Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control Study and Meta-Analysis.

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTOrs9939609A, HNF1Brs7501939T, HNF1Brs757210T, HNF1Brs4430796G, and JAZF1rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10-5, p = 9.39 × 10-54, p = 5.04 × 10-54, p = 1.19 × 10-71, and p = 1.66 × 10-18, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2rs10923931T and RBMS1rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10-4 and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. In addition to these results, eQTL analysis revealed that the HNF1Brs7501939, HNF1Brs757210, HNF1Brs4430796, NOTCH2rs10923931, and RBMS1rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context.

Manejo actual de la gastroenteritis aguda (GEA) con soluciones de rehidratación oral / Current management of acute gastroenteritis (AGE) with oral rehydration solutions

La gastroenteritis aguda (GEA) es un cuadro clínico caracterizado por diarrea de comienzo brusco, con mayor pérdida de agua por las heces y aumento del nú- mero de deposiciones. Con frecuencia se acompaña de vómitos y a veces cursa con fiebre y dolor abdominal tipo cólico. Es una de las causas más comunes de morbilidad pediátrica especialmente durante los primeros meses de la vida. La mayoría de los procesos se producen en niños menores de 2 años. Puede dividirse en infecciosa o no infecciosa. La infecciosa representa el 80 % y puede estar causada por virus, bacterias y excepcionalmente por hongos o parásitos. Pueden clasificarse de acuerdo al mecanismo fisiopatológico en: secretoras, invasivas, penetrantes, por alteración de la función o por disminución el área de absorción intestinal. El enfoque terapéutico de la GEA se basa en seis pilares considerados de “buena práctica” rehidratación rápida (3-4h), uso de SRO hipoosmolares (Na 60 mes/l, Glu 74-111 mM/l), continuar con la lactancia materna, realimentación precoz con dieta normal adecuada para la edad del niño, suplementar con líquidos de mantenimiento usando las SRO (10ml/kg por deposición) y no aportar medicación innecesaria (AU)

Acute gastroenteritis (AGE) is a clinical condition characterized by sudden appearance of diarrhoea, greater loss of water through faeces and increased number of depositions. Frequently, it is accompanied by vomits and sometimes by fever and abdominal colic-like pain. It is one of the most common causes of paediatric morbidity, especially during the first months of age. Most episodes take place in children under the age of two. AGE can be divided into infectious and non-infectious variants. Infectious variant represents 80% of all AGE and can be caused by virus, bacteria and, exceptionally, by fungus or parasites. AGE may be classified according to its physiopathology mechanism into secretory, invasive, penetrating, function-altering, or by decrease in the intestinal absorption area. The therapeutic approach to GEA is based on six good practice items: early rehydration (3- 4hrs), use of a hypo-osmolar ORS (Na 60 mes/l, Glu 74- 111 mM/l), continuation of breast-feeding, early return to normal diet according to children's age, supplement maintenance-liquids with ORS (10ml/kg per defecation) and not to provide unnecessary medication (AU)