Investigating association between inflammatory bowel disease and rotavirus vaccination in a paediatric cohort in the UK.

In the UK, the incidence and prevalence of inflammatory bowel disease (IBD) is increasing in paediatric populations. Environmental factors including acute gastroenteritis episodes (AGE) may impact IBD development. Infant rotavirus vaccination has been shown to significantly reduce AGE. This study aims to explore the association between vaccination with live oral rotavirus vaccines and IBD development. A population-based cohort study was used, analysing primary care data from the Clinical Practice Research Datalink Aurum. Participants included children born in the UK from 2010 to 2015, followed from a minimum of 6 months old to a maximum of 7 years old. The primary outcome was IBD, and the primary exposure was rotavirus vaccination. Cox regression analysis with random intercepts for general practices was undertaken, with adjustment for potential confounding factors. In a cohort of 907,477 children, IBD was recorded for 96 participants with an incidence rate of 2.1 per 100,000 person-years at risk. The univariable analysis hazard ratio (HR) for rotavirus vaccination was 1.45 (95% confidence interval (CI) 0.93-2.28). Adjustment in the multivariable model attenuated the HR to 1.19 (95% CI 0.53-2.69). This study shows no statistically significant association between rotavirus vaccination and development of IBD. However, it provides further evidence for the safety of live rotavirus vaccination.

Preliminary investigation of a significant national Cryptosporidium exceedance in the United Kingdom, August 2023 and ongoing.

Routine laboratory surveillance has identified an unprecedented and ongoing exceedance of Cryptosporidium spp. across the United Kingdom, notably driven by C. hominis transmission, since 14 August 2023. Information from 477 reported cases in England and Wales, followed up with a standardised exposure questionnaire as of 25 September 2023, identified foreign travel in 250 (54%) of 463 respondents and swimming in 234 (66%) of 353 cases. A significant, common exposure has not yet been identified in first analyses.

Motor unit dysregulation following 15 days of unilateral lower limb immobilisation.

Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function when compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular electromyography (iEMG) bilaterally recorded from the vastus lateralis (VL) during knee extensor contractions normalised to maximal voluntary contraction (MVC), pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in motor unit (MU) discharge and MU potential (MUP) characteristics. VL CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised limb. Parameters of MUP size were reduced by 11% to 24% with immobilisation, while neuromuscular junction (NMJ) transmission instability remained unchanged, and MU firing rate decreased by 8% to 11% at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU firing rate which may underpin the disproportionate reductions of strength relative to muscle size. KEY POINTS: Muscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. The reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to muscle. We have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size coincided with suppressed motor unit firing rate. These motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans.

Training-induced improvements in knee extensor force accuracy are associated with reduced vastus lateralis motor unit firing variability.

NEW FINDINGS: What is the central question of this study? Can bilateral knee extensor force accuracy be improved following 4 weeks of unilateral force accuracy training and are there any subsequent alterations to central and/or peripheral motor unit features? What is the main finding and its importance? In the trained limb only, knee extensor force tracking accuracy improved with reduced motor unit firing rate variability in the vastus lateralis, and there was no change to neuromuscular junction transmission instability. Interventional strategies to improve force accuracy may be directed to older/clinical populations where such improvements may aid performance of daily living activities. ABSTRACT: Muscle force output during sustained submaximal isometric contractions fluctuates around an average value and is partly influenced by variation in motor unit (MU) firing rates. MU firing rate (FR) variability seemingly reduces following exercise training interventions; however, much less is known with respect to peripheral MU properties. We therefore investigated whether targeted force accuracy training could lead to improved muscle functional capacity and control, in addition to determining any alterations of individual MU features. Ten healthy participants (seven females, three males, 27 ± 6 years, 170 ± 8 cm, 69 ± 16 kg) underwent a 4-week supervised, unilateral knee extensor force accuracy training intervention. The coefficient of variation for force (FORCECoV ) and sinusoidal wave force tracking accuracy (FORCESinu ) were determined at 25% maximal voluntary contraction (MVC) pre- and post-training. Intramuscular electromyography was utilised to record individual MU potentials from the vastus lateralis (VL) muscles at 25% MVC during sustained contractions, pre- and post-training. Knee extensor muscle strength remained unchanged following training, with no improvements in unilateral leg-balance. FORCECoV and FORCESinu significantly improved in only the trained knee extensors by ∼13% (P = 0.01) and ∼30% (P < 0.0001), respectively. MU FR variability significantly reduced in the trained VL by ∼16% (n = 8; P = 0.001), with no further alterations to MU FR or neuromuscular junction transmission instability. Our results suggest muscle force control and tracking accuracy is a trainable characteristic in the knee extensors, which is likely explained by the reduction in MU FR variability which was apparent in the trained limb only.

Equipment-free, unsupervised high intensity interval training elicits significant improvements in the physiological resilience of older adults.

BACKGROUND: Reduced cardiorespiratory fitness (CRF) is an independent risk factor for dependency, cognitive impairment and premature mortality. High-intensity interval training (HIIT) is a proven time-efficient stimulus for improving both CRF and other facets of cardiometabolic health also known to decline with advancing age. However, the efficacy of equipment-free, unsupervised HIIT to improve the physiological resilience of older adults is not known. METHODS: Thirty independent, community-dwelling older adults (71(SD: 5) years) were randomised to 4 weeks (12 sessions) equipment-free, supervised (in the laboratory (L-HIIT)) or unsupervised (at home (H-HIIT)) HIIT, or a no-intervention control (CON). HIIT involved 5, 1-minute intervals of a bodyweight exercise each interspersed with 90-seconds recovery. CRF, exercise tolerance, blood pressure (BP), body composition, muscle architecture, circulating lipids and glucose tolerance were assessed at baseline and after the intervention period. RESULTS: When compared to the control group, both HIIT protocols improved the primary outcome of CRF ((via anaerobic threshold) mean difference, L-HIIT: +2.27, H-HIIT: +2.29, both p < 0.01) in addition to exercise tolerance, systolic BP, total cholesterol, non-HDL cholesterol and m. vastus lateralis pennation angle, to the same extent. There was no improvement in these parameters in CON. There was no change in diastolic BP, glucose tolerance, whole-body composition or HDL cholesterol in any of the groups. CONCLUSIONS: This is the first study to show that short-term, time-efficient, equipment-free, HIIT is able to elicit improvements in the CRF of older adults irrespective of supervision status. Unsupervised HIIT may offer a novel approach to improve the physiological resilience of older adults, combating age-associated physiological decline, the rise of inactivity and the additional challenges currently posed by the COVID-19 pandemic. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov and coded: NCT03473990 .

Influence of sex on the age-related adaptations of neuromuscular function and motor unit properties in elite masters athletes.

KEY POINTS: Masters athletes maintain high levels of activity into older age and allow an examination of the effects of aging dissociated from the effects of increased sedentary behaviour. Evidence suggests masters athletes are more successful at motor unit remodelling, the reinnervation of denervated fibres acting to preserve muscle fibre number, but little data are available in females. Here we used intramuscular electromyography to demonstrate that motor units sampled from the tibialis anterior show indications of remodelling from middle into older age and which does not differ between males and females. The age-related trajectory of motor unit discharge characteristic differs according to sex, with female athletes progressing to a slower firing pattern that was not observed in males. Our findings indicate motor unit remodelling from middle to older age occurs to a similar extent in male and female athletes, with discharge rates progressively slowing in females only. ABSTRACT: Motor unit (MU) remodelling acts to minimise loss of muscle fibres following denervation in older age, which may be more successful in masters athletes. Evidence suggests performance and neuromuscular function decline with age in this population, although the majority of studies have focused on males, with little available data on female athletes. Functional assessments of strength, balance and motor control were performed in 30 masters athletes (16 male) aged 44-83 years. Intramuscular needle electrodes were used to sample individual motor unit potentials (MUPs) and near-fibre MUPs in the tibialis anterior (TA) during isometric contractions at 25% maximum voluntary contraction, and used to determine discharge characteristics (firing rate, variability) and biomarkers of peripheral MU remodelling (MUP size, complexity, stability). Multilevel mixed-effects linear regression models examined effects of age and sex. All aspects of neuromuscular function deteriorated with age (P < 0.05) with no age × sex interactions, although males were stronger (P < 0.001). Indicators of MU remodelling also progressively increased with age to a similar extent in both sexes (P < 0.05), whilst MU firing rate progressively decreased with age in females (p = 0.029), with a non-significant increase in males (p = 0.092). Masters athletes exhibit age-related declines in neuromuscular function that are largely equal across males and females. Notably, they also display features of MU remodelling with advancing age, probably acting to reduce muscle fibre loss. The age trajectory of MU firing rate assessed at a single contraction level differed between sexes, which may reflect a greater tendency for females to develop a slower muscle phenotype.

Paediatric rotavirus vaccination, coeliac disease and type 1 diabetes in children: a population-based cohort study.

BACKGROUND: Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We have previously shown that rotavirus vaccination can have beneficial off-target effects on syndromes, such as hospitalised seizures. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. METHODS: A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed up from 6 months to 7 years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. RESULTS: There were 880,629 children in the cohort (48.8% female). A total of 343,113 (39.0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93.4% were vaccinated. Study participants contributed 4,388,355 person-years, with median follow-up 5.66 person-years. There were 1657 CD cases, an incidence of 38.0 cases per 100,000 person-years. Compared with unvaccinated children, the adjusted HR for a CD was 1.05 (95% CI 0.86-1.28) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 17.1 cases per 100,000 person-years. In adjusted analysis, rotavirus vaccination was not associated with risk of T1D (HR = 0.89, 95% CI 0.68-1.19). CONCLUSIONS: Rotavirus vaccination has reduced diarrhoeal disease morbidity and mortality substantial since licencing in 2006. Our finding from this large cohort study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety.

Factors associated with electrical stimulation-induced performance fatigability are dependent upon stimulation location.

NEW FINDINGS: What is the central question of this study? How does peripheral nerve stimulation (PNS) compare with neuromuscular electrical stimulation (NMES) used clinically to reduce muscle atrophy? What is the main finding and its importance? NMES resulted in progressive increases in M-wave duration and delay of muscle relaxation throughout a single stimulation protocol, findings not observed with PNS. This suggests PNS recruits from a wider pool of muscle fibres/motor units, providing a more favourable alternative to NMES for rehabilitation intervention. ABSTRACT: Neuromuscular electrical stimulation (NMES) is increasingly viewed as a central tenet to minimise muscle loss during periods of disuse/illness - typically applied directly over a muscle belly. Peripheral nerve stimulation (PNS) is afforded less attention, despite providing a more global contractile stimulus to muscles. We investigated NMES versus PNS in relation to performance fatigability and peripheral contributions to voluntary force capacity. Two fatigue protocols were assessed separately: (1) over-quadriceps NMES and (2) peripheral (femoral) nerve stimulation (PNS). Before and after each session, a maximal voluntary contraction (MVC) was performed to assess force loss. Knee-extensor force was measured throughout to assess contractile function in response to submaximal electrical stimulation, and M-wave features quantified myoelectrical activity. NMES and PNS induced similar voluntary (MVC, NMES: -12 ± 9%, PNS: -10 ± 8%, both P < 0.001) and stimulated (NMES: -45 ± 12%, PNS -27 ± 27%, both P < 0.001) force reductions. Although distinct between protocols, myoelectrical indicators of muscle recruitment (M-wave area and amplitude) and nerve conduction time did not change throughout either protocol. Myoelectrical propagation speed, represented as M-wave duration, and the delay before muscle relaxation began both progressively increased during NMES only (P < 0.05 and P < 0.001, respectively). NMES myoelectrical changes suggested performance fatigability, indicating activation of superficial fibres only, which was not observed with PNS. This suggests PNS recruits a wider pool of muscle fibres and motor units and is a favourable alternative for rehabilitation. Future work should focus on implementing PNS interventions in clinically relevant scenarios such as immobilisation, care homes and critical illness.

What proportion of care home outbreaks are caused by norovirus? An analysis of viral causes of gastroenteritis outbreaks in care homes, North East England, 2016-2018.

BACKGROUND: Outbreaks of infectious gastroenteritis are common in care homes for the elderly. Norovirus can cause these outbreaks, but diagnosis is frequently based solely on clinical characteristics. Our objective in this study was to describe the epidemiology of norovirus and other gastrointestinal pathogens in these settings. METHODS: We analysed surveillance data from gastroenteritis outbreaks reported in North East England between 04 July 2016 to 01 July 2018. Stool samples taken during these outbreaks were tested for a range of viral and bacterial pathogens. We described the epidemiology of these outbreaks and explored the characteristics of norovirus outbreaks versus from other viral causes using multivariable logistic regression. RESULTS: From the 566 care home gastroenteritis outbreaks in this study, we found that norovirus was the pathogen most frequently isolated. Norovirus was detected in 64% of outbreaks with a pathogen identified. Sapovirus was found in 13%; rotavirus in 11%. We found that norovirus outbreaks were associated with higher attack rates (aOR 1.03, 95% CI 1.01-1.05) and fewer cases sampled (aOR 0.74, 95% CI 0.60-0.91), compared to outbreaks caused by other viral pathogens. CONCLUSIONS: These results are important as they quantify the contribution of norovirus to gastroenteritis outbreaks in care homes. Given this evidence, we emphasize the importance of non-specific outbreak interventions that can affect the impact of all such outbreaks. We further recommend that these findings are used to inform the implementation strategies of any norovirus-specific interventions such as a norovirus vaccine.

Estimating the burden of care home gastroenteritis outbreaks in England, 2014-2016.

BACKGROUND: Outbreaks of infectious gastroenteritis in care homes are common, with norovirus a frequent cause. In England there is no co-ordinated national surveillance system. We aimed to estimate the burden of these outbreaks. METHODS: Using a generalised linear mixed effects regression model we described the relationship between the observed number of care home outbreaks and covariates. Estimated model parameters were used to infer uplift in the number of outbreaks expected if all areas were subjected to enhanced surveillance. From this we then estimated the total burden of care home gastroenteritis outbreaks in this period. RESULTS: We estimated a total of 14,146 care home gastroenteritis outbreaks in England during 2014-2016; this is 47% higher than the reported total and a rate of 32.4 outbreaks per 100 care homes per year. The median number of outbreaks from the model estimates was 31 (IQR 20-46) compared to 19 (IQR 12-34) reported from routine surveillance. CONCLUSIONS: This estimated care home gastroenteritis burden in England indicates that current surveillance substantially underestimates the number of outbreaks, by almost half. Improving this surveillance could provide better epidemiological knowledge of the burden of norovirus to inform public health policy, particularly with the advent of norovirus vaccines.

How timely closure can reduce outbreak duration: gastroenteritis in care homes in North West England, 2012-2016.

BACKGROUND: Data on outbreaks of infectious gastroenteritis in care homes have been collected using an internet-based surveillance system in North West England since 2012. We analysed the burden and characteristics of care home outbreaks to inform future public health decision-making. METHODS: We described characteristics of care homes and summary measures of the outbreaks such as attack rate, duration and pathogen identified. The primary analysis outcome was duration of closure following an outbreak. We used negative binomial regression to estimate Incidence Rate Ratios (IRR) and confidence intervals (CI) for each explanatory variable. RESULTS: We recorded 795 outbreaks from 379 care homes (37.1 outbreaks per 100 care homes per year). In total 11,568 cases, 75 hospitalisations and 29 deaths were reported. Closure within three days of the first case (IRR = 0.442, 95%CI 0.366-0.534) was significantly associated with reduced duration of closure. The total size of the home (IRR = 1.426, 95%CI = 1.275-1.595) and the total attack rate (IRR = 1.434, 95%CI = 1.257-1.595) were significantly associated with increased duration of closure. CONCLUSIONS: Care homes that closed promptly had outbreaks of shorter duration. Care home providers, and those advising them on infection control, should aim to close homes quickly to prevent lengthy disruption to services.

National outbreak of Shiga toxin-producing Escherichia coli O157:H7 linked to mixed salad leaves, United Kingdom, 2016.

We investigated a large outbreak of Escherichia coli O157 in the United Kingdom (UK) with 165 cases between 31 May and 29 July 2016. No linked cases were reported in other countries. Cases were predominately female (n = 128) and adult (n = 150), 66 attended hospital and nine had features of haemorrhagic uraemic syndrome. A series of epidemiological studies (case-control, case-case, ingredients-based and venue-based studies) and supply chain investigations implicated mixed salad leaves from Supplier A as the likely outbreak vehicle. Whole genome sequencing (WGS) indicated a link with strains from the Mediterranean and informed the outbreak control team to request that Supplier A cease distributing salad leaves imported from Italy. Microbiological tests of samples of salad leaves from Supplier A were negative. We were unable to confirm the source of contamination or the contaminated constituent leaf although our evidence pointed to red batavia received from Italy as the most likely vehicle. Variations in Shiga toxin-producing E.coli surveillance and diagnosis may have prevented detection of cases outside the UK and highlights a need for greater standardisation. WGS was useful in targeting investigations, but greater coverage across Europe is needed to maximise its potential.

Novel application of the matched case-control design to compare food supply chains during an Escherichia coli O157 outbreak, United Kingdom, 2016.

There is a need for innovative methods to investigate outbreaks of food-borne infection linked to produce with a complex distribution network. The investigation of a large outbreak of Escherichia coli O157 PT34 infection in the United Kingdom in 2016 indicated that catering venues associated with multiple cases had used salad leaves sourced from one supplier. Our aim was to investigate whether catering venues linked to cases were more likely to have used salad leaves from this supplier. We conducted a matched case-control study, with catering venues as the units of analysis. We compared venues linked to cases to those without known linked cases. We included 43 study pairs and obtained information on salad leaf products received by each venue. The odds of a case venue being supplied with salad leaves by Supplier A were 7.67 times (95% confidence interval: 2.30-25.53) those of control venues. This association provided statistical evidence to support the findings of the other epidemiological investigations undertaken for this outbreak. This is a novel approach which is labour-intensive but which addresses the challenge of investigating exposures to food across a complex distribution network.

Community-based surveillance of norovirus disease: a systematic review.

BACKGROUND: Norovirus is a common cause of infectious gastrointestinal disease. Despite the increased ability to detect norovirus in affected people, the number of reported cases and outbreaks in the community is still substantially underestimated. We undertook a systematic review to determine the nature, scope and scale of community-based surveillance systems which capture information on norovirus disease. METHODS: We searched MEDLINE, EMBASE and Scopus for studies published between 01 January 1995 and 31 December 2015, using terms relating to norovirus and surveillance. Publications were screened independently by two reviewers using exclusion criteria. Data extraction from included papers was performed using a standardized data extraction form. Outcomes were descriptions of the methods reported in included papers, and any estimates of incidence rate of norovirus disease in each community, stratified by age. RESULTS: After exclusions, we reviewed 45 papers of which 23 described surveillance studies and 19 included estimates of incidence. The estimates of incidence varied by outcome measure, type of laboratory test and study population. There were two estimates of norovirus hospitalisation; 0.72 and 1.04 per 1000 person-years. Estimates of norovirus disease ranged between 0.024 cases per 1000 person-years and 60 cases per 1000 person-years and estimates of all gastroenteritis varied between 49 and 1100 cases per 1000 person-years. CONCLUSIONS: Our systematic review found few papers describing community-based surveillance for norovirus disease. Standardised age-specific estimates of norovirus incidence would be valuable for calculating the true global burden of norovirus disease; robust community surveillance systems would be able to produce this information. TRIAL REGISTRATION: PROSPERO 2016: CRD42016048659 .

Enforcement of science-using a Clostridium perfringens outbreak investigation to take legal action.

BACKGROUND: We report an outbreak of Clostridium perfringens in a care home in North East England. METHODS: A retrospective cohort study was used to investigate this outbreak. Faecal samples were obtained from symptomatic residents. Environmental Health Officers carried out a food hygiene inspection and formal statements were taken. RESULTS: Fifteen residents reported illness and the epidemic curve was suggestive of a point source outbreak. Results suggest that illness was associated with consumption of mince & vegetable pie and/or gravy. There were a number of issues with food served, in particular the mince products had been cooked, cooled, reheated and served again over a period of several days. Faecal sampling revealed the presence of C.perfringens enterotoxin gene and four samples were indistinguishable by fluorescent amplified fragment length polymorphism, indicating a likely common source. The operator of the home was charged with three offences under the General Food Regulations 2004 and the Food Hygiene (England) Regulations 2006 and was convicted on all counts. CONCLUSIONS: An outbreak of C.perfringens occurred in a care home. The likely cause was consumption of mince & vegetable pie and/or gravy. Epidemiological evidence can be used to help prosecute businesses with food safety offences in such circumstances.

The potential impact of media reporting in syndromic surveillance: an example using a possible Cryptosporidium exposure in North West England, August to September 2015.

During August 2015, a boil water notice (BWN) was issued across parts of North West England following the detection of Cryptosporidium oocysts in the public water supply. Using prospective syndromic surveillance, we detected statistically significant increases in the presentation of cases of gastroenteritis and diarrhoea to general practitioner services and related calls to the national health telephone advice service in those areas affected by the BWN. In the affected areas, average in-hours general practitioner consultations for gastroenteritis increased by 24.8% (from 13.49 to 16.84) during the BWN period; average diarrhoea consultations increased by 28.5% (from 8.33 to 10.71). Local public health investigations revealed no laboratory reported cases confirmed as being associated with the water supply. These findings suggest that the increases reported by syndromic surveillance of cases of gastroenteritis and diarrhoea likely resulted from changes in healthcare seeking behaviour driven by the intense local and national media coverage of the potential health risks during the event. This study has further highlighted the potential for media-driven bias in syndromic surveillance, and the challenges in disentangling true increases in community infection from those driven by media reporting.

Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study.

BACKGROUND: Increasing numbers of individuals with cystic fibrosis are becoming infected with the multidrug-resistant non-tuberculous mycobacterium (NTM) Mycobacterium abscessus, which causes progressive lung damage and is extremely challenging to treat. How this organism is acquired is not currently known, but there is growing concern that person-to-person transmission could occur. We aimed to define the mechanisms of acquisition of M abscessus in individuals with cystic fibrosis. METHOD: Whole genome sequencing and antimicrobial susceptibility testing were done on 168 consecutive isolates of M abscessus from 31 patients attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In parallel, we undertook detailed environmental testing for NTM and defined potential opportunities for transmission between patients both in and out of hospital using epidemiological data and social network analysis. FINDINGS: Phylogenetic analysis revealed two clustered outbreaks of near-identical isolates of the M abscessus subspecies massiliense (from 11 patients), differing by less than ten base pairs. This variation represents less diversity than that seen within isolates from a single individual, strongly indicating between-patient transmission. All patients within these clusters had numerous opportunities for within-hospital transmission from other individuals, while comprehensive environmental sampling, initiated during the outbreak, failed to detect any potential point source of NTM infection. The clusters of M abscessus subspecies massiliense showed evidence of transmission of mutations acquired during infection of an individual to other patients. Thus, isolates with constitutive resistance to amikacin and clarithromycin were isolated from several individuals never previously exposed to long-term macrolides or aminoglycosides, further indicating cross-infection. INTERPRETATION: Whole genome sequencing has revealed frequent transmission of multidrug resistant NTM between patients with cystic fibrosis despite conventional cross-infection measures. Although the exact transmission route is yet to be established, our epidemiological analysis suggests that it could be indirect. FUNDING: The Wellcome Trust, Papworth Hospital, NIHR Cambridge Biomedical Research Centre, UK Health Protection Agency, Medical Research Council, and the UKCRC Translational Infection Research Initiative.

Common synaptic inputs and persistent inward currents of vastus lateralis motor units are reduced in older male adults.

Although muscle atrophy may partially account for age-related strength decline, it is further influenced by alterations of neural input to muscle. Persistent inward currents (PIC) and the level of common synaptic inputs to motoneurons influence neuromuscular function. However, these have not yet been described in the aged human quadriceps. High-density surface electromyography (HDsEMG) signals were collected from the vastus lateralis of 15 young (mean ± SD, 23 ± 5 y) and 15 older (67 ± 9 y) men during submaximal sustained and 20-s ramped contractions. HDsEMG signals were decomposed to identify individual motor unit discharges, from which PIC amplitude and intramuscular coherence were estimated. Older participants produced significantly lower knee extensor torque (p < 0.001) and poorer force tracking ability (p < 0.001) than young. Older participants also had lower PIC amplitude (p = 0.001) and coherence estimates in the alpha frequency band (p < 0.001) during ramp contractions when compared to young. Persistent inward currents and common synaptic inputs are lower in the vastus lateralis of older males when compared to young. These data highlight altered neural input to the clinically and functionally important quadriceps, further underpinning age-related loss of function which may occur independently of the loss of muscle mass.

Exploring the utility of ultrasound to assess disuse atrophy in different muscles of the lower leg.

BACKGROUND: Skeletal muscle is a highly plastic tissue crucial for many functions associated with whole-body health across the life course. Magnetic resonance imaging (MRI) is the current gold standard for measuring skeletal muscle size. However, MRI is expensive, and access to facilities is often limited. B-mode ultrasonography (U/S) has been proposed as a potential alternative to MRI for the assessment of muscle size. However, to date, no work has explored the utility of U/S to assess disuse muscle atrophy (DMA) across muscles with different atrophy susceptibility profiles, an omission which may limit the clinical application of previous work. METHODS: To address this significant knowledge gap, 10 young men (22 ±  years, 24.1 ± 2.3 kg/m2) underwent 15-day unilateral leg immobilization using a knee-brace and air boot. Cross-sectional area (CSA) and muscle thickness (MT) of the tibialis anterior (TA) and medial gastrocnemius (MG) were assessed via U/S before and after immobilization, with CSA and muscle volume assessed via MRI. RESULTS: With both muscles combined, there were good correlations between each U/S and MRI measure, both before (e.g., CSAMRI vs. MTU/S and CSAU/S: r = 0.88 and 0.94, respectively, both P < 0.0001) and after (e.g., VOLMRI vs. MTU/S and CSAU/S: r = 0.90 and 0.96, respectively, both P < 0.0001) immobilization. The relationship between the methods was notably stronger for MG than TA at each time-point (e.g., CSAMRI vs. MTU/S: MG, r = 0.70, P = 0.0006; TA, r = 0.37, P = 0.10). There was no relationship between the degree of DMA determined by the two methods in either muscle (e.g., TA pre- vs. post-immobilization, VOLMRI: 136 ± 6 vs. 133 ± 5, P = 0.08; CSAU/S: 6.05 ± 0.3 vs. 5.92 ± 0.4, P = 0.70; relationship between methods: r = 0.12, P = 0.75). CONCLUSIONS: Both MTU/S and CSAU/S provide comparable static measures of lower leg muscle size compared with MRI, albeit with weaker agreement in TA compared to MG. Although both MTU/S and CSAU/S can discern differences in DMA susceptibility between muscles, neither can reliably assess degree of DMA. Based on the growing recognition of heterogeneous atrophy profiles between muscles, and the topical importance of less commonly studied muscles (i.e., TA for falls prevention in older adults), future research should aim to optimize accessible methods to determine muscle losses across the body.