Sexual Practices, Drug Use Behaviors, and Prevalence of HIV, Syphilis, Hepatitis B and C, and HTLV-1/2 in Immigrant and Non-immigrant Female Sex Workers in Argentina

Objective To study socio-demographics, sexual practices, drug use behaviors, and prevalences of HIV, syphilis, hepatitis B and C, HTLV-1 and HTLV-2 in immigrant (foreigner) and non-immigrant (local/native) female sex workers (FSW). Design This was a cross-sectional study in immigrant and non-immigrant FSW living in Buenos Aires, Argentina. Participants were interviewed using a standardized questionnaire. Results A total of 625 FSW were enrolled, of whom 169 (27%) were immigrant FSW from Paraguay, the Dominican Republic, Brazil, Peru, and Uruguay. The prevalence of syphilis and hepatitis C was significantly higher among Argentinean FSW than among immigrant FSW. However, hepatitis B prevalence was higher among immigrant FSW. Adjusted risk factor analysis comparing immigrant FSW with Argentinean FSW indicated that marital status (single), occupation (none), fee per sex act (≤US$7), workplace (bar and cabaret), and anal sex with clients were significantly associated with immigrant FSW status. Conclusions Effective HIV/STI prevention and medical care programs need to be tailored to the specific needs of both FSW groups in Argentina.Fil: Bautista, Christian T.. Walter Reed Army Institute of Research; Estados Unidos. US Naval Medical Research Center Detachment; Estados UnidosFil: Pando, María de los Ángeles. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. University of Maryland; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Reynaga, Elena. Asociación de Mujeres Meretrices de Argentina; ArgentinaFil: Marone, Ruben. NEXO; ArgentinaFil: Sateren, Warren B.. Walter Reed Army Institute of Research; Estados UnidosFil: Montano, Silvia M.. US Naval Medical Research Center Detachment; Estados UnidosFil: Sanchez, Jose L.. US Naval Medical Research Center Detachment; Estados Unidos. Walter Reed Army Institute of Research; Estados UnidosFil: Ávila, María Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia para el Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

La aplicación pos-monta del acetato de fluorogestona en la fertilidad y prolificidad de ovejas pelibuey

Evaluate the effect of vaginal sponges with 40 mg flurogestone acetate (FGA) placed for 12 days after mating on fertility and prolificacy in Pelibuey-ewes. The study was conducted from July to January of next year, 44 Pelibuey cycling-ewes of several ages and parity number were used. The control group was formed by 22 females and 22 treated group. In females of the treated group a vaginal sponge with 40 mg of FGA was applied three days after the service for 12 days, pregnancy diagnosis was performed 30 days later. FGA application increased (P < 0.05) fertility from 63.61% to 81.82%. Total new born lambs were higher (P < 0.01) in the group that received FGA in relationship to Control (20 vs. 32 lambs), and prolificacy was increased (P < 0.01) from 1.42 to 1.78 lambs by parturition in females that received FGA. That vaginal-sponges with 40 mg of FGA three days after service and with a permanency of 12 days before removed promotes reproductive performance in Pelibuey ewes under grassing condition.Evaluar el efecto de esponjas vaginales con 40 mg de acetato de fluorogestona (FGA), colocadas durante 12 días después de la monta, sobre la fertilidad y prolificidad en ovejas Pelibuey. El estudio se realizó de julio a enero del siguiente año, se utilizaron 44 ovejas Pelibuey de diferentes edades y número de parto, con actividad cíclica evidente. El grupo testigo lo formaron 22 hembras y el grupo tratado 22. A las hembras del grupo tratado se les aplicó una esponja vaginal con 40 mg de FGA, tres días después del servicio por 12 días, el diagnóstico de gestación se realizó a los 30 días. La aplicación de FGA incrementó (P < 0.05) la fertilidad de 63.61 a 81.82%. El total de crías en el grupo que recibió FGA fue mayor (P < 0.01) en relación al testigo (20 vs. 32 crías) y la prolificidad fue incrementada (P < 0.01) de 1.42 a 1.78 crías por parto en las hembras que recibieron FGA. La colocación de esponjas vaginales con 40 mg de FGA tres días después del servicio y con una permanencia de 12 días antes de su retiro, promueven la respuesta reproductiva en ovejas Pelibuey bajo condiciones de pastoreo

De novo mutations in epileptic encephalopathies

<p>Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown(1). Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the similar to 4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 x 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 x 10(-10) and P = 7.8 x 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P <10(-8)), as has been reported previously for autism spectrum disorders(2).</p>

Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy

Infantile spasms (IS) and Lennox-Gastaut syndrome (LGS) are epileptic encephalopathies characterized by early onset, intractable seizures, and poor developmental outcomes. De novo sequence mutations and copy number variants (CNVs) are causative in a subset of cases. We used exome sequence data in 349 trios with IS or LGS to identify putative de novo CNVs. We confirm 18 de novo CNVs in 17 patients (4.8%), 10 of which are likely pathogenic, giving a firm genetic diagnosis for 2.9% of patients. Confirmation of exome-predicted CNVs by array-based methods is still required due to false-positive rates of prediction algorithms. Our exome-based results are consistent with recent array-based studies in similar cohorts and highlight novel candidate genes for IS and LGS

Quantitative analysis of phenotypic elements augments traditional electroclinical classification of common familial epilepsies

ObjectiveClassification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks.MethodsWe used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes.ResultsA total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types.SignificanceQuantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox–Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient–parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population