Associations of sperm telomere length with semen parameters, clinical outcomes and lifestyle factors in human normozoospermic samples

Background Many studies have demonstrated that lifestyle factors can affect sperm quality and fertility. Sperm telomere length (STL) has been reported as potential biomarker or sperm quality. However, no studies have investigated how lifestyle factors can affect STL and associated clinical outcomes. Objectives The purpose of this manuscript is to investigate any association between STL with lifestyle factors, semen parameters and clinical outcomes. Materials and methods Sperm telomere length was measured using real‐time PCR in normozoospermic male partners (n = 66) of couples undergoing ART treatment. Each participant also completed a detailed questionnaire about general lifestyle. Linear regression univariate analysis and ANCOVA were performed to respectively determine correlations between STL and study parameters or identify statistically significant differences in STL while controlling for age, BMI and other factors. Results Using a linear regression model, STL is positively correlated with in vitro fertilization success (n = 65, r = 0.37, P = .004) but not with embryo cleavage rates and post‐implantation clinical outcomes including gestational age‐adjusted birth weight. No associations were observed between STL and sperm count, concentration or progressive motility. We further found that STL did not associate age, BMI, health or lifestyle factors. Discussion In somatic cells, the rate of telomere shortening is influenced by a number of lifestyle factors such as smoking, diet and occupation. However, little is known about how lifestyle factors affect STL and subsequently reproductive outcome. Out data suggest that STL might have an important role mechanistically for fertilization rate regardless of sperm parameters and lifestyle factors. Conclusion The results of this study demonstrate that STL is associated with in vitro fertilization rates, but not with semen parameters nor lifestyle factors. Further investigations are warranted to identify the potential variation of STL overtime to clarify its significance as a potential biomarker in ART

Gluten free diet adherence in coeliac disease. The role of psychological symptoms in bridging the intention–behaviour gap

This study examined the potential role of psychological symptoms in limiting the translation of positive intention into strict gluten free diet (GFD) adherence in coeliac disease (CD) within a theory of planned behaviour (TPB) framework. It was hypothesised that participants with more symptomatic psychological profiles would exhibit poorer adherence, primarily in the context of positive intentions. Coeliac disease participants (N = 390) completed online measures of gluten free diet adherence, psychological symptoms, coping behaviour, and TPB items. Intention and behaviour were moderately correlated, confirming the existence of the intention–behaviour gap. Psychological symptoms accounted for additional variance over and above TPB variables in GFD adherence but not intention. Participants who failed to act on their positive intentions displayed more psychological symptoms and greater reliance on maladaptive coping strategies than those with consistent intention–behaviour relationships (p < .01). The heightened incidence of psychological symptoms in CD has a small but significant negative impact on the ability to translate positive intentions into strict adherence. Directions for future research including interventions to improve GFD adherence are discussed

Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso. Revisión

Podeu consultar la versió en castellà del document a: http://dx.doi.org/10.1016/j.nefro.2015.07.005Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Different causes can induce the TMA process that characterises HUS. In this document we consider atypical HUS (aHUS) a sub-type of HUS in which the TMA phenomena are the consequence of the endotelial damage in the microvasculature of the kidneys and other organs due to a disregulation of the activity of the complement system. In recent years, a variety of aHUs-related mutations have been identified in genes of the complement system, which can explain approximately 60% of the aHUS cases, and a number of mutations and polymorphisms have been functionally characterised. These findings have stablished that aHUS is a consequence of the insufficient regulation of the activation of the complement on cell surfaces, leading to endotelial damage mediated by C5 and the complement terminal pathway. Eculizumab is a monoclonal antibody that inhibits the activation of C5 and blocks the generation of the pro-inflammatory molecule C5a and the formation of the cell membrane attack complex. In prospective studies in patients with aHUS, the use of Eculizumab has shown a fast and sustained interruption of the TMA process and it has been associated with significative long-term improvements in renal function, the interruption of plasma therapy and important reductions in the need of dialysis. According to the existing literature and the accumulated clinical experience, the Spanish aHUS Group published a consensus document with recommendations for the treatment of aHUs (Nefrologia 2013;33[1]:27-45). In the current online version of this document, we update the aetiological classification of TMAs, the pathophysiology of aHUS, its differential diagnosis and its therapeutic management

Meta Modeling for Business Process Improvement

Conducting business process improvement (BPI) initiatives is a topic of high priority for today’s companies. However, performing BPI projects has become challenging. This is due to rapidly changing customer requirements and an increase of inter-organizational business processes, which need to be considered from an end-to-end perspective. In addition, traditional BPI approaches are more and more perceived as overly complex and too resource-consuming in practice. Against this background, the paper proposes a BPI roadmap, which is an approach for systematically performing BPI projects and serves practitioners’ needs for manageable BPI methods. Based on this BPI roadmap, a domain-specific conceptual modeling method (DSMM) has been developed. The DSMM supports the efficient documentation and communication of the results that emerge during the application of the roadmap. Thus, conceptual modeling acts as a means for purposefully codifying the outcomes of a BPI project. Furthermore, a corresponding software prototype has been implemented using a meta modeling platform to assess the technical feasibility of the approach. Finally, the usability of the prototype has been empirically evaluated

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research