Similar Inflammatory Responses following Sprint Interval Training Performed in Hypoxia and Normoxia

Sprint interval training (SIT) is an efficient intervention capable of improving aerobic capacity and exercise performance. This experiment aimed to determine differences in training adaptations and the inflammatory responses following 2 weeks of SIT (30 s maximal work, 4 min recovery; 4–7 repetitions) performed in normoxia or hypoxia. Forty-two untrained participants [(mean ± SD), age 21 ±1 years, body mass 72.1 ±11.4 kg, and height 173 ±10 cm] were equally and randomly assigned to one of three groups; control (CONT; no training, n = 14), normoxic (NORM; SIT in FiO2: 0.21, n = 14), and normobaric hypoxic (HYP; SIT in FiO2: 0.15, n = 14). Participants completed a V ˙ O 2peak V˙O2peak test, a time to exhaustion (TTE) trial (power = 80% V ˙ O 2peak V˙O2peak) and had hematological [hemoglobin (Hb), haematocrit (Hct)] and inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-α (TNFα)] measured in a resting state, pre and post SIT. V ˙ O 2peak V˙O2peak (mL.kg−1.min−1) improved in HYP (+11.9%) and NORM (+9.8%), but not CON (+0.9%). Similarly TTE improved in HYP (+32.2%) and NORM (+33.0%), but not CON (+3.4%) whilst the power at the anaerobic threshold (AT; W.kg−1) also improved in HYP (+13.3%) and NORM (+8.0%), but not CON (–0.3%). AT (mL.kg−1.min−1) improved in HYP (+9.5%), but not NORM (+5%) or CON (–0.3%). No between group change occurred in 30 s sprint performance or Hb and Hct. IL-6 increased in HYP (+17.4%) and NORM (+20.1%), but not CON (+1.2%), respectively. TNF-α increased in HYP (+10.8%) NORM (+12.9%) and CON (+3.4%). SIT in HYP and NORM increased V ˙ O 2peak V˙O2peak, power at AT and TTE performance in untrained individuals, improvements in AT occurred only when SIT was performed in HYP. Increases in IL-6 and TNFα reflect a training induced inflammatory response to SIT; hypoxic conditions do not exacerbate this

An AI Approach to Identifying Novel Therapeutics for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that has a significant impact on quality of life and work capacity. Treatment of RA aims to control inflammation and alleviate pain; however, achieving remission with minimal toxicity is frequently not possible with the current suite of drugs. This review aims to summarise current treatment practices and highlight the urgent need for alternative pharmacogenomic approaches for novel drug discovery. These approaches can elucidate new relationships between drugs, genes, and diseases to identify additional effective and safe therapeutic options. This review discusses how computational approaches such as connectivity mapping offer the ability to repurpose FDA-approved drugs beyond their original treatment indication. This review also explores the concept of drug sensitisation to predict co-prescribed drugs with synergistic effects that produce enhanced anti-disease efficacy by involving multiple disease pathways. Challenges of this computational approach are discussed, including the availability of suitable high-quality datasets for comprehensive analysis and other data curation issues. The potential benefits include accelerated identification of novel drug combinations and the ability to trial and implement established treatments in a new index disease. This review underlines the huge opportunity to incorporate disease-related data and drug-related data to develop methods and algorithms that have strong potential to determine novel and effective treatment regimens

Tailoring Gold Nanoparticle Characteristics and the Impact on Aqueous-Phase Oxidation of Glycerol

Poly(vinyl alcohol) (PVA)-stabilized Au nanoparticles (NPs) were synthesized by colloidal methods in which temperature variations (−75 to 75 °C) and mixed H2O/EtOH solvent ratios (0, 50, and 100 vol/vol) were used. The resulting Au NPs were immobilized on TiO2 (P25), and their catalytic performance was investigated for the liquid phase oxidation of glycerol. For each unique solvent system, there was a systematic increase in the average Au particle diameter as the temperature of the colloidal preparation increased. Generation of the Au NPs in H2O at 1 °C resulted in a high observed activity compared with current Au/TiO2 catalysts (turnover frequency = 915 h–1). Interestingly, Au catalysts with similar average particle sizes but prepared under different conditions had contrasting catalytic performance. For the most active catalyst, aberration-corrected high angle annular dark field scanning transmission electron microscopy analysis identified the presence of isolated Au clusters (from 1 to 5 atoms) for the first time using a modified colloidal method, which was supported by experimental and computational CO adsorption studies. It is proposed that the variations in the populations of these species, in combination with other solvent/PVA effects, is responsible for the contrasting catalytic properties

Results of the British Society of Gastroenterology supporting women in gastroenterology mentoring scheme pilot.

Introduction: Mentorship has long been recognised as beneficial in the business world and has more recently been endorsed by medical and academic professional bodies. Recruitment of women into gastroenterology and leadership roles has traditionally been difficult. The Supporting Women in Gastroenterology network developed this pilot scheme for female gastroenterologists 5 years either side of the Completion Certificate of Specialist Training (CCST) to examine the role that mentorship could play in improving this discrepancy. Method: Female gastroenterology trainees and consultant gastroenterologists within 5 years either side of CCST were invited to participate as mentees. Consultant gastroenterologists of both genders were invited to become mentors. 35 pairs of mentor:mentees were matched and completed the scheme over 1 year. Training was provided. Results: The majority of the mentees found the sessions useful (82%) and enjoyable (77%), with the benefit of having time and space to discuss professional or personal challenges with a gastroenterologist who is not a colleague. In the longitudinal study of job satisfaction, work engagement, burnout, resilience, self-efficacy, self-compassion and work-life balance, burnout scale showed a small but non significant improvement over the year (probably an effect of small sample size). Personal accomplishment improved significantly. The main challenges were geography, available time to meet and pair matching. The majority of mentors surveyed found the scheme effective, satisfying, mutually beneficial (70%) and enjoyable (78%). Conclusion: Mentorship is shown to be beneficial despite the challenges and is likely to improve the recruitment and retention of women into gastroenterology and leadership roles, but is likely to benefit gastroenterologists of both genders

Eating well, living well and weight management: A co-produced semi-qualitative study of barriers and facilitators experienced by adults with intellectual disabilities

Adults with intellectual disabilities in England experience health inequalities. They are more likely than their non-disabled peers to be obese and at risk of serious medical conditions such as heart disease, stroke and type 2 diabetes. This semi-qualitative study engaged adults with intellectual disabilities in a co-production process to explore their perceived barriers and facilitators to eating well, living well and weight management. Nineteen participants with intellectual disabilities took part in four focus groups and one wider group discussion. They were supported by eight of their carers or support workers. Several barriers were identified including personal income restrictions, carers’ and support workers’ unmet training needs, a lack of accessible information, inaccessible services and societal barriers such as the widespread advertising of less healthy foodstuffs. A key theme of frustration with barriers emerged from analysis of participants’ responses. Practical solutions suggested by participants included provision of clear and accessible healthy lifestyle information, reasonable adjustments to services, training, ‘buddying’ support systems or schemes and collaborative working to improve policy and practice

Efficient and Fast Synthesis of Few-Layer Black Phosphorus via Microwave-Assisted Liquid-Phase Exfoliation

High‐quality, few‐layer black‐phosphorus (BP) flakes are prepared in a common organic solvent with very short processing times using microwave‐assisted liquid‐phase exfoliation. A comprehensive range of analysis, combined with density‐functional theory calculations, confirms that the product prepared using the microwave technique is few‐layer BP with small‐ and large‐area flakes. The suspended exfoliated BP sheets show excellent stability, while samples dispersed onto silicon from the suspensions exhibit low oxidation levels after several days in ambient conditions. This straightforward synthesis method is facile, efficient, and extremely fast, and does not involve use of any surfactant or ultrasonication steps and will facilitate future development of phosphorene research

What is stirring in the reservoir? Modelling mechanisms of henipavirus circulation in fruit bat hosts

Pathogen circulation among reservoir hosts is a precondition for zoonotic spillover. Unlike the acute, high morbidity infections typical in spillover hosts, infected reservoir hosts often exhibit low morbidity and mortality. Although it has been proposed that reservoir host infections may be persistent with recurrent episodes of shedding, direct evidence is often lacking. We construct a generalized SEIR (susceptible, exposed, infectious, recovered) framework encompassing 46 sub-models representing the full range of possible transitions among those four states of infection and immunity. We then use likelihood-based methods to fit these models to nine years of longitudinal data on henipavirus serology from a captive colony of Eidolon helvum bats in Ghana. We find that reinfection is necessary to explain observed dynamics; that acute infectious periods may be very short (hours to days); that immunity, if present, lasts about 1–2 years; and that recurring latent infection is likely. Although quantitative inference is sensitive to assumptions about serology, qualitative predictions are robust. Our novel approach helps clarify mechanisms of viral persistence and circulation in wild bats, including estimated ranges for key parameters such as the basic reproduction number and the duration of the infectious period. Our results inform how future field-based and experimental work could differentiate the processes of viral recurrence and reinfection in reservoir hosts. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’

Exploring the involvement of NLRP3 and Il-1β in Osteoarthritis of the Hand: Results from a Pilot Study

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1 plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1 and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1 and NLRP3, the serum levels of IL-1, IL-6, IL-17, and tumor necrosis factor- (TNF-) , and the protein levels of IL-1 and NLRP3. We also assessed the relationships between IL-1 and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1 and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1, IL-6, IL-17, and TNF- serum levels were determined by ELISA. IL-1 gene expression was significantly reduced (p=0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p=0.0063) and EHOA groups (p=0.0038). IL-1 serum levels were not significantly different across the groups; IL-6, IL-17, and TNF- were not detectable in any sample. IL-1 concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r=-0.446; p=0.0008) and in NEHOA (r=-0.608; p=0.004), while IL-1 gene expression was positively correlated with the number of joint swellings in the EHOA group (r=0.512; p=0.011). Taken together, our results, showing poorly detectable IL-1 concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level