The freeze-avoiding mountain pine beetle (Dendroctonus ponderosae) survives prolonged exposure to stressful cold by mitigating ionoregulatory collapse.

Insect performance is linked to environmental temperature, and surviving through winter represents a key challenge for temperate, alpine and polar species. To overwinter, insects have adapted a range of strategies to become truly cold hardy. However, although the mechanisms underlying the ability to avoid or tolerate freezing have been well studied, little attention has been given to the challenge of maintaining ion homeostasis at frigid temperatures in these species, despite this limiting cold tolerance for insects susceptible to mild chilling. Here, we investigated how prolonged exposure to temperatures just above the supercooling point affects ion balance in freeze-avoidant mountain pine beetle (Dendroctonus ponderosae) larvae in autumn, mid-winter and spring, and related it to organismal recovery times and survival. Hemolymph ion balance was gradually disrupted during the first day of exposure, characterized by hyperkalemia and hyponatremia, after which a plateau was reached and maintained for the rest of the 7-day experiment. The degree of ionoregulatory collapse correlated strongly with recovery times, which followed a similar asymptotical progression. Mortality increased slightly during extensive cold exposures, where hemolymph K+ concentration was highest, and a sigmoidal relationship was found between survival and hyperkalemia. Thus, the cold tolerance of the freeze-avoiding larvae of D. ponderosae appears limited by the ability to prevent ionoregulatory collapse in a manner similar to that of chill-susceptible insects, albeit at much lower temperatures. Based on these results, we propose that a prerequisite for the evolution of insect freeze avoidance may be a convergent or ancestral ability to maintain ion homeostasis during extreme cold stress.

Phalangeal microgeodic syndrome: case report of a young woman treated with pentoxifylline.

Phalangeal microgeodic syndrome (PMS) is a rare osteolytic disorder of unknown etiology that typically affects children up to 15 years old during colder months. Transient peripheral circulatory impairment probably underlines its pathogenesis. Conservative treatment with eviction of cold exposure is often successful. We report the case of a young woman presenting with joint pain in her feet, along with toe discoloration and redness, where a diagnosis of PMS was established based on magnetic resonance imaging findings and exclusion of other differential diagnostic entities. Pharmacological treatment was deemed necessary for symptomatic relief, but a trial of calcium channel blocker (CCB) was not tolerated by the patient. The patient was then started on pentoxifylline, with significant clinical improvement.

The peripheral vascular responses in non-freezing cold injury and matched controls.

NEW FINDINGS: What is the central question of this study? Does non-freezing cold injury (NFCI) alter normal peripheral vascular function? What is the main finding and its importance? Individuals with NFCI were more cold sensitive (rewarmed more slowly and felt more discomfort) than controls. Vascular tests indicated that extremity endothelial function was preserved with NFCI and that sympathetic vasoconstrictor response might be reduced. The pathophysiology underpinning the cold sensitivity associated with NFCI thus remains to be identified. ABSTRACT: The impact of non-freezing cold injury (NFCI) on peripheral vascular function was investigated. Individuals with NFCI (NFCI group) and closely matched controls with either similar (COLD group) or limited (CON group) previous cold exposure were compared (n = 16). Peripheral cutaneous vascular responses to deep inspiration (DI), occlusion (PORH), local cutaneous heating (LH) and iontophoresis of acetylcholine and sodium nitroprusside were investigated. The responses to a cold sensitivity test (CST) involving immersion of a foot in 15°C water for 2 min followed by spontaneous rewarming, and a foot cooling protocol (footplate cooled from 34°C to 15°C), were also examined. The vasoconstrictor response to DI was lower in NFCI compared to CON (toe: 73 (28)% vs. 91 (17)%; P = 0.003). The responses to PORH, LH and iontophoresis were not reduced compared to either COLD or CON. During the CST, toe skin temperature rewarmed more slowly in NFCI than COLD or CON (10 min: 27.4 (2.3)°C vs. 30.7 (3.7)°C and 31.7 (3.9)°C, P < 0.05, respectively); however, no differences were observed during the footplate cooling. NFCI were more cold-intolerant (P < 0.0001) and reported colder and more uncomfortable feet during the CST and footplate cooling than COLD and CON (P < 0.05). NFCI showed a decreased sensitivity to sympathetic vasoconstrictor activation than CON and greater cold sensitivity (CST) compared to COLD and CON. None of the other vascular function tests indicated endothelial dysfunction. However, NFCI perceived their extremities to be colder and more uncomfortable/painful than the controls.

Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.

NEW FINDINGS: What is the central question of this study? Are biomarkers of endothelial function, oxidative stress and inflammation altered by non-freezing cold injury (NFCI)? What is the main finding and its importance? Baseline plasma [interleukin-10] and [syndecan-1] were elevated in individuals with NFCI and cold-exposed control participants. Increased [endothelin-1] following thermal challenges might explain, in part, the increased pain/discomfort experienced with NFCI. Mild to moderate chronic NFCI does not appear to be associated with either oxidative stress or a pro-inflammatory state. Baseline [interleukin-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosis of NFCI. ABSTRACT: Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched control participants with (COLD, n = 17) or without (CON, n = 14) previous cold exposure. Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation [interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor alpha and E-selectin], oxidative stress [protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase and nitrotyrosine) and endothelial damage [von Willebrand factor, syndecan-1 and tissue type plasminogen activator (TTPA)]. Immediately after whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA]. At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P < 0.001 and P = 0.015, respectively) and COLD (P = 0.033 and P = 0.030, respectively) compared with CON participants. The [4-HNE] was elevated in CON compared with both NFCI (P = 0.002) and COLD (P < 0.001). [Endothelin-1] was elevated in NFCI compared with COLD (P < 0.001) post-heating. The [4-HNE] was lower in NFCI compared with CON post-heating (P = 0.032) and lower than both COLD (P = 0.02) and CON (P = 0.015) post-cooling. No between-group differences were seen for the other biomarkers. Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, but it is likely that a combination of tests will be required.

Peripheral sensory function in non-freezing cold injury patients and matched controls.

NEW FINDINGS: What is the central question of this study? Is peripheral sensory function impaired in the chronic phase of non-freezing cold injury (NFCI)? What is the main finding and its importance? Warm and mechanical detection thresholds are elevated and intraepidermal nerve fibre density is reduced in individuals with NFCI in their feet when compared to matched controls. This indicates impaired sensory function in individuals with NFCI. Interindividual variation was observed in all groups, and therefore a diagnostic cut-off for NFCI has yet to be established. Longitudinal studies are required to follow NFCI progression from formation to resolution ABSTRACT: The aim of this study was to compare peripheral sensory neural function of individuals with non-freezing cold injury (NFCI) with matched controls (without NFCI) with either similar (COLD) or minimal previous cold exposure (CON). Thirteen individuals with chronic NFCI in their feet were matched with the control groups for sex, age, race, fitness, body mass index and foot volume. All undertook quantitative sensory testing (QST) on the foot. Intraepidermal nerve fibre density (IENFD) was assessed 10 cm above the lateral malleolus in nine NFCI and 12 COLD participants. Warm detection threshold was higher at the great toe in NFCI than COLD (NFCI 45.93 (4.71)°C vs. COLD 43.44 (2.72)°C, P = 0.046), but was non-significantly different from CON (CON 43.92 (5.01)°C, P = 0.295). Mechanical detection threshold on the dorsum of the foot was higher in NFCI (23.61 (33.59) mN) than in CON (3.83 (3.69) mN, P = 0.003), but was non-significantly different from COLD (10.49 (5.76) mN, P > 0.999). Remaining QST measures did not differ significantly between groups. IENFD was lower in NFCI than COLD (NFCI 8.47 (2.36) fibre/mm2 vs. COLD 11.93 (4.04) fibre/mm2 , P = 0.020). Elevated warm and mechanical detection thresholds may indicate hyposensitivity to sensory stimuli in the injured foot for individuals with NFCI and may be due to reduced innervation given the reduction in IENFD. Longitudinal studies are required to identify the progression of sensory neuropathy from the formation of injury to its resolution, with appropriate control groups employed.

A numerical tool for assessing human thermal safety and thermal comfort in cold-weather activities.

This paper describes a newly developed software tool to evaluate human thermal safety and thermal comfort in cold-weather activities aimed at guiding users to arrange activity plans and select appropriate clothing ensembles. The software inputs include conditions of activity, environment, human body, and clothing ensemble. It outputs physiological temperatures, cold injury risks, thermal sensations, and thermal comforts in intuitive ways like cloud maps and curves. The software tool is characterized by (1) integration of a thermoregulatory model that predicts human thermophysiological responses under exercise conditions in cold environments, (2) the functions of clothing ensemble database and individual parameter database, (3) the human centric outputs that directly reflect human physiological and mental status, and (4) the user-friendly operation interface and output interface, as well as a wide applicability. The software is validated with human test studies covering ambient temperatures from - 30.6 to 5 °C, clothing ensembles from 1.34 to 3.20 clo, and activity intensities from 2 to 9 Mets. The average prediction RMSEs of core temperature, mean skin temperature, thermal sensation, and thermal comfort are 0.16 °C, 0.45 °C, 0.58, and 1.41, respectively. The software is an advanced expansion to current standards and guidance of cold exposure assessment and a meaningful tool for the fields of occupational health care, cold protection, and environmental ergonomics.

Survival in a Collapsed Stable for 37 Days After Avalanche Burial in 1755.

In 1755 in Bergemoletto, Italy, an avalanche buried 4 people (2 women, a girl, and a boy) and several animals in a stable. After 37 d in a pitch-dark confined space, 3 of the 4 people were rescued alive. The 3 survivors had only goat milk, a few chestnuts, a few kg of raw kid meat, and meltwater for nutrition. We describe the longest-known survival in an avalanche burial and discuss the medical and psychological problems of the survivors. The boy died. When they were extricated, all 3 survivors were exhausted, cachectic, and unable to stand or walk. They were severely malnourished and were experiencing tingling, tremors, and weakness in the legs; constipation; changes in taste; and amenorrhea. One of the women had persistent eye problems and developed symptoms consistent with post-traumatic stress disorder. The survivors were given slow refeeding. It took from 1 to 6 wk before they could walk. We compare this case to other long-duration burials, especially mining accidents, and describe the rescue and patient care after long-duration burials. This case demonstrates that people can overcome extremely adverse conditions and survive.

Performance of a Chemical Heat Blanket in Dry, Damp, and Wet Conditions Inside a Mountain Rescue Hypothermia Wrap.

INTRODUCTION: Casualties with accidental hypothermia are evacuated using multilayer wraps, typically including a chemical heat blanket (CHB), a vapor barrier, and an insulating outer bag. We investigated CHB performance against dry, damp, and wet fabric, in a multilayer wrap, in response to a case report indicating diminished performance when wet. METHODS: We wrapped a torso manikin in a base layer, CHB, vapor barrier, casualty bag, and vacuum mattress, recording CHB panel temperatures at intervals of up to 7 h. Experimental conditions were dry, damp, and wet clothing, with 2 blankets tested in each condition. We subsequently used a forward-looking infrared camera to assess whether the panels heated evenly and heat flux sensors to quantify heat transfer across 2 dry, 1 damp, and 1 wet fleece under CHB panels. RESULTS: Chemical heat blankets maintained heat output for >7 h inside the wraps. Median (IQR) panel steady state temperatures were 52°C (39-56°C) against dry fleece, 41°C (36-45°C) against damp fleece, and 30°C (29-33°C) against wet fleece. Peak panel temperature was 67°C. The heat flux results indicated that CHBs generated similar quantities of heat in dry and damp conditions, as the lower temperatures were compensated by more efficient transfer of heat across the moist clothing layer. Chemical heat blanket heat output was diminished in wet conditions. CONCLUSIONS: Rescuers should cut off saturated clothing in a protected environment before wrapping casualties, but damp clothing need not be removed. Because of the high peak temperatures recorded on the surfaces of CHBs, they should not be placed directly against skin, and compression straps should not be placed directly over CHBs.

Acral skin vasoreactivity and thermosensitivity to hand cooling following 5 days of intermittent whole body cold exposure.

We sought to examine whether short-term, whole body cold acclimation would modulate finger vasoreactivity and thermosensitivity to localized cooling. Fourteen men were equally assigned to either the experimental (CA) or the control (CON) group. The CA group was immersed to the chest in 14°C water for ≤120 min daily over a 5-day period while the skin temperature of the right-hand fingers was clamped at ∼35.5°C. The CON group was instructed to avoid any cold exposure during this period. Before and after the intervention, both groups performed, on two different consecutive days, a local cold provocation trial consisting of a 30-min hand immersion in 8°C water while immersed to the chest once in 21°C (mild-hypothermic trial; 0.5°C fall in rectal temperature from individual preimmersion values) and on the other occasion in 35.5°C (normothermic trial). In the CA group, the cold-induced reduction in finger temperature was less (mild-hypothermic trial: P = 0.05; normothermic trial: P = 0.02), and the incidence of the cold-induced vasodilation episodes was greater (in normothermic trials: P = 0.04) in the post- than in the preacclimation trials. The right-hand thermal discomfort was also attenuated (mild-hypothermic trial: P = 0.04; normothermic trial: P = 0.01). The finger temperature responses of the CON group did not vary between testing periods. Our findings suggest that repetitive whole body exposure to severe cold within a week may attenuate finger vasoreactivity and thermosensitivity to localized cooling. These regional thermo-adaptions were ascribed to central neural habituation produced by the iterative, generalized cold stimulation.

Clinical utilization of a sous vide device in the acute rewarming of frostbitten extremities.

The current standard of care for acute frostbite rewarming is the use of a circulating warm water bath at a temperature of 37 °C to 39 °C. There is no standardized method to achieve this. Manual management of a warm water bath can be inefficient and time consuming. This case describes the clinical use of a sous vide cooking device to create and maintain a circulating warm water bath to rewarm acute frostbite. A 34 year-old male presented to the emergency department with acute frostbite. Each of the patient's feet were placed in a water bath with a sous vide device attached to the side of the basin and set to 38 °C. Temperatures were recorded every 2 m from 2 thermometers. Once target temperature was achieved, the extremities were rewarmed for 30 m. The water baths required an average of 25 m to reach target temperature and maintained the target temperature within ±1 °C for the duration of the rewarming. The extremities were clinically thawed in one session and there were no adverse events. The patient was seen by plastic and vascular surgery and admitted to the hospital for conservative management. He was discharged on hospital day 3 and did not require any amputations. A sous vide device can be used clinically to heat and maintain a water bath and successfully rewarm frostbitten extremities in one 30 m cycle. No adverse events were reported and providers rated this as a convenient method of water bath management.

Occupational cold exposure and symptoms of carpal tunnel syndrome - a population-based study.

BACKGROUND: Cold exposure is an underrecognized occupational hazard that may increase the risk of peripheral nerve entrapment. The aim of this study was to determine if self-reported occupational exposure to contact and ambient cooling was associated with symptoms of carpal tunnel syndrome (CTS). METHODS: In this mainly cross-sectional study, surveys were conducted on a population-based sample of men and women between 18 and 70 years of age, living in northern Sweden. Cold exposure and presence of symptoms suggestive of CTS were subjectively reported. Associations between exposure and outcome were evaluated using logistic regression. RESULTS: The study included 2,703 women and 2,314 men, with a median age of 60 years (interquartile range 19). Symptoms of CTS were reported by 453 (9.2%). Being highly occupationally exposed (almost always) to contact cooling of the hands was associated with reporting CTS (OR 3.20; 95% CI 1.62-6.33), as was ambient cooling (OR 2.00; 95% CI 1.03-3.88) and severe ambient cooling (OR 4.02 95% CI 2.09-7.71), after adjusting for age, gender, body mass index, current daily smoking, diabetes mellitus, joint disease, and hand-arm vibration exposure. The point estimates increased with longer daily exposure duration. For workers exposed to severe ambient cooling for more than half of their working hours, in addition to performing heavy manual handling every day, the OR for reporting CTS was 7.25 (95% CI 3.88-13.53), with a positive additive interaction effect (expressed as relative excess risk due to interaction) of 4.67. CONCLUSIONS: Self-reported occupational exposure to contact and ambient cooling was associated with symptoms suggestive of CTS. There were statistically significant positive exposure-response patterns for time spent exposed to contact and ambient cooling at work in relation to reporting symptoms of CTS. Positive additive interaction effects between cold exposure and heavy manual handling were also found. Since there was important potential uncontrolled confounding regarding repetitive wrist movements and forceful gripping, the results need to be confirmed by other studies, preferably with longitudinal design and more detailed exposure assessment.

Transport viable heart tissue at physiological temperature yielded higher human cardiomyocytes compared to the conventional temperature.

This study investigated the optimum transport condition for heart tissue to recover single-cell cardiomyocytes for future in-vitro or in-vivo studies. The heart tissues were obtained from removing excessive myocardium discharged during the repair surgery of an excessive right atrial hypertrophy due to a congenital disease. The transportation temperature studied was the most used temperature (4 °C) or the conventional condition, compared to a physiological temperature(37 °C). The heart tissues were transported from the operating theatre to the lab maintained less than 30 min consistently. Single-cell isolation was enzymatically and mechanically performed using collagenase-V (160 U/mg) and proteinase-XXIV (7-14 U/mg) following the previously described protocol. The impact of temperature differences was observed by the density of cells harvested per mg tissue, cell viability, and the senescence signals, identified by the p21, p53 and caspase-9 mRNA expressions. Results the heart tissue transported at 37 °C yielded significantly higher viable cell density (p < 0.01) yielded viable cells significantly higher density (p < 0.01) than the 4 °C; 2,335 ± 849 cells per mg tissue, and 732 ± 425 cells per mg tissue, respectively. The percentage of viable cells in both groups showed no difference. Although the 37 °C group expressed the apoptosis genes such as p21, p53 and caspase9 by 2.5-, 5.41-, 5-fold respectively (p > 0.05). Nonetheless, the Nk×2.5 and MHC genes were expressed 1,7- and 3.56-fold higher than the 4 °C. and the c-Kit+ expression was 17.56-fold, however, statistically insignificant. Conclusion When needed for single-cell isolation, a heart tissue transported at 37 °C yielded higher cell density per mg tissue compared to at 4 °C, while other indicators of gene expressions for apoptosis, cardiac structural proteins, cardiac progenitor cells showed no difference. Further investigations of the isolated cells at different temperature conditions towards their proliferation and differentiation capacities in a 3-D scaffold would be essential.

Hypothermia and cold injuries in children and young people.

Although hypothermia and cold injuries are rare in children and young people in the UK, the risk is persistent and requires urgent medical management when it does occur. This article outlines some considerations for professionals who may be caring for hypothermic patients or those at risk of becoming hypothermic.

The effect of non-steroidal anti-inflammatory drugs with different mechanisms of action on the body temperature and cyclooxygenase pathway of the arachidonic acid cascade on the model of acute general cooling (air hypothermia) in rats.

NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.

The lincRNA XH123 is involved in cotton cold-stress regulation.

KEY MESSAGE: We characterize a functional lincRNA, XH123 in cotton seedling in defense of cold stress. The silencing of XH123 leads to increased sensitivity to cold stress and the decay of chloroplast. Cotton, which originated from the arid mid-American region, is one of the most important cash crops worldwide. Cultivated cotton is now widely spread throughout high-altitude regions such as those in the far northwest of Asia. In such areas, spring temperatures below 12 ℃ impose cold stress on cotton seedlings, with concomitant threat of lost yield and productivity. It is documented that cold stress can induce differential expression of long noncoding RNAs (lncRNAs) in cotton; however, it is not yet clear if these cold-responsive lncRNAs are actively involved with tolerance of cold stress at the molecular level. Here, we select ten long intergenic non-coding RNAs as candidate genes and use virus-induced gene silencing and additional cold treatments to examine their roles in the response to cold stress during the cotton seedling stage. One such gene, XH123, was revealed to be involved in tolerance of cold stress. Specifically, XH123-silenced plants demonstrated sensitivity to cold stress, exhibiting chloroplast damage and increased endogenous levels of reactive oxygen species. The transcriptome profile of XH123-silenced seedlings was similar to that of cold-stressed seedlings having the known cold stress gene PIF3 silenced. These results imply that the lincRNA XH123 is actively involved with cold stress regulation in cotton during the seedling stage.

In pursuit of the unicorn.

This short review was prompted by The Physiological Society's recent online symposium on variability. It does not deal with a specific methodology, but rather with the myth that certain environmentally-induced clinical conditions can be identified, quantified, simplified and monitored with a single methodology. Although this might be possible with some clinical conditions, others resist the prevailing reductionist approach of minimizing rather than exploring variation in pathogenesis and pathology, and will not be understood fully until the variation in cause and effect are embraced. This is likely to require comprehensive methodologies and collaboration.

Previous recreational cold exposure does not alter endothelial function or sensory thermal thresholds in the hands or feet.

NEW FINDINGS: What is the central question of this study? Does recreational cold exposure result in cold sensitivity and is this associated with endothelial dysfunction and impaired sensory thermal thresholds? What is the main finding and its importance? Previous cold exposure was correlated with cold sensitivity of the foot, which might indicate the development of a subclinical non-freezing cold injury. Endothelial function and thermal detection were not impaired in cold-sensitive individuals; therefore, further research is required to understand the pathophysiology of subclinical and clinical forms of non-freezing cold injury. ABSTRACT: In this study, we investigated whether cold-sensitive (CS) individuals, who rewarm more slowly after a mild cold challenge, have impaired endothelial function and sensory thermal thresholds (STTs) and whether this is related to reported cold exposure. Twenty-seven participants with varying previous cold exposure undertook three tests: an STT test, i.e. determination of warm and cold STTs of the fingers and dorsal foot; an endothelial function test, i.e. measurement of cutaneous vascular conductance (CVC) during iontophoresis of ACh on the forearm, finger and foot; and a CS test, involving immersion of a foot for 2 min in water at 15°C followed by 10 min of rewarming in air at 30°C. Toe skin temperature (Tsk ) measured during the CS test was used to form a CS group (<32°C before and 5 min after immersion) and an otherwise closely matched control group [Tsk >32°C; n = 9 (four women) for both groups]. A moderate relationship was found between cold exposure ranking and Tsk rewarming (r = 0.408, P = 0.035, n = 27) but not STT or endothelial function. The Tsk and blood flow were lower in CS compared with control subjects before and after foot immersion [Tsk , mean (SD): 30.3 (0.9) versus 34.8 (0.8) and 27.9 (0.8) versus 34.3 (0.8)°C, P < 0.001; and CVC: 1.08 (0.79) versus 3.82 (1.21) and 0.79 (0.52) versus 3.45 (1.07) flux mmHg-1 , n = 9, P < 0.001, respectively]. However, no physiologically significant differences were observed between groups for endothelial function or STT. A moderate correlation between previous cold exposure and toe Tsk rewarming after foot immersion was observed; however, CS was not associated with impaired endothelial function or reduced thermal detection.

Increased cold injuries and the effect of body mass index in patients with peripheral vascular disease.

BACKGROUND: Exposure to extremely or moderate low temperatures is associated with increased morbidity and mortality risk. Peripheral vascular disease (PVD) is a slow and progressive circulation disorder. Given that cold temperature causes constriction of the small arteries and veins in the skin, patients who suffer from peripheral circulation problems, like PVD, may be vulnerable to cold injuries. This study aimed to investigate the association between PVD and cold-induced injuries in the winter among Korean adults. We further analyzed the association stratified by body mass index (BMI) classification. METHODS: We used the 2002-2015 National Health Insurance Service-National Sample Cohort data and included a total of 535,186 adults as the study population. Patients with underlying PVD were identified by ICD-10 code I73. Cold-related illnesses were defined by ICD-10 codes (T690, T691, T698, T699, T330 ~ T339, T340 ~ T349, and T350 ~ T357). Body mass index (BMI) was categorized into underweight, normal weight, overweight, and obese. RESULTS: A total of 23.21% (n = 124,224) were PVD patients, and 0.59% (n = 3154) had cold-induced injuries. PVD patients were more likely to be diagnosed with cold injuries, but it was valid only in the underweight or normal weight groups. After adjusting for age, sex, income, cigarette smoking, alcohol consumption, regular exercise, high blood pressure, and hyperglycemia, PVD patients had a significantly increased odds ratio (OR) for cold injuries [adjusted OR = 1.11; 95% confidence intervals (95% CI): 1.01-1.21]. Increased OR for cold injuries in PVD patients was also observed in adults (adjusted OR = 1.14; 95% CI: 1.03-1.25 in Model 2), but not in the elderly. When we classified study subjects into the four BMI groups, the adjusted OR of cold injuries in PVD patients was significant in the underweight group (OR = 1.83; 95% CI, 1.26-2.66) and normal weight group (OR = 1.15; 95% CI, 1.03-1.27), not in those with overweight and obese. In adults, a consistent result was found in adults in the underweight group (OR = 1.63; 95% CI, 1.08-2.47 in Model 2) and normal weight group (OR = 1.19; 95% CI, 1.07-1.33 in Model 2). In the elderly, the adjusted OR for cold injuries was only significant in the underweight group (OR = 3.37; 95% CI, 1.08-10.53 in Model 2). CONCLUSIONS: We found a significant association between PVD and cold-induced injuries in the general population. BMI modified the association. Thus, the association observed appears to be clinically applicable to PVD patients being low to normal BMI.

Cold exposure causes cell death by depolarization-mediated Ca2+ overload in a chill-susceptible insect.

Cold tolerance of insects is arguably among the most important traits defining their geographical distribution. Even so, very little is known regarding the causes of cold injury in this species-rich group. In many insects it has been observed that cold injury coincides with a cellular depolarization caused by hypothermia and hyperkalemia that develop during chronic cold exposure. However, prior studies have been unable to determine if cold injury is caused by direct effects of hypothermia, by toxic effects of hyperkalemia, or by the depolarization that is associated with these perturbations. Here we use a fluorescent DNA-staining method to estimate cell viability of muscle and hindgut tissue from Locusta migratoria and show that the cellular injury is independent of the direct effects of hypothermia or toxic effects of hyperkalemia. Instead, we show that chill injury develops due to the associated cellular depolarization. We further hypothesized that the depolarization-induced injury was caused by opening of voltage-sensitive Ca2+ channels, causing a Ca2+ overload that triggers apoptotic/necrotic pathways. In accordance with this hypothesis, we show that hyperkalemic depolarization causes a marked increase in intracellular Ca2+ levels. Furthermore, using pharmacological manipulation of intra- and extracellular Ca2+ concentrations as well as Ca2+ channel conductance, we demonstrate that injury is prevented if transmembrane Ca2+ flux is prevented by removing extracellular Ca2+ or blocking Ca2+ influx. Together these findings demonstrate a causal relationship between cold-induced hyperkalemia, depolarization, and the development of chill injury through Ca2+-mediated necrosis/apoptosis.

Frostbite: Current status and advancements in therapeutics.

Frostbite is a severe ischemic injury which occurs due to the tissue vascular damage after sub-zero temperature tissue exposure. Deep frostbite can result in necrosis and may need amputation of affected tissue. Though a serious injury, it is not very well understood, and further scientific exploration is needed. This work explores the current understanding of the pathophysiology of frostbite. We reviewed the current status of the diagnostics, the drugs, the therapies and the surgical practices for prevention and management of frostbite. Advances in nanotechnology and drug delivery had improved the therapeutic outcomes significantly. This review also explored the latest advancements and researches done for development of newer therapeutics and diagnostics for frostbite care.