The effects of upper and lower limb exercise on the microvascular reactivity in limited cutaneous systemic sclerosis patients

Background: Aerobic exercise in general and high intensity interval training (HIIT) specifically is known to improve vascular function in a range of clinical conditions. HIIT in particular has demonstrated improvements in clinical outcomes, in conditions that have a strong macroangiopathic component. Nevertheless, the effect of HIIT on microcirculation in systemic sclerosis (SSc) patients is yet to be investigated. Therefore, the purpose of the study was to compare the effects of two HIIT protocols (cycle and arm cranking) on the microcirculation of the digital area in SSc patients. Methods: Thirty four limited cutaneous SSc patients (65.3 ± 11.6 years old) were randomly allocated in three groups (cycling, arm cranking and control group). The exercise groups underwent a twelve-week exercise program twice per week. All patients performed the baseline and post-exercise intervention measurements where physical fitness, functional ability, transcutaneous oxygen tension (ΔtcpO2), body composition and quality of life were assessed. Endothelial-dependent as well as-independent vasodilation were assessed in the middle and index fingers using LDF and incremental doses of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous flux data were expressed as cutaneous vascular conductance (CVC). Results: Peak oxygen uptake increased in both exercise groups (p<0.01, d=1.36). ΔtcpO2 demonstrated an increase in the arm cranking group only, with a large effect, but not found statistically significant,(p=0.59, d=0.93). Endothelial-dependent vasodilation improvement was greater in the arm cranking (p<0.05, d=1.07) in comparison to other groups. Both exercise groups improved life satisfaction (p<0.001) as well as reduced discomfort and pain due to Raynaud's phenomenon (p<0.05). Arm cranking seems to be the preferred mode of exercise for study participants as compared to cycling (p<0.05). No changes were observed in the body composition or the functional ability in both exercise groups. Conclusion: Our results suggest that arm cranking has the potential to improve the microvascular endothelial function in SSc patients. Also notably, our recommended training dose (e.g., a 12-week HIIT program, twice per week), appeared to be sufficient and tolerable for this population. Future research should focus on exploring the feasibility of a combined exercise such as aerobic and resistance training by assessing individual's experience and the quality of life in SSc patients. Trial registration: ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017, https://clinicaltrials.gov/ct2/show/NCT03058887?term=NCT03058887&rank=1 Key words: High intensity interval training, vascular function, quality of lif

Sensation during Active Behaviors

A substantial portion of our sensory experience happens during active behaviors such as walking around or paying attention. How do sensory systems work during such behaviors? Neural processing in sensory systems can be shaped by behavior in multiple ways ranging from a modulation of responsiveness or sharpening of tuning to a dynamic change of response properties or functional connectivity. Here, we review recent findings on the modulation of sensory processing during active behaviors in different systems: insect vision, rodent thalamus, and rodent sensory cortices. We discuss the circuit-level mechanisms that might lead to these modulations and their potential role in sensory function. Finally, we highlight the open questions and future perspectives of this exciting new field

Author Self-Citation in the General Medicine Literature

Background: Author self-citation contributes to the overall citation count of an article and the impact factor of the journal in which it appears. Little is known, however, about the extent of self-citation in the general clinical medicine literature. The objective of this study was to determine the extent and temporal pattern of author self-citation and the article characteristics associated with author self-citation. Methodology/Principal Findings: We performed a retrospective cohort study of articles published in three high impact general medical journals (JAMA, Lancet, and New England Journal of Medicine) between October 1, 1999 and March 31, 2000. We retrieved the number and percentage of author self-citations received by the article since publication, as of June 2008, from the Scopus citation database. Several article characteristics were extracted by two blinded, independent reviewers for each article in the cohort and analyzed in multivariable linear regression analyses. Since publication, author self-citations accounted for 6.5 % (95 % confidence interval 6.3–6.7%) of all citations received by the 328 articles in our sample. Selfcitation peaked in 2002, declining annually thereafter. Studies with more authors, in cardiovascular medicine or infectious disease, and with smaller sample size were associated with more author self-citations and higher percentage of author selfcitation (all p#0.01). Conclusions/Significance: Approximately 1 in 15 citations of articles in high-profile general medicine journals are autho

CONSORT 2010 statement: extension to randomised pilot and feasibility trials [on behalf of the PAFS consensus group*]

The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials. Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites

Co-activation: its association with weakness and specific neurological pathology

BACKGROUND: Net agonist muscle strength is in part determined by the degree of antagonist co-activation. The level of co-activation might vary in different neurological disorders causing weakness or might vary with agonist strength. AIM: This study investigated whether antagonist co-activation changed a) with the degree of muscle weakness and b) with the nature of the neurological lesion causing weakness. METHODS: Measures of isometric quadriceps and hamstrings strength were obtained. Antagonist (hamstring) co-activation during knee extension was calculated as a ratio of hamstrings over quadriceps activity both during an isometric and during a functional sit to stand (STS) task (using kinematics) in groups of patients with extrapyramidal (n = 15), upper motor neuron (UMN) (n = 12), lower motor neuron (LMN) with (n = 18) or without (n = 12) sensory loss, primary muscle or neuromuscular junction disorder (n = 17) and in healthy matched controls (n = 32). Independent t-tests or Mann Witney U tests were used to compare between the groups. Correlations between variables were also investigated. RESULTS: In healthy subjects mean (SD) co-activation of hamstrings during isometric knee extension was 11.8 (6.2)% and during STS was 20.5 (12.9)%. In patients, co-activation ranged from 7 to 17% during isometric knee extension and 15 to 25% during STS. Only the extrapyramidal group had lower co-activation levels than healthy matched controls (p < 0.05). Agonist isometric muscle strength and co-activation correlated only in muscle disease (r = -0.6, p < 0.05) and during STS in UMN disorders (r = -0.7, p < 0.5). CONCLUSION: It is concluded that antagonist co-activation does not systematically vary with the site of neurological pathology when compared to healthy matched controls or, in most patient groups, with strength. The lower co-activation levels found in the extrapyramidal group require confirmation and further investigation. Co-activation may be relevant to individuals with muscle weakness. Within patient serial studies in the presence of changing muscle strength may help to understand these relationships more clearly

Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

<p>Abstract</p> <p>Background</p> <p>Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients.</p> <p>Methods</p> <p>Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV₁) 40-85% predicted; FEV₁reversibility of ≥ 12% and ≥ 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV₁; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed.</p> <p>Results</p> <p>The intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV₁showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml) to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ≤ 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02).</p> <p>Conclusions</p> <p>FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.</p> <p>Trial registration</p> <p>Clinicaltrials.gov; <a href="http://www.clinicaltrials.gov/ct2/show/NCT00766090">NCT00766090</a>.</p

Tibial Loading Increases Osteogenic Gene Expression and Cortical Bone Volume in Mature and Middle-Aged Mice

There are conflicting data on whether age reduces the response of the skeleton to mechanical stimuli. We examined this question in female BALB/c mice of different ages, ranging from young to middle-aged (2, 4, 7, 12 months). We first assessed markers of bone turnover in control (non-loaded) mice. Serum osteocalcin and CTX declined significantly from 2 to 4 months (p<0.001). There were similar age-related declines in tibial mRNA expression of osteoblast- and osteoclast-related genes, most notably in late osteoblast/matrix genes. For example, Col1a1 expression declined 90% from 2 to 7 months (p<0.001). We then assessed tibial responses to mechanical loading using age-specific forces to produce similar peak strains (−1300 µε endocortical; −2350 µε periosteal). Axial tibial compression was applied to the right leg for 60 cycles/day on alternate days for 1 or 6 weeks. qPCR after 1 week revealed no effect of loading in young (2-month) mice, but significant increases in osteoblast/matrix genes in older mice. For example, in 12-month old mice Col1a1 was increased 6-fold in loaded tibias vs. controls (p = 0.001). In vivo microCT after 6 weeks revealed that loaded tibias in each age group had greater cortical bone volume (BV) than contralateral control tibias (p<0.05), due to relative periosteal expansion. The loading-induced increase in cortical BV was greatest in 4-month old mice (+13%; p<0.05 vs. other ages). In summary, non-loaded female BALB/c mice exhibit an age-related decline in measures related to bone formation. Yet when subjected to tibial compression, mice from 2–12 months have an increase in cortical bone volume. Older mice respond with an upregulation of osteoblast/matrix genes, which increase to levels comparable to young mice. We conclude that mechanical loading of the tibia is anabolic for cortical bone in young and middle-aged female BALB/c mice

Paternity alone does not predict long-term investment in juveniles by male baboons

Adult male chacma baboons (Papio hamadryas ursinus) form preferential associations, or friendships, with particular lactating females. Males exhibit high levels of affiliative contact with their friends’ infants and defend them from potentially infanticidal attacks (Palombit et al. 1997). Little is known about males’ associations with juveniles once they have passed the period of infanticidal risk. We conducted an observational, experimental, and genetic study of adult male and juvenile chacma baboons in the Moremi Reserve, Botswana. We identified preferential associations between males and juveniles and used behavioral data and a playback experiment to explore whether those associations have potential fitness benefits for juveniles. We determined whether males preferentially invest in care of their own offspring. We also determined how often males invest in care of their former friends’ offspring. The majority of juveniles exhibited preferential associations with one or two males, who had almost always been their mother’s friend during infancy. However, in only a subset of these relationships was the male the actual father, in part because many fathers died or disappeared before their offspring were weaned. Male caretakers intervened on behalf of their juvenile associates in social conflicts more often than they intervened on behalf of unconnected juveniles, and they did not appear to differentiate between genetic offspring and unrelated associates. Playbacks of juveniles’ distress calls elicited a stronger response from their caretakers than from control males. Chacma males may provide care to unrelated offspring of former friends because the costs associated with such care are low compared with the potentially high fitness costs of refusing aid to a juvenile who is a possible offspring