Dominguezfranck0800

Excessive bleeding following cardiac surgery is associated with worse outcomes. We aimed to analyze preoperative and operative factors associated with excessive bleeding in coronary artery bypass patients to better understand which patients are under increased risk.

The study was conducted as an observational study in a tertiary center for cardiac surgery by retrospective analysis of the hospital database. Patients were grouped according to chest tube output within the postoperative 24 h. Patients in the 4th percentile of chest tube output per kilogram were categorized as having excessive bleeding. Patients with excessive bleeding were compared with the other patients for preoperative and operative factors. Factors significant in univariate analysis were carried onto the multivariate analysis.

Patients with excessive bleeding were more likely to be males (91.4% vs. 78.7%, p = .002), have lower body mass index (BMI) (27.4 vs. 29.2, p < .001), and low platelets (6.9% vs. 1.5%, p = .006). Cardiopulmonary bypass (101.8vs. 110.9 min, p = .022) time was longer in the excessive bleeding group. Patients with excessive bleeding were more likely to have more than three vessels revascularized. Male sex, lower BMI, low platelets, and longer cardiopulmonary bypass time were independently associated with increased bleeding.

Male sex, lower BMI, low platelet count, and longer cardiopulmonary bypass time are associated with extensive bleeding after elective coronary artery bypass surgery(CABG). Patients with higher bleeding risk should be identified preoperatively to account for adverse outcomes after CABG.

Male sex, lower BMI, low platelet count, and longer cardiopulmonary bypass time are associated with extensive bleeding after elective coronary artery bypass surgery (CABG). Patients with higher bleeding risk should be identified preoperatively to account for adverse outcomes after CABG.Osteoclast bone resorption activity is critically regulated to maintain bone homeostasis. Osteoclasts resorb bone by producing protons and acid hydrolase via lysosomal secretion, however, a detailed mechanism remains elusive. PMEPA1 is a vesicular membrane protein, which binds to the NEDD4 family member of ubiquitin ligases. We have previously reported that Pmepa1 is highly expressed in bone resorbing osteoclasts, and regulates bone resorption. Here, we investigated the mechanism of bone resorption regulated by PMEPA1. Mutant mice lacking NEDD4-binding domains of PMEPA1 displayed enhanced bone volume, and reduced bone resorption activity in comparison with those of WT mice. Analysis with pH-sensitive fluorescence probe revealed that proton secretion from osteoclasts significantly decreased in Pmepa1 mutant osteoclasts. Immunofluorescence analysis revealed that PMEPA1 was colocalized with NEDD4, V0A3, and V0D2 subunits of vacuolar ATPase, which regulate the proton production of osteoclasts. ISRIB cost In addition, Nedd4 knockdown reduced bone resorption and proton secretion of osteoclasts. Furthermore, Pmepa1 mutation and Nedd4 knockdown altered the cytoplasmic distribution of components of V-ATPase and expression of autophagy-related proteins, suggesting that lysosomal secretion is affected. Collectively, these findings indicate that PMEPA1 controls proton secretion from osteoclasts via NEDD4 by regulating vesicular trafficking, and NEDD4 is an important regulator of bone resorption.A robust activity of the lysosomal Ca2+ channel TRPML1 is sufficient to correct cellular defects in neurodegeneration. Importantly, lysosomes are refilled by the endoplasmic reticulum (ER). However, it is unclear how TRPML1 function could be modulated by the ER. Here, we deal with this issue in rat primary cortical neurons exposed to different oxygen conditions affecting neuronal survival. Under normoxic conditions, TRPML1 (1) showed a wide distribution within soma and along neuronal processes; (2) was stimulated by the synthetic agonist ML-SA1 and the analog of its endogenous modulator, PI(3,5)P2 diC8; (3) its knockdown by siRNA strategy produced an ER Ca2+ accumulation; (4) co-localized and co-immunoprecipitated with the ER-located Ca2+ sensor stromal interacting molecule 1 (STIM1). In cortical neurons lacking STIM1, ML-SA1 and PI(3,5)P2 diC8 failed to induce Ca2+ release and, more deeply, they induced a negligible Ca2+ passage through the channel in neurons transfected with the genetically encoded Ca2+ indicator GCaMP3-ML1. Moreover, TRPML1/STIM1 interplay changed at low-oxygen conditions both proteins were downregulated during the ischemic preconditioning (IPC) while during IPC followed by 1 hour of normoxia, at which STIM1 is upregulated, TRPML1 protein was reduced. However, during oxygen and glucose deprivation (OGD) followed by reoxygenation, TRPML1 and STIM1 proteins peaked at 8 hours of reoxygenation, when the proteins were co-immunoprecipitated and reactive oxygen species (ROS) hyperproduction was measured in cortical neurons. This may lead to a persistent TRPML1 Ca2+ release and lysosomal Ca2+ loss. Collectively, we showed a new modulation exerted by STIM1 on TRPML1 activity that may differently intervene during hypoxia to regulate organellar Ca2+ homeostasis.

The main objective of this prospective and observational study was to investigate the effect of the preoperative hospitalisation period on early postoperative cognitive dysfunction (POCD) development in patients undergoing total hip replacement surgery under regional anaesthesia.

Between November 2013 and September 2014, 64 patients were enrolled in the study. Mini Mental Test (MMT) scores were obtained on the initial admission day (MMT1), 24hours prior to the surgery (MMT2) and 24hours after the surgery (MMT3). The patients were divided into two groups according to the MMT scores 'no cognitive dysfunction' (group 1) and 'cognitive dysfunction' (group 2). Differences between the groups were evaluated statistically. The statistical significance level was set as P<.05 in a 95% confidence interval.

The POCD incidence rate was calculated as 43.8% in all patients. The preoperative hospitalisation duration was significantly longer in patients with POCD than in patients without POCD (P<.001). The factors that affected POCD development were found to be advanced age (P<.001), high American Society of Anesthesiologists scores (P=.004), the presence of comorbid disease (P=.025), durations of surgery (P=.018) and decreased postoperative haematocrit levels (P=.014).

In this study, we observed that patients with early POCD had relatively longer preoperative hospitalisation periods than those in patients without POCD. We consider that prolonged preoperative hospitalisation may contribute to increased POCD incidence rates in patients with risk factors.

In this study, we observed that patients with early POCD had relatively longer preoperative hospitalisation periods than those in patients without POCD. We consider that prolonged preoperative hospitalisation may contribute to increased POCD incidence rates in patients with risk factors.Caulis Lonicerae, the dried stem of Lonicera japonica, has been confirmed to have antiinflammatory and antioxidant therapeutic effects. In the present study, we aimed to evaluate the functional mechanism of glycosides extracted from Caulis Lonicerae on the inflammatory proliferation of interleukin-1 beta (IL-1β)-mediated fibroblast-like synoviocytes (FLSs) from rats. Rat FLSs (RSC-364) co-cultured with lymphocytes induced by IL-1β were used as a cell model. Glycosides in a freeze-dried powder of aqueous extract from Caulis Lonicerae were identified using high-performance liquid chromatography-electrospray ionization/mass spectrometry. After treatment with glycosides, the inflammatory proliferation of FLS, induced by IL-1β, decreased significantly. Flow cytometry analysis showed that treatment with glycosides restored the abnormal balance of T cells by intervening in the proliferation and differentiation of helper T (Th) cells. Glycosides also inhibited the activation of Janus kinase signal transducer and activator of transcription (JAK-STAT) and nuclear factor (NF)-κB signaling pathways by suppressing the protein expression of key molecules in these pathways. Therefore, we concluded that the glycosides of Caulis Lonicerae can intervene in the differentiation of Th cells, suppressing the activation of JAK-STAT and NF-κB signaling pathways, contributing to the inhibitory effect on inflammatory proliferation of FLS co-cultured with lymphocytes induced by pro-inflammatory cytokines.Tissue-resident macrophages are required for homeostasis, but also contribute to tissue dysfunction in pathophysiological states. The sympathetic neurotransmitter norepinephrine (NE) induces an anti-inflammatory and tissue-reparative phenotype in macrophages. As NE has a well-established role in promoting triglyceride lipolysis in adipocytes, and macrophages accumulate triglyceride droplets in various physiological and disease states, we investigated the effect of NE on primary mouse bone marrow-derived macrophage triglyceride metabolism. Surprisingly, our data show that in contrast to the canonical role of NE in stimulating lipolysis, NE acting via beta2-adrenergic receptors (B2ARs) in macrophages promotes extracellular fatty acid uptake and their storage as triglycerides and reduces free fatty acid release from triglyceride-laden macrophages. We demonstrate that these responses are mediated by a B2AR activation-dependent increase in Hilpda and Dgat1 gene expression and activity. We further show that B2AR activation favors the storage of extracellular polyunsaturated fatty acids. Finally, we present evidence that macrophages isolated from hearts after myocardial injury, for which survival critically depends on leukocyte B2ARs, have a transcriptional signature indicative of a transient triglyceride accumulation. Overall, we describe a novel and unexpected role of NE in promoting triglyceride storage in macrophages that could have potential implications in multiple diseases.Anti-vascular endothelial growth factor (VEGF) therapies are now the first-line treatment for many ocular diseases, but some patients are non-responders to these therapies. The purpose of this study was to determine whether the level of adiponectin increased the pathogenesis of retinal edema and neovascularization in the retina of progressive ocular vascular diseases. We examined the role played by adiponectin in two types of cells and animal models which are retinal vein occlusion (RVO) and oxygen-induced retinopathy (OIR) mice. Our results showed that an injection of anti-adiponectin antibody ameliorated the retinal edema and ischemia through the depression of the expression level of VEGF-related factors and tight junction-related proteins in the retina of RVO mice. The intravitreal injection of anti-adiponectin antibody also decreased the degree of retinal neovascularization in an OIR mice. In addition, exposure of human retinal microvascular endothelial cells and human brain microvascular pericytes in culture to adiponectin increased both the vascular permeability and neovascularization through the increase of inflammatory factor and the dropout of the pericytes. These findings indicate that adiponectin plays a critical role in retinal edema and neovascularization, and adiponectin is a potential therapeutic target for the treatment of diabetic macular edema, proliferative diabetic retinopathy, and RVO.