Background. There is a lack of research considering acute fatigue responses to highand low-load resistance training as well as the comparison between male and female responses. Furthermore, limited studies have considered fatigue response testing with the inclusion of perceptions of discomfort and exertion. Methods. The present study included males (n = 9; 23.8 ± 6.4 years; 176.7 ± 6.2 cm; 73.9 ± 9.3 kg) and females (n = 8; 21.3 ± 0.9 years; 170.5 ± 6.1 cm; 65.5 ± 10.8 kg) who were assessed for differences in fatigue (i.e., loss of torque at maximal voluntary contraction (MVC)) immediately following isolated lumbar extension (ILEX) exercise at heavy-(HL) and light-(LL) loads (80% and 50% MVC, respectively). Participants also reported perceptual measures of effort (RPE-E) and discomfort (RPE-D) between different resistance training protocols. Results. Analysis of variance revealed significantly greater absolute and relative fatigue following LL compared to HL conditions (p < 0.001). Absolute fatigue significantly differed between males and females (p = 0.012), though relative fatigue was not significantly different (p = 0.160). However, effect sizes for absolute fatigue (HL; Males

Background Clinical outcome measurement in multiple sclerosis (MS) usually requires a physical visit. Remote activity monitoring (RAM) using wearable technology provides a rational alternative, especially desirable when distance is involved or in a pandemic setting. Objective To validate RAM in progressive MS using (1) traditional psychometric methods (2) brain atrophy. Methods 56 people with progressive MS participated in a longitudinal study over 2.5 years. An arm-worn RAM device measured activity over six days, every six months, and incorporated triaxial accelerometry and transcutaneous physiological variable measurement. Five RAM variables were assessed: physical activity duration, step count, active energy expenditure, metabolic equivalents and a composite RAM score incorporating all four variables. Other assessments every six months included EDSS, MSFC, MSIS-29, Chalder Fatigue Scale and Beck’s Depression Inventory. Annualized brain atrophy was measured using SIENA. Results RAM was tolerated well by people with MS; the device was worn 99.4% of the time. RAM had good convergent and divergent validity and was responsive, especially with respect to step count. Measurement of physical activity over one day was as responsive as six days. The composite RAM score positively correlated with brain volume loss. Conclusion Remote activity monitoring is a valid and acceptable outcome measure in MS.

Background Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a nonspecific marker of systemic inflammation. Expression as urinary neopterin-to-creatinine ratio (UNCR) normalizes for urinary hydration status. Major attractions include (a) urine vs blood sampling, (b) integration of inflammation over a longer period compared with serum sampling, and (c) high stability of neopterin and creatinine. Methods A high-throughput ultraperformance LC-MS method was developed to measure neopterin and creatinine together from the same urine sample. The assay was applied in several clinical scenarios: healthy controls, symptomatic infections, and multiple sclerosis. Area under the curve was compared between weekly and monthly sampling scenarios. Analysis of a single pooled sample was compared with averaging results from analysis of individual samples. Results The assay has excellent intraassay and interassay precision, linearity of dilution, and spike and recovery. Higher UNCR was demonstrated in female vs male individuals, older age, inflammatory disease (multiple sclerosis), and symptomatic infections. In healthy controls, fluctuations in inflammatory state also occurred in the absence of symptomatic infection or other inflammatory triggers. Analysis of a single pooled sample, made up from weekly urine samples, integrates inflammatory activity over time. Conclusions UNCR is a useful biomarker of systemic inflammation. The method presented offers simplicity, speed, robustness, reproducibility, efficiency, and proven utility in clinical scenarios. UNCR fluctuations underline the importance of longitudinal monitoring, vs a single time point, to capture a more representative estimate of an individual's inflammatory state over time.

Background Systemic infl ammation can aff ect disease expression in multiple sclerosis. The mechanism might involve blood-brain barrier disruption. We aimed to assess the eff ects of systemic infl ammation on disease progression in multiple sclerosis and the role of blood-brain barrier disruption. Methods We recruited adults with relapsing-remitting multiple sclerosis and healthy controls from the general population. Three-dimensional dynamic-contrast enhanced MRI was used to measure blood-brain barrier permeability in the normal-appearing white matter (NAWM). Urinary neopterin, a product of activated macrophages, was measured to provide a readout of systemic infl ammation. All study activities were performed in University Hospital Southampton after ethics approval (REC 12/SC/0176).

ObjectivesMuscles dominant in type I muscle fibres, such as the lumbar extensors, are often trained using lighter loads and higher repetition ranges. However, literature suggests that similar strength adaptations can be attained by the use of both heavier- (HL) and lighter-load (LL) resistance training across a number of appendicular muscle groups. Furthermore, LL resistance exercise to momentary failure might result in greater discomfort.DesignThe aims of the present study were to compare strength adaptations, as well as perceptual responses of effort (RPE-E) and discomfort (RPE-D), to isolated lumbar extension (ILEX) exercise using HL (80% of maximum voluntary contraction; MVC) and LL (50% MVC) in healthy males and females.MethodsTwenty-six participants (n = 14 males, n = 12 females) were divided in to sex counter-balanced HL (23 ± 5 years; 172.3 ± 9.8 cm; 71.0 ± 13.1 kg) and LL (22 ± 2 years; 175.3 ± 6.3 cm; 72.8 ± 9.5 kg) resistance training groups. All participants performed a single set of dynamic ILEX exercise 1 day/week for 6 weeks using either 80% (HL) or 50% (LL) of their MVC to momentary failure.ResultsAnalyses revealed significant pre- to post-intervention increases in isometric strength for both HL and LL, with no significant between-group differences (p > 0.05). Changes in strength index (area under torque curves) were 2,891 Nm degrees 95% CIs [1,612–4,169] and 2,865 Nm degrees 95% CIs [1,587–4,144] for HL and LL respectively. Changes in MVC were 51.7 Nm 95% CIs [24.4–79.1] and 46.0 Nm 95% CIs [18.6–73.3] for HL and LL respectively. Mean repetitions per set, total training time and discomfort were all significantly higher for LL compared to HL (26 ± 8 vs. 8 ± 3 repetitions, 158.5 ± 47 vs. 50.5 ± 15 s, and 7.8 ± 1.8 vs. 4.8 ± 2.5, respectively; all p < 0.005).ConclusionsThe present study supports that that low-volume, low-frequency ILEX resistance exercise can produce similar strength increases in the lumbar extensors using either HL or LL. As such personal trainers, trainees and strength coaches can consider other factors which might impact acute performance (e.g. effort and discomfort during the exercise). This data might prove beneficial in helping asymptomatic persons reduce the risk of low-back pain, and further research, might consider the use of HL exercise for chronic low-back pain symptomatic persons.

Dear Editor, Zonulin, or prehaptoglobin-2, mediates intestinal permeability in coeliac disease through the regulation of epithelial tight junctions. 1 Tight junction breakdown at the blood-brain barrier (BBB) is a common pathological finding in neurological disease, 2 and several in vitro and preclinical in vivo studies have suggested that zonulin plays a role in modulation of BBB permeability, 3-6 yet using multiple methods, we here consistently find that zonulin plays a negligible role in human BBB permeability.Zonulin is a member of the MASP (mannose-binding lectin-associated serine protease) family of proteins, and elevated serum zonulin levels have been reported in a number of neurological conditions such as multiple sclerosis 7 and Alzheimer's disease. 8 The significance of zonulin upregulation in these neurological diseases is not certain. Specifically, it is not clear whether zonulin is an epiphenomenon, or has an effect on the brain, whether directly or mediated through the gut-brain axis.To study the association between zonulin and BBB permeability in healthy individuals and patients with neurological disease, we employed two techniques to measure permeability across a range of molecular weights: Q Alb , or the quotient of cerebrospinal fluid to serum albumin (60 000 Da) in Study A and dynamic contrastenhanced magnetic resonance imaging with gadobutrol tracer (600 Da) in Study B (Supplemental Methods). Participant characteristics are shown in Table 1.Out of a total of 217 cases (including people with neurological conditions and control individuals) across both studies, 58 (27%) individuals tested negative for serum zonulin using a novel enzyme-linked immunosorbent assay (ELISA) (Supplemental Methods). Serum zonulin concentration followed a non-Gaussian distribution with a range of 0-11 µg/ml. There were no effects of sex, age or disease status (disease vs. control) on zonulin concentrations (analysis of covariance, F(3,216) = 1.06, p = .37). In order to assess zonulin using a complementary dual approach,This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

This study aims to develop quantitative MRI measures that are more statistically straightforward to correlate with clinical disability of progressive MS individuals, whose brains often show atrophy and tissue damage that vary amongst regions, which is hard to interpret clinically. The impacts of different software packages and MR contrasts on estimating brain atrophy were investigated. Individual DTI profiles characterised specific progression within each brain region, preserving the heterogeneity amongst individuals. Some of the measures were shown to capture the overall progression and correlate with clinical disability. In summary, this framework shows promise to integrate quantitative MRI into routine clinical care.

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