Cystic Fibrosis: How do CFTR mutations cause cystic fibrosis?

AbstractThe key defect in cystic fibrosis is loss of chloride conductance, but mutations of the cystic fibrosis gene product, the CFTR, have multiple effects on cell physiology; new results help to reconcile these facts

The conductive environment enhances gross motor function of girls with Rett syndrome. A pilot study

Introduction: Rett syndrome (RTT) is a neurological disorder usually associated with a mutation in the MECP2 gene. Conductive Education (CE) is an educational approach that has not yet been explored with regard to children with RTT. Objective: Assessing functional abilities of individuals with RTT due to CE intervention. Design: A single subject, AB design. Method: This study assessed the functional skills of three girls with RTT aged 3–5 years before and during participation in a CE programme. Results: Gross motor function improvements were observed at the end of the intervention period. Gross motor skills declined slightly in all participants over the summer holidays but improved again a few months after recommencement of the educational year. Conclusion: Replication of this study with more subjects is justified as is comparison with other educational methods. A home intervention programme should be constructed to prevent decline of skills over the summer vacation

Removal of filler material from large high energy formed parts

Filler material is removed by applying steam heat at 88.99 C to underside of workpiece and allowing filler to melt and drain from the waffle grids

Wolfe, JM et al (2006 Sensation and Perception

The nose smells what the eye sees: crossmodal visual facilitation of human olfactory perceptio

Key Components of Collaborative Research in the Context of Environmental Health: A Scoping Review

In a collaborative research process, the participation of interdisciplinary researchers and multi-sectoral stakeholders supports the co-creation, translation, and exchange of new knowledge. Following a scoping review methodology, we explored the collaborative research processes in the specific context of environment and human health research. Initially, our literature search strategy identified 1,328 publications. After several phases of reviewing and applying screening criteria to titles, abstracts, and full text, 45 publications were selected for final review. Data were charted by different topics and then collated, summarized, and analyzed thematically. From the different experiences and research approaches analyzed, we identified comprehensive details of the key components, facilitators, challenges, and best practices that impact the collaborative research process. Specifically, we identified the following seven emerging themes: (a) allocating time and resources, (b) addressing disciplinary and sectoral issues, (c) building relationships, (d) ensuring representation, (e) embedding participation in the research, (f) supporting ongoing collaboration, and (g) developing knowledge translation and exchange

Turbulent drag reduction by spanwise wall forcing. Part 2: High-Reynolds-number experiments

Here, we present measurements of turbulent drag reduction at high friction Reynolds numbers in the range of $4500 \le Re_\tau \le 15000$. The efficacy of the approach, using streamwise travelling waves of spanwise wall oscillations, is studied for two actuation regimes: (i) inner-scaled actuation (ISA), as investigated in Part 1 of this study, which targets the relatively high-frequency structures of the near-wall cycle, and (ii) outer-scaled actuation (OSA), which was recently presented by Marusic et al. (Nat. Commun., vol. 12, 2021) for high-$Re_\tau$ flows, targeting the lower-frequency, outer-scale motions. Multiple experimental techniques were used, including a floating-element balance to directly measure the skin-friction drag force, hot-wire anemometry to acquire long-time fluctuating velocity and wall-shear stress, and stereoscopic-PIV (particle image velocimetry) to measure the turbulence statistics of all three velocity components across the boundary layer. Under the ISA pathway, drag reduction of up to 25% was achieved, but mostly with net power saving losses due to the high-input power cost associated with the high-frequency actuation. The low-frequency OSA pathway, however, with its lower input power requirements, was found to consistently result in positive net power savings of 5 - 10%, for moderate drag reductions of 5 - 15%. The results suggest that OSA is an attractive pathway for energy-efficient drag reduction in high Reynolds number applications. Both ISA and OSA strategies are found to produce complex inter-scale interactions, leading to attenuation of the turbulent fluctuations across the boundary layer for a broad range of length and time scales

Mind the gap: Can we explain declining male reproductive health with known antiandrogens?

This article has been made available through the Brunel Open Access Publishing Fund.Several countries have experienced rises in cryptorchidisms, hypospadias and testicular germ cell cancer. The reasons for these trends are largely unknown, but Skakkebaek has proposed that these disorders form a testicular dysgenesis syndrome and can be traced to androgen insufficiency in foetal life. This suggests that antiandrogenic chemicals might contribute to risks, but few chemicals have been linked to these diseases in epidemiological studies. In animal studies with p,p0-dichlorodiphenyldichloroethylene, effects typical of disruptions of male sexual differentiation became apparent when the foetal levels of this androgen receptor (AR) antagonist approached values associated with responses in in vitro assays. This prompted us to analyse whether the 22 chemicals with AR antagonistic properties would produce mixture effects in an in vitro AR antagonism assay when combined at concentrations found in human serum. Other antiandrogenic modalities could not be considered. Two scenarios were investigated, one representative of average serum levels reported in European countries, the other in line with levels towards the high exposures. In both situations, the in vitro potency of the 22 selected AR antagonists was too low to produce combined AR antagonistic effects at the concentrations found in human serum, although the high exposure scenario came quite close to measurable effects. Nevertheless, our analysis exposes an explanation gap which can only be bridged by conjuring up as yet undiscovered high potency AR antagonists or, alternatively, high exposures to unknown agents of average potency

Increased Epithelial Gaps in the Small Intestine Are Predictive of Hospitalization and Surgery in Patients With Inflammatory Bowel Disease

Objectives: Epithelial gaps resulting from intestinal cell extrusions can be visualized with confocal laser endomicroscopy (CLE) during colonoscopy and increased in normal-appearing terminal ileum of inflammatory bowel disease (IBD) patients. Cell-shedding events on CLE were found to be predictive of disease relapse. The aim of this study was to assess the prognostic value of epithelial gap densities for major clinical events (hospitalization or surgery) in follow-up. Methods: We prospectively followed IBD patients undergoing colonoscopy with probe-based CLE (pCLE) for clinical events including symptom flares, medication changes, hospitalization, or surgery. Survival analysis methods were used to compare event times for the composite outcome of hospitalization or surgery using log-rank tests and Cox proportional hazards models. We also examined the relationship of gap density with IBD flares, need for anti-tumor necrosis factor therapy, disease duration, gender and endoscopic disease severity, and location. Results: A total of 21 Crohn's disease and 20 ulcerative colitis patients with a median follow-up of 14 (11–31) months were studied. Patients with elevated gap density were at significantly higher risk for hospitalization or surgery (log-rank test P=0.02). Gap density was a significant predictor for risk of major events, with a hazard ratio of 1.10 (95% confidence interval=1.01, 1.20) associated with each increase of 1% in gap density. Gap density was also correlated with IBD disease duration (Spearman's correlation coefficient rho=0.44, P=0.004), and was higher in male patients (9.0 vs. 3.6 gaps per 100 cells, P=0.038). Conclusions: Increased epithelial gaps in the small intestine as determined by pCLE are a predictor for future hospitalization or surgery in IBD patients