Cardiorespiratory Fitness Modulates The Acute Flow-Mediated Dilation Response Following High-Intensity But Not Moderate-Intensity Exercise In Elderly Men.

Impaired endothelial function is observed with ageing and with low cardiorespiratory fitness (VO2peak) whilst improvements in both are suggested to be reliant on higher-intensity exercise in the elderly. This may be due to the flow-mediated dilation (FMD) response to acute exercise of varying intensity. We examined the hypothesis that exercise-intensity alters the FMD response in healthy elderly adults, and would be modulated by VO2peak Forty-seven elderly men were stratified into lower- (VO2peak = 24.3±2.9 ml.kg(-1)min(-1), n=27) and higher-fit groups (VO2peak = 35.4±5.5 ml.kg(-1)min(-1), n=20) after a test of cycling peak power output (PPO). In randomised order, participants undertook 27 min moderate-intensity continuous (MICE; 40% PPO) or high-intensity interval cycling exercise (HIIE; 70% PPO), or no-exercise control. Brachial FMD was assessed at rest, 10 and 60 min after exercise. In control, FMD reduced in both groups (P=0.05). FMD increased after MICE in both groups [increase of 0.86 % (95% CI, 0.17 to 1.56), P=0.01], and normalised after 60 min. In the lower-fit, FMD reduced after HIIE [reduction of 0.85 % (95% CI, 0.12 to 1.58), P=0.02), and remained decreased at 60 min (P=0.05). In the higher-fit FMD was unchanged immediately after HIIE and increased after 60 min [increase of 1.52 % (95% CI, 0.41 to 2.62), P<0.01], which was correlated with VO2peak (r =0.41; P<0.01). Exercise-intensity alters the FMD response in elderly adults, and VO2peak modulates the FMD response following HIIE, but not MICE. The sustained decrease in FMD in the lower-fit may represent a signal for vascular adaptation or endothelial fatigue

Fermentation kinetics including product and substrate inhibitions plus biomass death: a mathematical analysis

Fermentation is generally modelled by kinetic equations giving the time evolutions for biomass, substrate, and product concentrations. Although these equations can be solved analytically in simple cases if substrate/product inhibition and biomass death are included, they are typically solved numerically. We propose an analytical treatment of the kinetic equations --including cell death and an arbitrary number of inhibitions-- in which constant yield needs not be assumed. Equations are solved in phase space, i.e. the biomass concentration is written explicitly as a function of the substrate concentration.Comment: 4 pages, 4 figure

Therapy: Metformin takes a new route to clinical efficacy.

International audienceMetformin is currently the first-line treatment option for patients with type 2 diabetes mellitus, yet its mechanism of action remains uncertain. A new study reveals the important role for the activation of a duodenal AMPK-dependent neuronal pathway in the acute antihyperglycaemic effect of metformin and the inhibition of hepatic glucose production

Acute Dietary Nitrate Supplementation Improves Flow Mediated Dilatation of the Superficial Femoral Artery in Healthy Older Males

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO3−) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 ± 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO3−) or placebo (NO3−-depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO2−) and NO3−, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3− and placebo. Placebo had no effect but NO3− led to an 8.6-fold increase in plasma NO2−, which was accompanied by an increase in FMD (NO3−: +1.18 ± 0.94% vs. placebo: 0.23 ± 1.13%, p = 0.002), and a reduction in AIx75 (NO3−: −8.7 ± 11.6% vs. placebo: −4.6 ± 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO3− improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO3− supplementation in older adult

Gravitational physics with antimatter

The production of low-energy antimatter provides unique opportunities to search for new physics in an unexplored regime. Testing gravitational interactions with antimatter is one such opportunity. Here a scenario based on Lorentz and CPT violation in the Standard- Model Extension is considered in which anomalous gravitational effects in antimatter could arise.Comment: 5 pages, presented at the International Conference on Exotic Atoms (EXA 2008) and the 9th International Conference on Low Energy Antiproton Physics (LEAP 2008), Vienna, Austria, September 200

The impact of the COVID-19 pandemic on referrals to musculoskeletal services from primary care and subsequent incidence of inflammatory rheumatic musculoskeletal disease: an observational study

Objectives To describe the impact of the COVID-19 pandemic upon referral patterns and incident diagnosis of inflammatory rheumatic and musculoskeletal diseases (iRMDs). Methods UK primary care data was used to describe referral patterns for patients with musculoskeletal conditions. Trends in referrals to musculoskeletal services and incident diagnoses of iRMDs (specifically rheumatoid arthritis (RA) and juvenile inflammatory arthritis (JIA)) were described using Joinpoint Regression and comparisons made between key pandemic time periods. Results The incidence of RA and JIA reduced by -13.3% and -17.4% per month respectively between January 2020 and April 2020, and then increased by 1.9% and 3.7% per month respectively between April 2020 and October 2021. The incidence of all diagnosed iRMDs was stable until October 2021. Referrals decreased between February 2020 and May 2020 by -16.8% per month from 4.8% to 2.4% in patients presenting with a musculoskeletal condition. After May 2020, referrals increased significantly (16.8% per month) to 4.5% in July 2020. Time from first musculoskeletal consultation to RA diagnosis, and referral to RA diagnosis increased in the early-pandemic period (rate ratio (RR) 1.11, 95%CI 1.07-1.15; RR 1.23, 95%CI 1.17-1.30) and remained consistently higher in the late-pandemic (RR 1.13, 95%CI 1.11-1.16; RR 1.27, 95%CI 1.23-1.32) periods respectively, compared to the pre-COVID-19 period. Conclusion Patients with underlying RA and JIA that developed during the pandemic may be yet to present, or be in the referral and/or diagnostic process. Clinicians should remain alert to this possibility and commissioners aware of these findings, enabling the appropriate planning and commissioning of services

The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns

Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research

P183 Establishing the epidemiology of rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis in England using primary care electronic health record data

Abstract Background/Aims The substantial personal and socioeconomic costs associated with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) make understanding their epidemiology crucial. The Clinical Practice Research Datalink (Aurum) is an electronic healthcare record (EHR) database, containing primary care records from ∼20% of English practices (&amp;gt;13 million patients currently registered). To determine RA/PsA/axial SpA epidemiology using EHR data, validated methods need to be applied to ascertain patients with these diagnoses. To address this, we updated and applied approaches validated in other primary care EHR databases in Aurum and described the annual incidence/point-prevalence of RA/PsA/axial SpA alongside patient characteristics (providing indirect evidence of coding accuracy). Methods Diagnosis and synthetic disease-modifying anti-rheumatic drug (DMARD) prescription code lists were constructed, and pre-defined approaches for ascertaining patients with RA/axial SpA/PsA applied. The annual incidence and point-prevalence of RA/PsA/axial SpA were calculated from 2004-2020. Samples were stratified by age/gender, and mean age and gender/ethnic-group relative frequencies described. The study was approved by the CPRD Independent Scientific Advisory Committee (reference 20_000244). Results From 2004-2019 the point-prevalence of RA/PsA increased annually, peaking in 2019 (RA 7.79/1,000; PsA 2.87/1,000) then falling slightly. From 2004-2020 the point-prevalence of axial SpA increased annually (except in 2018/2019), peaking in 2020 (1.13/1,000). Annual RA incidence was higher between 2013-2019 (when included in the Quality Outcomes Framework, ranging 0.491 to 0.521/1,000 person-years) than 2004-2012 (ranging 0.345 to 0.400/1,000 person-years). The annual incidence of PsA and axial SpA increased from 2006 (0.108 to a peak of 0.172/1,000 person-years) and 2010 (0.025 to a peak of 0.045/1,000 person-years), respectively. These years were when new disease classification criteria were introduced. Marked falls in the annual incidence of RA, PsA and axial SpA between 2019 and 2020 were seen, reducing by 40.1%, 67.4% and 38.1%, respectively, reflecting the impact of the COVID-19 pandemic on arthritis diagnoses. Stratifying incidence/prevalence by age/gender broadly showed expected patterns (although the incidence of axial SpA/PsA in women increased over time), and the mean age and gender proportions followed those previously reported. Conclusion The approaches we used to determine patients with RA, PsA, and axial SpA in Aurum led to incidence/prevalence estimates broadly consistent with published studies, and patient characteristics as would be expected. These data support the potential of the Aurum-updated ascertainment approaches for use in further studies of RA, PsA and axial SpA. Disclosure I. Scott: None. R. Whittle: None. J. Bailey: None. H. Twohig: None. S. Hider: None. C. Mallen: None. S. Muller: None. K. Jordan: None. </jats:sec

Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis epidemiology in England from 2004 to 2020: An observational study using primary care electronic health record data.

Background: Contemporary data on rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritits (SpA) epidemiology in England are lacking. This knowledge is crucial to planning healthcare services. We updated algorithms defining patients with diagnoses of RA, PsA, and axial SpA in primary care and applied them to describe their incidence and prevalence in the Clinical Practice Research Datalink Aurum, an electronic health record (EHR) database covering ∼20% of England. Methods: Algorithms for ascertaining patients with RA, axial SpA, and PsA diagnoses validated in primary care EHR databases using Read codes were updated (to account for the English NHS change to SNOMED CT diagnosis coding) and applied. Updated diagnosis and synthetic disease-modifying anti-rheumatic drug code lists were devised by rheumatologists and general practitioners. Annual incidence/point-prevalence of RA, PsA, and axial SpA diagnoses were calculated from 2004 to 2020 and stratified by age/sex. Findings: Point-prevalence of RA/PsA diagnoses increased annually, peaking in 2019 (RA 0·779% [95% confidence interval (CI) 0·773, 0·784]; PsA 0·287% [95% CI 0·284, 0·291]) then falling slightly. Point-prevalence of axial SpA diagnoses increased annually (except in 2018/2019), peaking in 2020 (0·113% [95% CI 0·111, 0·115]). RA diagnosis annual incidence was higher between 2013-2019 (after inclusion in the Quality and Outcomes Framework, range 49·1 [95% CI 47·7, 50·5] to 52·1 [95% CI 50·6, 53·6]/100,000 person-years) than 2004-2012 (range 34·5 [95% CI 33·2, 35·7] to 40·0 [95% CI 38·6, 41·4]/100,000 person-years). Increases in the annual incidence of PsA/axial SpA diagnosis occurred following new classification criteria publication. Annual incidence of RA, PsA and axial SpA diagnoses fell by 40·1%, 67·4%, and 38·1%, respectively between 2019 and 2020, likely reflecting the COVID-19 pandemic's impact on their diagnosis. Interpretation: Recorded RA, PsA, and axial SpA diagnoses are increasingly prevalent in England, underlining the importance of organising healthcare services to provide timely, treat-to-target care to optimise the health of >1% of adults in England. Funding: National Institute for Health and Care Research (NIHR300826)

Trends in gabapentinoid prescribing in UK primary care using the Clinical Practice Research Datalink: an observational study

Background The UK government reclassified gabapentin and pregabalin as ‘controlled drugs’ from April 2019. This study aimed to describe the trends in gabapentinoid prescribing before and immediately after reclassification, in the UK Clinical Practice Research Datalink, an electronic primary care health record broadly representative of the UK. Methods Separately for gabapentin and pregabalin, we calculated annual incident and prevalent prescribing rates from year of UK approval (April 1997 and 2004 respectively) to September 2019, and monthly incident and prevalent prescribing rates (October 2017–September 2019). Significant changes in temporal trends were determined using joinpoint regression. We also described potential prescribing indications, prior pain-related prescribing, and co-prescribing with potentially interacting medicines. Findings Incident gabapentin prescribing increased annually, peaking in 2016–17, at 625/100,000 patient years before falling steadily to 2019. Incident pregabalin prescribing peaked at 329/100,000 patient years in 2017–18 and did not fall significantly until 2019. Prevalent gabapentin and pregabalin prescribing increased annually to 2017–18 and 2018–19 respectively, before plateauing. Gabapentinoids were commonly co-prescribed with opioids (60%), antidepressants (52%), benzodiazepines (19%), and Z-drugs (10%). Interpretation Following a dramatic rise, incident gabapentinoid prescribing has started to fall but the specific impact of reclassification on prescribing rates remains unclear. Limited change in prevalent gabapentinoid prescribing during the 6 months following their reclassification as controlled drugs suggests little immediate impact on continued gabapentinoid prescribing for existing users. Funding National Institute for Health and Care Research (NIHR) Research for Patient Benefit Programme. NIHR Applied Research Collaboration West Midlands. NIHR School for Primary Care Research