Cold water ingestion improves exercise tolerance of heat-sensitive people with MS

© 2018 Lippincott Williams and Wilkins. All rights reserved. Purpose Heat intolerance commonly affects the exercise capacity of people with multiple sclerosis (MS) during bouts of hot weather. Cold water ingestion is a simple cooling strategy, but its efficacy for prolonging exercise capacity with MS remains undetermined. We sought to identify whether cold water ingestion blunts exercise-induced rises in body temperature and improves exercise tolerance in heat-sensitive individuals with MS. Methods On two separate occasions, 20 participants (10 relapsing-remitting MS (expanded disability status scale, 2-4.5); 10 age-matched healthy controls) cycled at ∼40% VO 2max at 30°C and 30% relative humidity until volitional exhaustion (or a maximum of 60 min). Every 15 min, participants ingested 3.2 mL·kg -1 of either 1.5°C (CLD) or 37°C (NEU) water. Rectal (T re ) temperature, mean skin (T sk ) temperature, and heart rate (HR) were measured throughout. Results All 10 controls but only 3 of 10 MS participants completed 60 min of exercise in NEU trial. The remaining 7 MS participants all cycled longer (P = 0.006) in CLD (46.4 ± 14.2 min) compared with NEU (32.7 ± 11.5 min), despite a similar absolute T re (NEU: 37.32°C ± 0.34°C; CLD: 37.28°C ± 0.26°C; P = 0.44), change in T re (NEU: 0.38°C ± 0.21°C; CLD: 0.34°C ± 0.24°C), absolute T sk (NEU: 34.48°C ± 0.47°C; CLD: 34.44°C ± 0.54°C; P = 0.82), and HR (NEU: 114 ± 20 bpm; CLD: 113 ± 18 bpm; P = 0.38) for the same exercise volume. Conclusions Cold water ingestion enhanced exercise tolerance of MS participants in the heat by ∼30% despite no differences in T re , T sk or HR. These findings support the use of a simple cooling strategy for mitigating heat intolerance with MS and lend insight into the potential role of cold-afferent thermoreceptors that reside in the abdomen and oral cavity in the modulation of exercise tolerance with MS in the heat

Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature

In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat-sensitivity/Uhthoff's phenomenon). While the impact of heat-sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a novel quantitative sensory test. Eight relapsing-remitting MS patients (3M/5F; 51.4 ± 9.1 y; EDSS score: 2.8 ± 1.1) and 8 age-matched controls (CTR; 5M/3F; 47.4 ± 9.1 y) rated perceived magnitude of two cold (26; 22°C) and warm (34; 38°C) stimuli applied to the dorsum of the hand, pre and post 30-min cycling in the heat (30°C air; 30% RH). Exercise produced similar increases in mean body temperature in MS (+0.39°C [95%CI: +0.21, +0.53] P = 0.001) and CTR (+0.41°C [95%CI: +0.25, +0.58] P = 0.001). These changes were sufficient to significantly decrease thermosensitivity to all cold (26°C stimulus: -9.1% [95%CI: -17.0, -1.5], P = 0.006; 22°C stimulus: -10.6% [95%CI: -17.3, -3.7], P = 0.027), but not warm, stimuli in MS. Contrariwise, CTR showed sensitivity reductions to colder stimuli only (22°C stimulus: -9.7% [95%CI: -16.4, -3.1], P = 0.011). The observation that reductions in thermal-sensitivity in MS were confined to the myelinated cold-sensitive pathway, and extended across a wider (including milder/colder) temperature range than what is observed in CTR, provides novel evidence on the impact of rising body temperature on afferent neural function in MS. Also, our findings support the use of our novel approach to investigate afferent sensory function in MS during heat stress. This article is protected by copyright. All rights reserved

Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth

Systemic delivery of siRNA to solid tumors remains challenging. In this study, we investigated the systemic delivery of a siRNA nanoparticle targeting ribonucleotide reductase subunit M2 (RRM2), and evaluated its intratumoral kinetics, efficacy and mechanism of action. Knockdown of RRM2 by an RNAi mechanism strongly inhibited cell growth in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines. In a mouse xenograft model of HNSCC, a single intravenous injection led to the accumulation of intact nanoparticles in the tumor that disassembled over a period of at least 3 days, leading to target gene knockdown lasting at least 10 days. A four-dose schedule of siRNA nanoparticle delivering RRM2 siRNA targeted to HNSCC tumors significantly reduced tumor progression by suppressing cell proliferation and inducing apoptosis. These results show promise for the use of RRM2 siRNA-based therapy for HNSCC and possibly NSCLC

Spatial distribution of transcript changes in the maize primary root elongation zone at low water potential

Background: Previous work showed that the maize primary root adapts to low Ψw (-1.6 MPa) by maintaining longitudinal expansion in the apical 3 mm (region 1), whereas in the adjacent 4 mm (region 2) longitudinal expansion reaches a maximum in well-watered roots but is progressively inhibited at low Ψw. To identify mechanisms that determine these responses to low Ψw, transcript expression was profiled in these regions of water-stressed and well-watered roots. In addition, comparison between region 2 of water-stressed roots and the zone of growth deceleration in well-watered roots (region 3) distinguished stress-responsive genes in region 2 from those involved in cell maturation. Results: Responses of gene expression to water stress in regions 1 and 2 were largely distinct. The largest functional categories of differentially expressed transcripts were reactive oxygen species and carbon metabolism in region 1, and membrane transport in region 2. Transcripts controlling sucrose hydrolysis distinguished well-watered and water-stressed states (invertase vs. sucrose synthase), and changes in expression of transcripts for starch synthesis indicated further alteration in carbon metabolism under water deficit. A role for inositols in the stress response was suggested, as was control of proline metabolism. Increased expression of transcripts for wall-loosening proteins in region 1, and for elements of ABA and ethylene signaling were also indicated in the response to water deficit. Conclusion: The analysis indicates that fundamentally different signaling and metabolic response mechanisms are involved in the response to water stress in different regions of the maize primary root elongation zone

Interventions associated with brown adipose tissue activation and the impact on energy expenditure and weight loss: A systematic review

BackgroundBrown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as β-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss.MethodsWe systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults.ResultsA total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as β-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials.ConclusionThough the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy

Investigation of Salt Tolerance Mechanisms across a Root Developmental Gradient in Almond Rootstocks

The intensive use of groundwater in agriculture under the current climate conditions leads to acceleration of soil salinization. Given that almond is a salt-sensitive crop, selection of salt-tolerant rootstocks can help maintain productivity under salinity stress. Selection for tolerant rootstocks at an early growth stage can reduce the investment of time and resources. However, salinity-sensitive markers and salinity tolerance mechanisms of almond species to assist this selection process are largely unknown. We established a microscopy-based approach to investigate mechanisms of stress tolerance in and identified cellular, root anatomical, and molecular traits associated with rootstocks exhibiting salt tolerance. We characterized three almond rootstocks: Empyrean-1 (E1), Controller-5 (C5), and Krymsk-86 (K86). Based on cellular and molecular evidence, our results show that E1 has a higher capacity for salt exclusion by a combination of upregulating ion transporter expression and enhanced deposition of suberin and lignin in the root apoplastic barriers, exodermis, and endodermis, in response to salt stress. Expression analyses revealed differential regulation of cation transporters, stress signaling, and biopolymer synthesis genes in the different rootstocks. This foundational study reveals the mechanisms of salinity tolerance in almond rootstocks from cellular and structural perspectives across a root developmental gradient and provides insights for future screens targeting stress response

The Freshman, vol. 5, no. 15

The Freshman was a weekly, student newsletter issued on Mondays throughout the academic year. The newsletter included calendar notices, coverage of campus social events, lectures, and athletic teams. The intent of the publication was to create unity, a sense of community, and class spirit among first year students

The Freshman, vol. 5, no. 12

The Freshman was a weekly, student newsletter issued on Mondays throughout the academic year. The newsletter included calendar notices, coverage of campus social events, lectures, and athletic teams. The intent of the publication was to create unity, a sense of community, and class spirit among first year students

The Freshman, vol. 5, no. 11

The Freshman was a weekly, student newsletter issued on Mondays throughout the academic year. The newsletter included calendar notices, coverage of campus social events, lectures, and athletic teams. The intent of the publication was to create unity, a sense of community, and class spirit among first year students