Shermanflynn8746

Aims Sodium-glucose co-transporter 2 (SGLT2) were originally developed as kidney-targeting anti-diabetic drugs. However, due to their beneficial cardiac off-target effects (as SGLT2 is not expressed in the heart), these antagonists currently receive intense clinical interest in the context of heart failure (HF) in patients with or without diabetes mellitus (DM). Since the mechanisms by which these beneficial effects are mediated are still unclear yet, inflammation that is present in DM and HF has been proposed as a potential pharmacological intervention strategy. Therefore, we tested the hypothesis that the SGLT2 inhibitor, empagliflozin, displays anti-inflammatory potential along with its glucose-lowering property. Methods and results Lipopolysaccharide (LPS) was used to induce inflammation in vitro and in vivo. In cardiomyocytes and macrophages empagliflozin attenuated LPS-induced TNFα and iNOS expression. Analysis of intracellular signalling pathways suggested that empagliflozin activates AMP kinase (AMPK) in both cell types with or without LPS-treatment. Moreover, the SGLT2 inhibitor increased the expression of anti-inflammatory M2 marker proteins in LPS-treated macrophages. Additionally, empagliflozin-mediated AMPK activation prevented LPS-induced ATP/ADP depletion. In vivo administration of LPS in mice impaired cardiac contractility and aortic endothelial relaxation in response to acetylcholine, whereby co-administration of empagliflozin preserved cardiovascular function. These findings were accompanied by improved cardiac AMPK phosphorylation and ATP/ADP, reduced cardiac iNOS, plasma TNFα and creatine kinase MB levels. Conclusion Our data identify a novel cardio protective mechanism of SGLT2 inhibitor, empagliflozin, suggesting that AMPK activation-mediated energy repletion and reduced inflammation contribute to the observed cardiovascular benefits of the drug in HF.Objective During the 2013-2016 period, Dengue, Chikungunya, and Zika affected more than 1 million people in Colombia. These arboviruses and their chronic manifestations pose a public health challenge. Therefore, we estimated the burden of disease by Dengue, Chikungunya, and Zika in Colombia between 2013-2016. Methods An exploratory ecological study was carried out using the disability-adjusted life years (DALYs) as a unit of measure. The mortality databases of the National Administrative Department of Statistics (DANE) and the morbidity databases of the National Public Health Surveillance System (SIVIGILA) were used. Deaths and cases for each arbovirus were grouped and then adjusted to control biases. Subsequently, we performed a sensitivity analysis. Results In the 2013-2016 period, 491,629.2 DALYs were lost due to arboviruses in Colombia. 26.6% of the DALYs corresponded to Dengue, 71.3%, to Chikungunya and; the remaining 2.2%, to Zika. The chronic complications represented 68.2%. The departments of Valle del Cauca, Tolima, Norte de Santander, Huila, and Bolívar represented 50.5% of the total DALYs. Conclusion The burden of disease by arboviruses in the 2013-2016 period exceeded the burden of other infectious diseases such as HIV/AIDS and tuberculosis in Colombia. Public health efforts must be made to mitigate new epidemics of these arboviruses.Medulloblastoma with myogenic differentiation is not a distinct entity but a pattern of differentiation seen in less then 1% of medulloblastomas. Although squash cytology of medulloblastoma is well described, there are no reports available describing squash cytomorphology of this unusual variant of medulloblastoma. Intraoperative squash smears on a 2-year-old girl with a midline posterior fossa space occupying lesion revealed features of an embryonal tumor composed of small, round, and blue cells. In addition, it had several large, round, eosinophilic rhabomyoblasts, and a few strap cells scattered among the sea of small blue cells. Subsequent histology showed features of a medulloblastoma, classic type with myogenic differentiation. Molecular subtyping, based on immunohistochemistry alone, was in keeping with a non-Wnt/non-SHH activated type. Here we describe the squash cytomorphological details of a case of medulloblastoma with myogenic differentiation, along with its cytological differentials.The association of severe dry eye disease with elevated osmolarity in the tear film is a subject of ongoing discussions. As the absolute value of osmolarity in tear film is highly variable, the daily variation in osmolarity (DVO) has recently been proposed to further identify the osmotic stress at the ocular surface. GSK1838705A cell line However, the DVO alone does not explain the variations in the available published data or allow their use in diagnostic testing or therapy. We therefore investigated and evaluated further details of osmokinetics and their importance for ocular surface disease on the basis of the available literature. Additionally, osmolarity was measured in the tear samples of volunteers in the morning hours between 8 - 10 a. m., midday noon-2 p. m., and afternoon between 3 - 5 p. m., i.e., during normal office hours. The results were compared with available published data which suggested that within the DVO, the daily maximal amplitude of osmotic variation (M-DVO) and the frequency of osmotic cycles (defined as daily osmolarity cycles, DOC) could be the main factors that further characterize osmokinetics. In addition, a decisive role could be the level of osmolarity at which the variation does occurs (L-DVO). The possible effects of these characteristics on ocular surface pathophysiology are discussed, along with their relationship to topical therapy with hypo-osmolar solutions, and the model of the osmotic roller coaster is introduced.Objective To study the structural and immunohistochemical features of placentas in women after assisted reproductive technology (ART) with allogeneic eggs (oocyte donation and surrogate motherhood). Study design The study involved 89 women whose pregnancy occurred as a result of in vitro fertilization (IVF) with a donor egg in a surrogate motherhood program (IVF-SM, n = 47 patients) or oocyte donation (IVF-DO, n = 42). The comparison group consisted of 21 patients in whom pregnancy occurred as a result of IVF with their own egg (IVF-OE). A clinical and anamnestic analysis of the pregnant women was carried out. Morphological and immunohistochemical studies were performed on placental material. Immunohistochemical analysis of CD8, CD56, CD138, and CD25/CD4 markers indicating the processes of impaired tolerance in placenta was carried out. -Results We observed a predominance of women aged >40 (range 42.7-3.91) years with a burdened somatic and obstetric-gynecological history and a high incidence of hypertensive pregnancy complications, such as gestational arterial hypertension (27.