Influence of intervals of radiant heat on performance and pacing dynamics during rowing exercise

Abstract: The purpose of this study was to investigate whether intervals of radiant heat during thermoneutral exercise altered either the performance outcome or the dynamics of pacing within the exercise bout. Eleven male participants ( ; 56 ± 12 ml∙kg-1∙min-1) performed three 5000m exercise trials on a rowing ergometer in three different conditions, in a random order. The participants were either: non-warmed (NW), warmed (W), or periodically warmed in intervals throughout each trial (IW). Warming was achieved using radiant heat lamps to raise the localised environmental temperature from 18 ˚C to 35 ˚C. Intervals of warming were applied over fixed periods of the 5000m bouts between 1000-2000m (W1) and 3000-4000m (W2). The results of the experiment demonstrated that performance time and average power output of the 5000m matched intensity trials were not significantly different between conditions (p=0.10 ; p=0.189). However, the application of warming significantly reduced intra-trial power output during the first (W1) interval in the IW condition (p=0.03) but not during the second (W2) warming interval (p=0.10). Tsk increased by 0.51˚C (p=0.05) in response to the application of warming during W1 in the IW condition and by 0.15 ˚C in W2 (p=0.28). No significant between-condition differences were observed in Tc throughout the trials. These findings suggest that an abrupt change to environmental conditions brought about through intervals of radiant warming can affect the transient pacing dynamics of an exercise bout, but not necessarily impact overall performance time. Performance time appears unaffected by intervals of radiant heat during an exercise bout, although further work is required in more challenging dynamic environmental conditions

Expanding the genome editing repertoire in Clostridium difficile for improved studies of sporulation and germination

Clostridium difficile is an anaerobic, Gram-positive, endospore-forming, pathogenic bacterium which is the leading cause of antibiotic-associated diarrhoea, and causes a significant burden to healthcare facilities and communities, worldwide. Bacterial endospores are one of the most resilient forms of life, able to withstand exposures to wet-heat, desiccation, UV radiation, oxygen, and some disinfectants, which would otherwise kill the vegetative cell form. Thus, endospores of C. difficile are able to persist in the environment and contaminate surfaces within healthcare settings. Once ingested, these spores pass into the anaerobic lower intestines and in susceptible individuals find favourable conditions in which to germinate, generating the toxin-producing vegetative cells responsible for C. difficile associated disease. Consequently, spores are the infectious agent of this disease and both sporulation and germination processes are essential for disease. Whilst these processes have been well studied in Bacillus subtilis, it is only recently, with the development of appropriate reverse genetics tools for clostridia, that the mechanisms of sporulation and germination have begun to be described for C. difficile. This study uses the currently available mutagenesis tools of ClosTron and allelic exchange to generate mutant spores lacking spore-specific proteins, and through a range of assays characterises the sporulation, germination and resistance properties of these mutants, to understand the roles of these proteins in C. difficile endospores. Furthermore, these genetics tools are established in a novel C. difficile strain with beneficial properties for studying the processes of sporulation and germination in vitro. Finally, this study establishes CRISPR/Cas9 genome editing in C. difficile for the first time to overcome the major pitfalls associated with the previously available reverse genetics tools. This mutagenesis method was found to offer fast, highly efficient genome editing of two different C. difficile strains and will be the method of choice for future studies in C. difficile

Exercise training for intermittent claudication:a narrative review and summary of guidelines for practitioners

Peripheral artery disease (PAD) is caused by atherosclerotic narrowing of the arteries supplying the lower limbs often resulting in intermittent claudication, evident as pain or cramping while walking. Supervised exercise training elicits clinically meaningful benefits in walking ability and quality of life. Walking is the modality of exercise with the strongest evidence and is recommended in several national and international guidelines. Alternate forms of exercise such as upper- or lower-body cycling may be used, if required by certain patients, although there is less evidence for these types of programmes. The evidence for progressive resistance training is growing and patients can also engage in strength-based training alongside a walking programme. For those unable to attend a supervised class (strongest evidence), home-based or ‘self-facilitated’ exercise programmes are known to improve walking distance when compared to simple advice. All exercise programmes, independent of the mode of delivery, should be progressive and individually prescribed where possible, considering disease severity, comorbidities and initial exercise capacity. All patients should aim to accumulate at least 30 min of aerobic activity, at least three times a week, for at least 3 months, ideally in the form of walking exercise to near-maximal claudication pain

Enhancing Cardiac Rehabilitation With Stress Management Training

BACKGROUND: Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. METHODS AND RESULTS: One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P=0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25-0.95; P=0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27-0.71; P<0.001). CONCLUSIONS: CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00981253

Generation of a fully erythromycin-sensitive strain of Clostridioides difficile using a novel CRISPR-Cas9 genome editing system

© 2019, The Author(s). Understanding the molecular pathogenesis of Clostridioides difficile has relied on the use of ermB-based mutagens in erythromycin-sensitive strains. However, the repeated subcultures required to isolate sensitive variants can lead to the acquisition of ancillary mutations that affect phenotype, including virulence. CRISPR-Cas9 allows the direct selection of mutants, reducing the number of subcultures and thereby minimising the likelihood of acquiring additional mutations. Accordingly, CRISPR-Cas9 was used to sequentially remove from the C. difficile 630 reference strain (NCTC 13307) two ermB genes and pyrE. The genomes of the strains generated (630Δerm* and 630Δerm*ΔpyrE, respectively) contained no ancillary mutations compared to the NCTC 13307 parental strain, making these strains the preferred option where erythromycin-sensitive 630 strains are required. Intriguingly, the cas9 gene of the plasmid used contained a proximal frameshift mutation. Despite this, the frequency of mutant isolation was high (96% and 89% for ermB and pyrE, respectively) indicating that a functional Cas9 is still being produced. Re-initiation of translation from an internal AUG start codon would produce a foreshortened protein lacking a RuvCI nucleolytic domain, effectively a ‘nickase’. The mutation allowed cas9 to be cloned downstream of the strong Pthl promoter. It may find application elsewhere where the use of strong, constitutive promoters is preferred

The BASES Expert Statement on Exercise Training for People with Intermittent Claudication due to Peripheral Arterial Disease

Lower-limb peripheral arterial disease (PAD) is a type of cardiovascular disease in which the blood vessels (arteries) that carry blood to the legs and feet are hardened and narrowed or blocked by the build-up of fatty plaques (called atheroma). It affects around 13% of adults over 50 years old, and major risk factors for its development include smoking, diabetes mellitus, and dyslipidaemia (Morley, Sharma, Horsch & Hinchliffe, 2018). The presence of PAD itself is also a risk factor for other cardiovascular problems, such as angina, heart attack and stroke. This is because the underlying disease process, atherosclerosis, is a systemic process, meaning that blood vessels elsewhere in the body may also be affected.The most common symptom of PAD is intermittent claudication (IC), which is muscle pain or discomfort in the legs and/or buttocks brought on by walking and relieved within minutes on rest (Figure 1). It occurs due to an inability to increase blood flow (and oxygen delivery) sufficiently to match the metabolic demands of the lower-limb muscles during exercise. The walking distance or speed at which symptoms occur depends on multiple factors including the severity and site of the arterial disease, walking pace, terrain, incline and footwear. Nevertheless, IC can cause marked reductions in functional capacity and quality of life (Morley et al., 2018).Treatments for IC, aimed at relieving symptoms and reducing the risk of further cardiovascular disease, include lifestyle changes (e.g., stopping smoking, exercising more), vasoactive drugs (e.g. naftidrofuryl oxalate), and revascularisation (i.e. angioplasty or bypass surgery). In 2012, the United Kingdom’s National Institute of Health and Care Excellence (NICE) published a clinical guideline on the management of PAD, which stated that a supervised exercise programme should be offered as a first-line therapy for IC (NICE, 2012). This statement provides an overview of the evidence on exercise training and recommendations for people delivering exercise programmes to this population

A novel conjugal donor strain for improved DNA transfer into Clostridium spp.

© 2019 The Authors Importance: The ability to transfer genetic material into a target organism is crucial for the development of a wide range of targeted genetic manipulation techniques. Overcoming the organisms’ native restriction systems which target foreign incoming DNA is one strategy that can increase the efficiency of genetic transfer. The novel E. coli donor strain described here employs this strategy, increasing the frequencies of conjugation into a range of clostridial strains, and therefore opening up the potential to implement novel gene manipulation techniques. Furthermore this novel donor strain has potential applications across a wide range of genetically recalcitrant organisms, and should be beneficial wherever the frequently occurring Type IV restriction systems are possessed by the target in question

Preferred exercise modalities in patients with intermittent claudication

Conventional supervised exercise programs (SEPs) for claudicants are traditionally based on time-constrained, groupbased structured programs usually at a hospital site. Uptake of an SEP is poor, despite the high-level evidence demonstrating its clinical effectiveness; therefore, alternative forms of exercise programs are needed which are more acceptable to patients. This study aimed to explore a range of exercise modalities to determine patient preferences for exercise delivery on a national level. This was a questionnaire survey to identify and incorporate patient preferences when designing a multicenter nationwide health-service evaluation of patient preference to exercise in the United Kingdom’s National Health Service (the PREFER study). Patients with documented stable intermittent claudication who were suitable for an SEP were given a questionnaire to fill out at their clinic visit. Data were recorded using the Bristol Online Survey tool (http://www.survey.bris.ac.uk/) and analyzed descriptively. Thirty complete questionnaires were analyzed. Participants were generally unilateral claudicants (80%) with symptoms for over 1 year (64%). Only 6 of the 30 patients had engaged in a lifelong routine of exercise. Eighty-seven percent of patients indicated that they had not taken part in an exercise program, but 73% of those indicated that they would be willing to participate to improve their walking. Most patients expressed a preference for a home exercise program (50%) followed by a hospital SEP. The majority of patients (43%) were happy to exercise 3 days per week using a walking-based program (53%). There was however no consensus on the duration or intensity of the exercise program. The SEP is the recommended first-line treatment for intermittent claudication patients; however, the vast majority of patients fail to engage with or complete an exercise program. This study demonstrates that exercise therapy should be individualized and take a patient-centered approach. Commissioning groups should incentivize hospitals and clinicians to engage with their patient populations to understand their needs and deliver an appropriate servic

What's a SNP between friends: The lineage of Clostridioides difficile R20291 can effect research outcomes

Clostridioides difficile R20291 is the most studied PCR-Ribotype 027 isolate. The two predominant lineages of this hypervirulent strain, however, exhibit substantive phenotypic differences and possess genomes that differ by a small number of nucleotide changes. It is important that the source of R20291 is taken into account in research outcomes