Cardiovascular Overexpression of XIN Helps prevent Dilated Cardiomyopathy Caused by TNNT2 ΔK210 Mutation.

AIMS/HYPOTHESIS It is unclear whether type 1 diabetes is a single disease or if endotypes exist. Our aim was to use a unique collection of pancreas samples recovered soon after disease onset to resolve this issue. METHODS Immunohistological analysis was used to determine the distribution of proinsulin and insulin in the islets of pancreas samples recovered soon after type 1 diabetes onset ( less then 2 years) from young people diagnosed at age less then 7 years, 7-12 years and ≥13 years. The patterns were correlated with the insulitis profiles in the inflamed islets of the same groups of individuals. C-peptide levels and the proinsulinC-peptide ratio were measured in the circulation of a cohort of living patients with longer duration of disease but who were diagnosed in these same age ranges. RESULTS Distinct patterns of proinsulin localisation were seen in the islets of people with recent-onset type 1 diabetes, which differed markedly between children diagnosed at less then 7 years and those diagnosed at ≥hat correlate with age at diagnosis. Recognition of such differences should inform the design of future immunotherapeutic interventions designed to arrest disease progression.BACKGROUND Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). METHODS A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. RESULTS Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). CONCLUSION ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.Adult spermatogenesis of Polygonia c-aureum was compared between non-diapausing and diapausing butterflies before overwintering. This butterfly has seasonal polyphenism, i.e., summer and autumnal forms. Summer form butterflies that emerged in summer reproduce shortly after emergence, while autumnal forms that emerged in autumn mate in spring. Immatures were reared under either a long photoperiod, which produced the summer form without diapause or under a short photoperiod, which produced the autumnal form with diapause. We found almost no differences in adult spermatogenesis between the two seasonal forms, indicating that adult spermatogenesis is not related to adult diapause. Although adult diapause in the autumnal form is maintained under short photoperiods and terminated under long photoperiods, such a photoperiod did not affect the spermatogenesis of the autumnal form. Our earlier studies indicate that relatively few eupyrene and apyrene sperm are produced after overwintering. Although apyrene spermatogenesis occurred in young adults, eupyrene spermatogenesis did in a small scale before overwintering. These results suggest strongly that male autumnal form butterflies prepare the sperm until overwintering, which had been formed during the larval, pupal and young adult stages.Open-access gene expression data sets provide a useful resource for identifying novel drug targets and biomarkers. The IGF1-PI3K pathway is a critical mediator of physiological cardiac enlargement/hypertrophy and protection. This study arose after mining a gene microarray data set from a previous study that compared heart tissue from cardiac-specific PI3K transgenic mouse models. The top-ranked candidate identified from the microarray data was clusterin. Clusterin has been proposed as a biomarker for multiple diseases including heart failure, and as a cancer drug target. Here, we show that clusterin gene expression is increased in hearts of transgenic mice with increased PI3K and decreased in mice with depressed cardiac PI3K. learn more In vitro, clusterin secretion was elevated in media from neonatal rat ventricular myocytes treated with IGF1. Furthermore, by mining gene expression data from hearts during normal mouse postnatal growth, we also report an increase in clusterin expression with postnatal heart growth. Given we show that clusterin is regulated by the IGF1-PI3K pathway in the heart, and this pathway mediates physiological cardiac hypertrophy and cardioprotection, caution is required when considering clusterin as a biomarker for heart failure and as a cancer target. Mining pre-existing cardiac profiling data sets may be a useful approach to assess whether regulating new drug targets is likely to lead to cardiac damage/toxicity.The cytochrome P450s (CYPs) constitute a family of enzymes maintaining vital functions in the body and are mostly recognized for their significant role in detoxification. Of the CYP subfamilies, CYP3A, is one of the most active in the clearance of drugs and other xenobiotics. During the last decades, much focus has been on exploring different models for human CYP3A regulation, expression and activity. In that respect, the growing knowledge of the porcine CYP3As is of great interest. Although many aspects of porcine CYP3A regulation and activity are still unknown, the current literature provides a basic understanding of the porcine CYP3As that can be used e.g., when translating results from studies done in the porcine model into human settings. In this review, the current knowledge about porcine CYP3A expression, regulation, activity and metabolic significance are highlighted. Future research needs are also identified.learn more