Correlates of Obsessive–Compulsive Disorder in a Sample of HIV-Positive, Methamphetamine-using Men Who have Sex with Men

Substance use has been identified as a risk factor for elevated levels of obsessive–compulsive disorder (OCD). This study examined methamphetamine use and sexual risk behaviors as correlates of OCD in a sample of 245 HIV-positive men having sex with men (MSM) in San Diego, CA. In a logistic regression analysis, OCD was associated with greater frequency of methamphetamine use, more depressive symptoms, seeking out risky venues and risky sexual partners when “high” on methamphetamine, and reporting fewer sex acts in the past 2 months. These data suggest the need for increased awareness and understanding of the role that OCD may play in the drug use behaviors and risky sexual practices of methamphetamine users

Characterization of MgtC, a Virulence Factor of Salmonella enterica Serovar Typhi

The MgtC is a virulence factor in Salmonella Typhimurium that is required for growth at low-Mg2+ concentrations and intramacrophage survival. This gene is codified in a conserved region of the Salmonella pathogenicity island 3 (SPI-3), and is also present in the chromosome of other Salmonella serovars. In this study we characterized the MgtC factor in S. Typhi, a human specific pathogen, by using mgtC and SPI-3 mutant strains. We found that MgtC is the most important factor codified in the SPI-3 of S. Typhi for growth in low-Mg2+ media and survival within human cells. In addition, by using reporter genes we determined that the low-Mg2+ concentration, acidic media and PhoP regulator induce mgtC expression in S. Typhi. We suggest that MgtC is the most important virulence factor codified in the SPI-3 of S. Typhi

The Mycotoxin Deoxynivalenol Potentiates Intestinal Inflammation by Salmonella Typhimurium in Porcine Ileal Loops

Background and Aims: Both deoxynivalenol (DON) and nontyphoidal salmonellosis are emerging threats with possible hazardous effects on both human and animal health. The objective of this study was to examine whether DON at low but relevant concentrations interacts with the intestinal inflammation induced by Salmonella Typhimurium. Methodology: By using a porcine intestinal ileal loop model, we investigated whether intake of low concentrations of DON interacts with the early intestinal inflammatory response induced by Salmonella Typhimurium. Results: A significant higher expression of IL-12 and TNF alpha and a clear potentiation of the expression of IL-1 beta, IL-8, MCP-1 and IL-6 was seen in loops co-exposed to 1 mu g/mL of DON and Salmonella Typhimurium compared to loops exposed to Salmonella Typhimurium alone. This potentiation coincided with a significantly enhanced Salmonella invasion in and translocation over the intestinal epithelial IPEC-J2 cells, exposed to non-cytotoxic concentrations of DON for 24 h. Exposure of Salmonella Typhimurium to 0.250 mu g/mL of DON affected the bacterial gene expression level of a limited number of genes, however none of these expression changes seemed to give an explanation for the increased invasion and translocation of Salmonella Typhimurium and the potentiated inflammatory response in combination with DON. Conclusion: These data imply that the intake of low and relevant concentrations of DON renders the intestinal epithelium more susceptible to Salmonella Typhimurium with a subsequent potentiation of the inflammatory response in the gut

Evaluation of 22 genetic variants with Crohn's Disease risk in the Ashkenazi Jewish population: a case-control study

<p>Abstract</p> <p>Background</p> <p>Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population.</p> <p>Methods</p> <p>We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, <it>NOD2</it>, <it>IL23R</it>, <it>IRGM</it>, <it>ATG16L1</it>, <it>PTGER4</it>, <it>NKX2-3</it>, <it>IL12B</it>, <it>PTPN2</it>, <it>TNFSF15 </it>and <it>STAT3</it>, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value.</p> <p>Results</p> <p>Three <it>NOD2 </it>SNPs, two <it>IL23R </it>SNPs, and one SNP each at <it>IRGM </it>and <it>PTGER4 </it>were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16).</p> <p>Conclusions</p> <p>CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.</p

Discordant Gene Expression Signatures and Related Phenotypic Differences in Lamin A- and A/C-Related Hutchinson-Gilford Progeria Syndrome (HGPS)

Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N), we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic) and lamin A and C-related (hereditary) HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657) in sporadic and hereditary HGPS, with 83.3% (75/90) concordant and 16.7% (15/90) discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNAK542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS

Atividade eletrencefalográfica paroxística no primeiro ano de vida de pacientes epiléticos

Foram estudadas, do ponto de vista eletrencefalográfico, 80 crianças epiléticas com a finalidade de investigar os aspectos qualitativos e quantitativos dos elementos patológicos paroxísticos. Os resultados demonstraram que: 1) as manifestações paroxísticas focais apareceram de modo dominante nas projeções têmporo-oecipitais; 2) o sono contribuiu para a identificação de duas ou mais alterações simultâneas nos traçados eletrencefalográficos; 3) a atividade paroxística de projeção difusa ou focai, evidencia distribuição topográfica independente do tipo de crise clínica; 4) as características bioelétricas da atividade paroxística não revelam diferenças significativas quando analisadas nos diferentes tipos de crises clínicas; 5) o início focal das crises generalizadas pode ser demonstrado pelo EEG, mas estes focos são em geral inconsistentes e mutantes; 6) o caráter inconstante das manifestações focais, a ausência de descargas generalizadas síncronas e o caráter variável do fenômeno convulsivo clínico, são conseqüências da imaturidade cerebral

Brain-based classification of youth with anxiety disorders: transdiagnostic examinations within the ENIGMA-Anxiety database using machine learning

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we built and validated supervised neuroanatomical machine learning models for individual-level inferences, using a case–control design and the largest known neuroimaging database on youth anxiety disorders: the ENIGMA-Anxiety Consortium (N = 3,343; age = 10–25 years; global sites = 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (panic disorder), but also transdiagnostically for all anxiety disorders when patients were subgrouped according to their sex, medication status and symptom severity (area under the receiver operating characteristic curve, 0.59–0.63). Classifications were driven by neuroanatomical features (cortical thickness, cortical surface area and subcortical volumes) in fronto-striato-limbic and temporoparietal regions. This benchmark study within a large, heterogeneous and multisite sample of youth with anxiety disorders reveals that only modest classification performances can be realistically achieved with machine learning using neuroanatomical data.NWORubicon 019.201SG.022Advanced Behavioural Research MethodsHealth and Well-bein