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Self‐talk is an effective mental training technique that has been shown to facilitate or debilitate an athlete's performance, depending on its valence. Although the effects of self‐talk have been supported by observing change in sport performance, little is known about how self‐talk can induce physiological changes. Specifically, it is important to understand if the type of self‐talk (positive, neutral, or negative) and can influence stress‐related parameters, such as perceived exertion, cardiorespiratory, and cortisol responses. The study's objective was therefore to investigate the top‐down effect of positive and negative self‐talk compared to a dissociative activity during an iso‐metabolic running exercise on autonomic regulation of cardiorespiratory function. Twenty‐nine well‐trained male runners [38 ± 13 years, 177 ± 7 cm and 73 ± 7 kg] volunteered to participate in a randomized‐group design study that included a negative self‐talk (NST), a positive self‐talk, and a dissociative group (DG). First, participants underwent an incremental running test on a treadmill to determine the maximal oxygen uptake (V̇O2max). Next, participants received a mental training session on self‐talk and created three positive and three negative self‐talk statements. Finally, participants underwent a 60‐min steady‐state running exercise on a treadmill at 70% of V̇O2max, during which they were cued at 20‐, 35‐, and 50‐min with their personal self‐created positive or negative self‐talk statements while the DG listened to a documentary. Cardiorespiratory parameters and rate of perceived exertion (RPE) were recorded throughout the 60‐min endurance exercise. In addition, salivary cortisol samples were obtained at waking and after treatment. Although oxygen uptake, carbon dioxide production, RPE, and heart rate significantly changed overtime during the 60‐min steady‐state running exercise, no significant main treatment effect was found. However, RPE scores, minute ventilation, breathing frequency, and salivary cortisol were significantly higher in the NST group compared to the two other groups. These data suggest that NST [emotion‐induced stress, as reflected by elevated cortisol] altered the breathing frequency response. In conclusion, manipulating self‐talk alters hormonal response patterns, modulates cardiorespiratory function, and influences perceived exertion. To date, there have been no studies specifically designed to explore the neural functional connections that would specifically elucidate the top‐down neurophysiological pathway associating self‐talk during exercise. This study demonstrates that emotion‐induced stress alters the neural functional connections as reflected in cardiovascular and hormonal responses. [ABSTRACT FROM AUTHOR]

Highlights • MS patients have extremely low levels of fitness regardless of levels of disability. • Poor cardiorespiratory fitness in MS associated with increased GABAergic intracortical inhibition. • Increased GABAergic intracortical inhibition may explain exacerbated feelings of MS fatigue. Abstract Objective Poor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown. Methods MS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP). Results Sixty-two percent of participants had fitness levels ranked below 10th percentile. Fitness was not associated with disability measured using the Expanded Disability Status Scale (EDSS). Regression analyses revealed that, cardiorespiratory fitness, when controlling for disease demographics, contributed 23.7% (p < 0.001) to the model explaining variance in CSP. Regression analysis using cardiorespiratory fitness and CSP as predictors showed that CSP alone explained 19.9% of variance in subjective fatigue (p = 0.002). Tumor necrosis factor was not associated with any variable. Conclusion Low fitness was associated with longer CSP in MS. Longer CSP was, in turn, related to greater MS fatigue. Significance MS patients had extremely low levels of cardiorespiratory fitness. Poor fitness predicted longer CSP, a marker of greater intracortical inhibition, which was linked to MS fatigue. Future research should examine whether aerobic training could shorten CSP and potentially lessen inhibition of cortical networks. [ABSTRACT FROM AUTHOR]

Moderate-intensity aerobic exercise training is an important treatment strategy to enhance functional recovery and decrease cardiometabolic risk factors after stroke. However, stroke related impairments limit access to ergometer-type exercise. The aims of the current study were (1) to evaluate whether our task-oriented circuit training protocol (intermittent functional training; IFT) could be used to sustain moderate-intensity aerobic workloads over a 10-week intervention period, and (2) to investigate its preliminary effects on cardiorespiratory fitness and metabolic profiles compared to constant-load ergometer-type exercise (CET). Forty chronic hemiparetic stroke survivors were randomized to receive 30 sessions of IFT or CET over ten weeks. Similar proportions of participants were randomized to IFT (7/19) and CET (9/18) sustained workloads associated with moderate-intensity aerobic exercise over the study period (p = 0.515). However, CET was associated with more substantial changes in maximal oxygen uptake (MD = 2.79 mL min−1 kg−1 CI: 0.84 to 4.74) compared to IFT (MD = 0.62 mL min−1 kg−1 CI: −0.38 to 1.62). Pre to post changes in C-reactive protein (−0.9 mg/L; p =0.017), short-term glycemia (+14.7 µmol/L; p = 0.026), and resting whole-body carbohydrate oxidation (+24.2 mg min−1; p = 0.046) were observed when considering both groups together. Accordingly, IFT can replicate the aerobic intensities sustained during traditional ergometer-type exercise training. More work is needed to evaluate the dose–response effects of such task-oriented circuit training protocols on secondary prevention targets across the continuum of stroke recovery. [ABSTRACT FROM AUTHOR]

Post-activation potentiation (PAP) conditioning has been reported to increase performance. Most research has examined PAP effects on strength/power activities, whereas the effects on endurance sports are understudied. The aim of this study was to characterize PAP conditioning stimulus effects on a subsequent 5x1 km running trial. A randomized, within subjects, repeated measures study utilized 12 male, endurance-trained athletes, who performed a full warm-up, conditioning exercise intervention (4x5 repetition maximum band-resisted squat jumps) or a control condition prior to a 5x1 km time trial run. Tests were conducted immediately prior to the intervention, after each kilometer, immediately following the 5x1 km run, and at seven and ten minutes post 5 km run. Measures included the interpolated twitch technique (ITT), evoked contractile properties, maximum voluntary isometric contractions (MVIC) plantar flexor force, drop jump, rating of perceived exertion, and heart rate. The PAP stimulus reduced the time to complete the run (3.6%; p = 0.07, d = 0.51), and decreased the time to complete kilometer one (8%; d = 1.08, p = 0.014). Jump height (p = 0.02; 9.2%) and reactive strength index (p = 0.035; 16%) increased with PAP. F100 (force produced in the first 100ms of the MVIC) and MVIC force with PAP increased at kilometers 3 (p = 0.04, d=0.84), 4 (p = 0.034, d = 0.29), and 7min post-run (p = 0.03, d = 0.60). Voluntary activation (ITT) increased at 7min post-run (p = 0.04, d = 0.59) with PAP, yet decreased at 7min post-run in the control condition (p = 0.03, d = 0.36). A prior band-resisted squat protocol decreased running time and improved neuromuscular properties in endurance athletes running 5x1 km. [ABSTRACT FROM AUTHOR]

Highlights • Atypical brain excitability asymmetry in MS may indicate neuroinflammation-mediated hyperexcitability. • Shifting excitability asymmetry significantly predicted more severe physical MS symptoms and cognitive processing. • Asymmetry ratio may be a useful biomarker of MS progression and measure benefit of treatments. Abstract Objectives Investigate whether asymmetrical corticospinal excitability exists in Multiple Sclerosis (MS) and its association with MS symptoms. Methods Bilateral resting and active motor thresholds (RMT, AMT) were gathered using transcranial magnetic stimulation among 82 MS patients. Corticospinal excitability (CSE) asymmetry was expressed as the ratio between weaker and stronger sides' RMT and AMT. Stronger and weaker side was determined by pinch and grip strength. We examined whether CSE asymmetry predicted symptoms. Results AMT asymmetry ratio revealed atypical CSE asymmetry whereby the hemisphere associated with the weaker hand was more excitable in early MS. After controlling for MS disease demographics, shifting of CSE asymmetry towards greater excitability in the stronger side significantly predicted more severe symptoms including Expanded Disease Severity Scale, nine-hole peg test, cognitive processing speed, walking speed, heat sensitivity, fatigue, and subjective impact of MS. Conclusion CSE asymmetry significantly predicted the severity of MS-related physical and objective cognitive symptoms. The phenomenon may be related to neuroinflammation-mediated hyperexcitability. Shifting of asymmetry toward less excitability on the weaker side may suggest the onset of a more neurodegenerative phase of the disease. Significance Shifting of hemispheric excitability, detected using a CSE asymmetry ratio, may be a useful biomarker to track disease progression and understand the benefits of treatments. [ABSTRACT FROM AUTHOR]

Background: Aerobic training has the potential to restore function, stimulate brain repair, and reduce inflammation in people with Multiple Sclerosis (MS). However, disability, fatigue, and heat sensitivity are major barriers to exercise for people with MS. We aimed to determine the feasibility of conducting vigorous harness-supported treadmill training in a room cooled to 16 °C (10 weeks; 3times/week) and examine the longer-term effects on markers of function, brain repair, and inflammation among those using ambulatory aids.Methods: Ten participants (9 females) aged 29 to 74 years with an Expanded Disability Status Scale ranging from 6 to 7 underwent training (40 to 65% heart rate reserve) starting at 80% self-selected walking speed. Feasibility of conducting vigorous training was assessed using a checklist, which included attendance rates, number of missed appointments, reasons for not attending, adverse events, safety hazards during training, reasons for dropout, tolerance to training load, subjective reporting of symptom worsening during and after exercise, and physiological responses to exercise. Functional outcomes were assessed before, after, and 3 months after training. Walking ability was measured using Timed 25 Foot Walk test and on an instrumented walkway at both fast and self-selected speeds. Fatigue was measured using fatigue/energy/vitality sub-scale of 36-Item Short-Form (SF-36) Health Survey, Fatigue Severity Scale, modified Fatigue Impact Scale. Aerobic fitness (maximal oxygen consumption) was measured using maximal graded exercise test (GXT). Quality-of-life was measured using SF-36 Health Survey. Serum levels of neurotrophin (brain-derived neurotrophic factor) and cytokine (interleukin-6) were assessed before and after GXT.Results: Eight of the ten participants completed training (attendance rates ≥ 80%). No adverse events were observed. Fast walking speed (cm/s), gait quality (double-support (%)) while walking at self-selected speed, fatigue (modified Fatigue Impact Scale), fitness (maximal workload achieved during GXT), and quality-of-life (physical functioning sub-scale of SF-36) improved significantly after training, and improvements were sustained after 3-months. Improvements in fitness (maximal respiratory exchange ratio and maximal oxygen consumption during GXT) were associated with increased brain-derived neurotrophic factor and decreased interleukin-6.Conclusion: Vigorous cool room training is feasible and can potentially improve walking, fatigue, fitness, and quality-of-life among people with moderate to severe MS-related disability.Trial Registration: The study was approved by the Newfoundland and Labrador Health Research Ethics Board (reference number: 2018.088) on 11/07/2018 prior to the enrollment of first participant (retrospectively registered at ClinicalTrials.gov: NCT04066972. Registered on 26 August 2019. [ABSTRACT FROM AUTHOR]

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy timescale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25% smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L) Χ 0.5 (D) Χ 1.3m (H)] stand-alone units for synthesis and purification/ formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards. [ABSTRACT FROM AUTHOR]

Abstract: As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time‐scale, we previously reported a refrigerator‐sized continuous flow system for the on‐demand production of essential medicines. Building on this technology, herein we report a second‐generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand‐alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards. [ABSTRACT FROM AUTHOR]

Magnetic iron oxide (Magnetite, Fe3O4) nanoparticles are widely utilized in magnetic resonance imaging (MRI) and drug delivery applications due to their superparamagnetism. Surface coatings are often employed to change the properties of the magnetite nanoparticles or to modulate their biological responses. In this study, magnetite nanoparticles were fabricated through hydrothermal synthesis. Hydrophobicity is often increased by surface modification with oleic acid. In this study, however, hydrophobicity was introduced through surface modification with n-octyltriethoxysilane. Both the uncoated (hydrophilic) and coated (hydrophobic) individual nanoparticle sizes measured below 20 nm in diameter, a size range in which magnetite nanoparticles exhibit superparamagnetism. Both types of nanoparticles formed aggregates which were characterized by SEM, TEM, and dynamic light scattering (DLS). The coating process significantly increased both individual particle diameter and aggregate sizes. We tested the neurotoxicity of newly synthesized nanoparticles with two mammalian cell lines, PC12 (rat pheochromocytoma) and ReNcell VM (human neural stem cells). Significant differences were observed in cytotoxicity profiles, which suggests that the cell type (rodent versus human) or the presence of serum matters for nanoparticle toxicology studies. Differences in nanoparticle associations/uptake between the two cell types were observed with Prussian Blue staining. Finally, safe concentrations which did not significantly affect neuronal differentiation profiles were identified for further development of the nanoparticles. [ABSTRACT FROM AUTHOR]