Escherichia coli Enteropatógena en Crías de Primate Aotus (Aotidae) con Diarrea en Cautiverio

Diarrhea is the most common sign of gastrointestinal disease in young primates kept in captivity. The study aimed to isolate and identify bacterial species present in young Aotus with diarrhoea. The animals were reared in captivity for experimental purposes. Faecal samples were collected using rectal swabs from 78 monkeys of 1 to 7 months old of A. nancymae (n=65) and A. vociferans (n=13) with diarrhoea, and 29 apparently healthy monkeys of 1 month old of A. nancymae (n=21) and A. vociferans (n=8) in the period 2002 to 2005. In the healthy group was most commonly identified E. coli, followed by Proteus vulgaris, P. mirabilis and Citrobacter freundii. A similar result was obtained in the group with diarrhea, plus Klebsiella oxytoca and Enterobacter aerogenes. Serotypes of enteropathogenic E. coli (EPEC) identified in the group with diarrhea were seven: O158, O142, O86, O125, O126, O55, and O111. The results showed that young alpacas with diarrhea have bacteria corresponding to the normal intestinal flora, and the primary isolated bacterium was E. coli.La diarrea es el signo más frecuente de enfermedad gastrointestinal en crías de primates mantenidas en cautiverio. El estudio tuvo como objetivo aislar e identificar especies bacterianas presentes en crías de Aotus con diarrea que son criadas en cautiverio con fines experimentales. Se tomaron muestras de heces mediante hisopado rectal a 78 ejemplares de 1 a 7 meses de edad de A. nancymae (n=65) y A. vociferans (n=13) con diarrea y a 29 ejemplares de 1 mes de edad, aparentemente sanos de A. nancymae (n=21) y A. vociferans (n=8), durante el periodo de 2002 a 2005. En el grupo control se identificó principalmente E. coli, además de Proteus vulgaris, P. mirabilis y Citrobacter freundii. Resultado similar fue registrado en el grupo con diarrea, además de Klebsiella oxitoca y Enterobacter aerogenes. Los serotipos de E. coli enteropatógena (EPEC) identificados en el grupo con diarrea fueron siete: O158, O142, O86, O125, O126, O55 y O111. Los resultados indican que las crías con diarrea tienen bacterias que corresponden a la flora intestinal normal, siendo E. coli la de mayor frecuencia

Hepatic encephalopathy-associated cerebral vasculopathy in acute-on-chronic liver failure: Alterations on endothelial factor release and influence on cerebrovascular function

The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F releases were increased, whereas thromboxane (TX) B was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI synthase, and TXA S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE. 1α 2 2 2This research was funded by the Ministerio de Economía y Competitividad (SAF2016-80305-P), CiberCV (Grant number: CB16/11/00286), the European Regional Development Grant (FEDER) (Comunidad de Madrid, grant number B2017/BMD- 3676), and R C D projects for young researchers, Universidad Autónoma de Madrid-Comunidad de Madrid (SI1-PJI-2019- 00321). RR-D received a fellowship from Juan de la Cierva Program (IJCI-2017-31399)

Vitamin D treatment prevents uremia-induced reductions in aortic microRNA-145 attenuating osteogenic differentiation despite hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia

Reconstructing the Indian Origin and Dispersal of the European Roma: A Maternal Genetic Perspective

Previous genetic, anthropological and linguistic studies have shown that Roma (Gypsies) constitute a founder population dispersed throughout Europe whose origins might be traced to the Indian subcontinent. Linguistic and anthropological evidence point to Indo-Aryan ethnic groups from North-western India as the ancestral parental population of Roma. Recently, a strong genetic hint supporting this theory came from a study of a private mutation causing primary congenital glaucoma. In the present study, complete mitochondrial control sequences of Iberian Roma and previously published maternal lineages of other European Roma were analyzed in order to establish the genetic affinities among Roma groups, determine the degree of admixture with neighbouring populations, infer the migration routes followed since the first arrival to Europe, and survey the origin of Roma within the Indian subcontinent. Our results show that the maternal lineage composition in the Roma groups follows a pattern of different migration routes, with several founder effects, and low effective population sizes along their dispersal. Our data allowed the confirmation of a North/West migration route shared by Polish, Lithuanian and Iberian Roma. Additionally, eleven Roma founder lineages were identified and degrees of admixture with host populations were estimated. Finally, the comparison with an extensive database of Indian sequences allowed us to identify the Punjab state, in North-western India, as the putative ancestral homeland of the European Roma, in agreement with previous linguistic and anthropological studies

Validación del "Cuestionario de ansiedad social para adultos" (CASO-A30) en universitarios españoles: similitudes y diferencias entre carreras universitarias y comunidades autónomas

Resumen: El objetivo de este trabajo es presentar las propiedades psicométricas del ?Cuestionario de ansiedad social para adultos? (CASO-A30) con universitarios y analizar las diferencias y similitudes en ansiedad social en esta muestra. Participaron 15504 estudiantes de 20 carreras universitarias de 17 comunidades autónomas españolas a los que se les aplicó el CASO-A30 y la ?Escala de ansiedad social de Liebowitz, versión de autoinforme? (LSAS-SR). Se obtuvieron cinco dimensiones a través de diversos análisis factoriales y de ecuaciones estructurales del CASO-A30: ?Hablar en público/Interacción con personas de autoridad?, ?Interacción con desconocidos?, ?Interacción con el sexo opuesto?, ?Expresión asertiva de molestia, desagrado o enfado? y ?Quedar en evidencia o en ridículo?. La consistencia interna fue de 0,91 y su validez concurrente (con la LSAS-SR) de 0,66. Se hallaron diferencias significativas entre hombres y mujeres, pero escasas diferencias entre las comunidades autónomas y las carreras. Estos resultados confirman la estructura pentafactorial y las buenas propiedades psicométricas del CASO-A30, que lo convierten en un instrumento adecuado para la evaluación de la ansiedad social en universitarios, tanto generalizada como específica, cuidando las diferencias de sexo.Abstract: This work presents the psychometric properties of the Social Anxiety Questionnaire for Adults (SAQ-A30) with university students and analyses the differences and similarities in social anxiety in the sample. The 15,504 participants, students of 20 degree subjects in 17 Spanish Autonomous Community regions, were applied the SAQ-A30 and the ?Liebowitz Social Anxiety Scale-Self Report? (LSAS-SR). A five-factor structure was obtained through several factor analyses as well as an exploratory structural equation modeling of the SAQ-A30: ?Speaking in public/Talking with people in authority?, ?Interactions with strangers?, ?Interactions with the opposite sex?, ?Assertive expression of annoyance, disgust or displeasure?, and ?Criticism and embarrassment?. Internal consistency was 0.91 and concurrent validity (paired with LSAS-SR) was 0.66. Significant differences were found between males and females, but there was scarce difference between regions and subjects studied. These results confirm the five-factor structure and the good psychometric characteristics of the SAQ-A30, which make it a suitable instrument for assessing both general and specific social anxiety in universities, taking into account sex differences.Este estudio ha sido financiado parcialmente por la Fundación para el Avance de la Psicología Clínica Conductual (FUNVECA), el Ministerio de Ciencia y Tecnología de España (BSO2003-07029/PSCE) y el Fondo Europeo de Desarrollo Regional (FEDER)

The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks

Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(−07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10(−05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the