The Effects of High-Intensity Multimodal Training in Apparently Healthy Populations: A Systematic Review.

BACKGROUND: High-intensity multimodal training (HIMT) is emerging as a popular training method that combines aerobic and resistance training throughout a single exercise session. The current literature is limited by a lack of terminology that broadly encompasses all styles of combined aerobic and resistance training. The magnitude of chronic or long-term (i.e.  ≥ 4 weeks) effects of HIMT participation on aerobic and muscular fitness also remains unclear. Additionally, one of many complex reasons for the growing popularity of HIMT may be attributed to the affective response to exercise, namely levels of enjoyment. However, this concept is not yet well understood across all styles of HIMT. A comprehensive systematic review is required to synthesise the available literature and attempt to provide an operational definition of HIMT to capture the breadth of combined training styles that exist. OBJECTIVE: The objective of this systematic review was to determine the chronic effects of HIMT participation on aerobic and muscular fitness and to compare HIMT to established concurrent training methods. Enjoyability and other adherence-related subjective responses were also examined in HIMT participants. This review critically assessed the level of evidence and feasibility of current HIMT guidelines. METHODS: A systematic literature search was conducted on PubMed, Web of Science and SPORTDiscus to identify studies up until March 2021. RESULTS: A total of 20 studies were included for review. Studies generally reported moderate to large effects on aerobic fitness and subjective responses in favour of HIMT interventions. Mixed outcomes were demonstrated in muscular fitness. These results should be treated with caution due to high risk of bias among included studies. CONCLUSIONS: Few studies have assessed the chronic effects of HIMT participation on aerobic, and musculoskeletal adaptations and subjective responses, in particular exercise enjoyment. Research conclusions are limited by heterogeneity of experimental protocols and outcome measures. Furthermore, the inability of the literature to make adequate comparisons between various styles of HIMT and other concurrent training protocols limits understandings of the efficacy of HIMT. Registration This systematic review was registered on the Open Science Framework (10.17605/OSF.IO/2RE4B; 26 March 2021)

Validity, reliability, and responsiveness of a self-reported foot and ankle score (SEFAS)

Background and purpose A questionnaire was introduced by the New Zealand Arthroplasty Registry for use when evaluating the outcome of total ankle replacement surgery. We evaluated the reliability, validity, and responsiveness of the modified Swedish version of the questionnaire (SEFAS) in patients with osteoarthritis or inflammatory arthritis before and/or after their ankle was replaced or fused. Patients and methods The questionnaire was translated into Swedish and cross-culturally adapted according to a standardized procedure. It was sent to 135 patients with ankle arthritis who were scheduled for or had undergone surgery, together with the foot and ankle outcome score (FAOS), the short form 36 (SF-36) score, and the EuroQol (EQ-5D) score. Construct validity was evaluated with Spearman's correlation coefficient when comparing SEFAS with FAOS, SF-36, and EQ-5D, content validity by calculating floor and ceiling effects, test-retest reliability with intraclass correlation coefficient (ICC), internal consistency with Cronbach's alpha (n = 62), agreement by Bland-Altman plot, and responsiveness by effect size and standardized response mean (n = 37). Results For construct validity, we correlated SEFAS with the other scores and 70% or more of our predefined hypotheses concerning correlations could be confirmed. There were no floor or ceiling effects. ICC was 0.92 (CI 95%: 0.88-0.95), Cronbach's alpha 0.96, effect size was 1.44, and the standardized response mean was 1.00. Interpretation SEFAS is a self-reported foot and ankle score with good validity, reliability and responsiveness, indicating that the score can be used to evaluate patients with osteoarthritis or inflammatory arthritis of the ankle and outcome of surgery

Objectively measured physical activity and longitudinal changes in adolescent body fatness: an observational cohort study.

BACKGROUND: The data regarding prospective associations between physical activity (PA) and adiposity in youth are inconsistent. OBJECTIVE: The objective of this study was to investigate associations between baseline levels of objectively measured PA and changes in adiposity over 2.5 years from mid-to-late adolescence. METHODS: This was an observational cohort study in 728 school students (43% boys) from Cambridgeshire, United Kingdom. Fat mass index (FMI, kg m(-2) ) was estimated at baseline (mean ± standard deviation age: 15 ± 0.3 years) and follow-up (17.5 ± 0.3 years) by anthropometry and bioelectrical impedance. Habitual PA was assessed at baseline by ≥3 d combined heart rate and movement sensing. Average daily PA energy expenditure (PAEE) and the time (min d(-1) ) spent in light, moderate and vigorous intensity PA (LPA, MPA and VPA, respectively) was estimated. Multilevel models were used to investigate associations between baseline PA and change in FMI (ΔFMI). Adjustment for baseline age, sex, follow-up duration, area-level socioeconomic status, season of PA assessment, sedentary time, energy intake and sleep duration was made; baseline FMI was also added in a second model. RESULTS: FMI increased significantly over follow-up (0.6 ± 1.2 kg m(-2) , P < 0.001). Baseline PAEE and LPA positively predicted ΔFMI in overfat participants (P ≤ 0.030), as did VPA in initially normal fat participants (P ≤ 0.044). There were further positive associations between PAEE and ΔFMI in normal fat participants, and between MPA and ΔFMI in both fat groups, when adjusted for baseline FMI (P ≤ 0.024). CONCLUSIONS: Baseline PAEE and its subcomponents were positively associated with small and unlikely clinically relevant increases in ΔFMI. These counter-intuitive findings may be explained by behavioural changes during the course of study follow-up.This work was supported by the Medical Research Council (Unit Programme number MC_UU_12015/3), the Wellcome Trust (grant 074296/Z/04/Z) and the British Heart Foundation (grant FS/12/58/29709 to KW).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/ijpo.1203

Prostaglandin insert dinoprostone versus trans-cervical balloon catheter for outpatient labour induction: a randomised controlled trial of feasibility (PROBIT-F)

Background The aim was to assess the feasibility of conducting a randomised controlled trial (RCT) of induction of labour comparing use of two methods in the outpatient setting. Methods An open-label feasibility RCT was conducted in two UK maternity units from October 2017 to March 2019. Women aged ≥ 16 years, undergoing induction of labour (IOL) at term, with intact membranes and deemed suitable for outpatient IOL according to local guidelines were considered eligible. They were randomised to cervical ripening balloon catheter (CRB) or vaginal dinoprostone (Propess). The participants completed a questionnaire and a sub-group underwent detailed interview. Service use and cost data were collected via the Adult Service Use Schedule (AD-SUS). Women who declined to participate were requested to complete a decliners’ questionnaire. Results During the study period, 274 eligible women were identified. Two hundred thirty (83.9%) were approached for participation of whom 84/230 (36.5%) agreed and 146 did not. Of these, 38 were randomised to Propess (n = 20) and CRB (n = 18). Decliner data were collected for 93 women. The reasons for declining were declining IOL (n = 22), preference for inpatient IOL (n = 22) and preference for a specific method, Propess (n = 19). The intended sample size of 120 was not reached due to restrictive criteria for suitability for outpatient IOL, participant preference for Propess and shortage of research staff. The intervention as randomised was received by 29/38 (76%) women. Spontaneous vaginal delivery was observed in 9/20 (45%) women in the dinoprostone group and 11/18 (61%) women in the CRB group. Severe maternal adverse events were recorded in one woman in each group. All babies were born with good condition and all except one (37/38, 97.4%) remained with the mother after delivery. No deaths were recorded. − 21% of women in the dinoprostone group were re-admitted prior to diagnosis of active labour compared to 12% in the CRB group. Conclusions A third of the approached eligible women agreed for randomisation. An RCT is not feasible in the current service context. Modifications to the eligibility criteria for outpatient IOL, better information provision and round the clock availability of research staff would be needed to reach sufficient numbers

A novel automated rodent tracker (ART), demonstrated in a mouse model of amyotrophic lateral sclerosis.

Background Generating quantitative metrics of rodent locomotion and general behaviours from video footage is important in behavioural neuroscience studies. However, there is not yet a free software system that can process large amounts of video data with minimal user interventions. New method Here we propose a new, automated rodent tracker (ART) that uses a simple rule-based system to quickly and robustly track rodent nose and body points, with minimal user input. Tracked points can then be used to identify behaviours, approximate body size and provide locomotion metrics, such as speed and distance. Results ART was demonstrated here on video recordings of a SOD1 mouse model, of amyotrophic lateral sclerosis, aged 30, 60, 90 and 120 days. Results showed a robust decline in locomotion speeds, as well as a reduction in object exploration and forward movement, with an increase in the time spent still. Body size approximations (centroid width), showed a significant decrease from P30. Comparison with existing method(s) ART performed to a very similar accuracy as manual tracking and Ethovision (a commercially available alternative), with average differences in coordinate points of 0.6 and 0.8 mm, respectively. However, it required much less user intervention than Ethovision (6 as opposed to 30 mouse clicks) and worked robustly over more videos. Conclusions ART provides an open-source option for behavioural analysis of rodents, performing to the same standards as commercially available software. It can be considered a validated, and accessible, alternative for researchers for whom non-invasive quantification of natural rodent behaviour is desirable

Dynamic clamp with StdpC software

Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording

Insecticide resistance and the future of malaria control in Zambia.

BACKGROUND: In line with the Global trend to improve malaria control efforts a major campaign of insecticide treated net distribution was initiated in 1999 and indoor residual spraying with DDT or pyrethroids was reintroduced in 2000 in Zambia. In 2006, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of these activities and the potential impact of emerging insecticide resistance on disease transmission. METHODS: Mosquitoes were captured daily through a series of 108 window exit traps located at 18 sentinel sites. Specimens were identified to species and analyzed for sporozoites. Adult Anopheles mosquitoes were collected resting indoors and larva collected in breeding sites were reared to F1 and F0 generations in the lab and tested for insecticide resistance following the standard WHO susceptibility assay protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 14 years. RESULTS: A total of 619 Anopheles gambiae s.l. and 228 Anopheles funestus s.l. were captured from window exit traps throughout the period, of which 203 were An. gambiae malaria vectors and 14 An. funestus s.s.. In 2010 resistance to DDT and the pyrethroids deltamethrin, lambda-cyhalothrin and permethrin was detected in both An. gambiae s.s. and An. funestus s.s.. No sporozoites were detected in either species. Prevalence of P. falciparum in the sentinel sites remained below 10% throughout the study period. CONCLUSION: Both An. gambiae s.s. and An. funestus s.s. were controlled effectively with the ITN and IRS programme in Zambia, maintaining a reduced disease transmission and burden. However, the discovery of DDT and pyrethroid resistance in the country threatens the sustainability of the vector control programme

Global microRNA depletion suppresses tumor angiogenesis

MicroRNAs delicately regulate the balance of angiogenesis. Here we show that depletion of all microRNAs suppresses tumor angiogenesis. We generated microRNA-deficient tumors by knocking out Dicer1. These tumors are highly hypoxic but poorly vascularized, suggestive of deficient angiogenesis signaling. Expression profiling revealed that angiogenesis genes were significantly down-regulated as a result of the microRNA deficiency. Factor inhibiting hypoxia-inducible factor 1 (HIF-1), FIH1, is derepressed under these conditions and suppresses HIF transcription. Knocking out FIH1 using CRISPR/Cas9-mediated genome engineering reversed the phenotypes of microRNA-deficient cells in HIF transcriptional activity, VEGF production, tumor hypoxia, and tumor angiogenesis. Using multiplexed CRISPR/Cas9, we deleted regions in FIH1 3′ untranslated regions (UTRs) that contain microRNA-binding sites, which derepresses FIH1 protein and represses hypoxia response. These data suggest that microRNAs promote tumor responses to hypoxia and angiogenesis by repressing FIH1.Swedish Research CouncilHoward Hughes Medical Institute (International Student Research Fellowship)National Institutes of Health (U.S.) (grant number R01-CA133404)MIT-Harvard Center of Cancer Nanotechnology Excellence (grant no. U54-CA151884)David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund)National Cancer Institute (U.S.) (Koch Institute Support (core) Grant P30-CA14051))National Institutes of Health (U.S.) (grant EB016101-01A1)Damon Runyon Cancer Research Foundation (Research Fellow (DRG-2117-12)

CHIIMP: An automated high-throughput microsatellite genotyping approach reveals greater allelic diversity in wild chimpanzees

Short tandem repeats (STRs), also known as microsatellites, are commonly used to non invasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq-based approach and tested its performance using previously genotyped fecal samples from long-term studied chimpanzees in Gombe National Park, Tanzania. Using data from eight microsatellite loci as a reference, we designed a bioinformatics platform that converts raw MiSeq reads into locus-specific files and automatically calls alleles after filtering stutter sequences and other PCR artifacts. Applying this method to the entire Gombe population, we confirmed previously reported genotypes, but also identified 31 new alleles that had been missed due to sequence differences and size homoplasy. The new genotypes, which increased the allelic diversity and heterozygosity in Gombe by 61% and 8%, respectively, were validated by replicate amplification and pedigree analyses. This demonstrated inheritance and resolved one case of an ambiguous paternity. Using both singleplex and multiplex locus amplification, we also genotyped fecal samples from chimpanzees in the Greater Mahale Ecosystem in Tanzania, demonstrating the utility of the MiSeq-based approach for genotyping non-habituated populations and performing comparative analyses across field sites. The new automated high-throughput analysis platform (available at https://github.com/ShawHahnLab/chiimp) will allow biologists to more accurately and effectively determine wildlife population size and structure, and thus obtain information critical for conservation efforts

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

Background Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies. Methods We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards. Results Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission. Conclusion Measure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia