Sex differences in the influence of type 2 diabetes (T2D)-related genes, parental history of T2D, and obesity on T2D development: a case-control study.

BACKGROUND: This study investigated the effect of sex and age at type 2 diabetes (T2D) diagnosis on the influence of T2D-related genes, parental history of T2D, and obesity on T2D development. METHODS: In this case-control study, 1012 T2D cases and 1008 healthy subjects were selected from the Diabetes in Mexico Study database. Participants were stratified by sex and age at T2D diagnosis (early, ≤ 45 years; late, ≥ 46 years). Sixty-nine T2D-associated single nucleotide polymorphisms were explored and the percentage contribution (R2) of T2D-related genes, parental history of T2D, and obesity (body mass index [BMI] and waist-hip ratio [WHR]) on T2D development was calculated using univariate and multivariate logistic regression models. RESULTS: T2D-related genes influenced T2D development most in males who were diagnosed early (R2 = 23.5%; females, R2 = 13.5%; males and females diagnosed late, R2 = 11.9% and R2 = 7.3%, respectively). With an early diagnosis, insulin production-related genes were more influential in males (76.0% of R2) while peripheral insulin resistance-associated genes were more influential in females (52.3% of R2). With a late diagnosis, insulin production-related genes from chromosome region 11p15.5 notably influenced males while peripheral insulin resistance and genes associated with inflammation and other processes notably influenced females. Influence of parental history was higher among those diagnosed early (males, 19.9%; females, 17.5%) versus late (males, 6.4%; females, 5,3%). Unilateral maternal T2D history was more influential than paternal T2D history. BMI influenced T2D development for all, while WHR exclusively influenced males. CONCLUSIONS: The influence of T2D-related genes, maternal T2D history, and fat distribution on T2D development was greater in males than females.

The prevalence of diabetes worldwide is slightly higher in men than in women, particularly in those aged 50 or younger (16.5% for men versus 13.5% for women). This suggests that hormonal differences could be critical in early development of Type 2 diabetes. Some known factors previously associated with T2D, such as genes, parental history of diabetes and obesity, could have a differential influence between both sexes for the development of T2D. We compared these factors between 1008 healthy individual and 1012 TD2 patients. In this comparison, we calculated the percentage of variability of the disease explained by each factor. As expected, the most noticeable differences between men and women were observed in T2D diagnoses before age 46. Genes had a greater effect in men than in women (23.5% vs. 13.5%). While genes involved in insulin production have a greater influence on men, genes involved in peripheric insulin resistance have a greater influence on women. The overall parental history of T2D influences similarly in males (19.9%) and females (17.5%), however, the unilateral genetic influence of the mother was much greater in males than in females. The influence of global and abdominal obesity played a greater role in men than in women. In T2D diagnoses after age of 45, the influence of genes and parental history of diabetes decreases markedly, and the relative influence of global obesity augments. However, while genes linked to insulin resistance and inflammation predominate in females, genes linked to insulin secretion predominate in males.

GDF11 restricts aberrant lipogenesis and changes in mitochondrial structure and function in human hepatocellular carcinoma cells.

Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features. Recently, it has been reported that GDF11 exerts tumor-suppressive properties in hepatocellular carcinoma cells, decreasing clonogenicity, proliferation, spheroid formation, and cellular function, all associated with a decrement in stemness features, resulting in mesenchymal to epithelial transition and loss of aggressiveness. The aim of the present work was to investigate the mechanism associated with the tumor-suppressive properties displayed by GDF11 in liver cancer cells. Hepatocellular carcinoma-derived cell lines were exposed to GDF11 (50 ng/ml), RNA-seq analysis in Huh7 cell line revealed that GDF11 exerted profound transcriptomic impact, which involved regulation of cholesterol metabolic process, steroid metabolic process as well as key signaling pathways, resembling endoplasmic reticulum-related functions. Cholesterol and triglycerides determination in Huh7 and Hep3B cells treated with GDF11 exhibited a significant decrement in the content of these lipids. The mTOR signaling pathway was downregulated, and this was associated with a reduction in key proteins involved in the mevalonate pathway. In addition, real-time metabolism assessed by Seahorse technology showed abridged glycolysis as well as glycolytic capacity, closely related to an impaired oxygen consumption rate and decrement in adenosine triphosphate production. Finally, transmission electron microscopy revealed mitochondrial abnormalities, such as cristae disarrangement, consistent with metabolic changes. Results provide evidence that GDF11 impairs cancer cell metabolism targeting lipid homeostasis, glycolysis, and mitochondria function and morphology.

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone.

An epidemic of Ebola virus disease (EVD) beginning in 2013 has claimed an estimated 11 310 lives in West Africa. As the EVD epidemic subsides, it is important for all who participated in the emergency Ebola response to reflect on strengths and weaknesses of the response. Such reflections should take into account perspectives not usually included in peer-reviewed publications and after-action reports, including those from the public sector, nongovernmental organizations (NGOs), survivors of Ebola, and Ebola-affected households and communities. In this article, we first describe how the international NGO Partners In Health (PIH) partnered with the Government of Sierra Leone and Wellbody Alliance (a local NGO) to respond to the EVD epidemic in 4 of the country's most Ebola-affected districts. We then describe how, in the aftermath of the epidemic, PIH is partnering with the public sector to strengthen the health system and resume delivery of regular health services. PIH's experience in Sierra Leone is one of multiple partnerships with different stakeholders. It is also one of rapid deployment of expatriate clinicians and logistics personnel in health facilities largely deprived of health professionals, medical supplies, and physical infrastructure required to deliver health services effectively and safely. Lessons learned by PIH and its partners in Sierra Leone can contribute to the ongoing discussion within the international community on how to ensure emergency preparedness and build resilient health systems in settings without either.

PPARα via HNF4α regulates the expression of genes encoding hepatic amino acid catabolizing enzymes to maintain metabolic homeostasis.

The liver is the main organ involved in the metabolism of amino acids (AA), which are oxidized by amino acid catabolizing enzymes (AACE). Peroxisome proliferator-activated receptor-α (PPARα) stimulates fatty acid ß-oxidation, and there is evidence that it can modulate hepatic AA oxidation during the transition of energy fuels. To understand the role and mechanism of PPARα's regulation of AA catabolism, the metabolic and molecular adaptations of Ppara-null mice were studied. The role of PPARα on AA metabolism was examined by in vitro and in vivo studies. In wild-type and Ppara-null mice, fed increasing concentrations of the dietary protein/carbohydrate ratio, we measured metabolic parameters, and livers were analyzed by microarray analysis, histology and Western blot. Functional enrichment analysis, EMSA and gene reporter assays were performed. Ppara-null mice presented increased expression of AACE in liver affecting AA, lipid and carbohydrate metabolism. Ppara-null mice had increased glucagon/insulin ratio (7.2-fold), higher serum urea (73.1 %), lower body protein content (19.7 %) and decreased several serum AA in response to a high-protein/low-carbohydrate diet. A functional network of differentially expressed genes, suggested that changes in the expression of AACE were regulated by an interrelationship between PPARα and HNF4α. Our data indicated that the expression of AACE is down-regulated through PPARα by attenuating HNF4α transcriptional activity as observed in the serine dehydratase gene promoter. PPARα via HNF4α maintains body protein metabolic homeostasis by down-regulating genes involved in amino acid catabolism for preserving body nitrogen.

Conocimiento etnobotanico tradicional y uso de plantas Medicinales en un area rural de la Región Metropolitana de Chile: estudio descriptivo / Traditional ethnobotanical knowledge and use of medicinal plants in a rural area of the metropolitan region of Chile: descriptive study

Con el fin de caracterizar y evaluar el conocimiento botánico perteneciente a la población en el área rural (poco abordado por la etnobotánica) se realizó un estudio a través de encuestas para aprender sobre plantas medicinales cultivadas y utilizadas en una zona rural de la Región Metropolitana (San Juan de Pirque). Las conclusiones son que los usuarios tienen un conocimiento híbrido (producto de los conocimientos tradicionales en combinación con la información de diversos tipos) de plantas medicinales. Hemos encontrado que la mayoría de las especies cultivadas en los jardines botánicos fueron especies introducidas y muy pocos las nativas. También, se les conocía por sus nombres comunes y no se detectaron nuevos nombres no descrito previamente en la literatura.

[Desmoid tumor: report of a case]. / Tumor desmoide: reporte de un caso.

The desmoid tumor is a solid tumor with soft parts and with various possible locations. It is not very frequent and of unknown presentation in our medium. We presented the case of a patient who was treated of extrinsic duodenal obstruction. A compression of the third section of the duodenum was found. The diagnosis was made by pathological anatomy.

Factores dietéticos y ruptura prematura de membranas: efecto de la vitamina C en la degradación de colágena en el corioamnios / Dietetic factors and premature membranes rupture: vitamin C effect on collagen degradation at amniochorion

Diferentes estudios han mostrado asociación entre la disponibilidad de vitamina C ( vit C) y el desarrollo de ruptura prematura de membranas (RPM). Sin embargo, no ha analizado el papel que desempeña la vit C en el metabolismo de la colágena en el tejido corioamniótico. En este trabajo se analizó el efecto de modulación de diferentes concentraciones de vit C en células en cultivo derivativas de amnios humano. Se utilizaron concentraciones de vit C de manera de cubrir el rango fisiológico (29.0 µg/mL). Luego de ser estimuladas, los medios de las células fueron analizados para actividad enzimática de metaloproteasas de matriz extracelular (MMP) y se cuantificó la cantidad relativa de MMP-1, MMP-2 y MMP-9 mediante inmunotransferencia, utilizando anticuerpos policlonales monoespecíficos. Tanto la actividad como la proteína en los medios de las células amnióticas, disminuyó de manera directa a la concentración de vit C, de manera que a las concentraciones más altas probadas (100 µg/mL) se obtuvo la menor actividad/cantidad de MMP. Los resultados anteriores aportan un dato hasta ahora no descrito y que permite establecer una conexión directa entre la disponibilidad de vitamina C y el aumento en la degradación de colágeno. De acuerdo a los resultados, a menor disponibilidad de vit C, mayor degradación de colágena, que debería llevar a pérdida de soporte mecánico y eventual ruptura de las membranas fetales