of melanoma in sentinel lymph nodes.
Repetitive and alternating lower limb movements are a specific component of human gait. Due to technical challenges, the neural mechanisms underlying such movements have not been previously studied with functional magnetic resonance imaging. In this study, we present a novel treadmill device employed to investigate the kinematics and the brain activation patterns involved in alternating and repetitive movements of the lower limbs. Once inside the scanner, 19 healthy subjects were guided by two visual cues and instructed to perform a motor task which involved repetitive and alternating movements of both lower limbs while selecting their individual comfortable amplitude on the treadmill. The device facilitated the performance of coordinated stepping while registering the concurrent lower-limb displacements, which allowed us to quantify some movement primary kinematic features such as amplitude and frequency. During stepping, significant blood oxygen level dependent signal increases were observed bilaterally in primary and secondary sensorimotor cortex, the supplementary motor area, premotor cortex, prefrontal cortex, superior and inferior parietal lobules, putamen and cerebellum, regions that are known to be involved in lower limb motor control. Brain activations related to individual adjustments during motor performance were identified in a right lateralized network including striatal, extrastriatal, and fronto-parietal areas.
The CB1 cannabinoid receptor regulates cortical progenitor proliferation during embryonic development, but the molecular mechanism of this action remains unknown. Here, we report that CB1-deficient mouse embryos show premature cell cycle exit, decreased Pax6- and Tbr2-positive cell number, and reduced mammalian target of rapamycin complex 1 (mTORC1) activation in the ventricular and subventricular cortical zones. Pharmacological stimulation of the CB1 receptor in cortical slices and progenitor cell cultures activated the mTORC1 pathway and increased the number of Pax6- and Tbr2-expressing cells. Likewise, acute CB1 knockdown in utero reduced mTORC1 activation and cannabinoid-induced Tbr2-positive cell generation. Luciferase reporter and chromatin immunoprecipitation assays revealed that the CB1 receptor drives Tbr2 expression downstream of Pax6 induction in an mTORC1-dependent manner. Altogether, our results demonstrate that the CB1 receptor tunes dorsal telencephalic progenitor proliferation by sustaining the transcriptional activity of the Pax6-Tbr2 axis via the mTORC1 pathway, and suggest that alterations of CB1 receptor signaling, by producing the missexpression of progenitor identity determinants may contribute to neurodevelopmental alterations.
Acne vulgaris as an inflammatory disease, with an excessive production of subdermal fat, modifies the dynamics of the bloodstream, and consequently temperature, on the affected skin zone. A high percentage of this heat interchange is manifested as electromagnetic radiation with far-infrared wavelengths, which can be captured through a thermal imaging camera. A technique based on thermal image analysis for efficiency assessment in acne vulgaris is described. The procedure is based on computing statistical parameters of thermal images captured from the affected skin zone being attended by an acne treatment. The proposed technique was used to determine the skin thermal behavior according to acne severity levels in different acne treatment stages. Infrared images of acne skin zones on eight patients, diagnosed with acne vulgaris and attended by one specific acne treatment, were weekly registered during 11 weeks. The infrared images were captured until no more improvement in affected zones was detected. The obtained results suggest a direct relationship between the used statistical parameters, particularly first- and second-order statistics, and the acne vulgaris severity level on the affected zones.
Mucopolysaccharidosis IV A (MPS IV A) is a lysosomal storage disease produced by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. Although genotype-phenotype correlations have been reported, these approaches have not enabled to establish a complete genotype-phenotype correlation, and they have not considered a ligand-enzyme interaction. In this study, we expanded the in silico evaluation of GALNS mutations by using several bioinformatics tools. Tertiary GALNS structure was modeled and used for molecular docking against galactose-6-sulfate, N-acetylgalactosamine-6-sulfate, keratan sulfate, chondroitin-6-sulfate, and the artificial substrate 4-methylumbelliferyl-?-D-galactopyranoside-6-sulfate. Furthermore, we considered the evolutionary residue conservation, change conservativeness, position within GALNS structure, and the impact of amino acid substitution on the structure and function of GALNS. Molecular docking showed that amino acids involved in ligand interaction correlated with those observed in other human sulfatases, and mutations within the active cavity reduced affinity of all evaluated ligands. Combination of several bioinformatics approaches allowed to explaine 90 % of the missense mutations affecting GALNS, and the prediction of the phenotype for another 21 missense mutations. In summary, we have shown for the first time a docking evaluation of natural and artificial ligands for human GALNS, and proposed an update in genotype-phenotype correlation for Morquio A, based on the use of multiple parameters to predict the disease severity.
In this article we present the causes of urethral stenosis in the adult male and review data about incidence. Regarding disease physiopathology we emphasize the inflammatory causes and, more specifically lichen sclerosus, as the clinical scenario that presents the greater difficulty for the management of urethral stenosis since we do not know its natural evolution. Regarding treatment of urethral stenosis we discuss the various options from excision and terminal-terminal anastomosis to oral mucosal graft augmentation urethroplasty, passing by two-step operations in more severe cases. Looking forward to the future a real gate opens with the application of tissue engineering to obtain oral mucosa.
In order to determine the frequency of seropositive cases of Bartonella henselae in children with regional adenitis treated in a national hospital in Peru, a cross-sectional study was conducted in 106 children with regional adenitis greater than 1 cm in diameter. The sample was selected from patients aged 5-11 years seen at the National Institute of Child Health for acute onset of regional adentitis, with more than five days of symptoms. B. henselae seropositivity was defined by indirect immunofluorescence test. We found that 86 children (81.1%) were positive for B.henselae. The median age of the patients was 7 years. In the bivariate analysis, the following associated factors were found: aged 5 years, history of fever, lymphadenopathy greater than 4 cm and reported contact with cat. In conclusion, children with regional adenitis treated in this national referral hospital showed a high frequency of positive serology for B. henselae.
Given the detailed respiratory waveform signal provided by the nasal cannula in polysomnographic (PSG) studies, to quantify sleep breathing disturbances by extracting a continuous variable based on the coefficient of variation of the envelope of that signal.
Genotoxicity in cells may occur in different ways, direct interaction, production of electrophilic metabolites, and secondary genotoxicity via oxidative stress. Chloroform, dichloromethane, and toluene are primarily metabolized in liver by CYP2E1, producing reactive electrophilic metabolites, and may also produce oxidative stress via the uncoupled CYP2E1 catalytic cycle. Additionally, GSTT1 also participates in dichloromethane activation. Despite the oxidative metabolism of these compounds and the production of oxidative adducts, their genotoxicity in the bone marrow micronucleus test is unclear. The objective of this work was to analyze whether the oxidative metabolism induced by the coexposure to these compounds would account for increased micronucleus frequency. We used an approach including the analysis of phase I, phase II, and antioxidant enzymes, oxidative stress biomarkers, and micronuclei in bone marrow (MNPCE) and hepatocytes (MNHEP). Rats were administered different doses of an artificial mixture of CLF/DCM/TOL, under two regimes. After one administration MNPCE frequency increased in correlation with induced GSTT1 activity and no oxidative stress occurred. Conversely, after three-day treatments oxidative stress was observed, without genotoxicity. The effects observed indicate that MNPCE by the coexposure to these VOCs could be increased via inducing the activity of metabolism enzymes.
There is a wide variability in the management of acute cholecystitis. A survey among the members of the Spanish Association of Surgeons (AEC) analyzed the preferences of Spanish surgeons for its surgical management. The majority of the 771 responders didn't declare any subspecialty (41.6%), 21% were HPB surgeons, followed by colorectal and upper-GI specialities. Early cholecystectomy during the first admission is the preferred method of management of 92.3% of surgeons, but only 42.7% succeed in adopting this practice. The most frequent reasons for changing their preferred practice were: Patients not fit for surgery (43.6%) and lack of availability of emergency operating room (35.2%). A total of 88.9% perform surgery laparoscopically. The majority of AEC surgeons advise index admission cholecystectomy for acute cholecystitis, although only half of them succeed in its actual implementation. There is room for improvement in the management of acute cholecystitis in Spanish hospitals.
A 44-year-old woman with recurrent parathyroid carcinoma (PTC) presents with moderately elevated parathyroid hormone and ionized calcium levels. Dual-phase Tc-MIBI SPECT study of the neck and chest demonstrated 2 new foci in keeping with neoplastic seeding. A restaging whole-body F-FDG PET/CT showed no evidence of FDG uptake in the region of the MIBI-positive foci or any evidence of distant metastases. The role of F-FDG PET/CT for imaging PTC is still somewhat limited because of the rarity of this disease. We present a case highlighting a potential pitfall for FDG PET in detecting PTC.
NaTrxh, a thioredoxin type h, shows differential expression between self-incompatible and self-compatible Nicotiana species. NaTrxh interacts in vitro with S-RNase and co-localizes with it in the extracellular matrix of the stylar transmitting tissue. NaTrxh contains N- and C-terminal extensions, a feature shared by thioredoxin h proteins of subgroup 2. To ascertain the function of these extensions in NaTrxh secretion and protein-protein interaction, we performed a deletion analysis on NaTrxh and fused the resulting variants to GFP.
The literature has rarely paid attention to the differential influence of intergroup contact on subtle and blatant prejudice. In this study, we hypothesized that the influence of intergroup contact on subtle prejudice will be smaller than its influence on blatant prejudice.
Epileptogenesis is a progressive process which culminates with spontaneous, recurrent and unpredictable epileptic seizures due to enhanced neuronal excitability. Well-characterized animal models of this process are needed to clarify its underlying molecular mechanisms, in which the role of nitric oxide has been a controversial component. We have used kindling with a sub-convulsive dose of pentylenetetrazole to objectively characterize early electroencephalographic changes during epileptogenesis. We used electroencephalographic recordings both during pentylenetetrazole (20 mg/kg) kindling for 20 days and then, 24 days later to quantify the number, duration and spectral power of epileptic discharges. The levels of nitric oxide were modulated locally in the cerebral cortex by pharmacological agents. The number of epileptiform discharges increased during the kindling protocol as well as 24 days later, revealing the induction of a self-sustaining epileptogenic process. Epileptic discharges were characterized by theta frequencies (4-10 Hz) that were associated with absence-like seizures. However, during kindling, the spectral power of the theta band progressively decreased, while the power of higher frequencies, in the beta band, increased. Nitric oxide in the cerebral cortex inhibited the number and amplitude of epileptic discharges. The electroencephalographic characterization of this kindling protocol provides a valuable tool to detect consequences of therapeutic interventions undertaken at initial phases of epileptogenesis, especially those targeted towards stopping this process. Increases of nitric oxide in the cerebral cortex could be a useful intervention to negatively modulate neuronal excitability, epileptic discharges and the progression of epileptogenesis.
One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies.
Understanding why host species differ so much in symbiont loads and how this depends on ecological host and symbiont traits is a major issue in the ecology of symbiosis. A first step in this inquiry is to know whether observed differences among host species are species-specific traits or more related with host-symbiont environmental conditions. Here we analysed the repeatability (R) of the intensity and the prevalence of feather mites to partition within- and among-host species variance components. We compiled the largest dataset so far available: 119 Paleartic passerine bird species, 75,944 individual birds, ca. 1.8 million mites, seven countries, 23 study years. Several analyses and approaches were made to estimate R and adjusted repeatability (R(adj)) after controlling for potential confounding factors (breeding period, weather, habitat, spatial autocorrelation and researcher identity). The prevalence of feather mites was moderately repeatable (R = 0.26-0.53; R(adj) = 0.32-0.57); smaller values were found for intensity (R = 0.19-0.30; R(adj?)= 0.18-0.30). These moderate repeatabilities show that prevalence and intensity of feather mites differ among species, but also that the high variation within species leads to considerable overlap among bird species. Differences in the prevalence and intensity of feather mites within bird species were small among habitats, suggesting that local factors are playing a secondary role. However, effects of local climatic conditions were partially observed for intensity.
Divergence of acoustic signals in a geographic scale results from diverse evolutionary forces acting in parallel and affecting directly inter-male vocal interactions among disjunct populations. Pleurodema thaul is a frog having an extensive latitudinal distribution in Chile along which males' advertisement calls exhibit an important variation. Using the playback paradigm we studied the evoked vocal responses of males of three populations of P. thaul in Chile, from northern, central and southern distribution. In each population, males were stimulated with standard synthetic calls having the acoustic structure of local and foreign populations. Males of both northern and central populations displayed strong vocal responses when were confronted with the synthetic call of their own populations, giving weaker responses to the call of the southern population. The southern population gave stronger responses to calls of the northern population than to the local call. Furthermore, males in all populations were stimulated with synthetic calls for which the dominant frequency, pulse rate and modulation depth were varied parametrically. Individuals from the northern and central populations gave lower responses to a synthetic call devoid of amplitude modulation relative to stimuli containing modulation depths between 30-100%, whereas the southern population responded similarly to all stimuli in this series. Geographic variation in the evoked vocal responses of males of P. thaul underlines the importance of inter-male interactions in driving the divergence of the acoustic traits and contributes evidence for a role of intra-sexual selection in the evolution of the sound communication system of this anuran.
Minimally invasive techniques for the surgical treatment of prostate cancer have aimed to achieve the same functional and oncological outcomes of open surgery with a significant decrease in postoperative morbidity and a subsequent decreasing hospital stay. These improvements are important in the current economic context. Our aim was to evaluate the feasibility and safety of hospital discharge 24 h after laparoscopic radical prostatectomy (LRP).
A 74-year-old man underwent an electrophysiological study because of Mobitz type II second-degree atrioventricular (AV) block with narrow QRS and frequent junctional extrasystoles. During the study, there were very frequent single His bundle depolarizations with multiple coupling intervals that reproduce the ECG findings. In this case, some His bundle extrasystoles result in retrograde concealed conduction and prolonged local refractoriness in the AV node that manifest as block of the next atrial impulse.
Fe overload is a common consequence of the anaemia treatment, increasing the oxidative stress and promoting the accumulation of damaged biomolecules, with the subsequently impairment of cell functions. Oxidative stress and the role of folic acid preventing free radical damage have been extensively studied; nevertheless, no studies are available about the influence of folic acid-supplemented goat milk consumption on the oxidative stress-mediated damage.
The management of obstructive lung disease, particularly emphysematous lung disease, is aggressively being pursued. The patient populations that will experience the greatest benefit with lung volume reduction are those that are the worst candidates for surgical intervention. Identifying a bronchoscopic approach that has a true impact on this patient population will be a major accomplishment in the management of patients with chronic obstructive pulmonary disease. This article highlights the work currently ongoing in the area of bronchoscopic lung volume reduction. There are tools now clinically available in some locations throughout the world, but no standardized technique exists.
Advanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation.
The study was designed to assess the effect of several Fe amounts and sources on haematological parameters, DNA, lipid and protein oxidative damage during the course of Fe-deficiency anaemia recovery. Peripheral DNA damage was assessed using an alkaline comet assay. The brain, liver, erythrocyte and duodenal mucosa lipid peroxidation and protein damage were assessed in control and anaemic rats after Fe repletion with three different sources (FeSO4, haem Fe, and FeSO4?+?haem Fe) and amounts (45, 12, and 31 mg Fe/kg diet) of Fe: F diet, H diet or C diet, respectively. After supplying the diets, the haematological parameters studied were recovered; being remarkable is the haemoglobin increase. The DNA damage was lower in rats with the H diet, as revealed by the percentage of DNA in head, tail and Olive tail moment compared in rats with the F (P?0.001) and C (P?0.05) diets. Lipid peroxidation was similar in all the tissues, except in the duodenal mucosa which was lower with H and C diets (P?0.001). The animals fed with C diet showed lower oxidative protein damage in the duodenal mucosa (P?0.001) and was also lower in the liver and erythrocytes for H and C diets (P?0.001). No differences were found in the brain under our experimental conditions. In conclusion, Fe supplementation with low doses of haem Fe or combined forms of non-haem and haem Fe (FeSO4?+?haem) are efficient in restoring the impaired haematological parameters and prevent the evoked oxidative stress associated with Fe supplements.
Portable systems and global communications open a broad spectrum for new health applications. In the framework of electrophysiological applications, several challenges are faced when developing portable systems embedded in Cloud computing services. In order to facilitate new developers in this area based on our experience, five areas of interest are presented in this paper where strategies can be applied for improving the performance of portable systems: transducer and conditioning, processing, wireless communications, battery and power management. Likewise, for Cloud services, scalability, portability, privacy and security guidelines have been highlighted.
Cross-Approximate Entropy (Cross-ApEn) is a useful measure to quantify the statistical dissimilarity of two time series. In spite of the advantage of Cross-ApEn over its one-dimensional counterpart (Approximate Entropy), only a few studies have applied it to biomedical signals, mainly due to its high computational cost. In this paper, we propose a fast GPU-based implementation of the Cross-ApEn that makes feasible its use over a large amount of multidimensional data. The scheme followed is fully scalable, thus maximizes the use of the GPU despite of the number of neural signals being processed. The approach consists in processing many trials or epochs simultaneously, with independence of its origin. In the case of MEG data, these trials can proceed from different input channels or subjects. The proposed implementation achieves an average speedup greater than 250× against a CPU parallel version running on a processor containing six cores. A dataset of 30 subjects containing 148 MEG channels (49 epochs of 1024 samples per channel) can be analyzed using our development in about 30min. The same processing takes 5 days on six cores and 15 days when running on a single core. The speedup is much larger if compared to a basic sequential Matlab(®) implementation, that would need 58 days per subject. To our knowledge, this is the first contribution of Cross-ApEn measure computation using GPUs. This study demonstrates that this hardware is, to the day, the best option for the signal processing of biomedical data with Cross-ApEn.
While phosphotyrosine modification is an established regulatory mechanism in eukaryotes, it is less well characterized in bacteria due to low prevalence. To gain insight into the extent and biological importance of tyrosine phosphorylation in Escherichia coli, we used immunoaffinity-based phosphotyrosine peptide enrichment combined with high resolution mass spectrometry analysis to comprehensively identify tyrosine phosphorylated proteins and accurately map phosphotyrosine sites. We identified a total of 512 unique phosphotyrosine sites on 342 proteins in E. coli K12 and the human pathogen enterohemorrhagic E. coli (EHEC) O157:H7, representing the largest phosphotyrosine proteome reported to date in bacteria. This large number of tyrosine phosphorylation sites allowed us to define five phosphotyrosine site motifs. Tyrosine phosphorylated proteins belong to various functional classes such as metabolism, gene expression and virulence. We demonstrate for the first time that proteins of a type III secretion system (T3SS), required for the attaching and effacing (A/E) lesion phenotype characteristic for intestinal colonization by certain EHEC strains, are tyrosine phosphorylated by bacterial kinases. Yet, A/E lesion and metabolic phenotypes were unaffected by the mutation of the two currently known tyrosine kinases, Etk and Wzc. Substantial residual tyrosine phosphorylation present in an etk wzc double mutant strongly indicated the presence of hitherto unknown tyrosine kinases in E. coli. We assess the functional importance of tyrosine phosphorylation and demonstrate that the phosphorylated tyrosine residue of the regulator SspA positively affects expression and secretion of T3SS proteins and formation of A/E lesions. Altogether, our study reveals that tyrosine phosphorylation in bacteria is more prevalent than previously recognized, and suggests the involvement of phosphotyrosine-mediated signaling in a broad range of cellular functions and virulence.
Depth information has been used in computer vision for a wide variety of tasks. Since active range sensors are currently available at low cost, high-quality depth maps can be used as relevant input for many applications. Background subtraction and video segmentation algorithms can be improved by fusing depth and color inputs, which are complementary and allow one to solve many classic color segmentation issues. In this paper, we describe one fusion method to combine color and depth based on an advanced color-based algorithm. This technique has been evaluated by means of a complete dataset recorded with Microsoft Kinect, which enables comparison with the original method. The proposed method outperforms the others in almost every test, showing more robustness to illumination changes, shadows, reflections and camouflage.
Gastric neuroendocrine carcinomas (NEC) are very rare, aggressive tumors of the stomach that are distinct from the more benign neuroendocrine tumors, sometimes referred to as "gastric carcinoids." We present 3 cases of gastric NEC representing various histological subtypes that were successfully staged and followed with F-FDG PET/CT, impacting therapeutic management in each case.
INTRODUCTION: The aim of this study is to determine the usefulness of the risk model developed by van Ramshorst et al., and a modification of the same, to predict the abdominal wound dehiscences risk in patients who underwent midline laparotomy incisions. MATERIALS AND METHODS: Observational longitudinal retrospective study. Sample: Patients who underwent midline laparotomy incisions in the General and Digestive Surgery Department of the Sabadells Hospital-Parc Taulís Health and University Corporation-Barcelona, between January 1, 2010 and June 30, 2010. Dependent variable: Abdominal wound dehiscence. Independent variables: Global risk score, preoperative risk score (postoperative variables were excluded), global and preoperative probabilities of developing abdominal wound dehiscence. RESULTS: Sample: 176 patients. Patients with abdominal wound dehiscence: 15 (8.5%). The global risk score of abdominal wound dehiscence group (mean: 4.97; IC 95%: 4.15-5.79) was better than the global risk score of No abdominal wound dehiscence group (mean: 3.41; IC 95%: 3.20-3.62). This difference is statistically significant (P<.001). The preoperative risk score of abdominal wound dehiscence group (mean: 3.27; IC 95%: 2.69-3.84) was better than the preoperative risk score of No abdominal wound dehiscence group (mean: 2.77; IC 95%: 2.64-2.89), also a statistically significant difference (P<.05). The global risk score (area under the ROC curve: 0.79) has better accuracy than the preoperative risk score (area under the ROC curve: 0.64). CONCLUSION: The risk model developed by van Ramshorst et al. to predict the abdominal wound dehiscences risk in the preoperative phase has a limited usefulness. Additional refinements in the preoperative risk score are needed to improve its accuracy.
Many neurodegenerative disorders, such as Alzheimers, Parkinsons and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the mutant proteins resistance to degradation or overexpression of the wild-type protein. We have developed a strategy to identify therapeutic entry points for such neurodegenerative disorders by screening for genetic networks that influence the levels of disease-driving proteins. We applied this approach, which integrates parallel cell-based and Drosophila genetic screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine tract in ataxin 1 (ATXN1). Our approach revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice. Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1. Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases.
Given the importance of oxidative stress associated to aging, it would be interesting to assess the effect of oral supplementation with antioxidant substances capable of diminishing oxidative aggression and free radicals generation associated to this condition. This study investigated the effects of AIN-93 M diet supplemented either with 2 % of propolis, or with 4 % of a natural product obtained from lyophilizate vegetables, selected by its antioxidant properties, in senescent healthy Wistar rats fed ad libitum over 3 months. Propolis supplementation leads to a lower level of glucose and cholesterol concentrations together with a reduction in protein oxidation. Plasma thiobarbituric acid-reactive substance levels were lower in the rats consuming the natural vegetable product and propolis possibly due to its antioxidant components, neutralizing the free radical produced, and thus preventing cellular damage. The results of the present study suggest a synergic effect of overall propolis compounds reducing the oxidative stress and glucose and cholesterol plasma levels associated with aging.
The Almadén area in Spain has a long history of mercury mining with prolonged human-induced activities that are related to mineral extraction and metallurgical processes before the closure of the mines and a more recent post period dominated by projects that reclaim the mine dumps and tailings and recuperating the entire mining area. Furthermore, socio-economic alternatives such as crop cultivation, livestock breeding and tourism are increasing in the area. Up till now, only scattered information on these activities is available from specific studies. However, improved acquisition systems using satellite borne data in the last decades opens up new possibilities to periodically study an area of interest. Therefore, comparing the influence of these activities on the environment and monitoring their impact on the ecosystem vastly improves decision making for the public policy makers to implement appropriate land management measures and control environmental degradation. The objective of this work is to monitor environmental changes affected by human-induced activities within the Almadén area occurring before, during and after the mine closure over a period of nearly three decades. To achieve this, data from numerous sources at different spatial scales and time periods are implemented into a methodology based on advanced remote sensing techniques. This includes field spectroradiometry measurements, laboratory analyses and satellite borne data of different surface covers to detect land cover and use changes throughout the mining area. Finally, monitoring results show that the distribution of areas affected by mercury mining is rapidly diminishing since activities ceased and that rehabilitated mining areas form a new landscape. This refers to mine tailings that have been sealed and revegetated as well as an open pit mine that has been converted to an "artificial" lake surface. Implementing a methodology based on remote sensing techniques that integrate data from several sources at different scales greatly improves the regional characterization and monitoring of an area dominated by mercury mining activities.
Calcium-fortified foods, especially milk and dairy products are recommended to be consumed daily for groups in risk of nutritional deficiency, including children, young adults, menopausal women, pregnant women and the elderly, however Ca-supplementation promotes gallstone formation because Ca is a nucleating factor. The objective of the current study was to assess the influence of cow or goat milk-based diets, either normal or Ca-supplemented, on bile composition, biochemical parameters and hepatic antioxidant status. Weanling male rats were randomly divided into six groups, fed standard, goat or cow milk-based diets, either with normal Ca content (5.0 g/kg), or Ca-supplemented (10.0 g/kg), for 2 weeks. Bile cholesterol concentration and output was higher in rats fed goat milk in comparison with those fed with standard and cow-milk-based diet. Ca-supplementation increased lithogenic index with the standard and cow-milk based diets, this change was not observed with the goat milk diet. Activities of plasma transaminases were also lower in the animals fed Ca-supplemented goat milk, in comparison with the other diets assayed. In general, Ca-supplement in the diet led to an increase in the hepatic oxidative damage, with an increase in the activities of all the antioxidant enzymes studied in the standard and cow milk diet, but not with goat milk. The habitual consumption of goat milk has positive effects on the plasma lipid profile, biliary composition and hepatic antioxidant defence. In addition, under our experimental conditions, Ca-supplementation of this type of milk does not increase the lithogenic index, or hepatic oxidative damage.
The objective of the study was to describe the clinical and epidemiological characteristics of complicated chickenpox cases seen at the National Institute of Childrens Health (INSN, Spanish acronym) of Peru from 2001 to 2011. A case series was collected, including a total of 1,073 children with complicated chickenpox. The median age was 2.5 years (IQR 1.1-4.8 years), of which 578 (54%) were male. The most frequent complications were secondary skin and soft tissue infections with 768 cases (72%). 13 deaths (1.4%) were recorded. In conclusion, the hospitalizations due to complicated chickenpox in the INSN included mostly children under five, with a short stay and a low proportion of deaths most complications being related to secondary skin and soft tissue infections.
Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS). The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes. Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved. Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm). In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation. Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells. Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery. The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.
Children with HIV/AIDS is a social issue,the approach to which transcends the health sector. The normative, political, institutional and service sector responses have specificities related to children. A proposed approach is based on the following points: health care, nutrition, education, family-socioeconomic status, psychosocial repercussions, protection, housing, stigmatization and discrimination. Based on these guidelines,a survey was conducted of an institutional responseapplying the Bioecological Model of Human Development. Life of children in the institution is described and analyzed. A group of 31 children and 30 adults participated in this ethnographic study. The institutional response concerning health, nutrition, education and basic care, is satisfactory. The main weaknesses identified were nondisclosure of the diagnosis, stigmatization and discrimination, institutionalization validation, psychoemotional repercussions and stigmatization management, and the research budget. The children acknowledge that the institution satisfies their basic-needs and disapprove of some stigmatizing and coercive practices. The reintegration of the children with their families is recommended as a future strategy based on evidence that shows it has better bio-psychosocial results and lower costs.
To determine the prevalence of gender violence (GV) suffered by student nurses and to identify its relationship with some sociodemographic and personal variables (social support and self-esteem) and their perception about their role as primary care providers.
Anisakiasis is a fish-borne parasitic disease caused by consumption of raw or undercooked fish or cephalopods parasited by Anisakis spp. third stage larvae. The pathological effects of the infection are the combined result of the mechanical action of the larva during tissue invasion, the direct tissue effects of the excretory/secretory products released by the parasite, and the complex interaction between the host immune system and the Anisakis antigens. The aim of this study was to develop an experimental model of infection with Anisakis spp. live larvae in rats, useful to study the acute and chronic histopathological effects of the Anisakis infection. Sprague-Dawley rats were subjected to esophageal catheterization to place larvae directly into the stomach. Reinfections at different intervals after the first infection were preformed. Live larvae were found anchored to the mucosa and passing through the wall of the stomach and showed a strong resistance being able to stay alive at different sites and at the different pH. Migration of larvae from the stomach to other organs out of the gastrointestinal tract was also observed. The histopathological study showed the acute inflammatory reaction, with predominance of polymorphonuclear eosinophils and a mild fibrotic reaction. The model of infection described is valid to study the behavior of the larvae inside the host body, the histopathological changes at the invasion site, and the effects of the repeated infections by ingestion of live larvae.
Genome-wide gene expression analyses of the human somatic cell cycle have indicated that the set of cycling genes differ between primary and cancer cells. By identifying genes that have cell cycle dependent expression in HaCaT human keratinocytes and comparing these with previously identified cell cycle genes, we have identified three distinct groups of cell cycle genes. First, housekeeping genes enriched for known cell cycle functions; second, cell type-specific genes enriched for HaCaT-specific functions; and third, Polycomb-regulated genes. These Polycomb-regulated genes are specifically upregulated during DNA replication, and consistent with being epigenetically silenced in other cell cycle phases, these genes have lower expression than other cell cycle genes. We also find similar patterns in foreskin fibroblasts, indicating that replication-dependent expression of Polycomb-silenced genes is a prevalent but unrecognized regulatory mechanism.
A study on simple reaction time (SRT) and choice reaction time in patients having diabetes is described in this paper. The study was applied to fourteen patients with type I diabetes, as well as to fourteen non-diabetic persons. The research is based on two visual signal perception experiments, both implemented on a computer based environment. The SRT experiment consisted on measuring participants reaction times to a light change event in a simulated traffic light scenario. The choice reaction time was studied through the performance indexes (d) achieved by participants in a two alternative forced experiment, where a known visual signal is identified from two noisy images. According to the obtained results, the diabetic patients SRTs were an average of 24% longer than the reaction time of non-diabetic persons, in the same way a significant average difference of 41% was obtained in the efficient index d too. A positive correlation of 0.6594 between the time periods since diabetes has been diagnosed and the average SRTs of diabetic patients was obtained, also significant correlation differences between age of all experiments participants and resulting variables, SRTs and d, were observed; for instance the correlation factor between participants ages and their average SRTs was -0.8529 for diabetic patients, meanwhile a value of -0.2905 was obtained for non-diabetic persons. The evidence suggests that the time period since diabetes has been diagnosed notably affects motor and sensorial systems maturity, and consequently conduction speed of sural and peroneal nerves.
Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1-selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation. These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.
Background. Evidence has shown that long-chain polyunsaturated fatty acids (LCPUFA), especially the ? -3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are beneficial for bone health and turnover. Objectives. This review summarizes findings from both in vivo and in vitro studies and the effects of LC PUFA on bone metabolism, as well as the relationship with the oxidative stress, the inflammatory process, and obesity. Results. Some studies in humans indicate that LCPUFA can increase bone formation, affect peak bone mass in adolescents, and reduce bone loss. However, the cellular mechanisms of action of the LCPUFA are complex and involve modulation of fatty acid metabolites such as prostaglandins, resolvins and protectins, several signaling pathways, cytokines, and growth factors, although in certain aspects there is still some controversy. LCPUFA affect receptor activator of nuclear factor ? ? (RANK), a receptor found on the osteoclast, causing bone resorption, which controls osteoclast formation. Conclusions. Since fatty acids are an endogenous source of reactive oxygen species, free radicals alter the process of bone turnover; however, although there are clinical evidences linking bone metabolism and dietary lipids, more clinical trials are necessary to prove whether ? -3 PUFA supplementation plays a major role in bone health.
A 29 weeks gestational age newborn, the product of a multiple gestation, was found to have a round mass in the umbilical cord; the resected lesion was an ectopic liver tissue (3 × 2 cm). She also had an imperforated hymen; otherwise, no other abnormalities were seen. The infant survived. Some possible mechanisms that may be associated with an ectopic liver tissue are presented.
The BMP/SMAD4 pathway has major effects on liver hepcidin levels. Bone morphogenetic protein-binding endothelial cell precursor-derived regulator (Bmper), a known regulator of BMP signaling, was found to be overexpressed at the mRNA and protein levels in liver of genetically hypotransferrinemic mice (Trf(hpx/hpx)). Soluble BMPER peptide inhibited BMP2- and BMP6-dependent hepcidin promoter activity in both HepG2 and HuH7 cells. These effects correlated with reduced cellular levels of pSMAD1/5/8. Addition of BMPER peptide to primary human hepatocytes abolished the BMP2-dependent increase in hepcidin mRNA, whereas injection of Bmper peptide into mice resulted in reduced liver hepcidin and increased serum iron levels. Thus Bmper may play an important role in suppressing hepcidin production in hypotransferrinemic mice.
The endocannabinoid system is known to regulate neural progenitor (NP) cell proliferation and neurogenesis. In particular, CB(2) cannabinoid receptors have been shown to promote NP proliferation. As CB(2) receptors are not expressed in differentiated neurons, CB(2)-selective agonists are promising candidates to manipulate NP proliferation and indirectly neurogenesis by overcoming the undesired psychoactive effects of neuronal CB(1) cannabinoid receptor activation. Here, by using NP cells, brain organotypic cultures, and in vivo animal models, we investigated the signal transduction mechanism involved in CB(2) receptor-induced NP cell proliferation and neurogenesis. Exposure of hippocampal HiB5 NP cells to the CB(2) receptor-selective agonist HU-308 led to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway, which, by inhibiting its downstream target p27Kip1, induced NP proliferation. Experiments conducted with the CB(2) receptor-selective antagonist SR144528, inhibitors of the PI3K/Akt/mTORC1 axis, and CB(2) receptor transient-transfection vector further supported that CB(2) receptors control NP cell proliferation via activation of mTORC1 signaling. Likewise, CB(2) receptor engagement induced cell proliferation in an mTORC1-dependent manner both in embryonic cortical slices and in adult hippocampal NPs. Thus, HU-308 increased ribosomal protein S6 phosphorylation and 5-bromo-2-deoxyuridine incorporation in wild-type but not CB(2) receptor-deficient NPs of the mouse subgranular zone. Moreover, adult hippocampal NP proliferation induced by HU-308 and excitotoxicity was blocked by the mTORC1 inhibitor rapamycin. Altogether, these findings provide a mechanism of action and a rationale for the use of nonpsychotomimetic CB(2) receptor-selective ligands as a novel strategy for the control of NP cell proliferation and neurogenesis.
Many angiosperms use specific interactions between pollen and pistil proteins as "self" recognition and/or rejection mechanisms to prevent self-fertilization. Self-incompatibility (SI) is encoded by a multiallelic S locus, comprising pollen and pistil S-determinants. In Papaver rhoeas, cognate pistil and pollen S-determinants, PrpS, a pollen-expressed transmembrane protein, and PrsS, a pistil-expressed secreted protein, interact to trigger a Ca(2+)-dependent signaling network, resulting in inhibition of pollen tube growth, cytoskeletal alterations, and programmed cell death (PCD) in incompatible pollen. We introduced the PrpS gene into Arabidopsis thaliana, a self-compatible model plant. Exposing transgenic A. thaliana pollen to recombinant Papaver PrsS protein triggered remarkably similar responses to those observed in incompatible Papaver pollen: S-specific inhibition and hallmark features of Papaver SI. Our findings demonstrate that Papaver PrpS is functional in a species with no SI system that diverged ~140 million years ago. This suggests that the Papaver SI system uses cellular targets that are, perhaps, common to all eudicots and that endogenous signaling components can be recruited to elicit a response that most likely never operated in this species. This will be of interest to biologists interested in the evolution of signaling networks in higher plants.
Despite Fe deficiency and overload having been widely studied, no studies are available about the influence of milk consumption on antioxidant defence and lipid peroxidation during the course of these highly prevalent cases. The objective of the present study was to assess the influence of cow or goat milk-based diets, either with normal or Fe-overload, on antioxidant defence and lipid peroxidation in the liver, brain and erythrocytes of control and anaemic rats after chronic Fe repletion. Weanling male rats were randomly divided into two groups: a control group receiving a normal-Fe diet (45 mg/kg) and an anaemic group receiving a low-Fe diet (5 mg/kg) for 40 d. Control and anaemic rats were fed goat or cow milk-based diets, either with normal Fe or Fe-overload (450 mg/kg), for 30 or 50 d. Fe-deficiency anaemia did not have any effect on antioxidant enzymes or lipid peroxidation in the organs studied. During chronic Fe repletion, superoxide dismutase (SOD) activity was higher in the group of animals fed the cow milk diet compared with the group consuming goat milk. The slight modification of catalase and glutathione peroxidise activities in animals fed the cow milk-based diet reveals that these enzymes are unable to neutralise and scavenge the high generation of free radicals produced. The animals fed the cow milk diet showed higher rates of lipid peroxidation compared with those receiving the goat milk diet, which directly correlated with the increase in SOD activity. It was concluded that goat milk has positive effects on antioxidant defence, even in a situation of Fe overload, limiting lipid peroxidation.
The poor quality and quantity of data collected in tribal communities today reflects a lack of true community participation and commitment. This is especially problematic for evaluation studies, in which the needs and desires of the community should be the central focus. This challenge can be met by emphasizing indigenous methods and voice. The authors provide an illustration of how to do this.
The nutritional deficiencies provoked by ethanol consumption, during gestation or lactation, can contribute to multiple birth defects in offspring. In order to improve our knowledge about selenium (Se) distribution in pups exposed to ethanol, the present study evaluated the effect of this drug on intestinal development and determined its action on duodenal absorption of selenomethionine (Se-Met). To determinate if supplementation could improve Se absorption and its serum values, we used two antioxidant supplemented regimens on dams, with selenium alone or selenium plus folic acid, and obtained six groups of pups: C (control), A (alcohol), CS (control + Se), AS (alcohol + Se), CFS (control + Se + folic acid) and AFS (alcohol + Se + folic acid). Duodenal Se-Met transport was performed using an in vivo perfusion method. Se levels were measured by graphite furnace atomic absorption spectrometry. The supplemented diets utilized had a positive influence on body growth, duodenal perimeter and Se content in ethanol-exposed pups. Ethanol exposure increased Se-Met duodenal absorption in all pups, supplemented or not, presenting the highest values of maximal velocity (V(max)) compared with their control counterparts. The affinity constant (K(m)) increased according to rank: A>AS>AFS groups. These results suggest that although antioxidant supplementation does not restore Se-Met absorption to normal values, it enhances the affinity of the transporters for the substrate and improves the damage caused by ethanol in the duodenal mucosa.
As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.
A 26-year-old man with a prior history of acute leukemia that was treated with a stem cell transplant (SCT) was referred for an F-18 FDG PET/CT to assess suspicious new gastric mucosal lesions. The lesions were FDG-avid and were histologically proven to be acute lymphoblastic leukemia (ALL). Extramedullary relapse of ALL after SCT is very rare, with only 60 cases reported in the literature, and the role of F-18 FDG PET/CT in monitoring for ALL relapse following SCT has not been previously investigated. This rare case report highlights the use of F-18 FDG PET/CT in staging gastric relapse of ALL following SCT.
Strenuous exercise induces inflammatory reactions together with high production of free radicals and subsequent muscle damage. This study was designed to investigate for the first time and simultaneously whether over-expression of inflammatory mediators, oxidative stress, and alterations in biochemical parameters induced by acute exercise could be prevented by melatonin. This indoleamine is a potent, endogenously produced free radical scavenger and a broad-spectrum antioxidant; consequently, it might have positive effects on the recovery following an exercise session. The participants were classified into two groups: melatonin-treated men (MG) and placebo-treated individuals (controls group, CG). The physical test consisted in a constant run that combined several degrees of high effort (mountain run and ultra-endurance). The total distance of the run was 50 km with almost 2800 m of ramp in permanent climbing and very changeable climatic conditions. Exercise was associated with a significant increase in TNF-?, IL-6, IL-1ra (in blood), and also an increase in 8-hydroxy-2-deoxyguanosine (8-OHdG) and isoprostane levels (in urine), and indicated the degree of oxidative stress and inflammation induced. Oral supplementation of melatonin during high-intensity exercise proved efficient in reducing the degree of oxidative stress (lower levels of lipid peroxidation, with a significant increase in antioxidative enzyme activities); this would lead to the maintenance of the cellular integrity and reduce secondary tissue damage. Data obtained also indicate that melatonin has potent protective effects, by preventing over-expression of pro-inflammatory mediators and inhibiting the effects of several pro-inflammatory cytokines. In summary, melatonin supplementation before strenuous exercise reduced muscle damage through modulation of oxidative stress and inflammation signaling associated with this physical challenge.
Friedreichs ataxia (FRDA) is an autosomal recessive disease caused by mutations that produce a deficiency in frataxin. Despite the importance of neurodegeneration in FRDA, little is known about the consequences of frataxin deficiency in neuronal cells. Here we describe a neuronal cell model for FRDA based on the use of lentiviral vectors that carry minigenes encoding frataxin-specific shRNAs that silence the expression of this gene. These lentivectors can knockdown frataxin expression in human neuroblastoma SH-SY5Y cells, which results in large-scale cell death in differentiated neuron-like cells but not in undifferentiated neuroblastoma cells. Frataxin-deficient neuron-like cells appear to die through apoptosis that is accompanied by up-regulation of p53, PUMA and Bax and activation of caspase-3. No significant autophagy is observed in frataxin-deficient neuron-like cells and the pharmacological activation of autophagy does not significantly increase neuronal cell death in response to the frataxin deficiency. Cell death triggered by frataxin knockdown can be impaired by interference with p53, caspase inhibitors and gene transfer of FXN. These results suggest that frataxin gene silencing in human neuron-like cells may constitute a useful cell model to characterize the molecular changes triggered by frataxin deficiency in neurons, as well as to search for therapies that may protect against neurodegeneration.
Olfactory ensheathing glia (OEG) cells are known to facilitate repair following axotomy of adult neurons, although the molecular mechanisms involved are not fully understood. We previously identified plasminogen activator inhibitor-1 (PAI-1), proteinase-activated receptor-1 (PAR-1), and thrombomodulin (TM) as candidates to regulate rat OEG-dependent axonal regeneration. In this study, we have validated the involvement of these proteins in promoting axonal regeneration by immortalized human OEGs. We studied the effect of silencing these proteins in OEGs on their capacity to promote the regeneration of severed adult retinal ganglion cells (RGCs) axons. Our results support the role of glial PAI-1 as a downstream effector of PAR-1 in promoting axon regeneration. In contrast, we found that TM inhibits OEG induced-axonal regeneration. We also assessed the signaling pathways downstream of PAR-1 that might modulate PAI-1 expression, observing that specifically inhibiting G?(i), Rho kinase, or PLC and PKC downregulated the expression of PAI-1 in OEGs, with a concomitant reduction in OEG-dependent axon regeneration in adult RGCs. Our findings support an important role for the thrombin system in regulating adult axonal regeneration by OEGs.
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