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Mcmillan MacMillan posted an update 6 months, 3 weeks ago
Flow cytometry allows multiparameter analysis on a single-cell basis and is currently the method of choice to rapidly assess heterogeneity of cell populations in suspension. With the research field of extracellular vesicles (EV) rapidly expanding, there is an increased demand to address heterogeneity of EV populations in biological samples. Although flow cytometry would be the ideal technique to do so, the available instruments are in general not equipped to optimally detect the dim light scatter signals generated by submicron-sized particles like EV. Although sideward scatter light and fluorescence are currently used as a threshold signal to identify EV within samples, the forward scatter light (FSC) parameter is often neglected due to the lack of resolution to distinguish EV-related signals from noise. However, after optimization of FSC detection by adjusting the size of the obscuration bar, we recently showed that certain EV-subsets could only be identified based on FSC. This observation made us to further. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.Tacrolimus (Tac) is an effective anti-rejection agent in kidney transplantation, but its off-target effects make withdrawal desirable. Although studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs unsuccessful Tac removal are unknown. https://www.selleckchem.com/products/tiplaxtinin-pai-039.html We performed microarray analyses of peripheral blood mononuclear cells (PBMC) RNA from subjects enrolled in the Clinical Trials in Organ Transplantation-09 study in which we randomized stable kidney transplant recipients to Tac withdrawal or maintenance of standard immunosuppression beginning 6 months after transplant. Eight of 14 subjects attempted but failed withdrawal, while six developed stable graft function for ≥2 years on mycophenolate mofetil plus prednisone. Whereas failed withdrawal upregulated immune activation genes, successful Tac withdrawal was associated with a downregulatory and proapoptotic gene program enriched within T cells. Functional analyses suggested stronger donor-reactive immunity in subjects who failed withdrawal without evidence of regulatory T cell dysfunction. Together, our data from a small, but unique, patient cohort support the conclusion that successful Tac withdrawal is not simply due to absence of donor-reactive immunity but rather is associated with an active immunological process.Background Recovery of gastrointestinal function is often delayed after major abdominal surgery, leading to postoperative ileus (POI). Enhanced recovery protocols recommend laxatives to reduce the duration of POI, but evidence is unclear. This systematic review aimed to assess the safety and efficacy of laxative use after major abdominal surgery. Methods Ovid MEDLINE, Embase, Cochrane Library and PubMed databases were searched from inception to May 2019 to identify eligible RCTs focused on elective open or minimally invasive major abdominal surgery. The primary outcome was time taken to passage of stool. Secondary outcomes were time taken to tolerance of diet, time taken to flatus, length of hospital stay, postoperative complications and readmission to hospital. Results Five RCTs with a total of 416 patients were included. Laxatives reduced the time to passage of stool (mean difference (MD) -0·83 (95 per cent c.i. -1·39 to -0·26) days; P = 0·004), but there was significant heterogeneity between studies for this outcome measure. There was no difference in time to passage of flatus (MD -0·17 (-0·59 to 0·25) days; P = 0·432), time to tolerance of diet (MD -0·01 (-0·12 to 0·10) days; P = 0·865) or length of hospital stay (MD 0·01(-1·36 to 1·38) days; P = 0·992). There were insufficient data available on postoperative complications for meta-analysis. Conclusion Routine postoperative laxative use after major abdominal surgery may result in earlier passage of stool but does not influence other postoperative recovery parameters. Better data are required for postoperative complications and validated outcome measures.While most of the time unconsidered, child and adolescent obesity has been also associated with impaired brain health and function that can definitely affect their social interaction and integration, and then well-being and mental health. The European Childhood Obesity Group recently gathered experts in the field who discussed the main available and reliable evidence regarding the role of physical activity on brain health and cognitive functioning in children and adolescents with obesity and who propose here their main conclusions and recommendations.Background Several somatic mutations in TRAF7 have been reported in cancers, whereas a few germline heterozygous mutations have been recently linked to a neurodevelopmental disorder, characterized by craniofacial dysmorphisms, congenital heart defects, and digital anomalies. Cases We report two subjects harboring de novo heterozygous missense variants in TRAF7, namely the recurrent 1964G>A(p.Arg655Gln) and the novel missense c.1204C>G(p.Leu402Val) variants. In addition to the typical hallmarks of the TRAF7-related disorder, both subjects presented with a recognizable “pear-shaped” skull due to multiple craniosynostosis, sinus pericranii, skull base/cranio-cervical junction anomalies, dysgyria, and inferior cerebellar vermis hypoplasia. Conclusions Hence, we expand the genotypic and phenotypic spectrum of this neurodevelopmental disorder, discussing possible implications for clinical management of subjects with germline TRAF7 mutations.Introduction The histopathological changes and immunohistochemical studies occurring in keloids in vivo after treatment by intralesional (IL) verapamil are not yet assessed. This study aimed to evaluate the efficacy and safety as well as the histological/immunohistochemical effects of intralesional verapamil on keloids. Patients and methods Thirty-one patients with 43 keloids were treated with IL verapamil at 3-week intervals until reaching complete flattening of the lesion or for a maximum of 6 sessions. Keloid biopsies were obtained before and after treatment for evaluation of histopathological changes and the immunohistochemical expression of VEGF and MMP9. Results Of 43 keloids, 6 keloids (14%) and 17 (39.5%) showed excellent and good improvement, respectively, with no significant side effects except for pain at the site of injection. Histopathological and immunohistochemical evaluations were consistent with the clinical observations after treatment, and there was a statistically significant decrease in VEGF and MMP9 expressions after treatment.