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Astrocyte heterogeneity is an emerging concept in which astrocytes within or between brain regions show variable morphological and/or gene expression profiles that presumably reflect different functional roles. Recent evidence indicates that retrotrapezoid nucleus (RTN) astrocytes sense changes in tissue CO2/ H+ to regulate respiratory activity; however, mechanism(s) by which they do so remain unclear. Alterations in inward K+ currents represent a potential mechanism by which CO2 /H+ signals may be conveyed to neurons. Here, we use slice electrophysiology in rats of either sex to show that RTN astrocytes intrinsically respond to CO2 /H+ by inhibition of an inward rectifying potassium (Kir ) conductance and depolarization of the membrane, while cortical astrocytes do not exhibit such CO2 /H+ -sensitive properties. Application of Ba2+ mimics the effect of CO2 /H+ on RTN astrocytes as measured by reductions in astrocyte Kir -like currents and increased RTN neuronal firing. These CO2 /H+ -sensitive currents increase developmentally, in parallel to an increased expression in Kir 4.1 and Kir 5.1 in the brainstem. Finally, the involvement of Kir 5.1 in the CO2 /H+ -sensitive current was verified using a Kir5.1 KO rat. These data suggest that Kir inhibition by CO2 /H+ may govern the degree to which astrocytes mediate downstream chemoreceptive signaling events through cell-autonomous mechanisms. These results identify Kir channels as potentially important regional CO2 /H+ sensors early in development, thus expanding our understanding of how astrocyte heterogeneity may uniquely support specific neural circuits and behaviors.High-throughput biological data-such as mass spectrometry (MS)-based proteomics data-suffer from systematic non-biological variance due to systematic errors. This hinders the estimation of "real" biological signals and, in turn, decreases the power of statistical tests and biases the identification of differentially expressed proteins. To remove such unintended variation, while retaining the biological signal of interest, analysis workflows for quantitative MS data typically comprise normalization prior to their statistical analysis. Several normalization methods, such as quantile normalization (QN), have originally been developed for microarray data. In contrast to microarray data proteomics data may contain features, in the form of protein intensities that are consistently high across experimental conditions and, hence, are encountered in the tails of the protein intensity distribution. If QN is applied in the presence of such proteins statistical inferences of the features' intensity profiles are impeded due to the biased estimation of their variance. A freely available, novel approach is introduced which serves as an improvement of the classical QN by preserving the biological signals of features in the tails of the intensity distribution and by accounting for sample-dependent missing values (MVs) The "tail-robust quantile normalization" (TRQN).Limited data exist regarding the impact of donation after circulatory death (DCD) allografts on outcomes following liver transplantation in fulminant hepatic failure (FHF). Utilizing the Scientific Registry of Transplant Recipients (SRTR), we compared outcomes after DCD in FHF to donation after brain death (DBD) in FHF and DCD in non-FHF over a 15-year period. selleck chemicals Primary outcome measures were graft and patient survival. A total of 117, 3437, and 4379 recipients underwent DCD-FHF, DBD-FHF and DCD-non-FHF, respectively. One-year graft survival in DCD-FHF was inferior to DBD-FHF (72.9% vs. 83.8%, p = .002), but comparable to DCD-non-FHF (72.9% vs. 82.7%, p = .23). However, 3- and 5-year graft survival in DCD-FHF were comparable to DBD-FHF (67.9 vs. 77.6%, p = .63; 57.8% vs. 73.2%, p = .27) and DCD-non-FHF (67.9% vs. 72.9%, p = .44; 57.8% vs. 66.6%, p = .06). One-, 3-, and 5-year patient survival were also comparable among the three groups. Graft and patient survival in DCD-FHF improved over the study period. Multivariable analysis identified recipient age, male gender, African American ethnicity, donor age, and cold ischemia time as predictors of graft and patient survival in FHF, while DCD status was only predictive of graft survival. Long-term graft survival and patient survival in DCD-FHF are comparable to DBD-FHF and DCD-non-FHF. Consideration of DCD in FHF could help expand the donor pool in this subset of critically ill patients.
Rectal prolapse is an uncommon but debilitating pelvic floor disorder that significantly decreases the quality of life of affected patients. Perineal stapled prolapse resection is a relatively new perineal approach that offers an promising alternative technique in the surgical management of rectal prolapse. It appears to be a simple, reproducible and efficient method. However, long-term outcomes are limited. The aims of this review are to assess the safety and effectiveness of perineal stapled prolapse resection in the management of rectal prolapse.
A systematic review of all articles describing this approach was searched using MEDLINE, Embase, PubMed, Cochrane, Scopus, Web of Science and China National Knowledge Infrastructure. Included in this review were all randomized and nonrandomized prospective and retrospective studies reporting patients (aged 16years and older) with complete rectal prolapse who underwent perineal stapled prolapse resection for the surgical treatment of the rectal prolapse.
A total of 408 patients across 20 articles were included. There were 58 cases of recurrence out of 368 patients over a median length of follow-up of 18 months (interquartile range 12-34months). The total weighted overall recurrence was 12%. There were 51 cases of postoperative complications in 350 cases, bleeding being the most common complication.
The recurrence rate is comparable to those of the well-established Altemeier and Delorme procedures. However, given the heterogeneity of studies and variations in lengths of follow-up, further randomized prospective studies are needed to adequately compare this technique against other procedures for complete rectal prolapse.
The recurrence rate is comparable to those of the well-established Altemeier and Delorme procedures. However, given the heterogeneity of studies and variations in lengths of follow-up, further randomized prospective studies are needed to adequately compare this technique against other procedures for complete rectal prolapse.
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