miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea.

OBJECTIVE: Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. DESIGN: Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. RESULTS: IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. CONCLUSIONS: Modulation of the intestinal epithelial barrier function in IBS-D involves both transcriptional and post-transcriptional mechanisms. These molecular mechanisms include miRNAs as master regulators in controlling the expression of TJ proteins and are associated with major clinical symptoms.

Malnutrition determinants in young children from Burkina Faso.

Childhood malnutrition remains a major challenge to public health in poor countries. Data on malnutrition determinants in African children are scarce. A cross-sectional survey was performed in eight villages of Burkina Faso in June 2009, including 460 children aged 6-31 months. Demographic, socioeconomic, parasitological, clinical and anthropometric characteristics were collected. The main outcome variable was weight-for-length (WFL) z-score (i.e. wasting). A multiple regression model identified village, age group, religion and the presence of younger siblings as significantly associated with wasting. Villages differed in their mean WFL z-score by up to one unit. Compared with younger children, the mean WFL z-score of children aged 24-35 months was 0.63 units higher than the WFL z-score in younger children. This study confirms the still unacceptable high level of malnutrition in young children of rural West Africa and supports the fact that childhood malnutrition is a complex phenomenon highly influenced by contextual variables.

Association of HLA-DRB1, interleukin-6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population--a candidate gene approach.

High-risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case-control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population-based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL-6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79-0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78-0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02-1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04-1.45 and OR = 1.29, 95% CI: 1.11-1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47-0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle.

Anomalías de Forma Dentaria / Dental shape anomalies

Se plantea que las Anomalías dentarias, son producto a fallas durante el desarrollo embrionario que ocasionan modificaciones estructurales en los tejidos dentarios duros. No todos los dientes sufren por igual estas alteraciones, se dice los permanentes son los más afectados, quizás por su posición secundaria en la lámina dental y dentro de ellos, los últimos de cada grupo dentario. Existen Anomalías de Número, de Tamaño, anomalías en la Estructura dental y de Formas, siendo esta última la más común. Dentro de estas alteraciones se encontraron la Fusión, Germinación, Concrescencia, Perla del esmalte, Taurodontismo, Dens in Dente, Dilaceración. Los dientes afectados son funcionalmente incapaces para realizar las funciones asignadas porque no presentan la morfología que los caracteriza, la magnitud de la incapacidad depende del grado de afectación. La mayor parte de estas variantes patológicas de la forma afectan a la corona del diente; mientras que algunas son relativamente frecuentes, la mayoría es poco prevalente, incluso afectan a grupos étnicos concretos. A continuación, se presenta un caso clínico de una de estas alteraciones morfológicas que, concretamente, afecta a la corona de un diente anterior.[AU]