Exercise for falls prevention in community-dwelling older adults: Trial and participant characteristics, interventions and bias in clinical trials from a systematic review

IntroductionThere is strong evidence that exercise prevents falls in community-dwelling older people. This review summarises trial and participant characteristics, intervention contents and study quality of 108 randomised trials evaluating exercise interventions for falls prevention in community-dwelling older adults.MethodsMEDLINE, EMBASE, CENTRAL and three other databases sourced randomised controlled trials of exercise as a single intervention to prevent falls in community-dwelling adults aged 60+ years to May 2018.Results108 trials with 146 intervention arms and 23 407 participants were included. Trials were undertaken in 25 countries, 90% of trials had predominantly female participants and 56% had elevated falls risk as an inclusion criterion. In 72% of trial interventions attendance rates exceeded 50% and/or 75% of participants attended 50% or more sessions. Characteristics of the trials within the three types of intervention programme that reduced falls were: (1) balance and functional training interventions lasting on average 25 weeks (IQR 16–52), 39% group based, 63% individually tailored; (2) Tai Chi interventions lasting on average 20 weeks (IQR 15–43), 71% group based, 7% tailored; (3) programmes with multiple types of exercise lasting on average 26 weeks (IQR 12–52), 54% group based, 75% tailored. Only 35% of trials had low risk of bias for allocation concealment, and 53% for attrition bias.ConclusionsThe characteristics of effective exercise interventions can guide clinicians and programme providers in developing optimal interventions based on current best evidence. Future trials should minimise likely sources of bias and comply with reporting guidelines

The switching dynamics of the bacterial flagellar motor

Many swimming bacteria are propelled by flagellar motors that stochastically switch between the clockwise and counterclockwise rotation direction. While the switching dynamics are one of the most important characteristics of flagellar motors, the mechanisms that control switching are poorly understood. We present a statistical-mechanical model of the flagellar rotary motor, which consists of a number of stator proteins that drive the rotation of a ring of rotor proteins, which in turn drives the rotation of a flagellar filament. At the heart of our model is the assumption that the rotor protein complex can exist in two conformational states corresponding to the two respective rotation directions, and that switching between these states depends on interactions with the stator proteins. This naturally couples the switching dynamics to the rotation dynamics, making the switch sensitive to torque and speed. Another key element of our model is that after a switching event, it takes time for the load to build up, due to polymorphic transitions of the filament. Our model predicts that this slow relaxation dynamics of the filament, in combination with the load dependence of the switching frequency, leads to a characteristic switching time, in agreement with recent observations.Comment: 7 pages, 6 figures, RevTeX

Bacteria in the cavity-restoration interface after varying periods of clinical service – SEM description of distribution and 16S rRNA gene sequence identification of isolates

Objectives To use extracted human teeth with amalgam (n = 26) or GIC (n = 3) restorations in service up to 20 years to evaluate microbiota at the cavity/restoration interface by SEM or culture. Materials and methods Extracted teeth with intracoronal restorations (n = 20) of known history (2–20 years) were fixed, split, and prepared for SEM to ascertain the pattern and structure of bacterial aggregates on cavity and restoration surfaces. Another 9 teeth were anaerobically decontaminated, split and sampled (cavity/restorations), and cultured (anaerobically, aerobically); recovered isolates were identified by 16S rRNA gene sequencing. Results SEM showed rods, cocci, and filaments in 11/20 teeth (55%) on cavity and corresponding restoration surfaces; 4/20 (20%) on neither surface; 1/20 (5%) on just cavity; and 4/20 (20%) on just restoration. Microbial growth extended from marginal openings into the deeper interfacial microspace to varying extents but was not always evident. Restoration size or age did not predict bacterial presence. Bacteria-free surfaces (cavity/amalgam) showed possible calcification. Cultivation yielded 160 isolates, mainly Gram-positive (86%) and facultative (81%); and morphotypes of rods (43%), cocci (36%), and cocco-bacilli (18%) belonging to Actinobacteria (45%) and Firmicutes (50%). The most frequent genera were Staphylococcus, Streptococcus, Actinomyces, and Lactobacillus. Biofilms on cavity and restoration appeared independent of each other. Conclusions Cavity and amalgam surfaces were independently colonised and some not. The penetration of microbiota into marginal gaps varied; resembled root caries and was dominated by Gram-positive species. Clinical relevance Marginal gaps around restorations are unavoidable but are not always colonised by bacteria after long-term clinical service. Calcification of biofilms in the restorative interface may prevent further colonisation. The viable microbiota in the restorative interface resembled root caries and may be subject to ecological fluxes of activity and arrest and therefore preventative management

The UN Sustainable Development Goals (SDGs): Contributions from the Humanities

It is widely agreed that achieving the United Nations Sustainable Development Goals requires the insights, knowledge and comparative perspectives of Humanities disciplines. The UNESCO Hangzhou Declaration of 2013 highlighted the importance of culture as ‘an enabler and driver of sustainable development’. Yet the Humanities have so far featured relatively little in work on the SDGs

Stomach Simulator for Analysis and Validation of Surgical Endoluminal Robots

A testing environment that imitates gastric geometry and contractile activity is necessary to analyse and validate endoluminal surgical robotic devices developed for gastric pathologies. To achieve this goal, a silicone stomach model and a mechanical setup to simulate gastric contractile motion were designed and fabricated. The developed stomach simulator was validated and its usefulness was demonstrated by means of internal pressure measurements and self-assembly tests of mock-ups of capsule devices. The results demonstrated that the stomach simulator is helpful for quantitative evaluation of endoluminal robotic devices before in-vitro/in-vivo experiments

Susceptibility to increased high energy dense sweet and savoury food intake in response to the COVID-19 lockdown: The role of craving control and acceptance coping strategies

Emerging evidence indicates that for some people, the COVID-19 lockdowns are a time of high risk for increased food intake. A clearer understanding of which individuals are most at risk of over-eating during the lockdown period is needed to inform interventions that promote healthy diets and prevent weight gain during lockdowns. An online survey collected during the COVID-19 lockdown (total n = 875; analysed n = 588; 33.4 ± 12.6 years; 82% UK-based; mostly white, educated, and not home schooling) investigated reported changes to the amount consumed and changes to intake of high energy dense (HED) sweet and savoury foods. The study also assessed which eating behaviour traits predicted a reported increase of HED sweet and savoury foods and tested whether coping responses moderated this relationship. Results showed that 48% of participants reported increased food intake in response to the COVID-19 lockdown. There was large individual variability in reported changes and lower craving control was the strongest predictor of increased HED sweet and savoury food intake. Low cognitive restraint also predicted greater increases in HED sweet snacks and HED savoury meal foods. Food responsiveness, enjoyment of food, emotional undereating, emotional overeating and satiety responsiveness were not significant predictors of changes to HED sweet and savoury food intake. High scores on acceptance coping responses attenuated the conditional effects of craving control on HED sweet snack intake. Consistent with previous findings, the current research suggests that low craving control is a risk factor for increased snack food intake during lockdown and may therefore represent a target for intervention

LotuS2: an ultrafast and highly accurate tool for amplicon sequencing analysis

Background: Amplicon sequencing is an established and cost-efficient method for profiling microbiomes. However, many available tools to process this data require both bioinformatics skills and high computational power to process big datasets. Furthermore, there are only few tools that allow for long read amplicon data analysis. To bridge this gap, we developed the LotuS2 (less OTU scripts 2) pipeline, enabling user-friendly, resource friendly, and versatile analysis of raw amplicon sequences.Results: In LotuS2, six different sequence clustering algorithms as well as extensive pre- and post-processing options allow for flexible data analysis by both experts, where parameters can be fully adjusted, and novices, where defaults are provided for different scenarios.We benchmarked three independent gut and soil datasets, where LotuS2 was on average 29 times faster compared to other pipelines, yet could better reproduce the alpha- and beta-diversity of technical replicate samples. Further benchmarking a mock community with known taxon composition showed that, compared to the other pipelines, LotuS2 recovered a higher fraction of correctly identified taxa and a higher fraction of reads assigned to true taxa (48% and 57% at species; 83% and 98% at genus level, respectively). At ASV/OTU level, precision and F-score were highest for LotuS2, as was the fraction of correctly reported 16S sequences.Conclusion: LotuS2 is a lightweight and user-friendly pipeline that is fast, precise, and streamlined, using extensive pre- and post-ASV/OTU clustering steps to further increase data quality. High data usage rates and reliability enable high-throughput microbiome analysis in minutes

Critical evaluation of HPV16 gene copy number quantification by SYBR green PCR

Background: Human papilloma virus (HPV) load and physical status are considered useful parameters for clinical evaluation of cervical squamous cell neoplasia. However, the errors implicit in HPV gene quantification by PCR are not well documented. We have undertaken the first rigorous evaluation of the errors that can be expected when using SYBR green qPCR for quantification of HPV type 16 gene copy numbers. We assessed a modified method, in which external calibration curves were generated from a single construct containing HPV16 E2, HPV16 E6 and the host gene hydroxymethylbilane synthase in a 1: 1: 1 ratio.Results: When testing dilutions of mixed HPV/host DNA in replicate runs, we observed errors in quantifying E2 and E6 amplicons of 5 - 40%, with greatest error at the lowest DNA template concentration (3 ng/mu l). Errors in determining viral copy numbers per diploid genome were 13 - 53%. Nevertheless, in cervical keratinocyte cell lines we observed reasonable agreement between viral loads determined by qPCR and Southern blotting. The mean E2/E6 ratio in episome-only cells was 1.04, but with a range of 0.76 - 1.32. In three integrant-only lines the mean E2/E6 ratios were 0.20, 0.72 and 2.61 (values confirmed by gene-specific Southern blotting). When E2/E6 ratios in fourteen HPV16-positive cervical carcinomas were analysed, conclusions regarding viral physical state could only be made in three cases, where the E2/E6 ratio was <= 0.06.Conclusion: Run-to-run variation in SYBR green qPCR produces unavoidable inaccuracies that should be allowed for when quantifying HPV gene copy number. While E6 copy numbers can be considered to provide a useable indication of viral loads, the E2/E6 ratio is of limited value. Previous studies may have overestimated the frequency of mixed episomal/integrant HPV infections

Long-term assessment of the NHS hybrid closed-loop real-world study on glycaemic outcomes, time-in-range, and quality of life in children and young people with type 1 diabetes

Hybrid closed-loop (HCL) systems seamlessly interface continuous glucose monitoring (CGM) with insulin pumps, employing specialised algorithms and user-initiated automated insulin delivery. This study aimed to assess the efficacy of HCLs at 12 months post-initiation on glycated haemoglobin (HbA1c), time-in-range (TIR), hypoglycaemia frequency, and quality of life measures among children and young people (CYP) with type 1 diabetes mellitus (T1DM) and their caregivers in a real-world setting. Conducted between August 1, 2021, and December 10, 2022, the prospective recruitment took place in eight paediatric diabetes centres across England under the National Health Service England’s (NHSE) HCL pilot real-world study. A cohort of 251 CYP (58% males, mean age 12.3 years) with T1DM participated (89% white, 3% Asian, 4% black, 3% mixed ethnicity, and 1% other). The study utilised three HCL systems: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA, USA) with the Dexcom G6® CGM (Dexcom, San Diego, CA, USA) sensor; (2) Medtronic MiniMed™ 780G with the Guardian 4 sensor (Medtronic, Northridge, CA, USA); and (3) the CamAPS FX (CamDiab, Cambridge, UK) with the Ypsomed insulin pump (Ypsomed Ltd, Escrick, UK) and Dexcom G6® CGM. All systems were fully funded by the NHS. Results demonstrated significant improvements in HbA1c (average reduction at 12 months 7 mmol/mol; P < 0.001), time-in-range (TIR) (average increase 13.4%; P < 0.001), hypoglycaemia frequency (50% reduction), hypoglycaemia fear, and quality of sleep (P < 0.001) among CYP over a 12-month period of HCL usage. Additionally, parents and carers experienced improvements in hypoglycaemia fear and quality of sleep after 6 and 12 months of use. In addition to the improvements in glycaemic management, these findings underscore the positive impact of HCL systems on both the well-being of CYP with T1DM and the individuals caring for them