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.

Essentials of
Neuroscience

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

In JoVE (1)

Other Publications (200)

Articles by Andrea T. Tovar in JoVE

 JoVE Clinical and Translational Medicine

Portable Intermodal Preferential Looking (IPL): Investigating Language Comprehension in Typically Developing Toddlers and Young Children with Autism

1Department of Psychology, University of Connecticut


JoVE 4331

A reliable home-based way to assess the language comprehension of very young typically developing children, as well as those with autism, is described. The method analyzes children's eye gaze while viewing side-by-side images but hearing an audio that matches only one image. Stimuli are designed with young participants in mind.

Other articles by Andrea T. Tovar on PubMed

Herbal Toxicity

Dietary Soy Protein Reduces Cardiac Lipid Accumulation and the Ceramide Concentration in High-fat Diet-fed Rats and Ob/ob Mice

Obesity is an epidemic condition strongly associated with cardiovascular morbidity and mortality. Heart disease secondary to obesity is associated with myocardial steatosis, leading to ceramide synthesis and cell dysfunction in a process known as lipotoxicity. Soy protein has been demonstrated to reduce lipotoxicity in the liver and pancreas in different rodent models of obesity. Thus, our purpose in the present work was to assess the effect of dietary soy protein on cardiac lipid accumulation and ceramide formation during obesity and to evaluate its effect in the following 2 rodent models of obesity: 1) a diet-induced obesity model in Sprague-Dawley rats was produced by feeding rats a control or a high-fat casein or soy protein diet for 180 d; and 2) wild-type and ob/ob mice were fed a casein or soy protein diet for 90 d. Soy protein intake led to lower cholesterol and triglyceride concentrations in the hearts of rats and ob/ob mice in association with a greater PPARalpha mRNA concentration and a lower level of sterol regulatory element binding protein-1 mRNA than those fed casein. The ceramide concentration was also lower in hearts of rats and ob/ob mice that were fed soy protein in association with lower serine palmitoyl transferase (SPT)-1 and tumor necrosis factor-alpha mRNA concentrations. These results indicate that dietary soy protein can reduce the heart ceramide concentration by reducing the expression of SPT-1, a key enzyme in the formation of this sphingolipid in the heart of obese rodents, and by reducing lipid accumulation. Thus, soy protein consumption may be considered as a dietary therapeutic approach for lipotoxic cardiomyopathy prevention.

DNA-AP Sites Generation by Etoposide in Whole Blood Cells

Etoposide is currently one of the most commonly used antitumor drugs. The mechanisms of action proposed for its antitumor activity are based mainly on its interaction with topoisomerase II. Etoposide effects in transformed cells have been described previously. The aim of the present study was to evaluate the genotoxic effects of this drug in non-transformed whole blood cells, such as occurs as collateral damage induced by some chemotherapies.

Reduction of Serum Lipids by Soy Protein and Soluble Fiber is Not Associated with the ABCG5/G8, Apolipoprotein E, and Apolipoprotein A1 Polymorphisms in a Group of Hyperlipidemic Mexican Subjects

Several studies have evaluated the effect of soy protein or soluble fiber on serum cholesterol in hypercholesterolemic subjects, with different results. We hypothesized that this response is associated with the presence of polymorphisms in genes encoding proteins involved in lipoprotein metabolism or reverse cholesterol transport. Thus, the aims of the present work were to study the effectiveness of a dietary portfolio consisting of a combination of soy protein and soluble fiber integrated in a low saturated fat (LSF) diet on blood lipids in a Mexican group with hyperlipidemia and to determine the association between responsiveness to the diet and the frequency of apolipoprotein (Apo) E and ApoA1 and ABCG5/8 polymorphisms. Forty-three hyperlipidemic subjects (20 men and 23 women) were given an LSF diet for 1 month, followed by an LSF diet that included 25 g of soy protein and 15 g of soluble fiber daily for 2 months. After the 3-month dietary intervention, serum total cholesterol (TC) significantly decreased by 20.6%, and serum triglycerides (TGs) decreased by 40.4%. Fifty-one percent of the subjects had a reduction more than 20% in serum TC, and 77% of the subjects had a reduction more than 20% in serum TG (hyperresponders). Approximately 14% of the hypercholesterolemic subjects had the ABCG8 (52 G/C) polymorphism, 65% had the ABCG5 (1950 C/G and G/G) polymorphism, 53.5% had the ApoA1 (-75 G/A and A/A) polymorphism, and 23.3% had the ApoE (3/4) polymorphism. Independently of genotype, the combination of cholesterol-lowering foods in an LSF diet significantly reduced serum TC and TG in Mexican hypercholesterolemic subjects.

[Liver Transplant from Living Donor]

Even though Spain has the highest donation rate in the world, our needs cannot be satisfied, specially in younger children. Living-related donor transplant is an alternative in those cases.

[Liver Bipartition As an Alternative to the Transplant]

Liver pediatric transplantation finds in the lack of donors its main limitation. An alternative in those cases is split liver grafts from bigger donors.

Perspectives of Latina and Non-Latina White Women on Barriers and Facilitators to Exercise in Pregnancy

Exercise during pregnancy has been associated with reduced risk of gestational diabetes mellitus, however, twice as many women are sedentary during pregnancy as compared to when they are not pregnant. We conducted 3 focus groups among 20 pregnant Latina and non-Latina white women to identify barriers and facilitators to exercise in pregnancy to inform a gestational diabetes mellitus intervention study. Quantitative analyses of demographic data, and qualitative analyses of focus groups were conducted. Women identified physical limitations and restrictions, lack of resources, energy, and time as powerful exercise barriers. Social support, access to resources, information, proper diet, scheduling, and the weather were identified as powerful facilitators. Intervention programs designed for pregnant women should facilitate social support, provide information and resources, as well as promote short-term and long-term benefits.

Intramural Ganglion Structures in Esophageal Atresia: a Morphologic and Immunohistochemical Study

Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E), and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF.

[Histology and Morphometry of the in the Freshwater Paracheirodon Axelrodi (Characiformes: Characidae)]

The visual system of Teleost fishes has a wide range of adaptations. The eye has suffered modifications, mainly towards better sensitivity and visual resolution according to specific environmental conditions. In that way, this organ is so important for survival. In spite of being the most commercialized Orinoquia species, and one of the most important ornamental fish worldwide, there are almost no studies on the communication systems of P. axelrodi (including vision). We studied the eye in ten individuals of P. axelrodi, with a mean total length of 2.7 cm (SD = 0.2, n = 20). We measured eye relative size (TRO) after sacrifice. Heads were processed for hematoxylin-eosin, and 8 microm thick sections were obtained. Images were digitalized for histological identification and morphometrics. The relation between TRO and body length was 9.8% (SD= 1.1, n= 20); lens was spherical with a relative size of 64.3% (SD = 4.9, n = 20). Rete mirabilis choroid was composed mainly by capillaries, while sclera was composed of cartilaginous tissue. Retina with eight layers and two membranes. An areae centrales was observed in the posterior retina. Iris covered by a simple cubic epithelium. Cornea of endotelial tissue with two membranes. Pupil almost circular, with a naso-caudal elongation. Measures of retina thickness were as follows: lateral retina 144.5 microm (SD = 5.4, n = 20), temporal retina 210.4 microm (SD = 14.8, n = 20). Lens measurements were: dorso-ventral 759.6 microm (SD = 31.7, n = 20), antero-posterior 763.4 microm (SD = 30.7, n = 20). Cornea thickness was 27.6 microm (SD = 4.3, n = 20); iris thickness was 18.9 microm (SD = 1.9, n = 20); rete mirabilis choroid 22.2 microm (SD = 3.2, n = 20) and sclera: 15.9 microm (SD = 1.2, n = 20). This species has a typical Teleost eye conformation. The retina was thicker in the posterior area, probably related to the presence of neuron groups. This modification allows for a better sharpness and visual resolution. The TRO, areae centrales in the retina, and thin cornea, suggests the need of a well developed visual system resulting from a predatory diet.

[Effectiveness of Cytology-based Cervical Cancer Screening in the Colombian Health System]

Despite the implementation of cytological screening since 1991, cervical cancer continuous to be the leading cause of cancer mortality among Colombian women.

[Presence of Antibodies to Cardiac Neuroreceptors in Patients with Chagas Disease]

The presence of antibodies against cardiac neuroreceptors has been established in several kinds of heart diseases as well as in Chagas disease. The antibody type most frequently identified is that which recognizes the muscarinic acetyl choline receptor type II (anti-m2MAChR).

The Role of Dietary Protein on Lipotoxicity

Lipotoxicity is a metabolic abnormality frequently observed during the development of obesity and is the main cause of several changes in the metabolic observed during metabolic syndrome. Consistent consumption of diets high in saturated fat or simple carbohydrates combined with low physical activity are the main causes of obesity and its comorbidities. However, the contribution of dietary protein and, in particular, the contribution due to the type of dietary protein, to the process of obesity and its metabolic consequences are less well-understood. In this review, we showed that the type of dietary protein has a significant contribution to the process of lipotoxicity through the modulation of insulin secretion and the regulation of adipocyte metabolic function. Consumption of soy protein stimulates insulin secretion to a lower extent than casein despite the fact that both are high-quality proteins. The amino acid profiles of soy protein and its isoflavones are responsible for the reduced insulin secretion. Also, soy protein increases insulin sensitivity, whereas casein has the opposite effect. Consequently, soy protein reduces SREBP-1 expression in the liver leading to low accumulation of hepatic triglycerides, despite the consumption of a high-fat diet. Furthermore, soy protein reduces adipocyte hypertrophy, hyperleptinemia, and free fatty acid concentration. Thus, the influx of FA into the liver decreases, and hepatic oxidation of FA increases. These metabolic changes result in a decrease in lipid depots and ceramide which reduce hepatic lipotoxicity, whereas casein produces the opposite effect. This study emphasizes that the type of dietary protein has an important effect on lipotoxicity.

Microscopic Magnetic Resonance in Congenital Diaphragmatic Hernia and Associated Malformations in Rats

The research on congenital diaphragmatic hernia (CDH) is often carried out on the nitrofen fetal rat model in which most investigations involve microdissections and fastidious assessment of serial sections of different anatomic areas. Current microscopic magnetic resonance (MMR) equipment allows detailed anatomic studies of alive, fresh or fixed fetuses. The purpose of the present study was to demonstrate that CDH itself and most of the associated malformations are adequately imaged and measured by MMR.

Adiponectin Receptor 2 is Regulated by Nutritional Status, Leptin and Pregnancy in a Tissue-specific Manner

The aim of the present work was to study the regulation of circulating adiponectin levels and the expression of adiponectin receptor 2 (Adipo-R2) in several rat tissues in relation to fasting, leptin challenge, pregnancy, and chronic undernutrition. Using real-time PCR, we found Adipo-R2 mRNA expression in the liver, stomach, white and brown adipose tissues (WAT and BAT) of adult rats. Immunohistochemical studies confirmed protein expression in the same tissues. Adipo-R2 mRNA levels were decreased in liver after fasting, with no changes in the other tissues. Leptin decreased Adipo-R2 expression in liver and stomach, but increased its expression in WAT and BAT. Chronic caloric restriction in normal rats increased Adipo-R2 gene expression in stomach, while it decreased hepatic Adipo-R2 levels in pregnant rats. Using radioimmunoassay, we found that plasma adiponectin levels were diminished by fasting and leptin. Conversely, circulating adiponectin was increased in food-restricted rats, whereas its levels decreased in food-restricted pregnant rats by the end of gestation. In conclusion our findings provide the first evidence that (a) Adipo-R2 mRNA is regulated in a tissue-specific manner by fasting, but leptin is not responsible for those changes; (b) chronic caloric restriction in normal and pregnant rats also regulate Adipo-R2 mRNA in a tissue-specific manner; and (c) Adipo-R2 mRNA does not show a clear correlation with plasma adiponectin levels.

Bacterial-type Oxygen Detoxification and Iron-sulfur Cluster Assembly in Amoebal Relict Mitochondria

The assembly of vital reactive iron-sulfur (Fe-S) cofactors in eukaryotes is mediated by proteins inherited from the original mitochondrial endosymbiont. Uniquely among eukaryotes, however, Entamoeba and Mastigamoeba lack such mitochondrial-type Fe-S cluster assembly proteins and possess instead an analogous bacterial-type system acquired by lateral gene transfer. Here we demonstrate, using immunomicroscopy and biochemical methods, that beyond their predicted cytosolic distribution the bacterial-type Fe-S cluster assembly proteins NifS and NifU have been recruited to function within the relict mitochondrial organelles (mitosomes) of Entamoeba histolytica. Both Nif proteins are 10-fold more concentrated within mitosomes compared with their cytosolic distribution suggesting that active Fe-S protein maturation occurs in these organelles. Quantitative immunoelectron microscopy showed that amoebal mitosomes are minute but highly abundant cellular structures that occupy up to 2% of the total cell volume. In addition, protein colocalization studies allowed identification of the amoebal hydroperoxide detoxification enzyme rubrerythrin as a mitosomal protein. This protein contains functional Fe-S centres and exhibits peroxidase activity in vitro. Our findings demonstrate the role of analogous protein replacement in mitochondrial organelle evolution and suggest that the relict mitochondrial organelles of Entamoeba are important sites of metabolic activity that function in Fe-S protein-mediated oxygen detoxification.

STAT3, P38 MAPK, and NF-kappaB Drive Unopposed Monocyte-dependent Fibroblast MMP-1 Secretion in Tuberculosis

Tissue destruction characterizes infection with Mycobacterium tuberculosis (Mtb). Type I collagen provides the lung's tensile strength, is extremely resistant to degradation, but is cleaved by matrix metalloproteinase (MMP)-1. Fibroblasts potentially secrete quantitatively more MMP-1 than other lung cells. We investigated mechanisms regulating Mtb-induced collagenolytic activity in fibroblasts in vitro and in patients. Lung fibroblasts were stimulated with conditioned media from Mtb-infected monocytes (CoMTb). CoMTb induced sustained increased MMP-1 (74 versus 16 ng/ml) and decreased tissue inhibitor of metalloproteinase (TIMP)-1 (8.6 versus 22.3 ng/ml) protein secretion. CoMTb induced a 2.7-fold increase in MMP-1 promoter activation and a 2.5-fold reduction in TIMP-1 promoter activation at 24 hours (P = 0.01). Consistent with this, TIMP-1 did not co-localize with fibroblasts in patient granulomas. MMP-1 up-regulation and TIMP-1 down-regulation were p38 (but not extracellular signal-regulated kinase or c-Jun N-terminal kinase) mitogen-activated protein kinase-dependent. STAT3 phosphorylation was detected in fibroblasts in vitro and in tuberculous granulomas. STAT3 inhibition reduced fibroblast MMP-1 secretion by 60% (P = 0.046). Deletion of the MMP-1 promoter NF-κB-binding site abrogated promoter induction in response to CoMTb. TNF-α, IL-1β, or Oncostatin M inhibition in CoMTb decreased MMP-1 secretion by 65, 63, and 25%, respectively. This cytokine cocktail activated the same signaling pathways in fibroblasts and induced MMP-1 secretion similar to that induced by CoMTb. This study demonstrates in a cellular model and in patients with tuberculosis that in addition to p38 and NF-κB, STAT3 has a key role in driving fibroblast-dependent unopposed MMP-1 production that may be key in tissue destruction in patients.

Protein Restriction During Pregnancy Affects Maternal Liver Lipid Metabolism and Fetal Brain Lipid Composition in the Rat

Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

Reproductive Axis Function and Gonadotropin Microheterogeneity in a Male Rat Model of Diet-induced Obesity

Obesity causes complex metabolic and endocrine changes that may lead to adverse outcomes, including hypogonadism. We herein studied the reproductive axis function in male rats under a high-fat diet and analyzed the impact of changes in glycosylation of pituitary LH on the bioactivity of this gonadotropin. Rats were fed with a diet enriched in saturated fat (20% of total calories) and euthanized on days 90 or 180 of diet. Long-term (180 days), high-fat feeding rats exhibited a metabolic profile compatible with insulin resistance and metabolic syndrome; they concomitantly showed decreased intrapituitary and serum LH concentrations, low serum testosterone levels, and elevated serum 17beta-estradiol concentrations. A fall in biological to immunological ratio of intrapituitary LH was detected in 180 days control diet-treated rats but not in high-fat-fed animals, as assessed by a homologous in vitro bioassay. Chromatofocusing of pituitary extracts yielded multiple LH charge isoforms; a trend towards decreased abundance of more basic isoforms (pH 9.99-9.0) was apparent in rats fed with the control diet for 180 days but not in those that were fed the diet enriched in saturated fat. It is concluded that long-term high-fat feeding alters the function of the pituitary-testicular axis, resulting in hypogonadotropic hypogonadism. The alterations in LH function found in these animals might be subserved by changes in hypothalamic GnRH output and/or sustained gonadotrope exposure to an altered sex steroid hormone milieu, representing a distinctly different regulatory mechanism whereby the pituitary attempts to counterbalance the effects of long-term obesity on reproductive function.

The Tasmanian Devil Transcriptome Reveals Schwann Cell Origins of a Clonally Transmissible Cancer

The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology.

Graft-vs-host Disease After Small Bowel Transplantation in Children

Graft-vs-host disease (GVHD) is a rare complication of transplantation of organs rich in immunocompetent cells. The goal of this study was to report the features of GVHD after small bowel transplantation (SBTx) in children.

Colonic Interposition for Esophageal Replacement in Children Remains a Good Choice: 33-year Median Follow-up of 65 Patients

Gastric pull-up has become the predominant technique for esophageal replacement because of allegedly deficient results of colon grafts. This retrospective study examines the long-term results in a large series of colonic interpositions.

Bronchopulmonary Innervation Defects in Infants and Rats with Congenital Diaphragmatic Hernia

Pulmonary morbidity in survivors of congenital diaphragmatic hernia (CDH) is caused by hypoplasia, barotraumas, or other reasons. We have previously shown deficient tracheal innervation in rats with CDH. Now we examine whether bronchopulmonary innervation is also abnormal in both infants and rats with CDH.

Comparative Survey of Conducting Polymers Containing Benzene, Naphthalene, and Anthracene Cores: Interplay of Localized Aromaticity and Polymer Electronic Structures

We present a systematic study to understand to what extent the localization of aromaticity in an orthogonal sense to the main polymer conjugation pathway will influence the observed optical and electrical properties as the polymers undergo oxidation and doping into conductive materials. Three classes of electropolymerizable monomers were prepared where the critical electronic unit was chosen to foster different degrees of aromatic localization pendant to the conjugation pathway: specifically, those based upon benzene, naphthalene, and anthracene cores. The expectation was that the benzene unit would foster extensive intramolecular delocalization upon adoption of the quinoidal electronic structure on account of the strong polyene character. On the other hand, resonance contributors can be rationalized for naphthalene and anthracene whereby one or two aromatic sextets evolve within the quinoidal structure thereby leading to a more localized electronic structure. Monomer and polymer electronics were probed with UV-vis spectroscopy and cyclic voltammetry as well as through in situ profiling of the conductive states of the respective polymers. A semiempirical analysis of the frontier orbital wave functions was employed to further understand the influences of competing aromaticity pendant to the polymer backbones. Our findings indicate the potential for complex and tunable pi-conjugated polymers whose properties can be externally controlled through local alterations of aromatic character within units fused or cross-conjugated to polymer main chains.

IGF Activation in a Molecular Subclass of Hepatocellular Carcinoma and Pre-clinical Efficacy of IGF-1R Blockage

IGF signaling has a relevant role in a variety of human malignancies. We analyzed the underlying molecular mechanisms of IGF signaling activation in early hepatocellular carcinoma (HCC; BCLC class 0 or A) and assessed novel targeted therapies blocking this pathway.

School's Out: What Are Urban Children Doing? The Summer Activity Study of Somerville Youth (SASSY)

Research indicates that in the United States, children experience healthier BMI and fitness levels during school vs. summer, but research is limited. The primary goal of this pilot study was to assess where children spend their time during the months that school is not in session and to learn about the different types of activities they engage in within different care settings. A secondary goal of this pilot study was to learn what children eat during the summer months.

Cancer Gene Discovery in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a deadly cancer, whose incidence is increasing worldwide. Albeit the main risk factors for HCC development have been clearly identified, such as hepatitis B and C virus infection and alcohol abuse, there is still preliminary understanding of the key drivers of this malignancy. Recent data suggest that genomic analysis of cirrhotic tissue - the pre-neoplastic carcinogenic field - may provide a read-out to identify at risk populations for cancer development. Given this contextual complexity, it is of utmost importance to characterize the molecular pathogenesis of this disease, and pinpoint the dominant pathways/drivers by integrative oncogenomic approaches and/or sophisticated experimental models. Identification of the dominant proliferative signals and key aberrations will allow for a more personalized therapy. Pathway-based approaches and functional experimental studies have aided in identifying the activation of different signaling cascades in HCC (e.g. epidermal growth factor, insulin-like growth factor, RAS, MTOR, WNT-betacatenin, etc.). However, the introduction of new high-throughput genomic technologies (e.g. microarrays, deep sequencing, etc.), and increased sophistication of computational biology (e.g. bioinformatics, biomodeling, etc.), opens the field to new strategies in oncogene and tumor suppressor discovery. These oncogenomic approaches are framed within emerging new disciplines such as systems biology, which integrates multiple inputs to explain cancer onset and progression. In addition, the consolidation of sophisticated animal models, such as mosaic cancer mouse models or the use of transposons for mutagenesis screens, have been instrumental for the identification of novel tumor drivers. We herein review some classical as well as some recent fast track approaches for oncogene discovery in HCC, and provide a comprehensive landscape of the currently known spectrum of molecular aberrations involved in hepatocarcinogenesis.

Changes in the Expression of Pluripotency-associated Genes During Preimplantation and Peri-implantation Stages in Bovine Cloned and in Vitro Produced Embryos

In cattle, embryos elongate before implantation and after hatching. Changes in gene expression during this transition are not well studied. Especially important are variations in the expression of pluripotency-associated genes as a result of assisted reproductive biotechnologies, such as cloning and in vitro fertilization (IVF). We hypothesize that there will be a decline in the expression of key pluripotency-associated genes and an increase in the expression of IFN-tau in elongated embryos when compared with day-7 blastocysts. To test this we generated cloned and IVF bovine day-7 blastocyst and day-17 elongated embryos (day 0 = day of nucleus transfer or IVF). Gene expression in all embryos was assessed via RT-qPCR. OCT4 was overexpressed (p < 0.05) in the cloned blastocysts when compared with IVF. No differences in gene expression at this stage between cloned and IVF embryos were found for EOMES, NANOG and FGF4. At elongation EOMES, NANOG and FGF4 were upregulated in IVF embryos (p < 0.05). IFN-tau and OCT4 were expressed at similar levels. There were changes in the expression levels for all transcripts between blastogenesis and elongation. NANOG, IFN-tau and EOMES were overexpressed in all the elongated embryos (p < 0.05), FGF4 was underexpressed in both treatments. OCT4 dropped drastically in the cloned elongated embryos, but not in the IVF. Interestingly only adult donor cells (but not fetal) from which the cloned embryos originated also expressed high levels of OCT4. Our findings might help to understand the shift of gene expression during elongation and to identify key markers of embryonic development useful for embryo screening purposes.

On-resin Dimerization Incorporates a Diverse Array of Pi-conjugated Functionality Within Aqueous Self-assembling Peptide Backbones

We report a convenient method to incorporate pi-electron units into peptides that assemble into amyloid-like supramolecular polymers, discussing the scope of the process and preliminary characterization of the resulting nanomaterials. Self-assembly manipulates these "electronic peptides" into delocalized sub-10 nm 1-D nanostructures under completely aqueous conditions.

Synthesis of Functionalizable Boron-containing Pi-electron Materials That Incorporate Formally Aromatic Fused Borepin Rings

Obstructive Sleep Apnoea and 24-h Blood Pressure in Patients with Resistant Hypertension

Obstructive sleep apnoea (OSA) is common in patients with resistant hypertension, but understanding of the pathogenic mechanisms linking both conditions is limited. This study assessed the prevalence of OSA and the relationships between OSA and 24-h blood pressure (BP) in 62 consecutive patients with resistant hypertension, defined as clinic BP values ≥ 140/90 despite the prescription of at least three drugs at adequate doses, including a diuretic. In order to exclude a 'white coat effect', only patients with ambulatory 24-h BP values ≥ 125/80 were recruited. Patients underwent polysomnography, 24-h ambulatory BP monitoring and completed the Epworth sleepiness scale (ESS). OSA was defined as an apnoea-hypopnoea index (AHI) ≥ 5 and excessive daytime sleepiness (EDS) by an ESS ≥ 10. A multiple linear regression analysis was used to assess the association of anthropometric data, OSA severity measures and ESS with 24-h systolic and diastolic BP. Mean 24-h BP values were 139.14/80.98 mmHg. Ninety per cent of patients had an AHI ≥ 5 and 70% had an AHI ≥ 30. Only the ESS was associated with 24-h diastolic BP [slope 0.775, 95% confidence interval (CI) 0.120-1.390, P < 0.02); age was associated negatively with 24-h diastolic BP (slope -0.64, 95% CI -0.874 to -0.411, P < 0.001). Compared with those without EDS, patients with EDS showed a significantly higher frequency of diastolic non-dipping pattern (69.2% versus 34.7%, P < 0.032). Our results demonstrate a high prevalence of severe OSA in patients with resistant hypertension and suggest that EDS could be a marker of a pathogenetic mechanism linking OSA and hypertension.

In Vitro Fermentability and Antioxidant Capacity of the Indigestible Fraction of Cooked Black Beans (Phaseolus Vulgaris L.), Lentils (Lens Culinaris L.) and Chickpeas (Cicer Arietinum L.)

Pulses represent an important source of protein, as well as digestible and indigestible carbohydrates. Little information is available on the indigestible carbohydrates and antioxidant capacity of legume seeds. The cooked seeds of three pulses (black bean, chickpea and lentil) were evaluated for their indigestible fraction (IF), polyphenols content, antioxidant capacity and in vitro fermentability, including short-chain fatty acid production.

Pimecrolimus Induces Apoptosis of Mast Cells in a Murine Model of Cutaneous Mastocytosis

Cutaneous mastocytosis (CM) is a common type of mastocytosis. Current treatment of CM is generally symptomatic. Pimecrolimus has been demonstrated as an effective anti-inflammatory drug for the treatment of inflammatory skin diseases, but whether it treats CM remains unknown.

Association of Cutaneous Red-to-purple Hemangiomas with Leptomeningeal Hemangiomas. a Clinical Study of Two Patients

Cutaneous hemangioma is a benign vascular tumor of infancy with an initial proliferating period that appears between 1 to 2 weeks of life, extends during 18 months to 2 years of life, and then slowly regresses during several years until it disappears completely. They are characterized by endothelial cell proliferation followed by diminishing hyperplasia and progressive fibrosis. Vascular malformations are present at birth, grow commensurately with the child, and are characterized histologically by a normal rate of endothelial cell turnover, flat endothelium, thin (normal) basal membrane and normal mast cells. These cutaneous anomalies are commonly associated with cerebellar malformations, main cerebral arteries anomalies, congenital cardiac anomalies and/or coarctation of the aorta and persistence of embryonic arteries. Cutaneous hemangiomas can be associated with intracranial or extracranial hemangiomas that regress at the same time as the cutaneous hemangiomas. Cutaneous hemangiomas may show different types of color. Cutaneous red-to-purple hemangiomas are uncommon and their bright-red color is evident from the first weeks of life and remains unaltered until the hemangioma disappears. The intracranial angiographic studies in our series of more than 50 cases with facial hemangioma showed that patients with red-to-purple hemangiomas are commonly associated with localized leptomeningeal hemangiomas either in the ipsilateral or contralateral side. These leptomingeal hemangiomas were visualized only by MR enhanced with gadolinium. Involution of the cutaneous and leptomeningeal hemangiomas seems to occur simultaneously as in other types of external and internal hemangiomas.

Continuous Positive Airway Pressure Treatment in Sleep Apnea Patients with Resistant Hypertension: a Randomized, Controlled Trial

This controlled trial assessed the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH).

Postoperative Self-report of Pain in Children: Interscale Agreement, Response to Analgesic, and Preference for a Faces Scale and a Visual Analogue Scale

To augment available validation data for the Faces Pain Scale - Revised (FPS-R) and to assess interscale agreement and preference in comparison with the Coloured Analogue Scale (CAS) in pediatric acute pain.

[Long-term Results in Ulcerative Colitis Treated with Proctocolectomy and Ileoanostomy in Children]

The treatment of Ulcerative Colitis (UC) unresponsive to current medical treatment involves total proctocolectomy and ileanostomy. The aim of this study was to assess the long term results in such patients.

[Prenatal Techniques to Prevent Central Nervous System Malformations in the Surgically Induced Model of Myelomeningocele]

To describe central nervous system malformations in the surgically induced model of Myelomeningocele (MMC) and their prevention using different prenatal treatments.

Effects of Axon Degeneration on Oligodendrocyte Lineage Cells: Dorsal Rhizotomy Evokes a Repair Response While Axon Degeneration Rostral to Spinal Contusion Induces Both Repair and Apoptosis

Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots producing massive axonal degeneration and microglial activation in the DC, and found no evidence of OL loss or apoptosis. Rather, the numbers of OL-lineage cells positive for NG2 and APC (CC1) increased, and BrdU studies suggested new OL formation. We then tested contusion SCI (cSCI) that results in comparable degeneration in the DC rostral to the injury, microglial activation, and apoptosis of DC OLs by eight days. NG2+ cell proliferation and oligodendrogenesis was seen as after rhizotomy. The net result of this combination of proliferation and apoptosis was a reduction in DC OLs, confirming earlier studies. Using an antibody to oxidized nucleic acids, we found rapid and prolonged RNA oxidation in OLs rostral to cSCI, but no evidence of oxidative stress in DC OLs after rhizotomy. These results suggest that signals associated with axonal degeneration are sufficient to induce OL proliferation, and that secondary injury processes associated with the central SCI, including oxidative stress, rather than axonal degeneration per se, are responsible for OL apoptosis.

Congenital Anomalies of the Esophagus

Congenital malformations of the esophagus are frequently encountered by pediatric surgeons, especially esophageal atresia with or without tracheo-esophageal fistula. However, the molecular mechanisms underlying the development of these various anomalies are not clear. Here we present a brief overview of the embryologic development of the tracheoesophageal tube, along with some of the genetic controls which, when defective can lead to abnormal separation of this tube.

[Following-up Females Having an Abnormal Pap Smear in Colombia]

Evaluating the opportunity and access to diagnosis and treatment for females having had an abnormal Pap smear (high-grade epithelial lesion and cervical cancer) in Colombia from June 2005 to June 2006.

Poly(cyclopropenone)s: Formal Inclusion of the Smallest Hückel Aromatic into Pi-conjugated Polymers

The synthesis of precursors to pi-conjugated cyclopropenium polymers is described. Monomers for chemical and electrochemical manipulation are easily prepared through electrophilic substitution of in situ generated cyclopropenium cations that are then hydrolyzed to the respective cyclopropenones. The unusually strong dipole moment associated with the cyclopropenone renders this core formally aromatic, an electronic structure that becomes more important within individual monomers upon protonation of the carbonyl function with trifluoroacetic acid or alkylation with triethyloxonium salts. The electronic properties of cyclopropenone polymers in their pristine states and after acidification are discussed along with conjugated carbonyl-containing polymers that are also acid sensitive but without the added element of aromaticity. We find that the increased contributions of cyclopropenium cation aromaticity restrict the quinoidal charge carriers due to the energetically less favorable proposition of disrupting the local aromatic stabilization.

Increase in HDL-C Concentration by a Dietary Portfolio with Soy Protein and Soluble Fiber is Associated with the Presence of the ABCA1R230C Variant in Hyperlipidemic Mexican Subjects

A dietary portfolio has been used to reduce blood lipids in hyperlipidemic subjects. To increase the effectiveness of these dietary treatments in specific populations, it is important to study the genetic variability associated with the development of certain types of hyperlipidemias. Low plasma high-density lipoprotein cholesterol (HDL-C) levels are the most common dyslipidemia in Mexican adults and are coupled with the presence of the ABCA1 R230C genotype. Therefore, the aim of this study was to assess the response of HDL-C concentration to a dietary portfolio in a group of Mexican hyperlipidemic subjects with ABCA1R230C (rs9282541) and R219K (rs2230806) polymorphisms.

Hypothalamic AMPK and Fatty Acid Metabolism Mediate Thyroid Regulation of Energy Balance

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

Small-molecule Inducer of Cancer Cell Polyploidy Promotes Apoptosis or Senescence: Implications for Therapy

Polyploidy results from deregulated cell division and has been considered an undesirable event leading to increased mutation rate and cancer development. However, polyploidy may also render cancer cells more vulnerable to chemotherapy. Here, we identify a small-molecule inducer of polyploidy, R1530, which interferes with tubulin polymerization and mitotic checkpoint function in cancer cells, leading to abortive mitosis, endoreduplication and polyploidy. In the presence of R1530, polyploid cancer cells underwent apoptosis or became senescent which translated into potent in vitro and in vivo efficacy. Normal proliferating cells were resistant to R1530-induced polyploidy thus supporting the rationale for cancer therapy by induced polyploidy. Mitotic checkpoint kinase BubR1 was found downregulated during R1530-induced exit from mitosis, a likely consequence of PLK4 inhibition. BubR1 knockdown in the presence of nocodazole induced an R1530-like phenotype, suggesting that BubR1 plays a key role in polyploidy induction by R1530 and could be exploited as a target for designing more specific polyploidy inducers.

Interleukin-6 Signaling in Liver-parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action

The contribution of interleukin (IL)-6 signaling in obesity-induced inflammation remains controversial. To specifically define the role of hepatic IL-6 signaling in insulin action and resistance, we have generated mice with hepatocyte-specific IL-6 receptor (IL-6R) alpha deficiency (IL-6Ralpha(L-KO) mice). These animals showed no alterations in body weight and fat content but exhibited a reduction in insulin sensitivity and glucose tolerance. Impaired glucose metabolism originated from attenuated insulin-stimulated glucose transport in skeletal muscle and fat. Surprisingly, hepatic IL-6Ralpha-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-alpha, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of IkappaBalpha. Neutralization of TNF-alpha or ablation of Kupffer cells restored glucose tolerance in IL-6Ralpha(L-KO) mice. Thus, our results reveal an unexpected role for hepatic IL-6 signaling to limit hepatic inflammation and to protect from local and systemic insulin resistance.

Cyclic Adenosine Monophosphate Induces Plasminogen Activator Inhibitor-1 Expression in Human Mast Cells

Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma. Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs; however, its effects on PAI-1 expression in MCs remain unknown. We reported cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP-response element binding protein binding to hypoxia response element-1 at -158 to -153bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation.

Development and Psychometric Testing of the Health Beliefs Related to Cardiovascular Disease Scale: Preliminary Findings

This paper is a report of an evaluation of the psychometric properties of the Health Beliefs Related to Cardiovascular Disease Scale designed to measure beliefs related to cardiovascular disease risk and diet and exercise in adults with diabetes.

[Quality of Vaginal Smear for Cervical Cancer Screening: a Concordance Study]

Cervical cancer is the leading cause of cancer deaths in the female population in Colombia. The low impact of Papanicolaou smears in reducing cervical cancer mortality in some countries has been attributed to their low reproducibility and high rates of false negatives.

The Use of Sirolimus As a Rescue Therapy in Pediatric Intestinal Transplant Recipients

To review our experience with SRL as a second-line therapy in our series of 45 SBTx recipients (1997-2009). Retrospective review of five children converted to SRL: 3 M/2 F; median of three yr old (range 20 months-18 yr); rescue indications, adverse events with SRL, resolution of tacrolimus-related side effects, incidence of rejection, PTLD, or GVHD were summarized. Tacrolimus was discontinued (average 13 months after transplant) because of refractory hemolytic anemia in four patients with decreased renal function and because of advanced renal failure and unclear neutropenia in one. PTLD and GVHD had been previously diagnosed in two. Tacrolimus-related side effects disappeared in all five although other immunosuppressants and splenectomy were used simultaneously or later in most of them. Adverse events reported after the conversion were infections (tuberculosis and Pneumocystis carinii in two) and mild hypertriglyceridemia. No rejection, GVHD, or PTLD episode was observed. Four patients are alive with excellent quality of life (median follow-up 18 months). Sirolimus is a safe rescue therapy in SBTx children when tacrolimus is not well tolerated. Renal function and hematologic disorders seem to improve, although other simultaneous strategies could be also involved. Further studies could demonstrate its efficacy as a first-line treatment.

The Impact of Misinformation

[Pneumonectomy in Children]

Pneumonectomy is seldom indicated in children and its long-term effects are not well known. The aim of the present study was to examine retrospectively the indications and the long-term sequelae in a relatively large cohort of patients treated at our institution.

[The Risk of Necrotizing Enterocolitis in Newborns with Congenital Heart Disease. a Single Institution-cohort Study]

Necrotizing enterocolitis (NEC) is the most common gastrointestinal surgical disease among neonates. Congenital heart disease (CHD) is also a significant cause of infant morbidity and mortality and it is usually associated with prematurity, low birth weight, pulmonary and gastrointestinal disease, conditions that also account for the development of NEC. Our aim is to analyze the incidence and the risk factors for NEC in neonates with CDH admitted to the Neonatal Intensive Care Unit (NICU) in a 6 years period.

[Bladder Malformations in a Model of Myelomeningocele. Preliminary Report]

To describe the presence of bladder malformations in a surgically induced model of myelomeningocele (MMC).

Phase Coexistence in Manganites: Doping and Structural Dependence

We present a study on the phase coexistence (PC) of paramagnetic insulating (PM-I) and ferromagnetic metallic (FM-M) phases in the La(1- y)(Ca(1-x)Sr(x))(y)MnO(3) system with 0.23 ≤ y ≤ 0.45. The study was performed by means of magnetization and electron spin resonance (ESR) measurements. At high temperatures the ESR spectrum consists of a single symmetric PM line. At T(C), a FM asymmetric line is observed shifted to low fields. In a ΔT temperature range both lines are visible, defining a range of PC. For x = 0, we obtained ΔT as a function of the carrier concentration y, finding that the largest ΔT corresponds to y = 0.25. For this y value, the extreme compounds are orthorhombic and rhombohedral for x = 0 and 1, respectively. The rhombohedral to orthorhombic temperature transition (T(RO)) was determined as a function of x. We found that [Formula: see text] only if T(C) < T(RO). The PM-I/FM-M phase coexistence was only observed in the orthorhombic phase while seems to be incompatible with the more symmetric rhombohedral phase.

A Dried Tofu-supplemented Diet Affects MRNA Expression of Inflammatory Cytokines in Human Blood

In order to develop a new model of diet research, blood was drawn from 12 adult volunteers for 3 wk on regular diets as controls, and for a subsequent 3 wk supplemented with 18.5 g of freeze-dried tofu (Koya tofu) every day. Triplicate aliquots of 0.06 mL each of whole blood were stimulated ex vivo with phytohemagglutinin (PHA)-P, heat aggregated human IgG (HAG), lipopolysaccharide (LPS), zymosan A, and anti-T cell receptor (TCR) monoclonal antibody to activate specific subsets of leukocytes, then the levels of various inflammatory cytokine mRNA were quantified by real time PCR. Koya tofu significantly (p<0.05) augmented the fold increase of PHA-induced tumor necrosis factor superfamily (TNFSF) 15, IL6, and IL8, HAG-induced TNFSF15 and IL8, LPS-induced IL6 and IL8, zymosan-induced TNFSF15, IL6 and IL8, and TCR-induced TNFSF2 in comparison to the regular diet. Such increase was due to the reduction of baseline mRNA expression, not the enhancement of mRNA induction after specific stimulations. Six (TNFSF15), 4 (IL6), and 3 (IL10) subjects showed significant reduction of baseline mRNA during the Koya tofu diet compared to that of the control diet. Despite large individual-to-individual and day-to-day variation of mRNA, the method employed in this study was sensitive enough to identify statistically significant results as a group as well as on an individual basis, which will be a foundation for tailored diet in the future. The results also indicated that Koya tofu had a power to alter mRNA expression in leukocytes, and TNFSF15, IL6, and IL10 would be biomarkers for soy.

[Chronic Idiopathic Intestinal Pseudoobstruction and Berdon Syndrome: Still a Diagnostic and Therapeutic Challenge for the Pediatric Surgeon]

Chronic Intestinal Pseudo Obstruction (CIPO) and Berdon Syndrome (BS) are motility disorders with still unclear pathophysiology, and challenging diagnosis and management. Patient and methods. 26 patients (8M/18F) treated of CIPO (21) or BS (5) at our institution between 1982-2009 were retrospectively reviewed and clinical, diagnostic, therapeutic and follow-up data were analyzed.

[Bean or Blue Rubber Blue Nevus Syndrome. Presentation of 6 Patients]

Bean or Blue Rubber Bleb Nevus Syndrome (BRBNS) is an uncommon disease characterized by multifocal venous malformations that predominantly affect the skin, soft tissues and gastrointestinal tract. Our objective is to familiarize the pediatric surgeon with this condition, promoting early diagnosis and seriated surgical treatment as therapeutic options. We have reviewed the diagnosis and treatment of 6 patients treated from 1993 to 2009.

[Need of Hepatic Bipartition or Split in the Transplant in Children]

To analyze the benefits of Split (for adult and for child) in liver transplantation.

(-)-(S)-N,N'-Bis[1-(1-naphth-yl)eth-yl]-oxalamide

The title mol-ecule, C(26)H(24)N(2)O(2), displays C(2) symmetry, with the mol-ecule located on a twofold axis perpendicular to the plane of the oxalamide unit -NH-CO-CO-NH-. The oxalamide core deviates from planarity, as reflected by the O=C-C=O and N-C-C-N torsion angles of 164.3 (5) and 163.2 (5)°, respectively. The naphthyl groups are oriented toward the same face of the oxalamide mean plane and make a dihedral angle of 43.76 (8)°. This conformation is suitable for the formation of inter-molecular N-H⋯O hydrogen bonds, giving noncentrosymmetric dimers incorporating R(2) (2)(10) ring motifs. These nonbonding inter-actions propagate along the 6(1) screw axis normal to the mol-ecular twofold axis, resulting in a single-stranded right-handed helix parallel to [001]. In the crystal, Δ helices are arranged side-by-side and inter-act through π-π contacts between naphthyl groups. The shortest centroid-centroid separation between inter-acting benzene rings is 3.623 (4) Å.

[Intestinal Transplant: in What Phase Are We?]

To analyze the evolution of Small Bowel Transplantation program since the beginning of the program. MATHERIAL AND METHODS: All children who underwent intestinal transplantation between 1997 and 2009 were retrospectively reviewed: epidemiological data, status before transplant, surgical technique, immunosupression, results, survival and long.term quality of life were analysed.

Capillary-lymphatic Malformation, Kaposiform Hemangioendothelioma and Delayed Kasabach-Merritt Phenomenon

According to International Society for the Study of Vascular Anomalies classification, vascular anomalies are mainly divided into two groups: vascular tumors and vascular malformations. Nevertheless, a small group of patients present clinical and/or histopathologic overlapping features. We report a case of a 4-month-old boy that presented a vascular lesion on his right buttock with involvement of abdominal wall muscles, abdominal cavity and drainage to primitive iliac by a tortuous drainage vein. Surgery was performed and histopathology demonstrated a combined vascular malformation. Six months later he developed a thrombocytopenia and repeat magnetic resonance imaging revealed a new solid mass involving the majority of the abdominal cavity. At 18 months of age the patient developed a Kasabach-Merrit phenomenon and treatment with vincristine, interferon and then acetyl-salicilic acid and dypiridamol was started. No response in platelet counts was obtained and one more surgery was perfomed. On this occasion a histopathologic study revealed vascular malformation areas intermingled with areas of kaposiform hemangioendothelioma. This patient demonstrates the Kasabach-Merritt phenomenon with kaposiform hemangioendothelioma arising within a pre-existing combined vascular malformation.

White Adipose Tissue Genome Wide-expression Profiling and Adipocyte Metabolic Functions After Soy Protein Consumption in Rats

Obesity is associated with an increase in adipose tissue mass due to an imbalance between high dietary energy intake and low physical activity; however, the type of dietary protein may contribute to its development. The aim of the present work was to study the effect of soy protein versus casein on white adipose tissue genome profiling, and the metabolic functions of adipocytes in rats with diet-induced obesity. The results showed that rats fed a Soy Protein High-Fat (Soy HF) diet gained less weight and had lower serum leptin concentration than rats fed a Casein High-Fat (Cas HF) diet, despite similar energy intake. Histological studies indicated that rats fed the Soy HF diet had significantly smaller adipocytes than those fed the Cas HF diet, and this was associated with a lower triglyceride/DNA content. Fatty acid synthesis in isolated adipocytes was reduced by the amount of fat consumed but not by the type of protein ingested. Expression of genes of fatty acid oxidation increased in adipose tissue of rats fed Soy diets; microarray analysis revealed that Soy protein consumption modified the expression of 90 genes involved in metabolic functions and inflammatory response in adipose tissue. Network analysis showed that the expression of leptin was regulated by the type of dietary protein and it was identified as a central regulator of the expression of lipid metabolism genes in adipose tissue. Thus, soy maintains the size and metabolic functions of adipose tissue through biochemical adaptations, adipokine secretion, and global changes in gene expression.

Bone Repair in Periodontal Defect Using a Composite of Allograft and Calcium Sulfate (DentoGen) and a Calcium Sulfate Barrier

Deep bone defects are caused by the progression of periodontal disease, which breaks down bone and connective tissue that hold teeth in place. In this case, a 37-year-old male patient presented a deep bone defect with advanced periodontal disease around an upper canine. Medical-grade calcium sulfate was mixed with demineralized freeze-dried bone allograft and used to repair and regenerate the defect. Analysis of the radiographs at the 5-month time point showed the bone had completely regenerated.

Mutation Analysis of GJB2 and GJB6 Genes in Southeastern Brazilians with Hereditary Nonsyndromic Deafness

In developed countries deafness has a genetic cause in over 60% of the cases. Contrastingly, in Brazil, it is estimated that only 16% of all deafnesses are caused by genetic factors. Among hereditary hearing deficiencies, approximately half is caused by mutations in the Gap Junction Protein Beta-2 (GJB2) gene, which encodes the protein Connexin 26 (Cx26). There are four mutations in this gene that present high prevalence in specific ethnical groups, namely, 35delG, 167delT, 235delC, and W24X. The 35delG mutation is the most frequent one, occurring in homozygosity or in compound heterozygosity with mutations in the GJB2 and GJB6 genes. This study aims to determine the prevalence of GJB2-35delG, GJB2-167delT, GJB2-235delC, GJB2-W24X, del (GJB6-D13S1830), and del (GJB6-D13S1854) mutations in patients with nonsyndromic deafness in the Espirito Santo State, Brazil. A total of 77 individuals were evaluated, from which 88.3% presented normal genotypes for all analyzed mutations, 1.3% were compound heterozygotes for 35delG-GJB2/D13S1830-GJB6, 1.3% were compound heterozygotes for 35delG/D13S1854-GJB6, 3.9% were homozygotes for the 35delG mutation and 5.2% were heterozygotes for 35delG/GJB2. The frequency of mutant alleles 35delG/GJB2, del (D13S1830/GJB6), and del (D13S1854/GJB6) was 7.8, 0.65, and 0.65%, respectively. Mutations 167delT, 235delC, and W24X were not detected. Determining the prevalence of specific mutations related to inherited deafness in a population can contribute to the development of more efficient and affordable molecular diagnostic protocols, and help in the genetic counseling of patients and their families.

Modifiable Predictors Associated with Having a Gestational Weight Gain Goal

The goal of this paper was to determine predictors of having a weight gain goal in early pregnancy. In 2008, we administered a 48-item survey to 249 pregnant women attending obstetric visits. We examined predictors of women having a goal concordant or discordant with 1990 Institute of Medicine (IOM) guidelines, vs. no goal, using binary and multinomial logistic regression. Of the 292 respondents, 116 (40%) had no gestational weight gain goal, 112 (39%) had a concordant goal and 61 (21%) had a goal discordant with IOM guidelines. Predictors of a guideline-concordant goal, vs. no goal, included sugar sweetened beverage consumption < vs. ≥ 1 serving per week (OR = 2.4, 95%CI: 1.1, 5.7), physical activity ≥ vs. <2.5 h per week (OR = 3.6, 95%CI: 1.7, 7.5), agreeing that 'I tried to keep weight down not to look pregnant' (OR = 14.3, 95%CI: 1.4, 140.5). Other predictors only of having a discordant goal (vs. no goal) included agreeing that 'as long as I am eating well, I don't care how much I gain' (OR = 0.3, 95%CI: 0.2, 0.8) and agreeing that 'if I gain too much weight one month, I try to keep from gaining the next' (OR = 4.1, 95%CI: 1.6, 10.4). Women whose doctors recommended weight gains consistent with IOM guidelines were more likely to have a concordant goal (vs. no goal) (OR = 5.3, 95%CI: 1.5, 18.6). Engaging in healthy behaviors and having health providers offer IOM weight gain recommendations may increase the likelihood of having a concordant gestational weight gain goal, which, in turn, is predictive of actual weight gains that fall within IOM guidelines.

A Murine Xenograft Model for a Transmissible Cancer in Tasmanian Devils

The number of Tasmanian devils in the wild is rapidly declining owing to a transmissible cancer, devil facial tumor disease (DFTD). Although progress has been made to understand the spread of this disease, crucial research on the pathogenesis of DFTD has been limited because of the threatened status of the host species. Here, the authors describe the development of a NOD/SCID (nonobese diabetic / severe combined immunodeficiency) mouse model that reproduces DFTD and provides a much-needed model to undertake studies into this intriguing transmissible cancer. Histologically, the DFTD produced in NOD/SCID mice (xenografted DFTD) was indistinguishable from the DFTD identified in Tasmanian devils. At the protein level, all xenografted DFTD tumors expressed periaxin, a marker that confirmed the diagnosis of DFTD. The karyotype of DFTD in NOD/SCID mice reproduced similar chromosomal alterations as seen in diseased devils. Furthermore, each NOD/SCID mouse inoculated with cultured DFTD tumor cells developed tumors, whereas DFTD did not develop in any of the inoculated immune-competent BALB/c mice.

Emergence of Oligoclonal Bands in Patients with Multiple Myeloma in Complete Remission After Induction Chemotherapy: Association with the Use of Novel Agents

The emergence of oligoclonal bands is associated with a favorable outcome after autologous stem cell transplantation in multiple myeloma. The aim of this study was to determine the prevalence of immunoglobulin oligoclonality in 33 patients with multiple myeloma in complete remission achieved with primary therapy with either cytotoxic agents (n = 18, 54.5%) or new induction regimens incorporating novel drugs (n = 15, 45.4%). Eleven patients (33.3%) developed oligoclonal bands. In the group treated with novel agents, this oligoclonal immune response was observed in 60% (9 of 15) of the patients versus only 11.1% (2 of 18) of those given cytotoxic therapy (P = 0.003). This is the first report showing a different frequency of oligoclonal humoral response in patients in complete remission achieved after conventional cytotoxic therapy versus induction incorporating novel agents. This difference could be due to a higher antitumor effect associated with the use of novel drugs, a stronger immune reconstitution, or both.

High-risk Hepatoblastoma: Results in a Pediatric Liver Transplantation Center

Aim of the study was assess the results of the treatment of High-Risk Hepatoblastoma (HRH) in a tertiary center where all liver surgery facilities, including pediatric transplantation (LT), are available.

Proinflammatory Gene Expression and Renal Lipogenesis Are Modulated by Dietary Protein Content in Obese Zucker Fa/fa Rats

Obesity is a risk factor for the development of chronic kidney disease (CKD) and end-stage renal disease. It is not clear whether the adoption of a high-protein diet in obese patients affects renal lipid metabolism or kidney function. Thus the aims of this study were to assess in obese Zuckerfa/fa rats the effects of different types and amounts of dietary protein on the expression of lipogenic and inflammatory genes, as well as renal lipid concentration and biochemical parameters of kidney function. Rats were fed different concentrations of soy protein or casein (20, 30, 45%) for 2 mo. Independent of the type of protein ingested, higher dietary protein intake led to higher serum triglycerides (TG) than rats fed adequate concentrations of protein. Additionally, the soy protein diet significantly increased serum TG compared with the casein diet. However, rats fed soy protein had significantly decreased serum cholesterol concentrations compared with those fed a casein diet. No significant differences in renal TG and cholesterol concentrations were observed between rats fed with either protein diets. Renal expression of sterol-regulatory element binding protein 2 (SREBP-2) and its target gene HMG-CoA reductase was significantly increased as the concentration of dietary protein increased. The highest protein diets were associated with greater expression of proinflammatory cytokines in the kidney, independent of the type of dietary protein. These results indicate that high soy or casein protein diets upregulate the expression of lipogenic and proinflammatory genes in the kidney.

Glial Restricted Precursor Cell Transplant with Cyclic Adenosine Monophosphate Improved Some Autonomic Functions but Resulted in a Reduced Graft Size After Spinal Cord Contusion Injury in Rats

Transplantation of glial restricted precursor (GRP) cells has been shown to reduce glial scarring after spinal cord injury (SCI) and, in combination with neuronal restricted precursor (NRP) cells or enhanced expression of neurotrophins, to improve recovery of function after SCI. We hypothesized that combining GRP transplants with rolipram and cAMP would improve functional recovery, similar to that seen after combining Schwann cell transplants with increasing cAMP. A short term study, (1) uninjured control, (2) SCI+vehicle, and (3) SCI+cAMP, showed that spinal cord [cAMP] was increased 14days after SCI. We used 51 male rats subjected to a thoracic SCI for a 12-week survival study: (1) SCI+vehicle, (2) SCI+GRP, (3) SCI+cAMP, (4) SCI+GRP+cAMP, and (5) uninjured endpoint age-matched control (AM). Rolipram was administered for 2weeks after SCI. At 9days after SCI, GRP transplantation and injection of dibutyryl-cAMP into the spinal cord were performed. GRP cells survived, differentiated, and formed extensive transplants that were well integrated with host tissue. Presence of GRP cells increased the amount of tissue in the lesion; however, cAMP reduced the graft size. White matter sparing at the lesion epicenter was not affected. Serotonergic input to the lumbosacral spinal cord was not affected by treatment, but the amount of serotonin immediately caudal to the lesion was reduced in the cAMP groups. Using telemetric monitoring of corpus spongiosum penis pressure we show that the cAMP groups regained the same number of micturitions per 24hours when compared to the AM group, however, the frequency of peak pressures was increased in these groups compared to the AM group. In contrast, the GRP groups had similar frequency of peak pressures compared to baseline and the AM group. Animals that received GRP cells regained the same number of erectile events per 24hours compared to baseline and the AM group. Since cAMP reduced the GRP transplant graft, and some modest positive effects were seen that could be attributable to both GRP or cAMP, future research is required to determine how cAMP affects survival, proliferation, and/or function of progenitor cells and how this is related to function. cAMP may not always be a desirable addition to a progenitor cell transplantation strategy after SCI.

Microscopic Magnetic Resonance Imaging of the Thoracic Venous System in Rats with Congenital Diaphragmatic Hernia

Infants and rats with congenital diaphragmatic hernia (CDH) have malformations of the heart and the great arteries caused by neural crest (NC) dysregulation during embryogenesis. Abnormally narrow jugular veins have been found in babies during cannulation for ECMO. However, the venous system has not been examined in depth so far. We hypothesized that abnormal patterning and/or size of the thoracic veins could occur in rats with CDH. This hypothesis was tested by microscopic magnetic resonance imaging (MMRI), a high-resolution tool able to detect subtle changes of vessels in small animals.

Abnormal Development of the Enteric Nervous System in Rat Embryos and Fetuses with Congenital Diaphragmatic Hernia

Esophageal dilatation, gastroesophageal reflux, and intestinal obstruction have been demonstrated in CDH survivors. Abnormal esophageal and intestinal innervations were recently found in rats and babies with this disease. Our aim was to further characterize these malformations in embryos and fetal rats exposed to nitrofen.

Technical Aspects of Spinal Cord Injections for Cell Transplantation. Clinical and Translational Considerations

Spinal cord injections may be used to transplant cellular suspensions for the experimental treatment of spinal cord injury. These injections cause some additional injury due to needle penetration, spinal cord motion during injection, creation of intraparenchymal pressure gradients and hydrodynamic dissection, instillation of a deforming cell mass and possible cord ischemia. It is important to understand these variables to maximize the safety of injections and avoid injury to spared structures. Surprisingly little knowledge exists regarding these variables. Further complicating spinal cord injections is the fact that intraparenchymal events are not evident during injections. As cell injections for spinal cord injury enter extensive clinical testing it is important to both optimize the procedures, and reduce the probability of technical failures. In this review current knowledge and key areas for knowledge advance are identified. These include a need for a more thorough understanding of how the spinal cord is affected by needle entry and dwell, needle-cord relative motion, instillation of highly concentrated cellular volumes, compliance of intact and damaged spinal cord tissue, radial tensile stresses and hydrodynamic forces created by injection, and the rates of pressure gradient dissipation in damaged and intact tissue. We propose that if the variables associated with injury can be identified, injection injury may be reduced and we illustrate the use of ultrasound to monitor injection in a spinal cord model. We also suggest that injectate backout or extrusion be reinterpreted as a clear indicator of excessive intraparenchymal pressure. The strengths and weaknesses of alternatives to direct intraparenchymal injection are also discussed.

Surgical Treatment of Chronic Inflammatory Bowel Disease in Children

Surgery for chronic inflammatory bowel disease (IBD) is increasingly often necessary in children. This study aimed at assessing the results of these operations in order to facilitate adequate preoperative counseling. We reviewed patients treated from 1992 to 2009. The operations, complications and functional outcome were recorded. For those with preserved rectal defecation, continence (Koivusalo score) and quality of life (standardized questionnaire) were assessed in the long term. Eighty five of 192 patients had Crohn disease (CD), 107 of 192 had ulcerative colitis (UC), and 3 of 192 had indeterminate colitis (IC). 12 of 85 CD patients (15%) aged 14 (12-19) years required 13 resections, 1 stricturoplasty, 1 transplantation and 6 other operations including 3 permanent enterostomies for anorectal involvement. Removal of the involved bowel led to significant improvement of nutritional status, growth and quality of life. The transplanted patient had a striking recovery but eventually died 1 year later of unrelated complications. 29 of 107 UC patients (26%) aged 11 (2-15) years required 87 operations. Nine had emergency colectomy for toxic megacolon (3, one death) or severe hemorrhage (6). 28 had restorative proctocolectomy and ileoanostomy (RPCIA) without (16) or with (12) J-pouch under protective ileostomy. Complications were frequent (40%). Permanent ileostomy was required in five children (17%). Twelve months postoperatively, RPCIA patients had 6.5 (2-13) stools/day; all were continent during daytime, and 25% have nocturnal leaks. Mean Koivusalo score (5-12) was 8.8 ± 2. Quality of life was good in all. All attended normal school and 7 the university, 4 work and 60% of those older than 18 years have sexual partners. Three of 107 children treated as UC with RPCIA had ultimately IC (3%) and were permanently diverted. The nature of IBD involves frustrating surgery. However, it may change life for CD patients and provide a reasonably good quality of life for UC after the first year. Pediatric surgeons should be able to provide adequate preoperative counseling to patients and families.

Oleoylethanolamide: Effects on Hypothalamic Transmitters and Gut Peptides Regulating Food Intake

Recently, it has been described the role of fatty acid ethanolamides in the control of feeding behavior. Oleoylethanolamide (OEA) is a member of this family of lipid mediators regulating feeding. OEA acts suppressing feeding behavior through, at least partially, a peripheral mechanism. However, the interaction between this acylethanolamide and other orexigenic or anorexigenic mediators is mostly not well characterized. The aim of this study was to evaluate whether anorectic actions of OEA were mediated through the modulation of central and peripheral signals involved in the regulation of feeding. Experiments were performed in male Wistar rats under free-feeding and fasting conditions. We measured hypothalamic neuropeptides and monoamines by in situ hybridization and HPLC respectively as well as plasmatic levels of relevant endocrine signals. OEA administration induced changes in hypothalamic monoaminergic activity and in the anorexigenic neuropeptide CART expressed in the paraventricular nucleus (PVN) but lacked effect on neuropeptides expression in nucleus arcuatus. In addition, OEA induced peripheral changes in gut peptides, with marked effects on PYY and Ghrelin. These results further suggest that anorexigenic properties of OEA are mediated by peripheral signals and by central alterations in neuropeptides expressed by feeding-involved hypothalamic structures receiving input from peripheral sensory systems, such as the PVN.

Ischemic Preconditioning of the Graft for Intestinal Transplantation in Rats

To test the hypothesis that two modalities of IPC should decrease acute rejection and BT after SBTx in rats. Orthotopic allogenic SBTx was performed from Wistar to BN. IPC was performed by 2 ' and 5 ' superior mesenteric artery clamping, following 2-min and 5-min reperfusion before graft cooling and retrieving. Donor-recipient sets were randomly allocated to five groups: IPC2m4d, IPC2m7d, IPC5min7d, and the control groups for the two end points; ctrl4d and ctrl7d. IRI, rejection, and BT were assessed after four or seven days depending on the groups. Measured variables included: histology, leukocyte activation by tissue MPO determination, and proinflammatory cytokines (IL-b and TNF-α) to assess inflammatory response. Leukocyte activation was significantly reduced in IPC2m7d in comparison with Ctrl and IPC5min7d. Rejection tended to be lower in IPC2min7d. Cytokine levels were contradictory and not consistent with histology. Finally, BT was less frequent in IPC2min4d group but this benefit was missed in animals with rejection (7d). Inflammatory response (MPO) was reduced and rejection tended to be lower after in IPC2m7d. Bacterial translocation was reduced in IPC2min4d but the benefit was missed at day 7.

Multiple Myeloma in Serologic Complete Remission After Autologous Stem Cell Transplantation: Impact of Bone Marrow Plasma Cell Assessment by Conventional Morphology on Disease Progression

The current definition of complete remission (CR) in multiple myeloma (MM) requires a negative serum and urine immunofixation (IFE) and <5% bone marrow plasma cells (BMPCs). The aim of this study was to determine the value of BMPCs count by standard microscopic evaluation in patients with MM in serologic CR after autologous stem cell transplantation (ASCT). Thirty-five patients with a median follow-up after ASCT of 7.3 years were studied. The percentage of BMPCs was an independent predictor of progression in multivariate model (hazard ratio 2.02, P = .009). Patients with >1.5% BMPCs (median: 0.8%) after ASCT had an increased risk of progression (P = .016) and a trend toward a shorter survival (P = .195). In conclusion, conventional morphology of bone marrow is a useful and rapid tool as a first step to assess the residual tumor mass in patients with MM in CR after ASCT, and it constitutes a strong predictor for disease progression.

The Dermatan Sulfate-dependent Anticoagulant Pathway is Mostly Preserved in Aneurysm and in Severe Atherosclerotic Lesions While the Heparan Sulfate Pathway is Disrupted

The pathogenesis of abdominal aortic aneurysm is associated with changes of several components of arterial wall. Vascular glycosaminoglycans contribute to the non-thrombogenic activity of blood vessels. We investigated whether modifications of glycosaminoglycans in human abdominal aortic aneurysm affect their anticoagulant properties.

Lack of Access Due to Costs Remains a Problem for Some in Massachusetts Despite the State's Health Reforms

Did the Massachusetts health reforms, which provided near-universal insurance coverage, also address problems of unmet need resulting from the cost of care and of inadequate preventive care for diverse patient groups? We found that nearly a quarter of adults who were in fair or poor health reported being unable to see a doctor because of cost during the implementation of the reforms. We also found that state residents earning less than $25,000 per year were much less likely than higher earners to receive screening for cardiovascular disease and cancer. The state needs to implement new strategies to build on the promise of universal coverage and address specific needs of vulnerable populations, such as limiting out-of-pocket spending for this group. Also, more data are needed on the social determinants of health to identify specific barriers related to cost and access for vulnerable groups that general insurance reforms may not address.

Combining Clinical, Pathology, and Gene Expression Data to Predict Recurrence of Hepatocellular Carcinoma

In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues.

MicroRNA-based Classification of Hepatocellular Carcinoma and Oncogenic Role of MiR-517a

Hepatocellular carcinoma (HCC) is a heterogeneous tumor that develops via activation of multiple pathways and molecular alterations. It has been a challenge to identify molecular classes of HCC and design treatment strategies for each specific subtype. MicroRNAs (miRNAs) are involved in HCC pathogenesis, and their expression profiles have been used to classify cancers. We analyzed miRNA expression in human HCC samples to identify molecular subclasses and oncogenic miRNAs.

Late Surgery for Spinal Deformities in Children Previously Treated for Neural Tumors

Surgery for neural tumors occasionally involves opening of the neural canal and/or costovertebral resection that may be followed by radiotherapy. Spinal deformities (SD) may occur in these cases. This study investigated the incidence, surgical indications and results of repair of late SD in a large series of patients with neural tumors.

Functionalized Dibenzoborepins As Components of Small Molecule and Polymeric π-conjugated Electronic Materials

We present the synthesis and characterization of dibenzo[b,f]borepins (DBBs) functionalized at the para and meta position with respect to the boron center in order to understand how regiochemical issues influence photophysical and electrochemical properties. An expanded synthetic repertoire is presented, using palladium catalysis (to perform Stille, Suzuki, Buchwald-Hartwig, and Sonogashira cross-coupling reactions) and lithium-halogen exchange to synthesize a series of extended π-conjugated DBBs. These chemistries are enabled by the use of a sterically bulky Mes* (2,4,6-tri-tert-butylphenyl) group on boron and the inclusion of reactive bromide handles on the DBB core. Photophysical, electrochemical, and computational analyses of these compounds indicate that relative to the protio-DBB the installation of groups at the meta positions decreases the optical band gap while para substitution raises the electron affinity of the system. Thus, both the HOMO-LUMO gap and specific frontier molecular orbital levels can be tuned by the installation of different conjugated substituents.

Tumor-specific Diagnostic Marker for Transmissible Facial Tumors of Tasmanian Devils: Immunohistochemistry Studies

Devil facial tumor disease (DFTD) is a transmissible neoplasm that is threatening the survival of the Tasmanian devil. Genetic analyses have indicated that the disease is a peripheral nerve sheath neoplasm of Schwann cell origin. DFTD cells express genes characteristic of myelinating Schwann cells, and periaxin, a Schwann cell protein, has been proposed as a marker for the disease. Diagnosis of DFTD is currently based on histopathology, cytogenetics, and clinical appearance of the disease in affected animals. As devils are susceptible to a variety of neoplastic processes, a specific diagnostic test is required to differentiate DFTD from cancers of similar morphological appearance. This study presents a thorough examination of the expression of a set of Schwann cell and other neural crest markers in DFTD tumors and normal devil tissues. Samples from 20 primary DFTD tumors and 10 DFTD metastases were evaluated by immunohistochemistry for the expression of periaxin, S100 protein, peripheral myelin protein 22, nerve growth factor receptor, nestin, neuron specific enolase, chromogranin A, and myelin basic protein. Of these, periaxin was confirmed as the most sensitive and specific marker, labeling the majority of DFTD cells in 100% of primary DFTD tumors and DFTD metastases. In normal tissues, periaxin showed specificity for Schwann cells in peripheral nerve bundles. This marker was then evaluated in cultured devil Schwann cells, DFTD cell lines, and xenografted DFTD tumors. Periaxin expression was maintained in all these models, validating its utility as a diagnostic marker for the disease.

Promoter Characterization and Role of CRE in the Basal Transcription of the Rat SNAT2 Gene

Small neutral amino acid transporter 2 (SNAT2) is the most abundant and ubiquitous transporter for zwitterionic short-chain amino acids. The activity of this amino acid transporter is stimulated in vivo or in vitro by glucagon or cAMP analogs. However, it is not known whether the increase in activity at the protein level is due to an increase in SNAT2 gene transcription. Thus, the aim of the present work was to study whether cAMP was able to stimulate SNAT2 gene expression and to localize and characterize the presence of cAMP response elements (CRE) in the promoter that controls the expression of the rat SNAT2 gene. We found that consumption of a high-protein diet that increased serum glucagon concentration or the administration of glucagon or incubation of hepatocytes with forskolin increased the SNAT2 mRNA level. We then isolated the 5' regulatory region of the SNAT2 gene and determined that the transcriptional start site was located 970 bp upstream of the translation start codon. We identified two potential CRE sites located at -354 and -48 bp. Our results, using deletion analysis of the 5' regulatory region of the SNAT2 gene, revealed that the CRE site located at -48 bp was fully responsible for SNAT2 regulation by cAMP. This evidence was strongly supported by mutation of the CRE site and EMSA and ChIP analysis. Alignment of rat, mouse, and human sequences revealed that this CRE site is highly conserved among species, indicating its essential role in the regulation of SNAT2 gene expression.

Pten Knockdown in Vivo Increases Excitatory Drive Onto Dentate Granule Cells

Some cases of autism spectrum disorder have mutations in the lipid phosphatase, phosphatase and tensin homolog on chromosome 10 (Pten). Tissue specific deletion of Pten in the hippocampus and cortex of mice causes anatomical and behavioral abnormalities similar to human autism. However, the impact of reductions in Pten on synaptic and circuit function remains unexplored. We used in vivo stereotaxic injections of lentivirus expressing a short hairpin RNA to knock down Pten in mouse neonatal and young adult dentate granule cells. We then assessed the morphology and synaptic physiology between 2 weeks and 4 months later. Confocal imaging of the hippocampus revealed a marked increase in granule cell size and an increase in dendritic spine density. The onset of morphological changes occurred earlier in neonatal mice than in young adults. We used whole-cell recordings from granule cells in acute slices to assess synaptic function after Pten knockdown. Consistent with the increase in dendritic spines, the frequency of excitatory miniature and spontaneous postsynaptic currents increased. However, there was little or no effect on IPSCs. Thus, Pten knockdown results in an imbalance between excitatory and inhibitory synaptic activity. Because reductions in Pten affected mature granule cells as well as developing granule cells, we suggest that the disruption of circuit function by Pten hypofunction may be ongoing well beyond early development.

Impact on Response and Survival of DNA Repair Single Nucleotide Polymorphisms in Relapsed or Refractory Multiple Myeloma Patients Treated with Thalidomide

Single nucleotide polymorphisms (SNPs) in 12 genes involving multidrug resistance, drug metabolic pathways, DNA repair systems and cytokines were examined in 28 patients with relapsed/refractory multiple myeloma (MM) treated with single agent thalidomide and the results were correlated with response, toxicity and overall survival (OS). The response rate was higher in patients with SNPs in ERCC1 (rs735482) (p=0.006), ERCC5 (rs17655) (p=0.04) or XRCC5 (rs1051685) (p=0.013). Longer OS was associated with the SNP in ERCC1 (rs735482) (p=0.005) and XRCC5 (rs1051685) (p=0.02). Finally, polymorphism in GSTT1 (rs4630) was associated with a lower frequency of thalidomide-induced peripheral neuropathy (p=0.04).

Utility of the Discriminant Analysis to Categorize Untrained Spanish Pure Bred Horses on the Basis of Biochemical and Muscle Variables Before and After a Standardized Exercise Test

We hypothesized that the information obtained from a discriminant analysis could be used to objectively discriminate horses untrained from early ages, in agreement with certain physiological characteristics. In the biopsies of 24 Spanish Pure Bred horses (1.5-3 years old) before and after a standardized exercise test (SET; 4-7 m/s with a change of velocity of 1m/s every 2 min) muscle enzymes, substrate and metabolites were determined. Also, diverse plasma and blood parameters were considered. Three pre-exercise groups (A1: six horses; A2: seven horses and A3: eleven horses) and two post-exercise groups (B1: sixteen horses; B2: eight horses) were defined from a correspondence analysis. Forward stepwise discriminant analysis selected 11 variables which differentiated the groups between each other both pre- and post-exercise. The results of the present study suggested the utility of a discriminant analysis to categorize horses in agreement with certain physiological variables. It could be used for establishing different types of training in each group by expert trainers.

Parafollicular C-cells of the Thyroid Are Decreased in Patients with Congenital Diaphragmatic Hernia

Parathyroid and thymic anomalies related to embryonic neural crest dysfunction have been demonstrated in rats with congenital diaphragmatic hernia (CDH). These rats, like infants with CDH, have conotruncal, facial, and other neurocristal defects. The present study examines whether parafollicular C-cells (CC) of the thyroid, whose embryogenesis is related to that of the parathyroids and thymus, might also be abnormal in babies with CDH.

Maldevelopment of the Cerebral Cortex in the Surgically Induced Model of Myelomeningocele: Implications for Fetal Neurosurgery

The purpose of this study is to describe the malformations of cortical development detected in a model of cerebrospinal fluid (CSF) leakage and the influence of surgical closure technique on developmental outcome.

MDM2 Antagonists Boost Antitumor Effect of Androgen Withdrawal: Implications for Therapy of Prostate Cancer

Hormone therapy is the standard of care for newly diagnosed or recurrent prostate cancers. It uses anti-androgen agents, castration, or both to eliminate cancer promoting effect of testicular androgen. The p53 tumor suppressor controls a major pathway that can block cell proliferation or induce apoptosis in response to diverse forms of oncogenic stress. Activation of the p53 pathway in cancer cells expressing wild-type p53 has been proposed as a novel therapeutic strategy and recently developed MDM2 antagonists, the nutlins, have validated this in preclinical models of cancer. The crosstalk between p53 and androgen receptor (AR) signaling suggest that p53 activation could augment antitumor outcome of androgen ablation in prostate cancer. Here, we test this hypothesis in vitro and in vivo using the MDM2 antagonist, nutlin-3 and the p53 wild-type prostate cancer cell line, LNCaP.

Preclinical Evaluation of the Novel Multi-targeted Agent R1530

This study describes the antiproliferative activity of the multikinase inhibitor R1530 in vitro and its antitumor and anti-angiogenic activity, pharmacokinetics, and tolerability in vivo.

Fabrication of 2D Protein Microstructures and 3D Polymer-protein Hybrid Microstructures by Two-photon Polymerization

Two-photon polymerization (TPP) offers the possibility of creating artificial cell scaffolds composed of micro- and nanostructures with spatial resolutions of less than 1 µm. For use in tissue engineering, the identification of a TPP-processable polymer that provides biocompatibility, biofunctionality and appropriate mechanical properties is a difficult task. ECM proteins such as collagen or fibronectin, which could mimic native tissues best, often lack the mechanical stability. Hence, by generating polymer-protein hybrid structures, the beneficial properties of proteins can be combined with the advantageous characteristics of polymers, such as sufficient mechanical stability. This study describes three steps toward facilitated application of TPP for biomaterial generation. (1) The efficiency of a low-cost ps-laser source is compared to a fs-laser source by testing several materials. A novel photoinitiator for polymerization with a ps-laser source is synthesized and proved to enable increased fabrication throughput. (2) The fabrication of 3D-microstructures with both systems and the fabrication of polymer-protein hybrid structures are demonstrated. (3) The tissue engineering capabilities of TPP are demonstrated by creating cross-linked gelatin microstructures, which clearly forced porcine chondrocytes to adapt their cell morphology.

Conjugated "B-entacenes": Polycyclic Aromatics Containing Two Borepin Rings

The synthesis and characterization of functionalized bora-acenes (B-entacenes) where Stille and Sonogashira cross-couplings were used to attach a series of electron-donating and -withdrawing substituents is reported. Photophysical, electrochemical, and computational analyses revealed that the LUMO level can be tuned by changing the para-conjugated substituent. Furthermore, the dimethylamino-functionalized molecule exhibited intense solvatochromism due to the intramolecular charge-transfer interaction.

The Effect of Montelukast in a Model of Gouty Arthritis Induced by Sodium Monourate Crystals

Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p < 0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

The Effects of Castration and Hormone Replacement on the Cross-sectional Area of Pubococcygeus Muscle Fibers in the Female Rat

In this study, we analyzed the effect of ovariectomy and gonadal hormone replacement on the cross-sectional area of pubococcygeus (Pcm) fibers. It was found that in comparison to intact animals, ovariectomized animals [for 2 or 6 weeks] had an increased cross-sectional area average in Pcm fibers. Ovariectomy also reduced the percentage of fibers with smaller cross-sectional area. In ovariectomized animals after 4 weeks of hormone replacement with an empty Silastic capsule or filled with testosterone propionate or dihydrotestosterone, significantly increased the cross-sectional area average and the percentage of fibers with larger size. However, 17β-estradiol but not estradiol benzoate treatment reduced the cross-sectional area average and increased the percentage of Pcm fibers with smaller size. Progesterone did not have an effect on the cross-sectional area of this muscle. We conclude that Pcm fibers of female rats are sensitive to gonadal hormones, and contrary to male castration, ovariectomy promotes an increase in their cross-sectional area. Also, we discuss according to other studies that an external mechanism which lies within the neuromuscular periphery could also participate in the modulatory hormonal effect on mass or muscle fiber size. Furthermore, in this process, estradiol is likely to regulate the fiber cross-sectional area growing produced by androgens.

Influence of Annulene Ratio on the Electrochemical and Spectroscopic Properties of Methano[10]annulene-thiophene Random Copolymers

We describe a series of copolymerization studies whereby the nonbenzenoid aromatic methano[10]annulene is incorporated into three different types of random copolymers, two based on polythiophenes (from bithiophene and terthiophene monomers) and one based on poly(ethylene dioxythiophene). Copolymers where the annulene component was in the majority had optical and electrochemical behaviors reminiscent of the annulene homopolymer. In contrast, we found that the annulene influenced polymer electronics at very low feed ratios where the commercial comonomer was in the majority. Copolymerizations are useful approaches to dilute the complex annulene monomers into functional polymers without losing the optoelectronic properties of the annulene homopolymers. These electrochemical results provide important design rules that can be employed for the chemical synthesis of related random copolymers.

Role for Insulin Signaling in Catecholaminergic Neurons in Control of Energy Homeostasis

Dopaminergic midbrain neurons integrate signals on food palatability and food-associated reward into the complex control of energy homeostasis. To define the role of insulin receptor (IR) signaling in this circuitry, we inactivated IR signaling in tyrosine hydroxylase (Th)-expressing cells of mice (IR(ΔTh)). IR inactivation in Th-expressing cells of mice resulted in increased body weight, increased fat mass, and hyperphagia. While insulin acutely stimulated firing frequency in 50% of dopaminergic VTA/SN neurons, this response was abolished in IR(ΔTh) mice. Moreover, these mice exhibited an altered response to cocaine under food-restricted conditions. Taken together, these data provide in vivo evidence for a critical role of insulin signaling in catecholaminergic neurons to control food intake and energy homeostasis.

Disentangling the Exposure Experience: the Roles of Community Context and Report-back of Environmental Exposure Data

This article examines participants' responses to receiving their results in a study of household exposure to endocrine disrupting compounds and other pollutants. The authors study how the "exposure experience"-the embodied, personal experience and understanding of chronic exposure to environmental pollutants-is shaped by community context and the report-back process itself. In addition, the authors investigate an activist, collective form of exposure experience. The authors analyze themes of expectations and learning, trust, and action. The findings reveal that while participants interpret scientific results to affirm lay knowledge of urban industrial toxics, they also absorb new information regarding other pollutant sources. By linking the public understanding of science literature to the illness and exposure experience concepts, this study unravels the complex relationship between lay experience and lay understanding of science. It also shows that to support policy development and/or social change, community-based participatory research efforts must attend to participants' understanding of science.

Fiber Concentrate from Orange (Citrus Sinensis L.) Bagase: Characterization and Application As Bakery Product Ingredient

Orange is a tropical fruit used in the juice industry, yielding important quantities of by products. The objective of this work was to obtain a dietary fiber-rich orange bagasse product (DFROBP), evaluate its chemical composition and its use in the preparation of a bakery product (muffin). Muffins containing two different levels of DFROBP were studied regarding chemical composition, in vitro starch digestibility, predicted glyceamic index and acceptability in a sensory test. DFROBP showed low fat and high dietary fiber contents. The soluble and insoluble dietary fiber fractions were balanced, which is of importance for the health beneficial effects of fiber sources. DFROBP-containing muffins showed the same rapidly digestible starch content as the reference muffin, whilst the slowly digestible starch level increased with the addition of DFROBP. However, the resistant starch content decreased when DFROBP increased in the muffin. The addition of DFROBP to muffin decreased the predicted glyceamic index, but no difference was found between the muffins prepared with the two DFROBP levels. The sensory score did not show difference between control muffin and that added with 10% of DFROBP. The addition of DFROBP to bakery products can be an alternative for people requiring low glyceamic response.

Deficient CX3CR1 Signaling Promotes Recovery After Mouse Spinal Cord Injury by Limiting the Recruitment and Activation of Ly6Clo/iNOS+ Macrophages

Macrophages exert divergent effects in the injured CNS, causing either neurotoxicity or regeneration. The mechanisms regulating these divergent functions are not understood but can be attributed to the recruitment of distinct macrophage subsets and the activation of specific intracellular signaling pathways. Here, we show that impaired signaling via the chemokine receptor CX3CR1 promotes recovery after traumatic spinal cord injury (SCI) in mice. Deficient CX3CR1 signaling in intraspinal microglia and monocyte-derived macrophages (MDMs) attenuates their ability to synthesize and release inflammatory cytokines and oxidative metabolites. Also, impaired CX3CR1 signaling abrogates the recruitment or maturation of MDMs with presumed neurotoxic effects after SCI. Indeed, in wild-type mice, Ly6C(lo)/iNOS(+)/MHCII(+)/CD11c(-) MDMs dominate the lesion site, whereas CCR2(+)/Ly6C(hi)/MHCII(-)/CD11c(+) monocytes predominate in the injured spinal cord of CX3CR1-deficient mice. Replacement of wild-type MDMs with those unable to signal via CX3CR1 resulted in anatomical and functional improvements after SCI. Thus, blockade of CX3CR1 signaling represents a selective anti-inflammatory therapy that is able to promote neuroprotection, in part by reducing inflammatory signaling in microglia and MDMs and recruitment of a novel monocyte subset.

The Innovative Socio-economic Interventions Against Tuberculosis (ISIAT) Project: an Operational Assessment

Tuberculosis (TB) affected households in impoverished shantytowns, Lima, Peru.

Suicide Attempts and Risk of Suicide in Patients with Fibromyalgia: a Survey in Spanish Patients

Depression, chronic pain and sleep disturbances frequently co-exist in FM and have shown to be independently related with suicidal behaviours. The present survey was performed to evaluate the prevalence of previous suicide attempts in patients with FM and its potential relationship with sociodemographic and clinical characteristics of the disease.

(S)-(+)-N-Benzyl-idene-1-(1-naphth-yl)ethyl-amine

In the title chiral aldimine, C(19)H(17)N, the azomethine group is not fully conjugated with the phenyl substituent: the dihedral angle between phenyl and C(*)-N=C mean planes is ϕ(3) = 23.0 (2)°. Compared with the earlier DFT-B3LYP/6-31 G(d) computations from the literature, the C=N-C(*)-C(naph-thyl) torsion angle, found at ϕ(2) = -118.0 (2)° in the X-ray structure, does not match the angle calculated for the potential minimum energy at ϕ(2) = 0°. However, this angle is close to the second potential energy minimum at ϕ(2) = -120° which is ca. 8.5 kJ mol(-1) above the global energy minimum. Thus, the reported X-ray structure corresponds to the second most likely (according to DFT) conformer, allowing the existence of other polymorphs to be anti-cipated.

Biochemical Characterization of Nuclear Receptors for Vitamin D3 and Glucocorticoids in Prostate Stroma Cell Microenvironment

The disruption of stromal cell signals in prostate tissue microenvironment influences the development of prostate cancer to androgen independence. 1α,25-Dihydroxyvitamin D(3) (1,25D(3)) and glucocorticoids, either alone or in combination, have been investigated as alternatives for the treatment of advanced prostate cancers that fails androgen therapies. The effects of glucocorticoids are mediated by the intracellular glucocorticoid receptor (GR). Similarly, the effect of 1,25D(3) is mediated by the 1,25D(3) nuclear receptor (VDR). In this study, fibroblasts from benign- (BAS) and carcinoma-associated stroma (CAS) were isolated from human prostates to characterize VDR and GR function as transcription factors in prostate stroma. The VDR-mediated transcriptional activity assessed using the CYP24-luciferase reporter was limited to 3-fold induction by 1,25D(3) in 9 out of 13 CAS (70%), as compared to >10-fold induction in the BAS clinical sample pair. Expression of His-tagged VDR (Ad-his-VDR) failed to recover the low transcriptional activity of the luciferase reporter in 7 out of 9 CAS. Interestingly, expression of Ad-his-VDR successfully recovered receptor-mediated induction in 2 out of the 9 CAS analyzed, suggesting that changes in the receptor protein itself was responsible for decreased response and resistance to 1,25D(3) action. Conversely, VDR-mediated transcriptional activity was more efficient in 4 out of 13 CAS (30%), as compared to the BAS sample pair. Consistent with the reduced response to 1,25D(3) observed in CAS, chromatin immunoprecipitation (ChIP) assays indicated decreased recruitment of coactivators SRC-1/CBP, without major changes in the recruitment of VDR to the CYP24 promoter. In addition, we observed that GR-mediated transcriptional activity was also altered in CAS, as compared to BAS. Disruption of coactivators SRC-1/CBP recruitment may promote hormone resistance in CaP, and highlights the relevance of molecular diagnosis and drug design in tumor cell microenvironment.

The Copper Regulon of the Human Fungal Pathogen Cryptococcus Neoformans H99

Cryptococcus neoformans is a human fungal pathogen that is the causative agent of cryptococcosis and fatal meningitis in immuno-compromised hosts. Recent studies suggest that copper (Cu) acquisition plays an important role in C. neoformans virulence, as mutants that lack Cuf1, which activates the Ctr4 high affinity Cu importer, are hypo-virulent in mouse models. To understand the constellation of Cu-responsive genes in C. neoformans and how their expression might contribute to virulence, we determined the transcript profile of C. neoformans in response to elevated Cu or Cu deficiency. We identified two metallothionein genes (CMT1 and CMT2), encoding cysteine-rich Cu binding and detoxifying proteins, whose expression is dramatically elevated in response to excess Cu. We identified a new C. neoformans Cu transporter, CnCtr1, that is induced by Cu deficiency and is distinct from CnCtr4 and which shows significant phylogenetic relationship to Ctr1 from other fungi. Surprisingly, in contrast to other fungi, we found that induction of both CnCTR1 and CnCTR4 expression under Cu limitation, and CMT1 and CMT2 in response to Cu excess, are dependent on the CnCuf1 Cu metalloregulatory transcription factor. These studies set the stage for the evaluation of the specific Cuf1 target genes required for virulence in C. neoformans.

Socket Preservation and Sinus Augmentation Using a Medical Grade Calcium Sulfate Hemihydrate and Mineralized Irradiated Cancellous Bone Allograft Composite

Abstract Regeneration and preservation of bone after the extraction of a tooth is necessary for the placement of a dental implant. The goal is to regenerate alveolar bone with minimal postoperative pain. Medical grade calcium sulfate hemihydrate (MGCSH) can be used alone or in combination with other bone grafts; it improves graft handling characteristics and particle containment of particle-based bone grafts. In this case series a 1:1 ratio mix of MGCSH and mineralized irradiated cancellous bone allograft (MICBA) was mixed with saline and grafted into an extraction socket in an effort to maintain alveolar height and width for future implant placement. MGCSH can be used in combination with other bone grafts and can improve handling characteristics and graft particle containment of particle-based bone grafts. Based on the following cases, it was found that a MGCSH:MICBA graft can potentially be an effective bone graft composite. It has the ability to act as a space maintainer and as an osteoconductive trellis for bone cells, promoting bone regeneration in the extraction socket. MGCSH, a cost-effective option, successfully improved MICBA handling characteristics, prevented soft tissue ingrowth and assisted in the regeneration of bone.

Starch Determination, Amylose Content and Susceptibility to in Vitro Amylolysis in Flours from the Roots of 25 Cassava Varieties

BACKGROUND: Cassava cultivars are classified following different criteria, such as cyanogenic glucoside content or starch content. Here, flours from the roots of 25 cassava varieties cultivated simultaneously in a single plantation, were characterized in terms of starch content (SC), amylose content (AC), α-amylolysis index (AI) and gel formation ability. Resistant starch content (RS) was measured in 10 of the samples. RESULTS: Cassava flours exhibited high SC, low AC and low AI values, with differences among varieties. Cluster analysis based on these parameters divided the cultivars in four groups differing mainly in SC and AC. AI and AC were inversely correlated (r = - 0.59, P < 0.05) in 18 of the cultivars, suggesting AC as an important factor governing the susceptibility to enzymatic hydrolysis of starch in raw cassava. Differences in susceptibility to amylolysis, assessed by RS, were also recorded in the sample subset analyzed. Most flours yielded pastes or gels upon heating and cooling. Gels differed in their subjective grade of firmness, but none exhibited syneresis, confirming the low retrogradation proclivity of cassava starch. CONCLUSION: Some differences were found among cassava samples, which may be ascribed to inter-cultivar variation. This information may have application in further agronomic studies or for developing industrial uses for this crop. Copyright © 2011 Society of Chemical Industry.

1-Million Droplet Array with Wide-field Fluorescence Imaging for Digital PCR

Digital droplet reactors are useful as chemical and biological containers to discretize reagents into picolitre or nanolitre volumes for analysis of single cells, organisms, or molecules. However, most DNA based assays require processing of samples on the order of tens of microlitres and contain as few as one to as many as millions of fragments to be detected. Presented in this work is a droplet microfluidic platform and fluorescence imaging setup designed to better meet the needs of the high-throughput and high-dynamic-range by integrating multiple high-throughput droplet processing schemes on the chip. The design is capable of generating over 1-million, monodisperse, 50 picolitre droplets in 2-7 minutes that then self-assemble into high density 3-dimensional sphere packing configurations in a large viewing chamber for visualization and analysis. This device then undergoes on-chip polymerase chain reaction (PCR) amplification and fluorescence detection to digitally quantify the sample's nucleic acid contents. Wide-field fluorescence images are captured using a low cost 21-megapixel digital camera and macro-lens with an 8-12 cm(2) field-of-view at 1× to 0.85× magnification, respectively. We demonstrate both end-point and real-time imaging ability to perform on-chip quantitative digital PCR analysis of the entire droplet array. Compared to previous work, this highly integrated design yields a 100-fold increase in the number of on-chip digitized reactors with simultaneous fluorescence imaging for digital PCR based assays.

Postpartum Screening for Diabetes Among Women with a History of Gestational Diabetes Mellitus

To make recommendations for future clinical, public health, and research practices for women with abnormal glucose tolerance during pregnancy, we reviewed the latest evidence regarding rates of postpartum diabetes screening and types of screening tests.

Using the Community Readiness Model to Select Communities for a Community-wide Obesity Prevention Intervention

To build on a growing interest in community-based obesity prevention programs, methods are needed for matching intervention strategies to local needs and assets. We used the Community Readiness Model (CRM), a structured interview guide and scoring system, to assess community readiness to act on childhood obesity prevention, furthering a replication study of a successful intervention. Using the CRM protocol, we conducted interviews with 4 stakeholders in each of 10 communities of similar size, socioeconomic status, and perceived readiness to implement a community-wide obesity prevention intervention. Communities were in California, Florida, Illinois, Massachusetts, New York, North Carolina, Pennsylvania, and Tennessee. The 4 stakeholders were the mayor or city manager, the school superintendent, the school food service director, and a community coalition representative. Interviews were recorded and professionally transcribed. Pairs of trained reviewers scored the transcriptions according to CRM protocol. The CRM assesses 9 stages of readiness for 6 dimensions: existing community efforts to prevent childhood obesity, community knowledge about the efforts, leadership, community climate, knowledge about the issue, and resources. We calculated an overall readiness score for each community from the dimension scores. Overall readiness scores ranged from 2.97 to 5.36 on the 9-point scale. The mean readiness score, 4.28 (SD, 0.68), corresponds with a "preplanning" level of readiness. Of the 6 dimensions, community climate varied the least (mean score, 3.11; SD, 0.64); leadership varied the most (mean score, 4.79; SD, 1.13). The CRM quantified a subjective concept, allowing for comparison among 10 communities. Dimension scores and qualitative data from interviews helped in the selection of 6 communities for a replication study.

Risk for Residual Adenocarcinoma in Situ or Cervical Adenocarcinoma in Women Undergoing Loop Electrosurgical Excision Procedure/conization for Adenocarcinoma in Situ

To evaluate the risk for residual adenocarcinoma in situ (AIS) or cervical adenocarcinoma in women undergoing loop electrosurgical excision procedure (LEEP)/conization as the initial management for AIS.

Dietary Type and Amount of Fat Modulate Lipid Metabolism Gene Expression in Liver and in Adipose Tissue in High-fat Diet-fed Rats

Dietary fat plays a central role in the development of obesity. However, the metabolic consequences of dietary fat can vary depending on their fatty acid composition. Therefore, the aim of the present work was to study the effect of the type and amount of dietary fat on the expression of genes controlling lipogenesis and fatty acid oxidation in the liver or adipose tissue of rats.

A Rhythm by Two Players: ECG Tracing Found in Conjoined Twins

Cluster K Mycobacteriophages: Insights into the Evolutionary Origins of Mycobacteriophage TM4

Five newly isolated mycobacteriophages--Angelica, CrimD, Adephagia, Anaya, and Pixie--have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them--with the exception of TM4--form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species.

[Noninvasive Positive Pressure Ventilation in Postoperative Period of Tracheal Surgery]

Reconstructive surgery of the airway often means prolonged periods of intubation during the post-operatory period, increasing the needs for drugs and favoring the appearance of infectious complications. We present an original system of ventilatory support with non-invasive positive pressure ventilation (NIPPV) using in patients subjected to reconstructive surgery of the airway.

Designing an Interactive Activity to Integrate Animal Physiology in the Context of Different Disciplines

Hyperkalemic Distal Renal Tubular Acidosis Caused by Immunosuppressant Treatment with Tacrolimus in a Liver Transplant Patient: Case Report

Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

Aligned Macroscopic Domains of Optoelectronic Nanostructures Prepared Via Shear-flow Assembly of Peptide Hydrogels

Current Controversies in the Surgical Treatment of Esophageal Atresia

Esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is a rare condition that can be nowadays succesfully treated. The current interest therefore is focused on the management of the difficult cases, on thoracoscopic approach, and on some aspects of the long-term results.

Comprehensive Evaluation of Cervical Cancer Screening Programs: the Case of Colombia

To identify critical screening program factors for reducing cervical cancer mortality in Colombia.

[Traumatic Diaphragmatic Hernia: a Vital Need for an Early Diagnosis]

Traumatic diaphragmatic hernia (HDT) is exceptional in children. Its diagnosis is usually delayed for appearing in the context of severe polytrauma. The aim is to analyze our series in relation to the severity scores.

[Correction of the Complicated Pectus Excavatum with Extracorporeal Circulation (ECC) Support]

The most serious complication in surgery of the pectus excavatum is the possible cardiac perforation. After its resolution, it is very likely that the relapse of the excavatum will be more severe due to the intense retrosternal fibrosis generated, involving cardiac structures and fixing them to the sternum. Reintervention requires modifications of the usual techniques and special monitoring due to the increased risk of cardiac and large vessel lesions. We present the case of 2 patients with severe pectus excavatum with a previous attempt for correction with cardiac perforation.

Independent Evaluation of the Effects of Glibenclamide on Reducing Progressive Hemorrhagic Necrosis After Cervical Spinal Cord Injury

These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence - Spinal Cord Injury (FORE-SCI) - Replication". Our goal was to replicate pre-clinical data from Simard et al. (2007) showing that glibenclamide, an FDA approved anti-diabetic drug that targets sulfonylurea receptor 1 (SUR1)-regulated Ca(2+) activated, [ATP](i)-sensitive nonspecific cation channels, attenuates secondary intraspinal hemorrhage and secondary neurodegeneration caused by hemicontusion injury in rat cervical spinal cord. In an initial replication attempt, the Infinite Horizons impactor was used to deliver a standard unilateral contusion injury near the spinal cord midline. Glibenclamide was administered continuously via osmotic pump beginning immediately post-SCI. The ability of glibenclamide to limit intraspinal hemorrhage was analyzed at 6, 12 and 24 h post-injury using a colorimetric assay. Acute recovery (24 h) of forelimb function was also assessed. Analysis of data from these initial studies revealed no difference between glibenclamide and vehicle-treated SCI rats. Later, it was determined that differences in primary trauma affect the efficacy of glibenclamide. Indeed, the magnitude and distribution of primary intraspinal hemorrhage was greater when the impact was directed to the dorsomedial region of the cervical hemicord (as in our initial replication experiment), as compared to the dorsolateral spinal cord (as in the Simard et al. experiment). In three subsequent experiments, injury was directed to the dorsolateral spinal cord. In each case, glibenclamide reduced post-traumatic hemorrhage 24-48 h post-injury. In the third experiment, we also assessed function and found that acute reduction of hemorrhage led to improved functional recovery. Thus, independent replication of the Simard et al. data was achieved. These data illustrate that the injury model and type of trauma can determine the efficacy of pre-clinical pharmacological treatments after SCI.

Soya Protein Attenuates Abnormalities of the Renin-angiotensin System in Adipose Tissue from Obese Rats

Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities.

Polymorphism Analysis of MTHFR, Factor II, and Factor V Genes in the Pomeranian Population of Espirito Santo, Brazil

Pomeranian populations worldwide immigrated originally from the north of Europe, and because of their preferential marriage, religion, and cultural habits, they show little or no reproductive mixing with local populations. Methylenetetrahydrofolate reductase gene (MTHFR) C677T, Factor V Leiden, and Factor II G20210A polymorphisms are linked to augmented clotting and their frequencies may vary according to population ethnicity. We aimed to assess the frequencies of these thrombophilic alleles in the Pomeranian population residing in Espirito Santo and compare with the general population of the Espirito Santo state, Brazil. A total of 200 individuals were analyzed. The intrapopulation fixation index of the MTHFR C677T polymorphism was 0.03736. The observed heterozygosity was 0.44 and 0.4 for the general and Pomeranian populations, respectively. According to the chi-square test, both populations are in Hardy-Weinberg equilibrium. Four polymorphic alleles were detected for Factor II (2.02%) and 8 for Factor V (4.81%). Our results show that there is gene flow between the general and the Pomeranian population of Espirito Santo, which should no longer be considered an isolated population.

Retinoic Acid Rescues Deficient Airway Innervation and Peristalsis of Hypoplastic Rat Lung Explants

Bronchial peristalsis modulates lung growth and is deficient in hypoplastic nitrofen-exposed rat lung explants. Retinoic acid (RA) rescues lung hypoplasia. This study examines whether decreased bronchial innervation contributes to this developmental deficiency and if RA is able to recover bronchial innervation and motility.

Brain Perfusion SPECT in Patients with PHACES Syndrome Under Propranolol Treatment

Children with PHACES syndrome (PS) and visual impairment or stridor show a dramatic and immediate response to propranolol. However, this beta-blocking drug could be responsible for an eventually increased risk of ischemic stroke due to the underlying cerebral vascular disease. To more accurately understand the effects of propranolol on brain vascularization, we examined PS patients treated with this drug for airway or visual complications using brain perfusion SPECT (Single Photon Emission Computed Tomography). In the past, this examination has been shown to be useful in the management of patients with different neurovascular disorders.

Lateral Cavity Acoustic Transducer As an On-chip Cell/particle Microfluidic Switch

A novel on-chip microfluidic switch is demonstrated that utilizes the acoustic microstreaming generated by an oscillating air-liquid interface to switch cells/particles into bifurcating microchannels. The air-liquid interface of the Lateral Cavity Acoustic Transducers (LCATs) can be actuated by an external acoustic energy source causing the interface to oscillate. The oscillating interface results in the generation of vortex-like microstreaming flow within a localized region of the surrounding liquid. This streaming was utilized here to deflect cells/particles into a collection outlet. It was demonstrated that the switching zone could be controlled by varying the actuation time of the LCAT. An LCAT based microfluidic switch is capable of achieving theoretical switching rates of 800 cells/particles per second. It was also demonstrated that K562 cells could be switched into a collection channel with cell viability comparable to that of controls as determined by Trypan blue exclusion assay.

A Dietary Pattern Including Nopal, Chia Seed, Soy Protein, and Oat Reduces Serum Triglycerides and Glucose Intolerance in Patients with Metabolic Syndrome

Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

Caregiver's Feeding Styles Questionnaire. Establishing Cutoff Points

Researchers use the Caregiver's Feeding Styles Questionnaire (CFSQ) to categorize parent feeding into authoritative, authoritarian, indulgent, and uninvolved styles. The CFSQ assesses self-reported feeding and classifies parents using median splits which are used in a substantial body of parenting literature and allow for direct comparison across studies on dimensions of demandingness and responsiveness. No national norms currently exist for the CFSQ. This paper establishes and recommends cutoff points most relevant for low-income, minority US samples that researchers and clinicians can use to assign parents to feeding styles. Median scores for five studies are examined and the average across these studies reported.

Measuring the Success of Community Science: the Northern California Household Exposure Study

Environmental health research involving community participation has increased substantially since the National Institute of Environmental Health Sciences (NIEHS) environmental justice and community-based participatory research (CBPR) partnerships began in the mid-1990s. The goals of these partnerships are to inform and empower better decisions about exposures, foster trust, and generate scientific knowledge to reduce environmental health disparities in low-income, minority communities. Peer-reviewed publication and clinical health outcomes alone are inadequate criteria to judge the success of projects in meeting these goals; therefore, new strategies for evaluating success are needed.

Optical Sensors with Molecularly Imprinted Nanospheres: a Promising Approach for Robust and Label-free Detection of Small Molecules

Molecularly imprinted nanospheres obtained by miniemulsion polymerization have been applied as the sensitive layer for label-free direct optical sensing of small molecules. Using these particles as the sensitive layer allowed for improving response times in comparison to sensors using MIP layers. As a model compound, well-characterized nanospheres imprinted against L-Boc-phenylalanine anilide (L-BFA) were chosen. For immobilization, a simple concept based on electrostatic adsorption was used, showing its applicability to different types of surfaces, leading to a good surface coverage. The sensor showed short response times, good selectivity, and high reversibility with a limit of detection down to 60 μM and a limit of quantitation of 94 μM. Furthermore, reproducibility, selectivity, and long-term stability of the sensitive layers were tested. The best results were achieved with an adsorption on aminopropylsilane layers, showing a chip-to-chip reproducibility of 22%. Furthermore, the sensors showed no loss in signal after a storage time of 1 year.

Abnormal Development of Lung Innervation in Experimental Esophageal Atresia

Patients with esophageal atresia and tracheo-esophageal fistula (EA-TEF) have chronic respiratory tract disease and deficient tracheal innervation. This study tests the hypothesis in rats with EA-TEF that deficient lung innervation could be one of the causes of respiratory disease.

Liver Transplantation in Children with Cystic Fibrosis: Experience in Our Centre and Preliminary Results with a Combined En Bloc Liver-pancreas Graft

Cystic fibrosis (CF) is a multisystemic disease, with some patients developing end-stage liver disease (ESLD), requiring liver transplantation (LT). These children usually present with severe mutations of the CFTR gene. Almost 100% of patients with severe mutations develop exocrine pancreatic insufficiency, leading later to endocrine insufficiency. Immunosuppression accelerates the development of insulin-dependent diabetes (IDD) in transplanted children with CF. Our aims were: (1) to analyze our experience with CF-related ESLD children who received LT, and the relationship to the development of IDD; (2) to report our preliminary results with en bloc liver-pancreas transplantation (CLPT).

A Reassessment of a Classic Neuroprotective Combination Therapy for Spinal Cord Injured Rats: LPS/pregnenolone/indomethacin

These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence-Spinal Cord Injury (FORE-SCI)-Replication". Our goal was to replicate data from a paper published by Dr. Lloyd Guth and colleagues in which combined injections of lipopolysaccharide, indomethacin and pregnenolone (referred to herein as LIP therapy) conferred marked neuroprotection in a pre-clinical model of spinal cord injury (SCI). Specifically, post-injury injection of the combination LIP therapy was found to significantly reduce tissue damage at/nearby the site of injury and significantly improve recovery of locomotor function. In this report, we confirm the primary observations made by Guth et al., however, the effects of LIP treatment were modest. Specifically, LIP treatment improved myelin and axon sparing, axonal sprouting while reducing lesion cavitation. However, spontaneous recovery of locomotion, as assessed using historical (Tarlov scoring) and more current rating scales (i.e., BBB scoring), was not affected by LIP treatment. Instead, more refined parameters of functional recovery (paw placement accuracy during grid walk) revealed a significant effect of treatment. Possible explanations for the neuroprotective effects of LIP therapy are described along with reasons why the magnitude of neuroprotection may have differed between this study and that of Guth and colleagues.

Unequivocal Identification of Brown Adipose Tissue in a Human Infant

We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.

Congenital Diaphragmatic Hernia

Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted.

Data Mining in Psychiatric Research

Mathematical sciences and computational methods have found new applications in fields like medicine over the last few decades. Modern data acquisition and data analysis protocols have been of great assistance to medical researchers and clinical scientists. Especially in psychiatry, technology and science have made new computational methods available to assist the development of predictive modeling and to identify diseases more accurately. Data mining (or knowledge discovery) aims to extract information from large datasets and solve challenging tasks, like patient assessment, early mental disease diagnosis, and drug efficacy assessment. Accurate and fast data analysis methods are very important, especially when dealing with severe psychiatric diseases like schizophrenia. In this paper, we focus on computational methods related to data analysis and more specifically to data mining. Then, we discuss some related research in the field of psychiatry.

Synthesis and Alignment of Discrete Polydiacetylene-peptide Nanostructures

Oligopeptides bearing internal diacetylene units are shown to self-assemble in water into one-dimensional nanostructures and aligned macroscopic hydrogels. The diacetylene units can be photopolymerized into polydiacetylenes that run coincident to the nanostructure and noodle long axes, and the resulting nanostructures show evidence for ambipolar charge transport. This self-assembly, alignment and polymerization technique provides a rapid way to produce globally aligned collections of conjugated polymer chains.

Diagnosis of Mycobacterial Infections in the Exotic Pet Patient with Emphasis on Birds

The term “mycobacteriosis” encompasses a variety of infectious diseases of animals caused by bacteria of the genus Mycobacterium, which are chronic and debilitating diseases. More than 35 Mycobacterium spp can cause mycobacteriosis. The wide range of possible clinical signs and physical exam findings can make the antemortem diagnosis inconsistent and challenging. Proper sample collection and test modality in relation to the state of the disease process are essential. Clinicians can determine a presumptive diagnosis of mycobacteriosis, but the definitive etiologic diagnosis of mycobacteriosis relies on the correct identification of the mycobacteria through microbiological and molecular diagnostic methods.

Lung Hypoplasia in Rats with Esophageal Atresia and Tracheo-esophageal Fistula

Survivors of esophageal atresia and tracheo-esophageal fistula (EA-TEF) often suffer chronic respiratory tract disease. EA-TEF results from abnormal emergence of the trachea from the foregut. This study in a rat model tests the hypothesis that primary lung maldevelopment might be a downstream consequence of this defect.

Development of a Mesoamerican Intra-genepool Genetic Map for Quantitative Trait Loci Detection in a Drought Tolerant × susceptible Common Bean (Phaseolus Vulgaris L.) Cross

Drought is a major constraint to common bean (Phaseolus vulgaris L.) production, especially in developing countries where irrigation for the crop is infrequent. The Mesoamerican genepool is the most widely grown subdivision of common beans that include small red, small cream and black seeded varieties. The objective of this study was to develop a reliable genetic map for a Mesoamerican × Mesoamerican drought tolerant × susceptible cross and to use this map to analyze the inheritance of yield traits under drought and fully irrigated conditions over 3 years of experiments. The source of drought tolerance used in the cross was the cream-seeded advanced line BAT477 crossed with the small red variety DOR364 and the population was made up of recombinant inbred lines in the F5 generation. Quantitative trait loci were detected by composite interval mapping for the traits of overall seed yield, yield per day, 100 seed weight, days to flowering and days to maturity for each field environment consisting of two treatments (irrigated and rainfed) and lattice design experiments with three repetitions for a total of six environments. The genetic map based on amplified fragment length polymorphism and random amplified polymorphic DNA markers was anchored with 60 simple sequence repeat (SSR) markers and had a total map length of 1,087.5 cM across 11 linkage groups covering the whole common bean genome with saturation of one marker every 5.9 cM. Gaps for the genetic map existed on linkage groups b03, b09 and b11 but overall there were only nine gaps larger than 15 cM. All traits were inherited quantitatively, with the greatest number for seed weight followed by yield per day, yield per se, days to flowering and days to maturity. The relevance of these results for breeding common beans is discussed in particular in the light of crop improvement for drought tolerance in the Mesoamerican genepool.

Plant and Animal Endemism in the Eastern Andean Slope: Challenges to Conservation

ABSTRACT: BACKGROUND: The Andes-Amazon basin of Peru and Bolivia is one of the most data-poor, biologically rich, and rapidly changing areas of the world. Conservation scientists agree that this area hosts extremely high endemism, perhaps the highest in the world, yet we know little about the geographic distributions of these species and ecosystems within country boundaries. To address this need, we have developed conservation data on endemic biodiversity (~800 species of birds, mammals, and amphibians) and terrestrial ecological systems (~90; groups of vegetation communities resulting the action of ecological processes, substrates, and/or environmental gradients) with which we conducted a fine scale conservation prioritization across the Amazon watershed of Peru and Bolivia. We modelled the geographic distributions of 435 endemic plants and all 347 endemic vertebrate species, from existing museum and herbaria specimens at a regional conservation practitioner's scale (1:250,000-1:1,000,000), based on the best available tools and geographic data. We mapped ecological systems, endemic species concentrations, and irreplaceable areas with respect to national level protected areas. RESULTS: We found that sizes of endemic species distributions ranged widely (< 20 km2 to > 200,000 km2) across the study area. Bird and mammal endemic species richness was greatest within a narrow 2500-3000 m elevation band along the length of the Andes Mountains. Endemic amphibian richness was highest at 1000-1500 m elevation and concentrated in the southern half of the study area. Geographical distribution of plant endemism was highly taxon-dependent. Irreplaceable areas, defined as locations with the highest number of species with narrow ranges, overlapped slightly with areas of high endemism, yet generally exhibited unique patterns across the study area by species group. We found that many endemic species and ecological systems are lacking national-level protection; a third of endemic species have distributions completely outside of national protected areas. Protected areas cover only 20% of areas of high endemism and 20% of irreplaceable areas. Almost 40% of the 91 ecological systems are in serious need of protection (=< 2% of their ranges protected). CONCLUSIONS: We identify for the first time, areas of high endemic species concentrations and high irreplaceability that have only been roughly indicated in the past at the continental scale. We conclude that new complementary protected areas are needed to safeguard these endemics and ecosystems. An expansion in protected areas will be challenged by geographically isolated micro-endemics, varied endemic patterns among taxa, increasing deforestation, resource extraction, and changes in climate. Relying on pre-existing collections, publically accessible datasets and tools, this working framework is exportable to other regions plagued by incomplete conservation data.

Social Representations of Human Papillomavirus in Bogotá, Colombia

Identifying DNA of Human papillomavirus (HPV) has been proposed as a new screening method for cervical cancer control. Conventionally, health education for screening programs is based on scientific information without considering any community cognitive processes. We examine HPV social representations of 124 men and women from diverse educational status living in Bogotá, Colombia. The social representation of HPV involves a series of figurative nuclei derived from meanings linked to scientific information. While women focused on symbols associated to contagion, men focused on its venereal character. Figurative nuclei also included long-term uncertainty, need or urgent treatment, and feelings of imminent death associated with cancer and chronic sexually transmitted infections. The social representation of HPV impeded many participants from clearly understanding written information about HPV transmission, clearance, and cancer risk; they are built into a framework of values, which must be deconstructed to allow women full participation in HPV screening programs.

Diet: Friend or Foe of Enteroendocrine Cells--how It Interacts with Enteroendocrine Cells

Gut hormones play a key role in the regulation of food intake, energy expenditure, glucose homeostasis, lipid metabolism, and a wide range of metabolic functions in response to food ingestion. These hormones are altered in metabolic diseases, such as obesity and type 2 diabetes, and are thus proposed to be possible targets for the prevention or treatment of these diseases. It is clear that food composition, macronutrients, and other non-nutrient components as well as the physical properties of food not only modulate the secretion of gut peptides but also modulate transcription and enteroendocrine cell differentiation, which ultimately modifies gut hormone response. The specific mechanisms or sensing machinery that respond to the different components of the diet have been studied for many years; however, over the last few years, new molecular genetic techniques have led to important advances, thereby allowing a deeper understanding of these mechanisms. This review addresses the current knowledge regarding enteroendocrine cells and how diet interacts with this machinery to stimulate and regulate the secretion of gut peptides. The potential for diet interventions as a promising strategy for modulating gut hormone responses to food ingestion and, ultimately, preventing or treating metabolic diseases is being emphasized considering that these diseases are currently a public health burden.

Gucy2f Zebrafish Knockdown--a Model for Gucy2d-related Leber Congenital Amaurosis

Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-post-fertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible.

Vaginal Agenesis or Distal Vaginal Atresia Associated with Anorectal Malformations

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is defined as Müllerian aplasia with vaginal agenesis and uterine remnants. It is commonly associated with renal and sometimes vertebral anomalies. The MRKH syndrome or distal vaginal atresia is sometimes associated with anorectal malformations. The purpose of this study was to describe 7 girls with vaginal agenesis or distal vaginal atresia and an anorectal malformation and review the literature.

Topiramate Treatment is Neuroprotective and Reduces Oligodendrocyte Loss After Cervical Spinal Cord Injury

Excess glutamate release and associated neurotoxicity contributes to cell death after spinal cord injury (SCI). Indeed, delayed administration of glutamate receptor antagonists after SCI in rodents improves tissue sparing and functional recovery. Despite their therapeutic potential, most glutamate receptor antagonists have detrimental side effects and have largely failed clinical trials. Topiramate is an AMPA-specific, glutamate receptor antagonists that is FDA-approved to treat CNS disorders. In the current study we tested whether topiramate treatment is neuroprotective after cervical contusion injury in rats. We report that topiramate, delivered 15-minutes after SCI, increases tissue sparing and preserves oligodendrocytes and neurons when compared to vehicle treatment. In addition, topiramate is more effective than the AMPA-receptor antagonist, NBQX. To the best of our knowledge, this is the first report documenting a neuroprotective effect of topiramate treatment after spinal cord injury.

Prognostic Impact of Serum Immunoglobulin Heavy/light Chain Ratio in Patients with Multiple Myeloma in Complete Remission After Autologous Stem cell Transplantation

Immunoglobulin heavy/light chain (HLC) ratios were studied in 37 patients with multiple myeloma in complete remission after autologous hematopoietic stem cell transplantation. Increased IgAκ/IgAλ and IgMκ/IgMλ ratios were associated with longer progression-free survival (P = .006 and .01, respectively). A statistical trend toward a longer overall survival was also observed for the IgAκ/IgAλ ratio (P = .068). Considering the original immunoglobulin isotype, our results indicate that an increased κ/λ ratio of the uninvolved isotype is associated with longer progression-free survival and overall survival. This is the first report demonstrating the association between the HLC ratio and sustained complete remission in patients with multiple myeloma. Our results suggest that the HLC ratio is a surrogate marker of immune recovery after myeloablative transplantation, rather than as a marker of minimal residual disease.

Heparin from Bovine Intestinal Mucosa: Glycans with Multiple Sulfation Patterns and Anticoagulant Effects

Pharmaceutical grade heparins from porcine intestine and bovine lung consist mainly of repeating tri-sulfated units, of the disaccharide →4-α-IdoA2S-1→4-α-GlcNS6S-1→. Heparin preparations from bovine intestine, in contrast, are more heterogeneous. Nuclear magnetic resonance (NMR) and disaccharide analysis after heparinase digestions show that heparin from bovine intestine contains α-glucosamine with significant substitutive variations: 64% are 6-O-sulfated and N -sulfated, as in porcine intestinal heparin while 36% are 6-desulfated. Desulfated α-iduronic acid units are contained in slightly lower proportions in bovine than in porcine heparin. NMR data also indicate N-, 3- and 6-trisulfated α-glucosamine (lower proportions) and α-GlcNS-1→4-α-GlcA and α-IdoA2S-1→4-α-GlcNAc (higher amounts) in bovine than in porcine heparin. Porcine and bovine heparins can be fractionated by anion exchange chromatography into three fractions containing different substitutions on the α-glucosamine units. Each individual fraction shows close disaccharide composition and anticoagulant activity, regardless of their origin (bovine or porcine intestine). However, these two heparins differ markedly in the proportions of the three fractions. Interestingly, fractions with the typical heparin disaccharides of porcine intestine are present in bovine intestinal heparin. These fractions contain high in vitro anticoagulant activity, reduced antithrombotic effect and high bleeding tendency. These observations indicate that the prediction of haemostatic effects of heparin preparations cannot rely exclusively on structural analysis and anticoagulant assays in vitro . Minor structural components may account for variations on in vivo effects. In conclusion, we suggest that pharmaceutical grade bovine intestinal heparin, even after purification procedures, is not an equivalent drug to porcine intestinal heparin.

A Diet Based on Multiple Functional Concepts Improves Cardiometabolic Risk Parameters in Healthy Subjects

Different foods can modulate cardiometabolic risk factors in persons already affected by metabolic alterations. The objective of this study was to assess, in healthy overweight individuals, the impact of a diet combining multiple functional concepts on risk markers associated with cardiometabolic diseases (CMD).

Argon-based Atmospheric Pressure Plasma Enhances Early Bone Response to Rough Titanium Surfaces

This study investigated the effect of an Argon-based atmospheric pressure plasma (APP) surface treatment operated chairside at atmospheric pressure conditions applied immediately prior to dental implant placement in a canine model. Surfaces investigated comprised: rough titanium surface (Ti) and rough titanium surface + Argon-based APP (Ti-Plasma). Surface energy was characterized by the Owens-Wendt-Rabel-Kaelble method and chemistry by X-ray photoelectron spectroscopy (XPS). Six adult beagles dogs received two plateau-root form implants (n = 1 each surface) in each radii, providing implants that remained 1 and 3 weeks in vivo. Histometric parameters assessed were bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). Statistical analysis was performed by Kruskall-Wallis (95% level of significance) and Dunn's post-hoc test. The XPS analysis showed peaks of Ti, C, and O for the Ti and Ti- Plasma surfaces. Both surfaces presented carbon primarily as hydrocarbon (C-C, C-H) with lower levels of oxidized carbon forms. The Ti-Plasma presented large increase in the Ti (+11%) and O (+16%) elements for the Ti- Plasma group along with a decrease of 23% in surface-adsorbed C content. At 1 week no difference was found in histometric parameters between groups. At 3 weeks significantly higher BIC (>300%) and mean BAFO (>30%) were observed for Ti-Plasma treated surfaces. From a morphologic standpoint, improved interaction between connective tissue was observed at 1 week, likely leading to more uniform and higher bone formation at 3 weeks for the Ti-Plasma treated implants was observed.

Assessment of a Chair-side Argon-based Non-thermal Plasma Treatment on the Surface Characteristics and Integration of Dental Implants with Textured Surfaces

The biomechanical effects of a non-thermal plasma (NTP) treatment, suitable for use in a dental office, on the surface character and integration of a textured dental implant surface in a beagle dog model were evaluated. The experiment compared a control treatment, which presented an alumina-blasted/acid-etched (AB/AE) surface, to two experimental treatments, in which the same AB/AE surface also received NTP treatment for a period of 20 or 60 s per implant quadrant (PLASMA 20' and PLASMA 60' groups, respectively). The surface of each specimen was characterized by electron microscopy and optical interferometry, and surface energy and surface chemistry were determined prior to and after plasma treatment. Two implants of each type were then placed at six bilateral locations in 6 dogs, and allowed to heal for 2 or 4 weeks. Following sacrifice, removal torque was evaluated as a function of animal, implant surface and time in vivo in a mixed model ANOVA. Compared to the CONTROL group, PLASMA 20' and 60' groups presented substantially higher surface energy levels, lower amounts of adsorbed C species and significantly higher torque levels (p=.001). Result indicated that the NTP treatment increased the surface energy and the biomechanical fixation of textured-surface dental implants at early times in vivo.

The Active Site of Methanol Synthesis over Cu/ZnO/Al2O3 Industrial Catalysts

One of the main stumbling blocks in developing rational design strategies for heterogeneous catalysis is that the complexity of the catalysts impairs efforts to characterize their active sites. We show how to identify the crucial atomic structure motif for the industrial Cu/ZnO/Al(2)O(3) methanol synthesis catalyst by using a combination of experimental evidence from bulk, surface-sensitive, and imaging methods collected on real high-performance catalytic systems in combination with density functional theory calculations. The active site consists of Cu steps decorated with Zn atoms, all stabilized by a series of well-defined bulk defects and surface species that need to be present jointly for the system to work.

Tumor Necrosis Factor Alpha Mediates GABA(A) Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons in Vivo

The proinflammatory cytokine TNFα contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNFα contributes to excitotoxicity by increasing GluA2-lacking AMPA receptor (AMPAR) trafficking to the neuronal plasma membrane. In vitro, increased AMPAR on the neuronal surface after TNFα exposure is associated with a rapid internalization of GABA(A) receptors (GABA(A)Rs), suggesting complex timing and dose dependency of the CNS's response to TNFα. However, the effect of TNFα on GABA(A)R trafficking in vivo remains unclear. We assessed the effect of TNFα nanoinjection on rapid GABA(A)R changes in rats (N = 30) using subcellular fractionation, quantitative western blotting, and confocal microscopy. GABA(A)R protein levels in membrane fractions of TNFα and vehicle-treated subjects were not significantly different by Western Blot, yet high-resolution quantitative confocal imaging revealed that TNFα induces GABA(A)R trafficking to synapses in a dose-dependent manner by 60 min. TNFα-mediated GABA(A)R trafficking represents a novel target for CNS excitotoxicity.

The Role of Nuclear Receptors in the Kidney in Obesity and Metabolic Syndrome

Nuclear receptors are ligand-activated transcriptional regulators of several key aspects of renal physiology and pathophysiology. As such, nuclear receptors control a large variety of metabolic processes, including kidney lipid metabolism, drug clearance, inflammation, fibrosis, cell differentiation, and oxidative stress. Derangement of nuclear receptor regulation, that is, mainly due to obesity may induce metabolic syndrome, may contribute to the pathogenesis and progression of chronic renal disease and may result in end-stage renal disease. This places nuclear receptors at the forefront of novel therapeutic approaches for a broad range of kidney disorders and diseases, including glomerulosclerosis, tubulointerstitial disease, renal lipotoxicity, kidney fibrosis, and hypertension. This review focuses on the importance of the transcription factors peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor beta, peroxisome proliferator-activated receptor gamma, liver X receptors, farnesoid X receptor, and the pregnane X receptor/steroid and xenobiotic receptor (PXR) on the physiology and pathophysiology of renal diseases associated with obesity and metabolic syndrome.

Impact of MiRSNPs on Survival and Progression in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

A distinctive new group of polymorphisms is constituted by single-nucleotide polymorphism (SNP) in miRNA processing machinery in miRNA precursor molecules and in miRNA-binding sites, known as miRSNPs. The aim of this study was to ascertain the prognostic impact of six miRSNPs in patients with multiple myeloma and analyze the functional consequences.

Meta-B-entacenes: New Polycyclic Aromatics Incorporating Two Fused Borepin Rings

The synthesis of new boron-containing acenes (meta-B-entacenes) is reported. These compounds exhibit slightly non-planar core geometries with blue-shifted spectral properties and more negative electrochemical reduction potentials relative to known para isomers. Polarizable π-extended architectures were realized via cross-coupling procedures with chloro-functionalized precursors.

Triphenylene Silanes for Direct Surface Anchoring in Binary Mixed Self-assembled Monolayers

New triphenylene-based silanes 2-(ω-(chlorodimethylsilyl)-n-alkyl)-3,6,7,10,11-penta-m-alkoxytriphenylene 4 (Tm-Cn) with n = 8 or 9 and m = 7, 8, 9, 10, or 11 were synthesized, and their self-assembly behavior in the liquid state and at glass and silicon oxide surfaces was investigated. The mesomorphic properties of triphenylene silanes 4 (Tm-Cn) and their precursors 3 (Tm-Cn) were determined by differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X-ray diffraction. From the small-angle X-ray scattering (SAXS) regime, a preferential discotic lamellar mesophase can be deduced, and wide-angle X-ray scattering (WAXS) highlights the liquid-like characteristics of the alkyl side chains. To transfer these bulk structural properties to thin films, self-assembled monolayers (SAMs) were obtained by adsorption from solution and characterized by water contact angle measurements, null ellipsometry, and atomic force microscopy (AFM). Employing the concentration as an additional degree of freedom, binary SAMs of 2-(ω-(chlorodimethylsilyl)-undecyl)-3,6,7,10,11-penta-decyloxytriphenylene 4 (T10-C11) were coassembled with chlorodecyldimethylsilane or chlorodimethyloctadecylsilane, and their capability as model systems for organic templating was evaluated. The structure of the resulting binary mixed SAMs was analyzed by water contact angle measurements, null ellipsometry, and X-ray reflectivity (XRR) in combination with theoretical modeling by a multidimensional Parratt algorithm and AFM. The composition dependence of film thickness and roughness can be explained by a microscopic model including the steric hindrance of the respective molecular constituents.

Feeding Styles and Child Weight Status Among Recent Immigrant Mother-child Dyads

Research has shown that parental feeding styles may influence children's food consumption, energy intake, and ultimately, weight status. We examine this relationship, among recent immigrants to the US. Given that immigrant parents and children are at greater risk for becoming overweight/obese with increased time in the US, identification of risk factors for weight gain is critical.

Amino-terminal Ligands Prolong NMDA Receptor-mediated EPSCs

The amino-terminal domains of NMDA receptor subunits are important for receptor assembly and desensitization, and incorporate the high-affinity binding sites for zinc and ifenprodil. These amino-terminal ligands are thought of as subunit-specific receptor inhibitors. However, multiple NMDA receptor subtypes contribute to EPSCs at wild-type hippocampal synapses. To understand the action of amino-terminal ligands, we first used cultured hippocampal neurons from N2A and N2B knock-out mice. EPSCs from these neurons have properties that are consistent with N1/N2B and N1/N2A diheteromeric receptors, respectively. As expected, zinc reduced the EPSC peak amplitude from N2B KO neurons, but surprisingly also prolonged the deactivation, resulting in a marked redistribution of charge. Consistent with prolongation of the EPSC, zinc produced a longer latency to first opening of glutamate-bound receptors, which resulted in a decrease in the number of receptors that opened by the peak. Ifenprodil had similar effects on EPSCs from N2A KO neurons. In neurons from wild-type mice, zinc or ifenprodil reduced the EPSC peak, but only zinc caused significant charge redistribution, consistent with a small contribution of N1/N2B diheteromers in these neurons. Our results indicate that ligand binding to amino-terminal domains can alter the behavior of synaptic NMDA receptors under the nonequilibrium conditions of glutamate release during synaptic transmission. By prolonging EPSCs, amino-terminal ligands could markedly affect the computational properties of NMDA receptors and could potentially be exploited for therapeutic purposes.

Bortezomib/dexamethasone Followed by Autologous Stem Cell Transplantation As Front Line Treatment for Light-chain Deposition Disease

Limited data has been published on the treatment results in patients with light-chain deposition disease (LCDD). Whenever possible, high-dose melphalan followed by autologous stem cell transplantation (ASCT) has been the first treatment option, achieving somehow better results than conventional therapy. However, and based on the promising results obtained by treating patients with light-chain amyloidosis with bortezomib/dexamethasone, new treatment options appear in LCDD. Herein, we describe three patients with LCDD treated with bortezomib/dexamethasone followed by high-dose melphalan and autologous transplantation. We believe that this new approach should be the treatment of choice in this disease. In addition, those patients achieving hematologic complete response after ASCT could benefit from a kidney transplant if the renal impairment requiring dialysis persists.

ACL Reconstruction Using a Novel Hybrid Scaffold Composed of Polyarylate Fibers and Collagen Fibers

The objective was to perform an initial in vivo evaluation of a novel braided hybrid polyarylate and collagen fiber scaffold for the reconstruction of the anterior cruciate ligament (ACL). The braided hybrid scaffold is composed of 75% poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate)(12,10), [p(DTD DD)] fibers and 25% type I bovine collagen fibers. The scaffold is designed to temporarily bear mechanical loads and gradually degrade as neoligament tissue is deposited. Scaffolds were electron beam sterilized and used to reconstruct the ACL in five Finnish Dorset crossed-bred sheep in this feasibility study. At 4 (n = 1) and 12 (n = 4) weeks post-op, scaffolds were retrieved and analyzed for cellular ingrowth and strength retention. There was extensive cell infiltration and vascularity, which increased with time. Tissue ingrowth occurred throughout the cross section in the midsubstance of the scaffolds. After 12 weeks all scaffolds were intact. Femur-scaffold-tibia complex (FSTC) explanted at 12 weeks had a yield load of 42 ± 22 N and a stiffness of 9 ± 3 N mm(-1) . All scaffolds were well tolerated in the intraarticular space and induced tissue ingrowth, including new blood vessels, fibroblasts, inflammatory cells, and newly deposited collagen, throughout the cross section of the scaffold. Tissue ingrowth is critical to the success of a degradable scaffold for ACL reconstruction. Long-term studies in a large animal model are required to determine the efficacy of these novel hybrid scaffolds for ACL reconstruction. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

The Inclusion of a Partial Meal Replacement with or Without Inulin to a Calorie Restricted Diet Contributes to Reach Recommended Intakes of Micronutrients and Decrease Plasma Triglycerides: A Randomized Clinical Trial in Obese Mexican Women

ABSTRACT:

Immigrating to the US: What Brazilian, Latin American and Haitian Women Have to Say About Changes to Their Lifestyle That May Be Associated with Obesity

Our goal was to explore the perceived determinants of obesity in Brazilian, Latin American and Haitian women. This is part of an ongoing community-based participatory intervention. Focus groups by immigrant group were conducted and themes extracted. Women expressed differences in beliefs, attitudes, and barriers regarding diet and physical activity in the US versus their home country. Participants thought food in the US is "less natural," there is less time for preparation, and there is more variety. The weather is a barrier to physical activity in the US and work is more physically demanding. Job-related efforts were not considered physical activity. They reported higher levels of stress, less control of their time and less social support in the US. Providing immigrants with appropriate support and education early in the acculturation process has the potential to help prevent obesity.

Soy Protein Isoflavones Differentially Regulate Liver X Receptor Isoforms to Modulate Lipid Metabolism and Cholesterol Transport in the Liver and Intestine in Mice

Liver X receptor (LXR)α regulates the genes involved in cholesterol, fatty acid and glucose metabolism. Soy protein (SP) consumption reduces the hepatic accumulation of cholesterol and triacylglycerol, and improves insulin sensitivity. However, it is not known whether these effects are mediated via LXRα. We therefore investigated whether the consumption of SP regulates metabolic changes in cholesterol metabolism and insulin sensitivity via LXRα.

Activation of the P53 Pathway by Small-molecule-induced MDM2 and MDMX Dimerization

Activation of p53 tumor suppressor by antagonizing its negative regulator murine double minute (MDM)2 has been considered an attractive strategy for cancer therapy and several classes of p53-MDM2 binding inhibitors have been developed. However, these compounds do not inhibit the p53-MDMX interaction, and their effectiveness can be compromised in tumors overexpressing MDMX. Here, we identify small molecules that potently block p53 binding with both MDM2 and MDMX by inhibitor-driven homo- and/or heterodimerization of MDM2 and MDMX proteins. Structural studies revealed that the inhibitors bind into and occlude the p53 pockets of MDM2 and MDMX by inducing the formation of dimeric protein complexes kept together by a dimeric small-molecule core. This mode of action effectively stabilized p53 and activated p53 signaling in cancer cells, leading to cell cycle arrest and apoptosis. Dual MDM2/MDMX antagonists restored p53 apoptotic activity in the presence of high levels of MDMX and may offer a more effective therapeutic modality for MDMX-overexpressing cancers.

Enhancing Extraction Socket Therapy with a Biphasic Calcium Sulfate

Studies have shown that tooth extraction results in loss of bone volume, which compromises dental implant placement. Prevention of site collapse at the time of extraction is recommended. In this 4-month case series, 40 patients were treated with an innovative biphasic calcium sulfate graft, demonstrating its ability to preserve or augment socket volume and resorb in the time period desired between extraction and implant placement. Some representative samples were retrieved at the time of implant placement and evaluated histologically and morphometrically for vital bone formation.

Promoting Health at the Community Level: Thinking Globally, Acting Locally

Prevention of childhood obesity is a societal priority. Despite our knowledge about the scope of the problem and the determinants that lead to it, we have yet to produce meaningful declines in obesity rates. Recent attention has been given to interventions that employ multiple strategies across multiple settings involving whole communities given their promising results. The next era of science calls for interdisciplinary teams who will envision a whole system approach to advance the community-based obesity prevention model. This perspective describes some of the more recent discussions of community-based methodologies such as the ANGELO (Analysis Grid for Environments Linked to Obesity) framework, best-practice principles, and a whole system intervention approach to obesity prevention. The proposed required elements to advance community-based research to address childhood obesity are: A systems perspective and approach, training of future leaders in community research methodology and social change, applying transdisciplinary strategies, funding to conduct rigorous trials to determine efficacy and effectiveness, enhanced design and analysis approaches, new and improved tools and methodologies to collect quantitative and qualitative data, enhanced community engagement models and sustainability frameworks, advancement of a bold public policy agenda, economic modeling, and acknowledgment of the approach as viable. To reverse childhood obesity, we need to embrace and integrate complex strategies at multiple levels within communities across the globe.

Healthy-lifestyle Behaviors Associated with Overweight and Obesity in US Rural Children

There are disproportionately higher rates of overweight and obesity in poor rural communities but studies exploring children's health-related behaviors that may assist in designing effective interventions are limited. We examined the association between overweight and obesity prevalence of 401 ethnically/racially diverse, rural school-aged children and healthy-lifestyle behaviors: improving diet quality, obtaining adequate sleep, limiting screen-time viewing, and consulting a physician about a child's weight.

Development of the Live Well Curriculum for Recent Immigrants: a Community-based Participatory Approach

There are few weight gain prevention interventions aimed at new immigrants. Live Well, a community-based participatory research (CBPR) study, was designed to address this gap.

Cognitive Assessment Protocol Design in the ISSYS (Investigating Silent Strokes in HYpertensives: A Magnetic Resonance Imaging Study)

Hypertension and silent cerebrovascular lesions (SCL) detected by brain magnetic resonance imaging (MRI) are associated with an increased risk of cognitive decline. In a prospective observational study in 1000 hypertensive patients, aged 50-70years, with no prior history of stroke or dementia, we will study the presence of mild cognitive impairment (MCI) and the relationship between SCL and cognition. All participants will be assessed by means of the Dementia Rating Scale-2 (DRS-2) and will undergo a brain MRI. In order to better characterize MCI and future dementia risk in our cohort, those patients that are suspected to be cognitively impaired according to the DRS-2 results will have a further neurological evaluation and complete neuropsychological testing. Follow-up for the entire cohort is planned to last for at least 3years.

Use of Palliative Radiotherapy in Brain and Bone Metastases (VARA II Study)

ABSTRACT:

Dynamic Muscle Loading and Mechanotransduction

Mechanical Properties of Human Bone Surrounding Plateau Root Form Implants Retrieved After 0.3-24 Years of Function

Bone remodeling, along with tissue biomechanics, is critical for the clinical success of endosseous implants. This study evaluated the long-term evolution of the elastic modulus (GPa) and hardness (GPa) of cortical bone around human retrieved plateau root form implants. Thirty implant-in-bone specimens showing no clinical failure were retrieved from patients at different in-vivo times (0.3 to ~24 years) due to retreatment needs. After dehydration, specimens were embedded in methacrylate-based resin, sectioned along the bucco-lingual long axis and fixed to acrylic plates and nondecalcified processed to slides with ~50 μm in thickness. Nanoindentation testing was carried out under wet conditions on bone areas within the first three plateaus. Indentations (n = 120 per implant total) were performed with a maximum load of 300 μN (loading rate: 60 μN/s) followed by a holding and unloading time of 10 s and 2 s, respectively. Elastic modulus (E, GPa) and hardness (H, GPa) were computed. Both E and H values presented increased values as time in vivo elapsed (E: r = 0.84; H: r = 0.78). Significantly higher values for E and H were found after 5 years in vivo (p < 0.001). Maxillary or mandibulary arches or positioning did not affect mechanical properties, nor did implant surface treatment on the long-term bone biomechanical response (E: p ≥ 0.09; H: p ≥ 0.3). This work suggests that human cortical bone around plateau root form implants presents an increase in elastic modulus and hardness during the first 5 years following implantation and presents stable mechanical properties thereafter.

Meningitis Due to Cryptococcus Neoformans: Treatment with Posaconazole

Background: Central nervous system infections caused by Cryptococcus neoformans remain to be opportunistic infections with high mortality in severely immunocompromised patients such as patients with AIDS. Amphotericin B deoxycholate and fluconazole remain to be the drugs of choice; however, in consideration of the intolerance to amphotericin B deoxycholate and the possible resistance to fluconazole, it is necessary to evaluate other azoles, such as posaconazole, that have demonstrated lower adverse events. The objective of this study was to describe the characteristics and clinical and microbiological response of the use of posaconazole in patients with CNS infections caused by C. neoformans. Methods: We designed a case study that included eight patients diagnosed with AIDS and cryptococcal meningitis. Seven patients were treated with 800 mg of posaconazole orally for 28 days. Results: During the second week of treatment, a cerebrospinal fluid (CSF) culture was performed and was negative for the development of C. neoformans. The patients showed an improvement in signs and symptoms of impairment of the CNS such as reduction of cephalea, fever, visual disturbances such as double vision, meningism and papilledema, and improved alertness and environmental awareness. Conclusions: CNS fungal infections usually occur in immunocompromised patients. The use of systemic antifungal agents contributes to the development of fungal resistance. The results of this study suggest that posaconazole is a good alternative in the treatment of fungal CNS infection due to C. neoformans.

Stiff Gelatin Hydrogels Can Be Photo-chemically Synthesized from Low Viscous Gelatin Solutions Using Molecularly Functionalized Gelatin with a High Degree of Methacrylation

Gelatin is a very promising matrix material for in vitro cell culture and tissue engineering, e.g. due to its native RGD content. For the generation of medical soft tissue implants chemical modification of gelatin improves the mechanical properties of gelatin hydrogels and the viscous behavior of gelatin solutions for liquid handling. We present a systematic study on the influence of high degrees of methacrylation on the properties of gelatin solutions and photo-chemically crosslinked hydrogels. Changes from shear thinning to shear thickening behavior of gelatin solutions were observed depending on mass fraction and degree of methacrylation. Degrees of swelling of crosslinked hydrogels ranged from 194 to 770 % and storage moduli G' from 368 to 5 kPa, comparable to various natural tissues including several types of cartilage. Crosslinked gels proofed to be cytocompatible according to extract testings based on DIN ISO 10933-5 and in contact with porcine chondrocytes.

Whole Grain Consumption is Inversely Associated with BMI Z-score in Rural School-aged Children

OBJECTIVE: To examine the relationship between intake of whole grains and BMI Z-score in rural children. DESIGN: General linear models and logistic regression were used to examine the cross-sectional associations between whole grain intake and BMI Z-score, prevalence and odds ratios of overweight and obesity. Dietary intake was assessed using the Block Food Screener for ages 2-17 years. Children were classified into three categories according to servings of whole grain intake: <1·0 serving/d, 1·0-1·5 servings/d and >1·5 servings/d. SETTING: The CHANGE (Creating Healthy, Active and Nurturing Growing-up Environments) study, an obesity prevention intervention in elementary schools in eight rural US communities in California, Mississippi, Kentucky and South Carolina. SUBJECTS: Seven hundred and ninety-two children attending 3rd-6th grade. RESULTS: After adjusting for age, sex, race/ethnicity, physical activity and state of residence, whole grain intake was inversely associated with BMI Z-score (0·90 v. 0·61 in the lowest v. the highest whole grain intake category; P trend = 0·01). Children who consumed >1·5 servings of whole grains/d had a 40 % lower risk of being obese (OR = 0·60; 95 % CI 0·38, 0·95, P = 0·02) compared with children who consumed <1·0 serving/d. Further adjustment for potential dietary predictors of body weight (fruit, vegetable and dairy intakes) did not change the observed associations. CONCLUSIONS: Increasing the intake of whole grains as part of an overall healthy lifestyle may be beneficial for children to achieve and maintain a healthy weight.

Buccal and Lingual Bone Level Alterations After Immediate Implantation of Four Implant Surfaces: a Study in Dogs

OBJECTIVES: Bone formation and maintenance around implants placed immediately after tooth extraction may be affected by implant surface treatment and compromise long-term esthetic results. This study morphometrically evaluated buccal bone loss and bone-to-implant contact (BIC) of four implant systems placed immediately after tooth extraction in a dog model. MATERIAL AND METHODS: The premolars of eight beagle dogs were bilaterally extracted with a full-thickness flap, and root-form dental implants were placed on the root extraction socket. Implants (n = 16 each) with different surface treatments were placed from sites 1 to 4 and alternated between animals to allow evaluation of the same number of implants at sites and evaluation time points. Implant surface treatments were as follows: anodized, discrete crystalline deposition, SLActive, and microblasted. The left and right side provided implants that stayed for 2 and 4 weeks, respectively. Submerged healing was allowed and bone-to-implant contact (BIC) and buccal bone loss were morphometrically measured. Linear mixed models (P < 0.05) were used to assess differences between groups, across time, and their interaction. RESULTS: Buccal bone loss was observed to approximately double between 2 and 4 weeks (P = 0.01). BIC also increased between 2 and 4 weeks, by 20-25% (P = 0.01). These changes were statistically similar for each surface. CONCLUSION: When placed immediately after tooth extraction, the evaluated histomorphometric parameters vary only with time.

Physicochemical Characterization and In Vivo Evaluation of Amorphous and Partially Crystalline Calcium Phosphate Coatings Fabricated on Ti-6Al-4V Implants by the Plasma Spray Method

Objective. To characterize the topographic and chemical properties of 2 bioceramic coated plateau root form implant surfaces and evaluate their histomorphometric differences at 6 and 12 weeks in vivo. Methods. Plasma sprayed hydroxyapatite (PSHA) and amorphous calcium phosphate (ACP) surfaces were characterized by scanning electron microscopy (SEM), interferometry (IFM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). Implants were placed in the radius epiphysis, and the right limb of dogs provided implants that remained for 6 weeks, and the left limb provided implants that remained 12 weeks in vivo. Thin sections were prepared for bone-to-implant contact (BIC) and bone-area-fraction occupancy (BAFO) measurements (evaluated by Friedman analysis P < 0.05). Results. Significantly, higher S(a) (P < 0.03) and S(q) (P < 0.02) were observed for ACP relative to PSHA. Chemical analysis revealed significantly higher HA, calcium phosphate, and calcium pyrophosphate for the PSHA surface. BIC and BAFO measurements showed no differences between surfaces. Lamellar bone formation in close contact with implant surfaces and within the healing chambers was observed for both groups. Conclusion. Given topographical and chemical differences between PSHA and ACP surfaces, bone morphology and histomorphometric evaluated parameters showed that both surfaces were osseoconductive in plateau root form implants.

A Study of the SCN5A Gene in a Cohort of 76 Patients with Brugada Syndrome

We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype-phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy-six non-related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild-type probands. There were non-significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.

Matrix Bound Heparan Sulfate Is Essential for the Growth and Pluripotency of Human Embryonic Stem Cells

Human embryonic stem (hES) cell production of heparan sulfate influences cell fate and pluripotency. Human ES cells remain pluripotent in vitro through the action of growth factors signaling, and the activity of these factors depends on interaction with specific receptors and also with heparan sulfate. Here we tested the hypothesis that matrix-associated heparan sulfate is enough to maintain hES cells under low FGF-2 concentration in the absence of live feeder cells. To pursue this goal, we compared hES cells cultured either on coated plates containing live murine embryonic fibroblasts (MEFs) or on a matrix derived from ethanol-fixed MEFs. Human ES cells were analyzed for the expression of pluripotency markers and the ability to form embryoid bodies. Human ES cells cultured either on live mouse fibroblasts or onto a matrix derived from fixed fibroblasts expressed similar levels of Oct-4, SOX-2, Nanog, TRA-1-60 and SSEA-4 and they were also able to form cavitated embryoid bodies. Heparan sulfate-depleted matrix lost the ability to support the adherence and growth of hES cells, confirming that this glycosaminoglycan, bound to extracellular matrix, is enough for the growth and attachment of hES cells. Finally, we observed that the ethanol-fixed matrix decreases by 30% the levels of Neu5Gc in hES cells, indicating that this procedure reduces xeno-contamination. Our data suggest that matrix bound heparan sulfate is required for the growth and pluripotency of hES cells and that ethanol-fixed MEFs may be used as a 'live cell'-free substrate for stem cells.

Opuntia Ficus Indica (Nopal) Attenuates Hepatic Steatosis and Oxidative Stress in Obese Zucker (fa/fa) Rats

Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

Nano Hydroxyapatite-coated Implants Improve Bone Nanomechanical Properties

Nanostructure modification of dental implants has long been sought as a means to improve osseointegration through enhanced biomimicry of host structures. Several methods have been proposed and demonstrated for creating nanotopographic features; here we describe a nanoscale hydroxyapatite (HA)-coated implant surface and hypothesize that it will hasten osseointegration and improve its quality relative to that of non-coated implants. Twenty threaded titanium alloy implants, half prepared with a stable HA nanoparticle surface and half grit-blasted, acid-etched, and heat-treated (HT), were inserted into rabbit femurs. Pre-operatively, the implants were morphologically and topographically characterized. After 3 weeks of healing, the samples were retrieved for histomorphometry. The nanomechanical properties of the surrounding bone were evaluated by nanoindentation. While both implants revealed similar bone-to-implant contact, the nanoindentation demonstrated that the tissue quality was significantly enhanced around the HA-coated implants, validating the postulated hypothesis.

Amniotic Fluid Stem Cells Rescue Both In Vitro And In Vivo Growth, Innervation And Motility In Nitrofen-Exposed Hypoplastic Rat Lungs Through Paracrine Effects

Background: Lung hypoplasia can be prevented in vitro by retinoic acid (RA). Recent evidence suggests that amniotic fluid stem (AFS) cells may integrate injured lungs and influence their recovery. We tests the hypothesis that AFS cells might improve lung growth and motility by paracrine mechanisms.Material and methods: Pregnant rats received either nitrofen or vehicle on E9.5. In vitro E13 embryonic lungs were cultured in presence of culture medium alone or with RA, basophils or AFS cells. In vivo GFP+rat-AFS-cells were transplanted in nitrofen-exposed rats on E10.5. E13 lung explants were cultured before analysis. The surface, the number of terminal buds and the frequency of bronchial contractions were assessed. PGP 9.5 and α-actin protein levels were measured. The lung explants transplanted with AFS cells were stained for α-actin, PGP9.5 and TTF-1. FGF10, VEGFα, and TGFβ1 levels secreted by the AFS cells in the culture medium were measured. Comparison between groups was made by Anova tests.Results: In vitro The surface, the number of terminal buds and the bronchial peristalsis were increased in nitrofen+AFS-cells explants in comparison with nitrofen-exposed lungs. Whilenitrofen+RA lungs were similar to nitrofen+AFS ones, basophils did not normalize these measurements. PGP9.5 protein was decreased in nitrofen lungs, but after adding AFS cells, the value was similar to controls. No differences were found in the expression of α-actin. In vivo Surface, number of terminal buds and peristalsis were similar to control after injection of AFS cells in nitrofen-exposed rats. Colocalization with TTF-1-positive cells was found. The levels of FGF10 and VEGFα were increased in nitrofen+AFS-cells explants setting, while the levels of TGFβ1 were similar to controls.Conclusions: Lung growth, bronchial motility and innervation are decreased in nitrofen explants and rescued by AFS cells both in vitro and in vivo, similarly to what observed before with RA. AFS cells beneficial effect was probably related to paracrine action of growth factors secretion.

Subcutaneous Panniculitis-Like T-Cell Lymphoma in Two Pediatric Patients: An HIV-Positive Adolescent and a 4-Month-Old Infant

Subcutaneous Panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of childhood non-Hodgkin lymphoma. Subcutaneous Panniculitis-like T-cell lymphoma has an aggressive variant associated with the hemophagocytic syndrome (HPS). Patients without HPS show resolution of the disease with prednisone or immunosuppressive therapy unlike other T-cell lymphomas. One HIV-positive adolescent and one infant with multiple subcutaneous masses are presented and the literature is reviewed. Lesional cells were consistent with SPTCL alpha-beta type. Our cases, without HPS, showed complete resolution of their lesions when treated with non-aggressive therapies. Patients with SPTCL alpha-beta should be treated conservatively.

[Technical Aspects of Experimental Intestinal Transplant]

Our objective is to analyze the variables that influence the outcome of Small Bowel Transplantation (SBT) in rats in an experimental microsurgery program. The surgical technique and perioperative care are described in detail.

Orthopaedic Case of the Month: A 14-Year-Old Boy With a Medial Thigh Soft Tissue Mass

Lessons Learned Obtaining Informed Consent in Research with Vulnerable Populations in Community Health Center Settings

ABSTRACT: BACKGROUND: To improve equity in access to medical research, successful strategies are needed to recruit diverse populations. Here, we examine experiences of community health center (CHC) staff who guided an informed consent process to overcome recruitment barriers in a medical record review study. METHODS: We conducted ten semi-structured interviews with CHC staff members. Interviews were audiotaped, transcribed, and structurally and thematically coded. We used NVivo, an ethnographic data management software program, to analyze themes related to recruitment challenges. RESULTS: CHC interviewees reported that a key challenge to recruitment included the difficult balance between institutional review board (IRB) requirements for informed consent, and conveying an appropriate level of risk to patients. CHC staff perceived that the requirements of IRB certification itself posed a barrier to allowing diverse staff to participate in recruitment efforts. A key barrier to recruitment also included the lack of updated contact information on CHC patients. CHC interviewees reported that the successes they experienced reflected an alignment between study aims and CHC goals, and trusted relationships between CHCs and staff and the patients they recruited. CONCLUSIONS: Making IRB training more accessible to CHC-based staff, improving consent form clarity for participants, and developing processes for routinely updating patient information would greatly lower recruitment barriers for diverse populations in health services research.

Abnormal Control of Lung Branching in Experimental Esophageal Atresia

PURPOSE: Esophageal atresia and tracheo-esophageal fistula (EA-TEF) result from abnormal division of the foregut into esophagus and trachea thus, it may influence airway branching and lung development. The present study examined lung morphogenesis in fetuses with EA-TEF focusing in the expression of FGF10 and its receptor FGFR2 IIIb. METHODS: Pregnant rats received either 1.75 mg/kg i.p. adriamycin or vehicle on E7, E8 and E9. Embryos were recovered at E15, E18 and E21 and lungs processed for immunohistochemistry and RT-PCR. Three groups were studied: control, adriamycin-exposed with EA-TEF, and adriamycin-exposed without EA-TEF. Comparisons were performed with Mann-Whitney or t tests (significance level, 5 %). RESULTS: Lung weight at E15 and E18 were significantly lower in adriaEA fetuses in which the relative mRNA levels of FGF10 were significantly higher. These differences disappeared near term. The receptor FGFR2 IIIb messenger was only significantly increased in adria noEA fetuses at E15. Immunohistochemical study was consistent with these findings. CONCLUSIONS: Abnormal expression of FGF10 during earlier stages of development, when the lungs are smaller than controls, suggests a compensatory response aimed at "catching up" delayed tracheobronchial branching. Whether similar changes take place in the human condition and influence respiratory physiology remain to be determined.

HIV Testing and Counselling in Colombia: Evidence from a National Health Survey and Recommendations for Health-care Services

The purpose of this study was to assess the prevalence of, and the factors associated with HIV testing and pre- and post-test counselling (PPTC) in Colombia. Cross-sectional data from the National Health Survey carried out during 2007 were analysed. Data were gathered from records of 29,760 individuals between the ages of 18 and 69 from the main regions of the country. Only 19.7% of the sample had taken an HIV test. Men, people with no education, those not affiliated with the health-care system, residents of rural areas and those aged older than 65 were less likely to have been tested for HIV; 42% of those tested did not receive pre-test counselling and 56.9% received no report of the results. Considering the low prevalence of HIV testing among the Colombian population, it is necessary to design and apply guidelines for HIV screening in all health-care settings and to conduct targeted testing in high-risk sub-populations. A national norm of PPTC in those who undergo HIV testing should be examined.

Underuse of Radiotherapy in Lung Cancer Has Negative Consequences for Patients

INTRODUCTION:: Radiotherapy has proven to be an effective treatment when used alone or with other therapies. However, underuse of radiotherapy has been observed in various studies. The objective of this investigation was to assess the use of radiotherapy as initial treatment for lung cancer in a southern region of Europe. METHODS:: A systematic review of lung cancer treatment guidelines and observational studies was performed to estimate expected radiation rates and the associated survival outcomes. We then reviewed the clinical and treatment records of all patients undergoing radiotherapy for lung cancer during 2007 in all the 12 public hospitals in Andalusia with radiotherapy facilities. Data were grouped according to type of hospital, patient, treatment characteristics, histological type, and tumor stage. RESULTS:: In 2007, of the 3051 patients estimated to be diagnosed with lung cancer, 610 were treated with initial radiotherapy with an overall radiation rate of 20%, which significantly differed among provinces (range, 8.5%-25.6%, p < 0.001). Given the expected radiation rate of 1383 patients, 773 more patients of lung cancer (25%) should have been treated. According to the literature, the maximum increased survival attributable to the use of radiotherapy in patients diagnosed with non-small-cell lung cancer ranges from 1.8 to 14.1 months. The underuse estimated in the region would correspond to a loss of more than 3000 months in survival time. CONCLUSIONS:: The observed underuse of radiotherapy in lung cancer in our region should be a matter of concern, given its negative and measurable impact on the survival of the patients.

Acculturation and Gestational Weight Gain in a Predominantly Puerto Rican Population

ABSTRACT: BACKGROUND: Identifying risk factors that affect excess weight gain during pregnancy is critical, especially among women who are at a higher risk for obesity. The goal of this study was to determine if acculturation, a possible risk factor, was associated with gestational weight gain in a predominantly Puerto Rican population. METHODS: We utilized data from Proyecto Buena Salud, a prospective cohort study of Hispanic women in Western Massachusetts, United States. Height, weight and gestational age were abstracted from medical records among participants with full-term pregnancies (n=952). Gestational weight gain was calculated as the difference between delivery and prepregnancy weight. Acculturation (measured via a psychological acculturation scale, generation in the US, place of birth and spoken language preference) was assessed in early pregnancy. RESULTS: Adjusting for age, parity, perceived stress, gestational age, and prepregnancy weight, women who had at least one parent born in Puerto Rico/Dominican Republic (PR/DR) and both grandparents born in PR/DR had a significantly higher mean total gestational weight gain (0.9 kg for at least one parent born in PR/DR and 2.2kg for grandparents born in PR/DR) and rate of weight gain (0.03 kg/wk for at least one parent born in PR/DR and 0.06 kg/wk for grandparents born in PR/DR) vs. women who were of PR/DR born. Similarly, women born in the US had significantly higher mean total gestational weight gain (1.0 kg) and rate of weight gain (0.03 kg/wk) vs. women who were PR/ DR born. Spoken language preference and psychological acculturation were not significantly associated with total or rate of pregnancy weight gain. CONCLUSION: We found that psychological acculturation was not associated with gestational weight gain while place of birth and higher generation in the US were significantly associated with higher gestational weight gain. We interpret these findings to suggest the potential importance of the US "obesogenic" environment in influencing unhealthy pregnancy weight gains over specific aspects of psychological acculturation.

Analysis of Genome Instability in Breast Cancer

Breast cancer is a heterogeneous disease, previously associated with genomic instability. Our aim was to analyze microsatellite markers in order to determine patterns and levels of instability, as well as possible correlations with histopathological parameters. Polymerase chain reaction was used to characterize microsatellite instability (MSI) and loss of heterozygosity (LOH) in 107 breast carcinomas at twelve microsatellite loci. Some of the markers were selected because of their relation to steroid hormone metabolism, which seems to be related to sporadic breast cancer risk. D5S346 and D17S250 markers showed a statistically significant frequency of MSI. LOH in D3S1611, D17S250, AR and ER-β were associated with some parameters of worse prognosis. Marker group analysis showed that CYP19, AR and ER-β were related to histological grade III, ER-negative and PR-negative cases. Our results suggest that marker group analysis may be preferred to the single marker strategy, being predictive of worst prognosis when single markers are unable to provide such information. A further evaluation of steroid metabolism genes and their association with low penetrance genes in breast cancer may be useful.

Simplified Drilling Technique Does Not Decrease Dental Implant Osseointegration: A Preliminary Report

Background: To date, very few experimental studies have addressed the effect of bone drilling technique and sequence on dental implant osseointegration. In this study, we hypothesized that there would be no differences in osseointegration when reducing the number of drills for osteotomy compared to the conventional drilling protocols. Methods: Seventy-two implants (diameter 3.75 mm and diameter 4.2 mm, n=36 for each diameter) were bilaterally placed in the tibia of 18 beagles for 1, 3, and 5 weeks. Half of the implants of each diameter were placed using a simplified drilling procedure (pilot and final drill) and the other half were placed using a conventional drilling procedure (all drills in sequence). The retrieved samples were subjected to histologic/histomorphometric evaluation. Results: Histology showed that new bone formed around the implant and inflammation or bone resorption was not evident for both groups. Histomorphometrically, the simplified group presented significantly higher bone-to-implant contact and bone area fraction occupancy as compared to the conventional group after 1 week, however, no differences were detected at 3 and 5 weeks. Conclusion: It can be suggested that bone responses to the implant with the simplified protocol is comparable to the conventional protocol.

Osteolysis and Lymphatic Anomalies. A Review of 54 Consecutive Cases

Abstract Background: Progressive osteolysis caused by lympathic malformations is a rare condition that should be known by specialists involved in the study of lymphatic disorders because they are necessarily involved in the treatment. The purpose of the present study is to report on a large series of patients to illustrate the multiple clinical pictures and the wide range of therapeutic measures necessary for arresting bone destruction and lymphatic leak. Methods and Results: Inclusion criteria were osteolysis associated with lymphatic malformation that required treatment. Diagnosis was based on history, plain X-rays, MRI, and demonstration of the lymphatic nature of the lesions with D2-40 immunohistochemistry. Treatment was based on resection of the bone lytic lesion or soft tissue lymphatic masses, control of chylothorax or chyloperitoneum, interferon, zoledronic acid, and radiotherapy. The study included 54 patients (25 females and 29 males) with a median age of 9 years (range 2 to 65). Eight patients had focal osteolysis without soft tissue lymphatic anomaly, 15 multifocal osteolysis without soft tissue lymphatic anomaly, 7 focal osteolysis associated with soft tissue lymphatic anomaly, and 24 multifocal osteolysis with soft tissue lymphatic anomaly. Among the wide variety of pharmacological therapies provided, only one protocol showed a consistent positive effect (end of ostelytic progression) in 17 patients who received a course of 6 to 15 months of interferon alpha-2B at 1.5 million units/m(2) body surface area/day in association with zoledronic acid at 0.05 mg/kg/month. Thirty-two patients underwent multiple surgical procedures in order to remove the soft tissue involved, correct orthopedic problems, or improve chylothorax, and three were treated with radiotherapy which was successful in one case. Conclusions: Osteolysis from lymphatic origin is a devastating surgical condition. Therapeutic options have to be considered separately if the disease is active or inactive and according to the targeted organ (skin, bone, or viscera). Total removal of the lymphatic anomaly is rarely possible, but its subtotal excision together with pharmacological antiangiogenic therapy in selected patients under surveillance of a multidisciplinary group familiarized with the disease, minimize the progression of both, lymphatic invasion, osteolysis, and their serious complications.

Bone Morphometric Evaluation Around Immediately Placed Implants Covered with Porcine-Derived Pericardium Membrane: An Experimental Study in Dogs

Objective. To investigate whether porcine-derived bioresorbable pericardium membrane coverage enhances the osseointegration around implants placed in fresh extraction sockets. Study Design. Twenty-four commercially available endosseous implants were placed in the fresh extraction sockets of the mandibular first molar of mature beagles (n = 6). On one side, implants and osteotomy sites were covered with porcine-derived bioresorbable pericardium membranes, whereas on the other side, no membranes were used. After 6 weeks, samples were retrieved and were histologically processed for histomorphometric analysis. Results. The histological observation showed that bone loss and soft tissue migration in the coronal region of the implant were evident for the control group, whereas bone fill was evident up to the neck of the implant for the membrane-covered group. Bone-to-implant contact was significantly higher for the membrane-covered group compared to the control group, 75% and 45% (P < 0.02), respectively. Conclusion. The experimental membranes proved to regenerate bone around implants placed in fresh extraction sockets without soft tissue intrusion.

Bone Apposition to Laminin-1 Coated Implants: Histologic and 3D Evaluation

Laminin-1 has been reported as one of the factors responsible for the nucleation of calcium phosphates and, in vitro, has been reported to selectively recruit osteoprogenitors. This article focused on its in vivo effects, and evaluated the effect of laminin-1 local application on osseointegration. Polished cylindrical hydroxyapatite implants were coated with laminin-1 (test) and the bone responses in the rabbit tibiae after 2 and 4 weeks were evaluated and compared to the non-coated implants (control). Before the samples were processed for histological sectioning, they were three-dimensionally analysed with micro computed tomography (μCT). Both evaluation methods were analysed with regards to bone area around the implant and bone to implant contact. From the histologic observation, new bone formation around the laminin-1 coated implant at 2 weeks seemed to have increased the amount of supporting bone around the implant, however, at 4 weeks, the two groups presented no notable differences. The two-dimensional and three-dimensional morphometric evaluation revealed that both histologic and three-dimensional analysis showed some tendency in favour of the test group implants, however there was no statistical significance between the test and control group results.

Osseointegration Assessment of Chairside Argon-based Nonthermal Plasma-treated Ca-P Coated Dental Implants

This study investigated the effect of an Argon-based nonthermal plasma (NTP) surface treatment-operated chairside at atmospheric pressure conditions applied immediately prior to dental implant placement in a canine model. Surfaces investigated comprised: Calcium-Phosphate (CaP) and CaP + NTP (CaP-Plasma). Surface energy was characterized by the Owens-Wendt-Rabel-Kaelble method and chemistry by X-ray photoelectron spectroscopy (XPS). Six adult beagles dogs received 2 plateau-root form implants (n = 1 each surface) in each radii, providing implants that remained 1 and 3 weeks in vivo. Histometric parameters assessed were bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). Statistical analysis was performed by Kruskall-Wallis (95% level of significance) and Dunn's post-hoc test. The XPS analysis showed peaks of Ca, C, O, and P for the CaP and CaP-Plasma surfaces. Both surfaces presented carbon primarily as hydrocarbon (CC, CH) with lower levels of oxidized carbon forms. The CaP surface presented atomic percent values of 38, 42, 11, and 7 for C, O, Ca, and P, respectively, and the CaP-Plasma presented increases in O, Ca, and P atomic percent levels at 53, 12, and 13, respectively, in addition to a decrease in C content at 18 atomic percent. At 1 week no difference was found in histometric parameters between groups. At 3 weeks significantly higher BIC and BAFO were observed for CaP-Plasma treated surfaces. Surface elemental chemistry was modified by the Ar-based NTP. Ar-based NTP improved bone formation around plateau-root form implants at 3 weeks compared with CaP treatment alone. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:98-103, 2013.

Waiting
simple hit counter