Glucose ingestion does not improve maximal isokinetic force

The purpose of this study was to assess maximal isokinetic leg extension force in response to glucose ingestion and to determine whether any performance changes occur in a time-dependent manner. Seventeen young (22.1+/-3.9 years), lean (%BF: 14.3+/-8.0; %BF Males: 9.7+/-4.2; %BF Females: 23.7+/-4.2) and recreationally active (>150min/week of physical activity) male (n=11) and female participants completed the trials. Using a double-blinded cross-over design, participants performed sets of 3 maximum isokinetic efforts on a dynamometer (HumacNorm) before and after (5-, 15-, 30-, 45-, 60-, 75- and 90-min post) ingesting either a carbohydrate (75 g glucose) or isovolumic placebo (saccharin-flavored) drink. Blood glucose and EMG were recorded concurrent with force output (max peak force; mean peak force). Despite a significant rise in blood glucose (mean glycemic excursion = 4.01+/-1.18 mmol/L), there were no significant interactions in any (absolute or percentage) force (mean peak force: p>=0.683; max peak force: p>=0.567) or EMG (mean peak EMG: p>=0.119; max peak EMG: p>=0.247) parameters measured. The ingestion of glucose resulted in a 3.4% reduction in mean force across subsequent time points (highest: +2.1% at 15min; lowest: -8.6% at 90min post ingestion), however this effect was small (d<0.1). The ingestion of glucose does not alter performance of maximal isokinetic efforts in recreationally active young individuals. Additionally, there were no differences in force when assessed as a function of time following glucose ingestion. Consequently, in the absence of fatigue, carbohydrate ingestion is unlikely to present any ergogenic benefits to athletes performing resistance-based exercise

Changes in muscle activation following balance and technique training and a season of Australian football

Objectives: Determine if balance and technique training implemented adjunct to 1001 male Australian football players’ training influenced the activation/strength of the muscles crossing the knee during pre-planned and unplanned sidestepping. Design: Randomized Control Trial. Methods: Each Australian football player participated in either 28 weeks of balance and technique training or ‘sham’ training. Twenty-eight Australian football players (balance and technique training, n = 12; ‘sham’ training, n = 16) completed biomechanical testing pre-to-post training. Peak knee moments and directed co-contraction ratios in three degrees of freedom, as well as total muscle activation were calculated during pre-planned and unplanned sidestepping. Results: No significant differences in muscle activation/strength were observed between the ‘sham’ training and balance and technique training groups. Following a season of Australian football, knee extensor (p = 0.023) and semimembranosus (p = 0.006) muscle activation increased during both pre-planned sidestepping and unplanned sidestepping. Following a season of Australian football, total muscle activation was 30% lower and peak valgus knee moments 80% greater (p = 0.022) during unplanned sidestepping when compared with pre-planned sidestepping. Conclusions: When implemented in a community level training environment, balance and technique training was not effective in changing the activation of the muscles crossing the knee during side stepping. Following a season of Australian football, players are better able to support both frontal and sagittal plane knee moments. When compared to pre-planned sidestepping, Australian football players may be at increased risk of anterior cruciate ligament injury during unplanned sidestepping in the latter half of an Australian football season

A longitudinal study of impact and early stance loads during gait following arthroscopic partial meniscectomy

People following arthroscopic partial medial meniscectomy (APM) are at increased risk of developing knee osteoarthritis. High impact loading and peak loading early in the stance phase of gait may play a role in the pathogenesis of knee osteoarthritis. This was a secondary analysis of longitudinal data to investigate loading-related indices at baseline in an APM group (3 months post-surgery) and a healthy control group, and again 2 years later (follow-up). At baseline, 82 participants with medial APM and 38 healthy controls were assessed, with 66 and 23 re-assessed at follow-up, respectively. Outcome measures included: (i) heel strike transient (HST) presence and magnitude, (ii) maximum loading rate, (iii) peak vertical force (Fz) during early stance. At baseline, maximum loading rate was lower in the operated leg (APM) and non-operated leg (non-APM leg) compared to controls (p≤0.03) and peak Fz was lower in the APM leg compared to non-APM leg (p≤0.01). Over 2 years, peak Fz increased in the APM leg compared to the non-APM leg and controls (p≤0.01). Following recent APM, people may adapt their gait to protect the operated knee from excessive loads, as evidenced by a lower maximum loading rate in the APM leg compared to controls, and a reduced peak Fz in the APM leg compared to the non-APM leg. No differences at follow-up may suggest an eventual return to more typical gait. However, the increase in peak Fz in the APM leg may be of concern for long-term joint health given the compromised function of the meniscus

Mechanisms underpinning longitudinal increases in the knee adduction moment following arthroscopic partial meniscectomy

Background Knee osteoarthritis is common following arthroscopic partial meniscectomy and a higher external peak knee adduction moment is believed to be a contributor. The peak knee adduction moment has been shown to increase over 2 years (from 3-months post-arthroscopic partial meniscectomy). The aim of this study was to evaluate mechanisms underpinning the increase in peak knee adduction moment over 2 years observed in people 3-months following arthroscopic partial meniscectomy. Methods Sixty-six participants with medial arthroscopic partial meniscectomy were assessed at baseline and again 2 years later. Parameters were evaluated at time of peak knee adduction moment as participants walked barefoot at their self-selected normal and fast pace for both time points. Findings For normal pace walking, an increase in frontal plane ground reaction force-to-knee lever arm accounted for 30% of the increase in peak knee adduction moment (B = 0.806 [95% CI 0.501–1.110], P < 0.001). For fast pace walking, an increase in the frontal plane ground reaction force magnitude accounted for 21% of the increase in peak knee adduction moment (B = 2.343 [95% CI 1.219–3.468], P < 0.001); with an increase in tibia varus angle accounting for a further 15% (B = 0.310 [95% CI 0.145–0.474], P < 0.001). Interpretation Our data suggest that an increase in lever arm and increase in frontal plane ground reaction force magnitude are contributors to the increased knee adduction moment observed over time in people following arthroscopic partial meniscectomy

Quasistatic delamination of sandwich-like Kirchhoff-Love plates

A quasistatic rate-independent adhesive delamination problem of laminated plates with a finite thickness is considered. By letting the thickness of the plates go to zero, a rate-independent delamination model for a laminated Kirchhoff-Love plate is obtained as limit of these quasistatic processes. The same dimension reduction procedure is eventually applied to processes which are sensitive to delamination modes, namely opening vs. shearing is distinguishe

STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): An international consortium of randomised placebo-controlled trials

Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis.  Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation.  Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council