Hedecoffey1081
BACKGROUND Receptor tyrosine kinases of the epidermal growth factor receptor (EGFR) family such as human epidermal receptor-2 (HER2) are involved in the development and progression of esophageal adenocarcinoma (EAC). Prior studies have demonstrated that group IIa secretory phospholipase A2 (sPLA2 IIa) can function as a ligand for the EGFR family of receptors and lead to an increase in receptor signaling. AIMS We hypothesized that sPLA2 IIa inhibition downregulates the expression of EGFR and HER-2 in EAC and through this mechanism decreases proliferation in EAC. METHODS Normal human esophageal epithelium, Barrett's esophagus (BE), and EAC tissue samples were assayed for baseline expression of EGFR, HER-2, and sPLA2 IIa. sPLA2 IIa was attenuated via inhibitor or lentiviral knockdown in esophageal cell lines, and cells were assayed for EGFR and HER2 expression as well as proliferation. FLO1 EAC cells were injected into the flank of nude mice. After randomization, mice received daily group IIA sPLA2 inhibitor or a control solution, and tumor volume was measured with calipers. RESULTS sPLA2 IIa, EGFR, and HER2 expression increased across the spectrum of normal esophageal epithelium to EAC. sPLA2 IIa inhibition and knockdown decreased the expression of HER-2 and EGFR and proliferation. Mice treated with sPLA2 IIa inhibitor had smaller tumors than controls. CONCLUSIONS sPLA2 IIa inhibition decreases EGFR and HER2 expression and lowers proliferation of human EAC. The discovery of sPLA2 IIa inhibition's ability to attenuate growth factor receptor signaling underscores the exciting potential of sPLA2 IIa inhibitors as therapeutics in the treatment of EAC.INTRODUCTION Due to the paucity of randomized controlled trials, meta-analyses of incisional hernia repair can hardly give any insights into the influence factors on the various outcome criteria. Therefore, a multivariable analysis of data from the Herniamed Registry was undertaken with the aim to define potential influencing factors for the outcome. METHODS Multivariable analysis of the data available for 22,895 patients with primary elective incisional hernia repair was performed to assess the confirmatory predefined potential influence factors and their association with the perioperative and 1-year follow-up outcomes. A model validation procedure was implemented using a bootstrap algorithm in order to account for the robustness of results. RESULTS Higher European Hernia Society (EHS) width classification, open procedure, female gender, and preoperative pain have a highly significant association with an unfavorable outcome in incisional hernia repair. Larger defect width and open operation have a highly significantly unfavorable relation to the postoperative surgical complications, general complications, and the complication-related reoperations, while female gender and preoperative pain have a highly significantly unfavorable association with the rates of pain at rest, pain on exertion, and chronic pain requiring treatment at 1-year follow-up. The recurrence rate is significantly unfavorably influenced by higher EHS width classification, higher BMI, and lateral EHS classification. CONCLUSION Higher EHS width classification, open procedure, female gender, higher BMI, and lateral EHS classification, as well as preoperative pain are the most important unfavorable influencing factors associated with a worse outcome in incisional hernia repair.INTRODUCTION Currently, the need for additional myofascial release (AMR) in addition to retromuscular dissection during open Rives-Stoppa hernia repair is determined intraoperatively based on the discretion of the surgeon. We developed a novel method to objectively predict the need for AMR preoperatively using computed tomography (CT)-measured rectus width to hernia width ratio (RDR). METHODS A retrospective chart review of all patients who underwent open retro-muscular mesh repair of midline ventral hernia between August 1, 2007 and February 1, 2018, who had a preoperative CT scan within 1 year prior to their operation. The primary endpoint was the ability of the defect ratio to predict the need for AMR in pursuit of fascial closure. The secondary endpoint was the ability of Component Separation Index (CSI) to predict the need for AMR to obtain fascial closure. RESULTS Of 342 patients, 208 repaired with rectus abdominis release alone (RM group), while 134 required AMR (RM + group). An RDR of > 1.34 on area under the curve analysis predicted the need for AMR with 77.6% accuracy. There was a linear decrease in the need for AMR with increasing RDR RDR 2 portends fascial closure with rectus abdominis myofascial release alone in 90% of cases.The thymus plays an integral role in immune system regulation, modulating the development, diversity, and selection of T lymphocytes, a critical feature for the prevention of T cell-mediated autoimmunity. Thymoma is a rare tumor of the thymus. Autoimmune diseases and paraneoplastic syndromes such as myasthenia gravis, pure red blood cell aplasia, and systemic lupus erythematosus, although relatively uncommon, have been described in association with thymomas. Rare cases of post-thymectomy autoimmune related diseases, including systemic lupus erythematosus and pure red cell aplasia, have been reported in the literature. Here, we present the case of a 65-year-old male who developed systemic lupus erythematosus 2 years after thymectomy in the setting of thymoma-associated pure red cell aplasia.The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren's syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still's disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. , acute interstitial pneumonia, myocarditis, leucopenia, lymphopenia, thrombocytopenia and cytokine storm with features akin to secondary hemophagocytic lymphohistiocytosis.• Although preliminary results may be encouraging, high-quality clinical trials are needed to better understand the role of drugs commonly used in rheumatology like hydroxychloroquine and tocilizumab in COVID-19.• Until further evidence emerges, it may be cautiously recommended to continue glucocorticoids and other disease-modifying antirheumatic drugs (DMARDs) in patients receiving these therapies, with discontinuation of DMARDs during infections as per standard practice.OBJECTIVE This study addresses racial/ethnic differences in adverse health care utilization among individuals with comorbid anxiety disorder and cardiometabolic syndrome (CMetS) risk factors. METHODS Utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data, logistic regression models were estimated to determine the likelihood of receiving CMetS-related medical treatment in the emergency department (ED) or via inpatient services and to determine if the likelihood is associated with race/ethnicity. Adjusted models controlled for age, sex, and insurance type. RESULTS Significant racial-ethnic differences were observed for utilization (any emergency department and/or inpatient visit). The odds of non-Hispanic Black respondents reporting emergency department and/or inpatient utilization was 2.39 (p less then 0.05) times the odds of non-Hispanic White respondents. CONCLUSION Racial-ethnic variation in adverse healthcare utilization suggests an opportunity to improve care and outcomes for persons diagnosed with comorbid anxiety disorder and cardiometabolic syndrome. Integrated interventions could simultaneously improve mental health and facilitate CMetS disease self-management.BACKGROUND AND OBJECTIVE Bentysrepinine (Y101), a derivative of repensine (a compound isolated from Dichondra repens Forst), is a novel phenylalanine dipeptide currently under development for the treatment of hepatitis B virus (HBV). The objectives of these studies were to assess the safety, tolerability and pharmacokinetics of bentysrepinine in healthy Chinese subjects. METHODS Two randomised, double-blind, placebo-controlled trials evaluated a single oral dose (50-900 mg, study 01) and multiple doses (300 mg and 600 mg, study 02), and a randomised, open, crossover food-effect study (600 mg, study 03) of bentysrepinine was established. Safety and tolerability were assessed by adverse event (AE) reporting, clinical laboratory tests, physical examinations, vital sign monitoring and electrocardiogram (ECG). Plasma, urine and faecal samples were analysed using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods to investigate the pharmacokinetics of bentysrepinine. RESULTS Ninety-four sub, and CTR20140543 (www.chinadrugtrials.org.cn).BACKGROUND As waxy maize is considered a key economic crop in Korea, an understanding of its genetic variation and differentiation is fundamental for the selective plant breeding. The maize genome is primarily composed of transposable elements, for which large and stable insertions generate variations that reflect selection during evolution. OBJECTIVES This study was to elucidate the genetic diversity based on the contribution of TEs and to investigate the effect of Mu transposition on the genetic divergence of waxy and common maize. We also performed an association analysis on these inbred lines to determine the Mu insertions associated with agronomic traits. METHODS In this study, we utilized a Mutator-based transposon display method to study the genetic diversity and population structure of 40 waxy and 40 common inbred lines of maize in the Gangwon Agricultural Research and Extension Services collection at the Maize Research Institute. RESULTS We detected polymorphisms in 86.33% of 278 Mutator (Mu) anchored loci, reflecting the activity of the Mu element and its contribution to genetic variation. Common maize showed a substantial amount of genetic diversity, which was greater than that observed in waxy maize. Principal-coordinate and neighbor-joining cluster analyzes consistently supported the presence of two genetically distinct groups. However, the distribution of genetic variation within the populations was much higher than the genetic differentiation among the populations. To explore the contribution of the Mu element to phenotypic variation, we analyzed the associations with ten important agronomical traits. On the basis of the combined results from two models (QGLM and Q + KLM), we found significant associations between seven Mu loci and four different traits. CONCLUSIONS These results will assist waxy maize breeders in choosing parental lines and be useful for marker-assisted selection.