Contributions of Griffith Pugh to Success on Mt. Everest and His Impact on the Advancement of Altitude and Environmental Physiology.

Griffith Pugh, MD (1909-1994), was a pioneer in altitude physiology. During World War II, he developed training protocols in Lebanon to improve soldier performance at altitude and in the cold. In 1951 he was chosen to join the British Everest team as a scientist. In preparation, he developed strategies for success on a training expedition on Cho Oyu in 1952. Results from Cho Oyu led to the use of supplemental oxygen at higher flow rates during ascent than used previously (4 L/min vs 2 L/min) and continued use (at a reduced rate of 2 L/min) during descent, enabling increased performance and improved mental acuity. Oxygen was also used during sleep, leading to improved sleep and warmth. Adequate hydration (∼3 L/day) was also stressed, and a more appealing diet led to improved nutrition and condition of the climbers. Improved hygiene practices and acclimatization protocols were also developed. These strategies contributed to the first successful summiting of Mount Everest in 1953. Pugh was then appointed as the lead scientist for a ground-breaking eight-and-a-half-month research expedition where the team was the first to overwinter at high altitude (5800 m) in the Himalayas. This current work summarizes Pugh's scientific contributions as they relate to success on Mount Everest and in inspiring future altitude research by generations of successful researchers.

Centering racial justice for Black/African American and Indigenous American people in commercial tobacco product regulation.

Although overall health in the United States (US) has improved dramatically during the past century, long-standing health inequities, particularly the unequal and unjust burden of tobacco-related disease and death among racialized populations, persist. A considerable gap exists in our understanding of how commercial tobacco product regulations and policies cause and/or exacerbate race-based health inequities among Black/African American (B/AA) and Indigenous American people. The purpose of this paper is to 1) describe how existing US commercial tobacco regulatory policies may contribute to structural racism and undermine the full benefits of tobacco prevention and control efforts among B/AA and Indigenous American groups; and 2) initiate a call to action for researchers and regulators of tobacco products to examine policies using an equity lens. These actions are imperative if empirically-informed regulation of commercial tobacco products is to address health equity.

Effects of training with a neuro-mechano stimulator rehabilitation bicycle on functional recovery and paired-reflex depression of the soleus in individuals with incomplete paralysis: a proof-of-principle study.

Aim: The present study describes the training effects of a novel motorized bicycle-like device for individuals with incomplete spinal cord injury. Methods: Participants were five individuals with motor incomplete spinal cord injury (56 ± 7 years). Four of five participants received two 30-min sessions of training: one with, and one without, mechanical stimulation on the plantar surface of the foot; soleus paired H-reflex depression was examined before and after each session. Three of five participants received 24 sessions of 30-min of training (long-training). Following the long-training, balance, walking and spasticity improvements were assessed using validated clinical outcome measures, in addition to the H-reflex assessment. Results: One cycling session with mechanical stimulation yielded 14% and 32% more reflex depression in participants with moderate spasticity (n = 2/4). The same trend was not observed in non-spastic participants (n = 2/4). All participants who participated in the long-training had spasticity and showed reduced spasticity, improved walking speed, endurance and balance. Conclusions: Overall, participants with spasticity showed increased soleus H-reflex suppression after one training session with mechanical stimulation and reduced spasticity scores after long training. We interpret this as evidence that the training influenced both presynaptic and postsynaptic inhibitory mechanisms acting on soleus motoneurons. Therefore, this training has the potential to be a non-invasive complementary therapy to reduce spasticity after incomplete spinal cord injury.

Human Responses to 5 Heated Hypothermia Wrap Systems in a Cold Environment.

INTRODUCTION: We compared the effectiveness of 5 heated hypothermia wrap systems. METHODS: Physiologic and subjective responses were determined in 5 normothermic subjects (1 female) for 5 heated hypothermia wraps (with vapor barrier and chemical heat sources) during 60 min of exposure to a temperature of -22°C. The 5 systems were 1) user-assembled; 2) Doctor Down Rescue Wrap; 3) hypothermia prevention and management kit (HPMK); 4) MARSARS Hypothermia Stabilizer Bag; and 5) Wiggy's Victims Casualty Hypothermia Bag. Core and skin temperature, metabolic heat production, skin heat loss, and body net heat gain were determined. Subjective responses were also evaluated for whole body cold discomfort, overall shivering rating, overall temperature rating, and preferential ranking. RESULTS: The Doctor Down and user-assembled systems were generally more effective, with higher skin temperatures and lower metabolic heat production; they allowed less heat loss, resulting in higher net heat gain (P<0.05). HPMK had the lowest skin temperature and highest shivering heat production and scored worse than the other 4 systems for the "whole body cold discomfort" and "overall temperature" ratings (P<0.05). CONCLUSIONS: The user-assembled and Doctor Down systems were most effective, and subjects were coldest with the HPMK system. However, it is likely that any of the tested systems would be viable options for wilderness responders, and the choice would depend on considerations of cost; volume, as it relates to available space; and weight, as it relates to ability to carry or transport the system to the patient.

Altered transcription of glutamatergic and glycinergic receptors in spinal cord dorsal horn following spinal cord transection is minimally affected by passive exercise of the hindlimbs.

Gene expression is altered following a spinal transection (STx) in both motor and sensory systems. Exercise has been shown to influence gene expression in both systems post-STx. Gene expression alterations have also been shown in the dorsal root ganglia and nociceptive laminae of the spinal cord following either an incomplete spinal cord injury (SCI) or a contusive SCI. However, the effect of STx and exercise on gene expression in spinal cord laminae I-III has not fully been examined. Therefore, the purpose of this study was to determine whether gene expression in laminae I-III is altered following STx and determine whether superimposed passive exercise of the hindlimbs would influence gene expression post-STx in laminae I-III. Laser capture microdissection was used to selectively harvest laminae I-III of lumbar spinal cord sections, and quantitative RT-PCR was used to examine relative expression of 23 selected genes in samples collected from control, STx and STx plus exercise rats. We demonstrate that post-STx, gene expression for metabotropic glutamate receptors 1, 5 and 8 were up-regulated, whereas ionotropic glutamatergic receptor (Glur2) and glycinergic subunit GLRA1 expression was down-regulated. Daily exercise attenuated the down-regulation of Glur2 gene expression in laminae I-III. Our results demonstrate that in a STx model, gene expression is altered in laminae I-III and that although passive exercise influences gene expression in both the motor and sensory systems, it had a minimal effect on gene expression in laminae I-III post-STx.

Serotonin controls initiation of locomotion and afferent modulation of coordination via 5-HT7 receptors in adult rats.

KEY POINTS: Experiments on neonatal rodent spinal cord showed that serotonin (5-HT), acting via 5-HT7 receptors, is required for initiation of locomotion and for controlling the action of interneurons responsible for inter- and intralimb coordination, but the importance of the 5-HT system in adult locomotion is not clear. Blockade of spinal 5-HT7 receptors interfered with voluntary locomotion in adult rats and fictive locomotion in paralysed decerebrate rats with no afferent feedback, consistent with a requirement for activation of descending 5-HT neurons for production of locomotion. The direct control of coordinating interneurons by 5-HT7 receptors observed in neonatal animals was not found during fictive locomotion, revealing a developmental shift from direct control of locomotor interneurons in neonates to control of afferent input from the moving limb in adults. An understanding of the afferents controlled by 5-HT during locomotion is required for optimal use of rehabilitation therapies involving the use of serotonergic drugs. ABSTRACT: Serotonergic pathways to the spinal cord are implicated in the control of locomotion based on studies using serotonin type 7 (5-HT7 ) receptor agonists and antagonists and 5-HT7 receptor knockout mice. Blockade of these receptors is thought to interfere with the activity of coordinating interneurons, a conclusion derived primarily from in vitro studies on isolated spinal cord of neonatal rats and mice. Developmental changes in the effects of serotonin (5-HT) on spinal neurons have recently been described, and there is increasing data on control of sensory input by 5-HT7 receptors on dorsal root ganglion cells and/or dorsal horn neurons, leading us to determine the effects of 5-HT7 receptor blockade on voluntary overground locomotion and on locomotion without afferent input from the moving limb (fictive locomotion) in adult animals. Intrathecal injections of the selective 5-HT7 antagonist SB269970 in adult intact rats suppressed locomotion by partial paralysis of hindlimbs. This occurred without a direct effect on motoneurons as revealed by an investigation of reflex activity. The antagonist disrupted intra- and interlimb coordination during locomotion in all intact animals but not during fictive locomotion induced by stimulation of the mesencephalic locomotor region (MLR). MLR-evoked fictive locomotion was transiently blocked, then the amplitude and frequency of rhythmic activity were reduced by SB269970, consistent with the notion that the MLR activates 5-HT neurons, leading to excitation of central pattern generator neurons with 5-HT7 receptors. Effects on coordination in adults required the presence of afferent input, suggesting a switch to 5-HT7 receptor-mediated control of sensory pathways during development.

α-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats.

Small-diameter sensory dysfunction resulting from diabetes has received much attention in the literature, whereas the impact of diabetes on α-motoneurons (MN) has not. In addition, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass micropipettes recorded hindlimb MN properties from identified flexor and extensor MN. MN were separated within their groups on the basis of input conductance, which created high- and low-input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP1/2) was found in low-conductance MN for the diabetic group only, whereas AHP½ tended to be shorter in the obese group (19%). Significant positive correlations were found among rheobase and input conductance for both lean and obese animals. No differences were found between the groups for afterhyperpolarization amplitude (AHPamp), input conductance, rheobase, or any of the rhythmic firing properties (frequency-current slope and spike-frequency adaptation index). MN properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar MN. Despite the resistance of MN to the impact of diabetes, the reduced AHP1/2 decay and the tendency for a reduction in AHPamp may be the first sign of change to MN function.NEW & NOTEWORTHY Knowledge about the impact of obesity and diabetes on the biophysical properties of motoneurons is lacking. We found that diabetes reduces the duration of the afterhyperpolarization and that motoneuron function is unchanged by obesity. A reduced afterhyperpolarization may impact discharge characteristics and may be the first sign of change to motoneuron function.

Force regulation and electrical properties of motor units in overloaded muscle.

INTRODUCTION: The influence of long-term muscle overload on force regulation and electrical properties of motor units (MUs) was investigated in rats. METHODS: Compensatory overload of the medial gastrocnemius was induced by tenotomy of its synergists. Electrophysiological experiments were performed on functionally isolated MUs 3 months after the surgery. RESULTS: Force-frequency curves for overloaded MUs were shifted rightward compared with control, thus MUs developed the same relative tetanic forces at higher frequencies. Higher force increase was achieved in response to an increase in stimulation frequency in overloaded fast MUs compared with control. The optimal tetanic contraction, characterized by the highest force-time area per pulse, was evoked at higher stimulation frequencies for all overloaded MUs except FF. Only minor adaptive changes in MU action potentials occurred. CONCLUSIONS: Compensatory muscle overload leads to substantial modifications in MU force development mechanisms, which are MU-type-specific and influence whole muscle force regulation.

Understanding Tobacco Use Behaviors Among African Americans: Progress, Critical Gaps, and Opportunities.

INTRODUCTION: Although multiple factors likely influence the differences between African Americans (AAs) and whites in cardiovascular disease and lung cancer mortality rates, historical patterns of tobacco use, particularly cigarette smoking, are the major contributors. This issue of Nicotine & Tobacco Research presents original research, a review, and commentaries that will serve to advance our understanding of several relevant behavioral similarities and differences between AAs and whites. BEHAVIORAL ANALYSIS: Here, we illustrate how the diverging trends in cigarette smoking between AA and white high school seniors observed since the mid-1970s were influenced by patterns of ever use and current use among ever users. During 1977 to 2014, the percentage of current users among ever users was higher, but less variable, among whites than AAs. Among adults, trends in self-reported cigarette smoking among non-Hispanic AAs and non-Hispanic whites are available since 1978. The trends observed were likely due in part to the maturation of the high school senior cohorts from the 1970s and 1980s when AA smoking rates declined sharply relative to whites. Later age of initiation among AAs and less quitting among older AAs, relative to whites, also contribute. CONCLUSIONS: Further research on multiple topics, including the continuation of use among ever users, use of multiple combusted and noncombusted products, provision of cessation support services, influence of discrimination, and validity of self-report would expand the science base. Strategies to reduce the marketing and availability of menthol and other characterizing flavorings and to enrich environments would promote the public's health.

The African American Youth Smoking Experience: An Overview.

INTRODUCTION: Beginning in the late 1970s, a very sharp decline in cigarette smoking prevalence was observed among African American (AA) high school seniors compared with a more modest decline among whites. This historic decline resulted in a lower prevalence of cigarette smoking among AA youth that has persisted for several decades. METHODS: We synthesized information contained in the research literature and tobacco industry documents to provide an account of past influences on cigarette smoking behavior among AA youth to help understand the reasons for these historically lower rates of cigarette smoking. RESULTS: While a number of protective factors including cigarette price increases, religiosity, parental opposition, sports participation, body image, and negative attitudes towards cigarette smoking may have all played a role in maintaining lower rates of cigarette smoking among AA youth as compared to white youth, the efforts of the tobacco industry seem to have prevented the effectiveness of these factors from carrying over into adulthood. CONCLUSION: Continuing public health efforts that prevent cigarette smoking initiation and maintain lower cigarette smoking rates among AA youth throughout adulthood have the potential to help reduce the negative health consequences of smoking in this population. IMPLICATIONS: While AA youth continue to have a lower prevalence of cigarette smoking than white youth, they are still at risk of increasing their smoking behavior due to aggressive targeted marketing by the tobacco industry. Because AAs suffer disproportionately from tobacco-related disease, and have higher incidence and mortality rates from lung cancer, efforts to prevent smoking initiation and maintain lower cigarette smoking rates among AA youth have the potential to significantly lower lung cancer death rates among AA adults.

Serotonin receptor and KCC2 gene expression in lumbar flexor and extensor motoneurons posttransection with and without passive cycling.

Sacrocaudal motoneuron gene expression is altered following a spinal transection. Of interest here is the regulation of serotonin (5-HT) receptors (R), glutamate receptor, metabotropic 1 (mGluR1), and potassium-chloride cotransporter (KCC2), which mediate motoneuron excitability, locomotor recovery, and spasticity posttransection. The examination of these genes in lumbar motoneurons posttransection has not been studied, which is necessary for developing potential pharmacological interventions aimed at restoring locomotion and/or reducing spasticity. Also, if activity is to be used to promote recovery or reduce spasticity postinjury, a further examination of neuromuscular activity on gene expression posttransection is warranted. The purpose of this study was to examine motoneuronal gene expression of 5-HT receptors, KCC2, and mGluR1 at 3 mo following a complete thoracic spinal cord transection, with and without the inclusion of daily passive cycling. Physiological hindlimb extensor and flexor motoneurons were differentially identified with two retrograde fluorescent tracers, allowing for the identification and separate harvesting of extensor and flexor motoneurons with laser capture microdissection and the subsequent examination of mRNA content using quantitative RT-PCR analysis. We demonstrate that posttransection 5-HT1AR, 5-HT2CR, and mGluR1 expression was downregulated, whereas the 5-HT2AR was upregulated. These alterations in gene expression were observed in both flexor and extensor motoneurons, whereas passive cycling influenced gene expression in extensor but not flexor motoneurons. Passive cycling in extensor motoneurons further enhanced 5-HT2AR expression and increased 5-HT7R and KCC2 expression. Our results demonstrate that passive cycling influences serotonin receptor and KCC2 gene expression and that extensor motoneurons compared with flexor motoneurons may be more plastic to activity-based interventions posttransection.

Comparison of Distal Limb Warming With Fluidotherapy and Warm Water Immersion for Mild Hypothermia Rewarming.

OBJECTIVE: The purpose of the study was to determine the effectiveness of Fluidotherapy rewarming through the distal extremities for mildly hypothermic, vigorously shivering subjects. Fluidotherapy is a dry heat modality in which cellulose particles are suspended by warm air circulation. METHODS: Seven subjects (2 female) were cooled on 3 occasions in 8˚C water for 60 minutes, or to a core temperature of 35°C. They were then dried and rewarmed in a seated position by 1) shivering only; 2) Fluidotherapy applied to the distal extremities (46 ± 1°C, mean ± SD); or 3) water immersion of the distal extremities (44 ± 1°C). The order of rewarming followed a balanced design. Esophageal temperature, skin temperature, heart rate, oxygen consumption, and heat flux were measured. RESULTS: The warm water produced the highest rewarming rate, 6.1°C·h(-1), 95% CI: 5.3-6.9, compared with Fluidotherapy, 2.2°C·h(-1), 95% CI: 1.4-3.0, and shivering only, 2.0°C·h(-1), 95% CI: 1.2-2.8. The Fluidotherapy and warm water conditions increased skin temperature and inhibited shivering heat production, thus reducing metabolic heat production (166 ± 42 W and 181 ± 45 W, respectively), compared with shivering only (322 ± 142 W). Warm water provided a significantly higher net heat gain (398.0 ± 52 W) than shivering only (288.4 ± 115 W). CONCLUSIONS: Fluidotherapy was not as effective as warm water for rewarming mildly hypothermic subjects. Although Fluidotherapy is more portable and technically simpler, it provides a lower rate of rewarming that is similar to shivering only. It does help decrease shivering heat production, lowering energy expenditure and cardiac work, and could be considered in a hospital setting, if convenient.

Effects of lifestyle intervention on dietary intake, physical activity level, and gestational weight gain in pregnant women with different pre-pregnancy Body Mass Index in a randomized control trial.

BACKGROUND: The objectives of this study were to assess the efficacy of lifestyle intervention on gestational weight gain in pregnant women with normal and above normal body mass index (BMI) in a randomized controlled trial. METHODS: A total of 116 pregnant women (<20 weeks of pregnancy) without diabetes were enrolled and 113 pregnant women completed the program. Participants were randomized into intervention and control groups. Women in the intervention group received weekly trainer-led group exercise sessions, instructed home exercise for 3-5-times/week during 20-36 weeks of gestation, and dietary counseling twice during pregnancy. Participants in the control group did not receive the intervention. All participants completed a physical activity questionnaire and a 3-day food record at enrolment and 2 months after enrolment. RESULTS: The participants in the intervention group with normal pre-pregnancy BMI (≤24.9 kg/M2, n = 30) had lower gestational weight gain (GWG), offspring birth weight and excessive gestational weight gain (EGWG) on pregnancy weight gain compared to the control group (n = 27, p < 0.05). Those weight related-changes were not detected between the intervention (n = 27) and control group (n = 29) in the above normal pre-pregnancy BMI participants. Intervention reduced total calorie, total fat, saturated fat and cholesterol intake were detected in women with normal or above normal pre-pregnancy BMI compared to the control group (p < 0.05 or 0.01). Increased physical activity and reduced carbohydrate intake were detected in women with normal (p < 0.05), but not above normal, pre-pregnancy BMI at 2 months after the onset of the intervention compared to the control group. CONCLUSION: The results of the present study demonstrated that the lifestyle intervention program decreased EGWG, GWG, offspring birth weight in pregnant women with normal, but not above normal, pre-pregnancy BMI, which was associated with increased physical activity and decreased carbohydrate intake. TRIAL REGISTRATION: NCT00486629.

Comparison of heat donation through the head or torso on mild hypothermia rewarming.

OBJECTIVE: The purpose of the study was to compare the effectiveness of head vs torso warming in rewarming mildly hypothermic, vigorously shivering subjects using a similar source of heat donation. METHODS: Six subjects (1 female) were cooled on 3 occasions in 8 ºC water for 60 minutes or to a core temperature of 35 ºC. They were then dried, insulated, and rewarmed by 1) shivering only; 2) charcoal heater applied to the head; or 3) charcoal heater applied to the torso. The order of rewarming methods followed a balanced design. Esophageal temperature, skin temperature, heart rate, oxygen consumption, and heat flux were measured. RESULTS: There were no significant differences in rewarming rate among the 3 conditions. Torso warming increased skin temperature and inhibited shivering heat production, thus providing similar net heat gain (268 ± 66 W) as did shivering only (355 ± 105 W). Head warming did not inhibit average shivering heat production (290 ± 72 W); it thus provided a greater net heat gain during 35 to 60 minutes of rewarming than did shivering only. CONCLUSIONS: Head warming is as effective as torso warming for rewarming mildly hypothermic victims. Head warming may be the preferred method of rewarming in the field management of hypothermic patients if: 1) extreme conditions in which removal of the insulation and exposure of the torso to the cold is contraindicated; 2) excessive movement is contraindicated (eg, potential spinal injury or severe hypothermia that has a risk of ventricular fibrillation); or 3) if emergency personnel are working on the torso.

Removal of supraspinal input reveals a difference in the flexor and extensor monosynaptic reflex response to quipazine independent of motoneuron excitation.

The purpose of this study was to determine if quipazine, a serotonergic agonist, differentially modulates flexor and extensor motor output. This was achieved by examining the monosynaptic reflex (MSR) of the tibial (extensor) and peroneal (flexor) nerves, by determining the basic and rhythmic properties of extensor and flexor motoneurons, and by recording extracellular Ia field potentials of the tibial and peroneal nerves in the in vivo adult decerebrate rat in both spinal intact and acute spinalized preparations. In the spinal intact preparation, the tibial and peroneal MSR amplitude significantly increased compared with baseline in response to quipazine, with no difference between nerves (P < 0.05). In the spinalized preparation, the MSR was significantly increased in both the tibial and peroneal nerves with the latter increasing more than the former (5.7 vs. 3.6 times; P < 0.05). Intracellular motoneuron experiments demonstrated that rheobase decreased, while input resistance, afterhyperpolarization amplitude, and the firing rate at a given current injection increased in motoneurons following quipazine administration with no differences between extensor and flexor motoneurons. Both the tibial and peroneal nerve extracellular Ia field potentials increased with the peroneal demonstrating a significantly greater increase (7 vs. 38%; P < 0.05) following quipazine. It is concluded that in the spinal intact preparation quipazine does not have a differential effect on flexor or extensor motor output. However, in the acute spinalized preparation, quipazine preferentially affects the flexor MSR compared with the extensor MSR, likely due to the removal of a descending tonic inhibition on flexor Ia afferents.

Substance use among Chinese, Filipino, and Vietnamese adult men living in San Jose, Daly City, and San Francisco, and its implications on ATOD prevention services.

This intervention study collected data on Chinese, Filipino, and Vietnamese high-risk adults to ascertain similarities and differences in drug use patterns. Study participants (N = 126) participated in a 5-week intervention study to mitigate substance abuse and the prevalence of hepatitis C and HIV among high-risk adults in San Francisco, San Mateo, and Santa Clara Counties of California. Data reported were collected at baseline. The National Outcome Measures questionnaire was used to document individual substance use in the past 30 days. Filipinos reported higher use rates for alcohol, cigarettes, marijuana, and crack cocaine in the past 30 days compared with their Chinese and Vietnamese counterparts; these differences proved to be statistically significant (p ≤ .03). Data analysis also showed that the alcohol use of Filipino and Vietnamese homosexual men was significantly greater than their Chinese counterparts (p = .04). A statistically significant inverse association was found for alcohol use for those in the criminal justice system during the past 30 days (odds ratio [OR] = 0.37, p = .03). In addition, a positive association for other tobacco use (OR = 11.98, p = .00) was reported for those in the criminal justice system. Age group analyses indicated a positive association for those between 18-25 years old for alcohol use (OR = 5.40, p = .00). These data confirm the importance of disaggregation of data. If collapsed into a general Asian or Asian and Pacific Islander ethnic group category, as is often the case, the unique behaviors of the individual groups would be lost.

Spinal and corticospinal excitability in response to reductions in skin and core temperatures via whole-body cooling.

Cold stress impairs fine and gross motor movements. Although peripheral effects of muscle cooling on performance are well understood, less is known about central mechanisms. This study characterized corticospinal and spinal excitability during surface cooling, reducing skin (Tsk) and esophageal (Tes) temperatures. Ten subjects (3 females) wore a liquid-perfused suit and were cooled (9 °C perfusate, 90 min) and rewarmed (41 °C perfusate, 30 min). Transcranial magnetic stimulation (eliciting motor evoked potentials [MEPs]), as well as transmastoid (eliciting cervicomedullary evoked potentials [CMEPs]) and brachial plexus (eliciting maximal compound motor action potentials [Mmax]) electrical stimulation, were applied at baseline, every 20 min during cooling, and following rewarming. Sixty minutes of cooling reduced Tsk by 9.6 °C (P < 0.001), but Tes remained unchanged (P = 0.92). Tes then decreased by ∼0.6 °C in the next 30 min of cooling (P < 0.001). Eight subjects shivered. During rewarming, shivering was abolished, and Tsk returned to baseline, while Tes did not increase. During cooling and rewarming, Mmax, MEP, and MEP/Mmax remained unchanged from baseline. However, CMEP and CMEP/Mmax increased during cooling by ∼85% and 79% (P < 0.001), respectively, and remained elevated post-rewarming. The results suggest that spinal excitability is facilitated by reduced Tsk during cooling and reduced Tes during warming, while corticospinal excitability remains unchanged. ClinicalTrials.gov ID: NCT04253730. Novelty: This is the first study to characterize corticospinal and spinal excitability during whole-body cooling and rewarming in humans. Whole body cooling did not affect corticospinal excitability. Spinal excitability was facilitated during reductions in both skin and core temperatures.

Whole-body hypothermia has central and peripheral influences on elbow flexor performance.

The superimposed twitch technique was used to study the effect of whole-body hypothermia on maximal voluntary activation of elbow flexors. Seven subjects [26.4 ± 4 years old (mean ± SD)] were exposed to 60 min of either immersion in 8°C water (hypothermia) or sitting in 22°C air (control). Voluntary activation was assessed during brief (3 s) maximal voluntary contractions (MVCs) and then during a 2 min fatiguing sustained MVC. Hypothermia (core temperature 34.8 ± 0.9°C) decreased maximal voluntary torque from 98.2 ± 1.0 to 82.8 ± 5.8% MVC (P < 0.001) and increased central conduction time from 7.9 ± 0.4 to 9.1 ± 0.7 ms (P < 0.05). Hypothermia also decreased maximal resting twitch amplitude from 17.6 ± 4.0 to 10.0 ± 1.7% MVC (P < 0.005) and increased the time-to-peak twitch tension from 55.4 ± 4.0 to 79.0 ± 11.7 ms (P < 0.001). During the 2 min contraction, hypothermia decreased initial torque (P < 0.01) but attenuated the subsequent rate of torque decline (control from 95.5 ± 4 to 29.4 ± 8% MVC; and hypothermia from 85.3 ± 8 to 37.3 ± 5% MVC; P < 0.01). Cortical superimposed twitches increased as fatigue developed but were always lower in the hypothermic conditions. Cortical superimposed twitches increased from a value of 0.4 ± 0.3% MVC prefatigue to 3.9 ± 1.4% MVC postfatigue (P < 0.001) in the hypothermic conditions and from 1.7 ± 0.9 to 5.5 ± 2.3% MVC in control conditions. Our results suggest that hypothermia decreases MVCs primarily via peripheral mechanisms and attenuates the rate of fatigue development by reducing central fatigue.

Effects of exercise and muscle type on BDNF, NT-4/5, and TrKB expression in skeletal muscle.

Muscle-derived neurotrophins are thought to contribute to the adaptation of skeletal muscle to exercise, but the effects of brief exercise interventions on BDNF, NT-4/5, and trkB are not understood. RNA was extracted for RT-PCR from soleus and medial gastrocnemius of Sprague-Dawley rats exercised on a treadmill at speeds up to 20 m/min at 5% incline for 5 or 10 days. BDNF expression was elevated in soleus following 5 days (184%, P < 0.001) but not 10 days of exercise. NT-4/5 and trkB were not affected at either time-point. BDNF mRNA was significantly higher in soleus at rest when compared with medial gastrocnemius (193%, P < 0.05). No significant effects of muscle type were detected for NT-4/5 and trkB. Our results indicate differential control of BDNF expression between soleus and medial gastrocnemius following 5 days of exercise. BDNF may be a protein with an uncharacterized contribution to the acute adaptation of skeletal muscle to exercise, whereas NT-4/5 shows no response.

Menthol cigarettes: moving toward a broader definition of harm.

RATIONALE: The current practice of the tobacco industry of primarily focusing on the extent that menthol cigarettes contribute or do not contribute to excess morbidity and mortality in various diseases does not, in and of itself, fully illuminate the harm caused by these products. In fact, this practice actually masks and obscures the public health harm associated with menthol cigarettes. Given this, this commentary develops and presents a broader definition of harm in which to view menthol cigarettes and as the necessary and underlying rationale of why this candy-flavored ingredient should be removed from all tobacco products. METHODS: This paper relies on the scientific presentations of the 2nd Conference on Menthol Cigarettes, and the peer-reviewed literature on menthol cigarettes. OUTCOMES: A broader definition of harm from menthol cigarettes must be analyzed from a broad public health perspective and take into account youth uptake and initiation, menthol's ability to augment addiction through unique sensory properties, spurious health messages associated with these products, menthol's role in cessation inhibition and relapse promotion, and the blatant predatory marketing of these products to the most vulnerable sectors of society. CONCLUSIONS: The Food and Drug Administration (FDA) should apply the same logic that outlawed other candy flavorings and apply it to menthol cigarettes; in the end, all candy flavorings, including menthol, only serve to make the poisons inherent in tobacco smoke go down easier. Additionally, the mobilization of communities most affected by the menthol cigarettes, the FDA, and candy flavorings and the tobacco industry's machinations will be discussed.