Increased prevalence of irritable bowel syndrome in patients with bronchial asthma

AbstractIrritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract. IBS may represent a primary disorder of gastrointestinal motility, accompanied with motor dysfunction in various extraintestinal sites. Recent studies suggest that IBS is associated with bronchial hyper-responsiveness and bronchial asthma might be more prevalent in IBS patients than in control subjects. The aim of our study was to assess the prevalence of IBS in a cohort of asthmatic patients. We evaluated 150 patients with bronchial asthma (71 males and 79 females, aged 45.1±14.9 years) and two control groups including 130 patients with other pulmonary disorder and 120 healthy subjects. All subjects enrolled (asthmatic and controls) completed the Greek version of the Bowel Disease Questionnaire (BDQ). BDQ is a, previously validated, self-report instrument to measure gastrointestinal symptoms. Diagnosis of IBS was based on Rome II criteria. The IBS prevalence was significantly higher in asthmatics (62/150, 41.3%) than in subjects with other pulmonary disorders (29/130, 22.3%,P <0.001) and healthy ones (25/120, 20.8%, P<0.001). For all subjects studied, the prevalence of IBS was significantly higher in females (78/214, 36.4%) than in males (38/186, 20.4%, P<0.001). The IBS prevalence in asthmatic males was 29.5% vs. 15.2% in male patients with other pulmonary disorders (P=0.002) and 14.2% in male healthy subjects (P=0.002). The IBS prevalence in asthmatic females was 51.8% vs. 28.1% in females patients with other pulmonary disorders (P<0.001) and 26.5% in females healthy subjects (P<0.001). None of the asthma medications were associated with increased or decreased likelihood of IBS. We conclude that patients with bronchial asthma have an increased prevalence of IBS. Further studies are needed to clarify the potential pathogenetic mechanisms underlying the association between IBS and asthma

On Asynchronous Session Semantics

This paper studies a behavioural theory of the π-calculus with session types under the fundamental principles of the practice of distributed computing — asynchronous communication which is order-preserving inside each connection (session), augmented with asynchronous inspection of events (message arrivals). A new theory of bisimulations is introduced, distinct from either standard asynchronous or synchronous bisimilarity, accurately capturing the semantic nature of session-based asynchronously communicating processes augmented with event primitives. The bisimilarity coincides with the reduction-closed barbed congruence. We examine its properties and compare them with existing semantics. Using the behavioural theory, we verify that the program transformation of multithreaded into event-driven session based processes, using Lauer-Needham duality, is type and semantic preserving

Roles of fibrin α- and γ-chain specific cross-linking by FXIIIa in fibrin structure and function

Factor XIII is responsible for the cross-linking of fibrin γ-chains in the early stages of clot formation, whilst α-chain cross-linking occurs at a slower rate. Although γ- and α-chain cross-linking was previously shown to contribute to clot stiffness, the role of cross-linking of both chains in determining clot structure is currently unknown. Therefore, the aim of this study was to determine the role of individual α- and γ-chain cross-linking during clot formation, and its effects on clot structure. We made use of a recombinant fibrinogen (γQ398N/Q399N/K406R), which does not allow for γ-chain cross-linking. In the absence of cross-linking, intact D-D interface was shown to play a potential role in fibre appearance time, clot stiffness and elasticity. Cross-linking of the fibrin α-chain played a role in the thickening of the fibrin fibres over time, and decreased lysis rate in the absence of α2-antiplasmin. We also showed that α-chain cross-linking played a role in the timing of fibre appearance, straightening fibres, increasing clot stiffness and reducing clot deformation. Cross-linking of the γ-chain played a role in fibrin fibre appearance time and fibre density. Our results show that α- and γ-chain cross-linking play independent and specific roles in fibrin clot formation and structure

ARIADNE - A novel optical LArTPC: technical design report and initial characterisation using a secondary beam from the CERN PS and cosmic muons

ARIADNE is a 1-ton (330 kg fiducial mass) dual-phase liquid argon (LAr) time projection chamber (TPC) featuring a novel optical readout. Four electron-multiplying charge-coupled device (EMCCD) cameras are mounted externally, and these capture the secondary scintillation light produced in the holes of a thick electron gas multiplier (THGEM). Track reconstruction using this novel readout approach is demonstrated. Optical readout has the potential to be a cost effective alternative to charge readout in future LArTPCs. In this paper, the technical design of the detector is detailed. Results of mixed particle detection using a secondary beam from the CERN PS (representing the first ever optical images of argon interactions in a dual-phase LArTPC at a beamline) and cosmic muon detection at the University of Liverpool are also presented.Comment: 58 pages, 40 figures. Changes from previous version based on pre-publication review: improved quality of various figures, improved clarity of some definitions and reduced longer sentences for better readability, fixed typos and formatting error

Molecular analysis of archival diagnostic prostate cancer biopsies identifies genomic similarities in cases with progression post-radiotherapy, and those with de novo metastatic disease

Purpose It is important to identify molecular features that improve prostate cancer (PCa) risk stratification before radical treatment with curative intent. Molecular analysis of historical diagnostic formalin-fixed paraffin-embedded (FFPE) prostate biopsies from cohorts with post-radiotherapy (RT) long-term clinical follow-up has been limited. Utilizing parallel sequencing modalities, we performed a proof-of-principle sequencing analysis of historical diagnostic FFPE prostate biopsies. We compared patients with i) stable PCa post-primary or salvage RT (sPCa), ii) progressing PCa post-RT (pPCa), and iii) de novo metastatic PCa (mPCa). Experimental Design A cohort of 19 patients with diagnostic prostate biopsies (n=6 sPCa, n=5 pPCa, n=8 mPCa) and mean 4 years 10 months follow-up (diagnosed 2009-2016) underwent nucleic acid extraction from demarcated malignancy. Samples underwent 3’RNA sequencing (3’RNAseq) (n=19), nanoString analysis (n=12) and Illumina 850k methylation (n=8) sequencing. Bioinformatic analysis was performed to coherently identify differentially expressed genes (DEGs) and methylated genomic regions (MGRs). Results 18 of 19 samples provided useable 3’RNAseq data. Principal Component Analysis (PCA) demonstrated similar expression profiles between pPCa and mPCa cases, versus sPCa. Coherently differentially methylated probes between these groups identified ∼600 differentially MGRs. The top 50 genes with increased expression in pPCa patients were associated with reduced progression-free survival post-RT (p<0.0001) in an external cohort. Conclusions 3’RNAseq, nanoString and 850K-methylation analyses are each achievable from historical FFPE diagnostic pre-treatment prostate biopsies, unlocking the potential to utilize large cohorts of historic clinical samples. Profiling similarities between individuals with pPCa and mPCa suggests biological similarities and historical radiological staging limitations, which warrant further investigation

The Gender Divide That Fails Football’s Bottom Line: The Commercial Case for Gender Equality

Gender diversity in football is often seen as an add-on, a burden, a cost. But today is International Women’s Day. And we at Fair Game decided to celebrate the benefits of gender diversity in football. Fair Game’s values are those of sustainability, integrity, and community. 51% of communities are made up of women. Financial sustainability depends on engaging with ALL current and future fans. And integrity comes from actions, not words. And so we are launching this report. Football becoming more gender-inclusive is not just morally and socially right – it is also commercially beneficial

Exploring the relationship between mediterranean diet adherence and subjective well-being among Greek and Cypriot adults

Associations between subjective well-being (SWB) and dietary habits, employment status, and habitual activities are increasingly capturing the focus of researchers as well as policymakers worldwide. This study aimed to explore these associations in a sample of the population in Greece and Cyprus via an online survey. In total, 936 questionnaires (470: Cyprus, 466: Greece) were analyzed to study the associations between the Mediterranean Diet (MD) (using the 14-item MEDAS score, (14-MEDAS)), subjective well-being (SWB), and several socioeconomic factors. Key remarks of this survey highlight the positive impact of MD adherence on some well-being items. Namely, statistically significant differences were found on the following items: Satisfied with life (p 10). Other lifestyle habits such as spending time with friends and family, spending time in nature, and habitual physical activity were associated with aspects of SWB such as Life satisfaction, Life worthwhile, Feeling happy, and energetic. The findings support adherence to the MD, since it is associated with higher life satisfaction and self-reported happiness in this sample and should be considered when developing health policies on well-being.Fundação para a Ciência e a Tecnologia; European Union; Spanish Ministry of Science Innovation and Universities; Autonomous Community of the Region of Murcia; Italian Ministry of Universityinfo:eu-repo/semantics/publishedVersio

Glycated albumin modulates the contact system with implications for the kallikrein-kinin and intrinsic coagulation systems

Background Human serum albumin (HSA) is the most abundant plasma protein and is sensitive to glycation in vivo. The chronic hyperglycemic conditions in patients with diabetes mellitus (DM) induce a nonenzymatic Maillard reaction that denatures plasma proteins and forms advanced glycation end products (AGEs). HSA-AGE is a prevalent misfolded protein in patients with DM and is associated with factor XII activation and downstream proinflammatory kallikrein-kinin system activity without any associated procoagulant activity of the intrinsic pathway. Objectives This study aimed to determine the relevance of HSA-AGE toward diabetic pathophysiology. Methods The plasma obtained from patients with DM and euglycemic volunteers was probed for activation of FXII, prekallikrein (PK), and cleaved high-molecular-weight kininogen by immunoblotting. Constitutive plasma kallikrein activity was determined via chromogenic assay. Activation and kinetic modulation of FXII, PK, FXI, FIX, and FX via in vitro–generated HSA-AGE were explored using chromogenic assays, plasma-clotting assays, and an in vitro flow model using whole blood. Results Plasma obtained from patients with DM contained increased plasma AGEs, activated FXIIa, and resultant cleaved cleaved high-molecular-weight kininogen. Elevated constitutive plasma kallikrein enzymatic activity was identified, which positively correlated with glycated hemoglobin levels, representing the first evidence of this phenomenon. HSA-AGE, generated in vitro, triggered FXIIa-dependent PK activation but limited the intrinsic coagulation pathway activation by inhibiting FXIa and FIXa-dependent FX activation in plasma. Conclusion These data indicate a proinflammatory role of HSA-AGEs in the pathophysiology of DM via FXII and kallikrein-kinin system activation. A procoagulant effect of FXII activation was lost through the inhibition of FXIa and FIXa dependent FX activation by HSA-AGEs

Synthesis and biological evaluation of cyclobutane-based β3 integrin antagonists: A novel approach to targeting integrins for cancer therapy

YesThe Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.This work was supported by the EPSRC (RCUK Academic Fellowship and Grant EP/H002626/1 to H.M.S.) and Prostate Cancer UK (Pilot Grant PA10-01). F.O.F.O.A-S.. was funded by the Public Authority for Applied Education and Training, Kuwait (PhD studentship)