Brown adipose tissue (BAT), an important regulator of thermogenic and metabolic processes, is considered a promising target to combat metabolic disorders. The neurotransmitter and hormone serotonin (5HT) is a major modulator of energy homeostasis, with its central and peripheral pools acting in opposing ways. To better understand how individual variations in 5HT homeostasis influence the thermogenic functionality of BAT, we used a rat model consisting of two sublines with constitutively increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, developed by selective breeding for platelet 5HT parameters. We have shown that animals with constitutively low 5HT activity maintained at a standard housing temperature (22 °C) have greater interscapular BAT (iBAT) mass and higher iBAT metabolic activity (as evidenced by measurements of iBAT temperature and glucose uptake), accompanied by increased iBAT mRNA expression of key thermogenic genes, compared to animals with high 5HT tone. In response to further thermogenic challenges-intermittent cold exposure or treatment with a β3-adrenergic agonist-5HT sublines show several functional and molecular differences linking constitutively low endogenous 5HT tone to higher BAT activity/capacity. Overall, the results support a role of 5-HT in the control of BAT thermogenesis They also suggest that individuals with lower 5HT activity may be more sensitive to β3-adrenergic drugs.

The adverse effects of ambient temperature on human health are receiving increasing attention, yet evidence of its impact on intracerebral hemorrhage (ICH) onset is limited. Here, the relationship between ambient temperature and ICH was evaluated. A time-stratified case-crossover analysis was performed based on 4051 ICH patients admitted to five stroke units in Tianjin between January 2014 and December 2020. Conditional logistic regression was applied to evaluate the associations between the daily mean temperature (Tm) or daily temperature range (DTR) and ICH onset. We found a negative association between Tm and ICH onset (OR = 0.977, 95% CI 0.968-0.987) but not between DTR and ICH onset. In stratified analyses, men and individuals aged ≥ 60 years were more susceptible to low-ambient temperature effects; corresponding adjusted ORs were 0.970 (95% CI 0.956-0.983) and 0.969 (95% CI 0.957-0.982), respectively. Tm significantly affected patients with deep ICH (OR = 0.976, 95% CI 0.965-0.988), but had no effect on lobar ICH. There was also seasonal heterogeneity in the effect of Tm on ICH onset, with Tm being negatively associated with ICH onset only in the warm season (OR = 0.961, 95% CI 0.941-0.982). Results suggest that the low-ambient temperature might trigger ICH onset, especially for the male and elderly population, providing important health guidance to prevent cold exposure-induced ICH.

The function and regulation of rapid-eye-movement (REM) sleep is a topic of ongoing debate. It is often assumed that REM sleep is a homeostatically regulated process and that a need for REM sleep builds up, either during prior wakefulness or during preceding slow wave sleep. In the current study, we tested this hypothesis in six diurnal tree shrews (Tupaia belangeri), small mammals closely related to primates. All animals were individually housed and kept under a 12:12 light-dark cycle with an ambient temperature of 24 °C. We recorded sleep and temperature in the tree shrews for 3 consecutive 24 h days. During the second night, we exposed the animals to a low ambient temperature of 4 °C, a procedure that is known to suppress REM sleep. Cold exposure caused a significant drop in brain temperature and body temperature and also resulted in a strong and selective suppression of REM sleep by 64.9%. However, contrary to our expectation, the loss of REM sleep was not recovered during the subsequent day and night. These findings in a diurnal mammal confirm that the expression of REM sleep is highly sensitive to environmental temperature but do not support the view that REM sleep is homeostatically regulated in this species.

Previous evidence has associated non-optimal ambient temperature with an increased risk of myocardial infarction. However, no studies have shown an association between ambient temperature and biomarkers in the myocardium. This study aimed to investigate the association of ambient temperature with creatine kinase MB (CK-MB) and creatine kinase (CK). A total of 94,784 men aged 20-50 years were included in this study. We performed blood biochemical tests on the participants and used the daily average temperature to represent ambient temperature. The daily average ambient temperature was calculated by hourly observational data from meteorological indicators in Beijing. Lag effects were observed within 0-7 days. General additive models were used to observe nonlinear associations of ambient temperature with CK-MB and CK. Linear models were used to fit the associations of cold or heat with CK-MB and CK, respectively, after confirming the inflection point of ambient temperature. The OR value of abnormal CK-MB (CK) for a 1 °C increase or decrease was calculated by logistic regression. In the results, a V-shaped relationship between CK-MB and ambient temperature and a linear relationship between CK and ambient temperature were observed. Cold exposure was associated with increased CK-MB and CK levels. For a 1 °C decrease, CK-MB increased by 0.044 U/L (95 % CI: 0.017, 0.070 U/L) at lag day 0, and CK increased by 1.44 U/L (0.44, 2.44 U/L) at lag day 4 (the lag day with the strongest effect). The OR of high CK-MB was 1.047 (1.017, 1.077) at lag day 0, and the OR of high CK was 1.066 (1.038, 1.095) at lag day 4 for a 1 °C decrease. No heat-related elevation of CK-MB or CK was observed. In general, cold exposure is associated with increased levels of CK-MB and CK in humans, which may be associated with myocardial injury. Our findings illustrate the possible adverse effects of cold exposure on the myocardium from a biomarker perspective.

The study aimed to determine the prevalence and incidence proportion of local cold injuries in northern Sweden, and identify associated factors. It was based on prospective data from surveys in 2015 and 2021 sent to a population-based sample in northern Sweden. Multiple binary logistic regression was performed. The study included 5,017 subjects (response rate 44.4%). The prevalence of cold injuries in the hands was 11.4%, feet 12.6%, and face 19.9%, while the incidence proportion was 1.0%, 1.0%, and 0.9%, respectively. Male gender was associated with incident cold injuries in the hands (OR 1.69; 95% CI 1.31-1.28), feet (OR 1.34; 95% CI 1.04-1.73), and face (OR 1.53; 95% CI 1.15-2.03); mental stress with cold injuries in the hands (OR 1.55; 95% CI 1.16-2.05) and feet (OR 1.39; 95% CI 1.04-1.88); previous stroke with cold injuries in the hands (OR 2.64; 95% CI 1.09-6.40) and face (OR 3.09; 95% CI 1.26-7.56); and Raynaud\'s phenomenon with cold injuries in the hands (OR 2.48; 95% CI 1.80-3.41) and feet (OR 2.07; 95% CI 1.50-2.87). We conclude that male gender, mental stress, previous stroke, and Raynaud\'s phenomenon increased the probability of contracting local cold injuries.

A pranayama-inspired breathing technique, cold exposure, and their combined application were assessed for their potential to reduce perceived stress in adults and compared to a control group. An experiment involving four groups was conducted, yielding separate cells for breathing technique-only and cold exposure-only, as well as a combined treatment and a control group. Eighty-six individuals participated in the study. Perceived stress is measured employing the 10-item version of the Perceived Stress Scale (PSS-10) and the 20-item version of the Perceived Stress Questionnaire (PSQ). The instruments exhibit a substantial correlation (r = 0.842, p < 0.001). The combined group exhibited a medium to large positive effect on perceived stress compared to the control group. The breathing technique and cold exposure on their own were not found to yield substantial effects, indicating synergies between both exercises. Combinations of breathing techniques and cold exposure may be employed to decrease individuals\' perceived stress.

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.

To determine if occupational exposure to cold environments is associated with incident airway symptoms in previously healthy workers.
A prospective, survey-based, closed-cohort study was conducted on a sample of 5017 men and women between 18 and 70 years of age, living in northern Sweden. Data on occupation, occupational and leisure-time cold exposure, airway symptoms, general health, and tobacco habits were collected during the winters of 2015 (baseline) and 2021 (follow-up). Stepwise multiple logistic regression was used to determine associations between baseline variables and incident airway symptoms.
For individuals working at baseline, without physician-diagnosed asthma or chronic obstructive pulmonary disease, reporting any occupational cold exposure was associated with incident wheeze (OR 1.41; 95% CI 1.06-1.87) and incident productive cough (OR 1.37; 95% CI 1.06-1.77), but not incident long-standing cough (OR 0.98; 95% CI 0.74-1.29), after adjusting for age, body mass index, daily smoking, and occupational physical workload. Detailed analysis of the occupational cold exposure rating did not reveal clear exposure-response patterns for any of the outcomes.
Occupational cold exposure was robustly associated with incident wheeze and productive cough in previously healthy workers. This adds further support to the notion that cold air is harmful for the airways, and that a structured risk assessment regarding occupational cold exposure could be considered for inclusion in the Swedish workplace legislation. Further studies are needed to elaborate on exposure-response functions, as well as suggest thresholds for hazardous cold exposure.

BACKGROUND: Cinnamomum cassia Presl (Rougui) has character of xin、gan、wen, belongs to Jing of heart、lung、bladder, and has the effect of dispersing cold and relieving pain. It is widely used to resolve the exterior and dissipate cold in Treatise on Febrile Diseases (Shang Han Lun), such as Chaihu Guizhi Ganjiang Tang and Guizhi Renshen Tang. Both these two prescriptions contain Cinnamomum cassia Presl and Zingiber officinale Rosc (Ganjiang). Rougui-Ganjiang herb-pair (RGHP) can warm viscera and remove cold, which is widely used in Shang Han Lun. And in modern times, recent studies have showed that cinnamon and ginger also have the effect of thermogenesis and regulating the body temperature, respectively.
OBJECTIVE: To maintain the body thermal homeostasis and prevent cold invasion of main organs, in this study, we assessed the underlying physiological changes induced by RGHP in mice exposed to -20 °C and explored the mechanisms for the thermogenic actions of RGHP in brown adipose tissue (BAT) by network pharmacology and molecular docking.
METHODS: Male Kunming (KM) mice were fed normal diet with orally administration of distilled water or ethanol RGHP extract (three doses: 375,750 and 1500 mg/kg) for 21 days, once per day and then exposed to -20 °C for 2 h. The core temperature, activity ability and the degree of frostbite in mice, morphological and ATP content of adipocytes were measured. In addition, the network pharmacology was employed to predict the targets of RGHP\' s thermogenesis effect on BAT. Pathway analysis and biological process with key genes was carried out through KEGG and GO analysis, respectively. Furthermore, the core ingredients and targets obtained by network pharmacology were verified by molecular docking and Western blot assays.
RESULTS: RGHP can significantly increase the core body temperature, reduce the degree of frostbite and enhance the activity ability of mice after cold exposure. Meanwhile, it can also improve the lipid morphology and decrease ATP production in BAT. A network pharmacology-based analysis identified 246 ingredients from RGHP (two herbs), which related to 222 target genes. There were 8 common genes between 222 compounds target genes and 62 thermogenesis associated target genes, which linked to 49 potential compounds. There are 24 ingredients which degree are greater than the average. Among them, we found that oleic acid, EIC, 6-gingerol, eugenol, isohomogenol and sitogluside could be detected in mice plasma. The cAMP-PPAR signaling pathway was enriched for thermogenesis after KEGG analysis with 8 genes. Molecular docking analysis and Western blot assay further confirmed that oleic acid, 6-gingerol, eugenol and isohomogenol were potential active ingredients for RGHP\'s heat production effect. And UCP1, PGC-1α, PPARα and PPARγ are key thermogenesis proteins.
CONCLUSIONS: RGHP treatment can significantly maintain the rectal temperature of mice by enhancing the BAT heat production. RGHP exhibited the heat production effect, which might be mainly attributed to increasing thermogenesis through the cAMP-PPAR signaling pathway in cold exposure mice. Oleic acid, 6-gingerol, eugenol and isohomogenol might be considered the potential therapeutic ingredients which affect the key targets of thermogenesis effect.

Cold sensitivity, a common and disabling sequela of hand injury, can be assessed using the Cold Intolerance Symptom Severity (CISS) questionnaire, rating symptoms on a scale from 4 to 100. The primary objective of this study was to define a clinical cut-off for abnormal cold sensitivity based on the CISS score in a healthy working-age population. The secondary objective was to investigate how age, gender and previous injuries and diseases influence CISS scoring. In this study, 1239 out of 1582 selected healthy subjects of working age living in northern Sweden completed the questionnaire, yielding a response rate of 78%. The 95th percentile for the CISS score was 49.5 for men and 53.0 for women. The effects of age, gender and previous injuries and diseases were minor and not considered clinically relevant. The results support that a CISS score above 50 should be considered as abnormal cold sensitivity.Level of evidence: III.