An In Vitro Model of the Glomerular Capillary Wall Using Electrospun Collagen Nanofibres in a Bioartificial Composite Basement Membrane

The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC) and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

Investigating Frequency of GSTT1 and GSTM1 Genes Null Genotype in Men with Varicocele and Its Association with the Sperm Parameters

Introduction: GSTM and GSTT are subclasses of glutathione s-transferase that is present on human sperm surface and plays an important role against oxidative stress. This study aimed to investigate the polymorphisms of GSTT1 and GSTM1 in regard to sperm parameters. Methods: This case-control study involved 46 men with varicocele and 48 men without varicocele. Semen analyses were carried out according to WHO guidelines. Blood DNA was extracted using salting out procedures. Polymorphism of GSTT1 and GSTM1 genes was determined trough multiplex-PCR respectively. Results: Frequencies of GSTM1 null genotype in men with varicocelc and men without varicocele groups were 60.9 and 41.7 respectively. There were no statistically significant differences between Gstm1 null and positive genotype in two groups (p>0.05). Frequencies of gstt1 null genotype in case and control groups were 47.8 and 50 respectively. There were no statistically significant relationship between gstt1 null and positive genotype in two groups (p>0.05). Conclusions: Deficiency of enzyme activity in gstm1 null genotype did not affect morphology as well as slow and quick progressive of sperm but caused the significant decrease in count of sperm between gstm1 null and positive genotype. In the case of gstt1, gstt1 null genotype did not affect sperm parameters that may be related to compensate activity of other genes in this super family

The Study of Total IgE Reference Range in Healthy Adults in Tehran, Iran

"nBackground: IgE is an antibody class that regarded as an important factor in the pathogenesis of allergic diseases, asthma, im­mune responses to parasitic infection and it could be responsible for the late- phase allergic response. The objective of this study was to evaluate total IgE in healthy Iranian adults, establishment of reference range of total IgE and assess helpful­ness of this value in clinical diagnosis atopic and allergic diseases."nMethod: Three hundred sixty six healthy adults from blood transfusion volunteers (18 to 60 years) were selected in this study. A specific questionnaire (including demographic factors, smoking status and ...) was filled out for each person. Also, we evaluated effect of race and education on total IgE. These adults had no history of allergic disease. The total serum IgE level using a commercial enzyme immunoassay and CBC (Eosinophil count) was determined in them."nResults: Mean of age was 37.32± 10.93 yrs and 219 cases were males and 147 females. The geometric mean of total IgE was 20.84 IU/ml (2-373 IU/ml) (95% percentile= 250) (95% confidence interval=46.27-62.70). No differences was observed between mean of IgE log in males and females (P= NS) but mean of total IgE log in females is more than males."nConclusion: Normal range of serum total IgE obtained in this study could be helpful for diagnosis of IgE-dependent allergic dis­ease, as reference ranges in Iranian healthy adults