Analysis of natural killer cell functions in patients with hereditary hemochromatosis

Hereditary hemochromatosis (HH) is an autosomal-recessive disorder of the iron metabolism. Patients are typically affected by dysregulated iron levels, which can lead to iron accumulation within essential organs, such as liver, heart and pancreas. Furthermore, many HH patients are also afflicted by several immune defects and increased occurrence of autoimmune diseases that are linked to human homeostatic iron regulator protein (HFE) in the immune response. Here we examined immune cell phenotype and function in 21 HH patients compared to 21 healthy controls with a focus on Natural Killer (NK) cells. We observed increased basal and stimulated production of pro-inflammatory cytokines such as IL-1β or IL-18 in HH patients compared to healthy controls. However, we did not find major changes in the phenotype, the amount or the cytotoxic function of NK cells in HH patients. Instead, our data show a general decrease in the total number of granulocytes in HH patients (2774 ± 958 per μl versus 3457 ± 1122 per μl in healthy controls). These data demonstrate that NK cells of HH patients are not significantly affected and that the patients’ treatment by regular phlebotomy is sufficient to avoid systemic iron overload and its consequences to the immune system

Definição de faixas de conforto e desconforto térmico para espaços abertos em Curitiba, PR, com o índice UTCI

O planejamento e a readequação urbana de espaços abertos são capazes de promover a melhoria das condições térmicas externas, influenciando positivamente o uso de espaços abertos. Neste contexto, foi realizada uma pesquisa para analisar o conforto térmico de transeuntes em ruas de pedestre em Curitiba, Paraná. Este artigo tem como objetivo definir faixas de conforto e desconforto térmico para Curitiba, propondo tais faixas para o índice UTCI (Universal Thermal Climate Index) para as condições climáticas locais a partir de um percentual aceitável de pessoas insatisfeitas com o ambiente térmico no espaço aberto. Para tal, foram analisados dados climáticos e dados pessoais obtidos por meio de monitoramento de campo em ruas de pedestre. Conclui-se que o índice UTCI teve boa capacidade preditiva para a amostra analisada e que as diferenças entre os subgrupos gênero, idade e índice de massa corpórea eram pequenas. A partir das análises das respostas reais de sensação térmica sugerem-se as seguintes faixas de conforto/desconforto térmico: desconforto para o frio, Ta ≤ 15°C; conforto, 15°C < Ta < 24°C e desconforto para o calor, Ta ≥ 24°C. A análise do índice UTCI mostrou a necessidade de calibração das faixas, sendo sugeridas as seguintes faixas para situações climáticas similares às de Curitiba: desconforto para o frio, Ta ≤ 15°C; conforto, 15°C < Ta < 27°C e desconforto para o calor, Ta ≥ 27°C

Sex differences in temperature-related all-cause mortality in the Netherlands

Purpose: Over the last few decades, a global increase in both cold and heat extremes has been observed with significant impacts on human mortality. Although it is well-identified that older individuals (> 65 years) are most prone to temperature-related mortality, there is no consensus on the effect of sex. The current study investigated if sex differences in temperature-related mortality exist in the Netherlands. Methods: Twenty-three-year ambient temperature data of the Netherlands were combined with daily mortality data which were subdivided into sex and three age classes (< 65 years, 65–80 years, ≥ 80 years). Distributed lag non-linear models were used to analyze the effect of ambient temperature on mortality and determine sex differences in mortality attributable to the cold and heat, which is defined as mean daily temperatures below and above the Minimum Mortality Temperature, respectively. Results: Attributable fractions in the heat were higher in females, especially in the oldest group under extreme heat (≥ 97.5th percentile), whilst no sex differences were found in the cold. Cold- and heat-related mortality was most prominent in the oldest age group (≥ 80 years) and to a smaller extent in the age group between 65–80 years. In the age group < 65 years temperature-related mortality was only significant for males in the heat. Conclusion: Mortality in the Netherlands represents the typical V- or hockey-stick shaped curve with a higher daily mortality in the cold and heat than at milder temperatures in both males and females, especially in the age group ≥ 80 years. Heat-related mortality was higher in females than in males, especially in the oldest age group (≥ 80 years) under extreme heat, whilst in the cold no sex differences were found. The underlying cause may be of physiological or behavioral nature, but more research is necessary

The evaluation of biothermal conditions for various forms of climatic therapy based on UTCI adjusted for activity

The objective of this study was to assess biothermal conditions in the selected Polish health resorts for specific forms of climatic therapy. We calculated Universal Thermal Climate Index (UTCI) for ten-year period (2008-2017) and then added adjustment terms, taking into account changes in metabolic rates during various physical activities from resting to vigorous exercise. The adjusted UTCI values increased with rising activity, implying that warmer parts of the year were unsuitable for intensive forms of climatotherapy. These results demonstrate that the UTCI adjustment procedure provides well-balanced assessments of bioclimatic conditions for the purpose of climatic treatment considering the level of activity

Do one-hour exposures provide a valid assessment of physiological heat strain?

For time- and cost-efficient heat stress assessment procedures at workplaces or in experimental studies, short-time measurement periods (e.g. 1 h) are sometimes employed in lieu of whole shift observations assuming that the short time period will provide valid figures of equilibrium physiological responses. We studied the influence of exposure duration on physiological heat strain considering the modifying effects of clothing and heat acclimation using a database of 564 climatic chamber exposures performed by 28 young males under heat stress conditions with widely varying air temperature and humidity levels. We compared heart rates, rectal and mean skin temperatures, and sweat rates recorded after 1 h with the values averaged over the third hour of exposure representing steady-state. One-hour measurements agreed with equilibrium values for rather low strain levels only, with heart rates below 100 bpm and rectal temperatures below 37.2 °C. On average, one-hour values underestimated all heat strain parameters. This underestimation error was only moderately influenced by clothing and heat acclimation status, but increased significantly with air temperature and humidity, reaching considerable magnitude under hot-humid conditions associated with elevated heat strain. Regression analyses of the prediction error depending on the equilibrium response revealed that underestimation increased with equilibrium strain level. This correlation was strongest for heart rate and core temperature, and was shown to potentially cause a misclassification of hazardous working conditions as safe by given heat strain criteria. PRACTICAL RELEVANCE: The severe underestimation of heat strain due to short measurement periods, as observed under hot-humid conditions and/or when associated with high physiological strain, will immediately impact the exposed personnel, but will also inform occupational health professionals and standard writers regarding the heat stress assessment for work shifts with high activity levels or with protective clothing

Temperature–Humidity-Dependent Wind Effects on Physiological Heat Strain of Moderately Exercising Individuals Reproduced by the Universal Thermal Climate Index (UTCI)

Increasing wind speed alleviates physiological heat strain; however, health policies have advised against using ventilators or fans under heat wave conditions with air temperatures above the typical skin temperature of 35 °C. Recent research, mostly with sedentary participants, suggests mitigating the effects of wind at even higher temperatures, depending on the humidity level. Our study aimed at exploring and quantifying whether such results are transferable to moderate exercise levels, and whether the Universal Thermal Climate Index (UTCI) reproduces those effects. We measured heart rates, core and skin temperatures, and sweat rates in 198 laboratory experiments completed by five young, semi-nude, heat-acclimated, moderately exercising males walking the treadmill at 4 km/h on the level for three hours under widely varying temperature–humidity combinations and two wind conditions. We quantified the cooling effect of increasing the wind speed from 0.3 to 2 m/s by fitting generalized additive models predicting the physiological heat stress responses depending on ambient temperature, humidity, and wind speed. We then compared the observed wind effects to the assessment performed by the UTCI. Increasing the wind speed lowered the physiological heat strain for air temperatures below 35 °C, but also for higher temperatures with humidity levels above 2 kPa water vapor pressure concerning heart rate and core temperature, and 3 kPa concerning skin temperature and sweat rate, respectively. The UTCI assessment of wind effects correlated positively with the observed changes in physiological responses, showing the closest agreement (r = 0.9) for skin temperature and sweat rate, where wind is known for elevating the relevant convective and evaporative heat transfer. These results demonstrate the potential of the UTCI for adequately assessing sustainable strategies for heat stress mitigation involving fans or ventilators, depending on temperature and humidity, for moderately exercising individuals

Accuracy of metabolic rate estimates from heart rate under heat stress—an empirical validation study concerning ISO 8996

The standard ISO 8996 provides methods for the determination of metabolic rate from measured oxygen consumption (MVO2), as well as simplified estimation algorithms based on heart rate (MHR). We quantified the accuracy of these methods by comparing MHR with MVO2 measured in 373 climatic chamber experiments under different workloads and widely varying heat stress conditions. While our results confirmed the 5% accuracy level for MVO2, MHR considerably overestimatedMVO2 due to the rise in core temperature concomitantly increasing heart rate by approximately 30 bpm/°C resulting in an overall error of 43%. After individually correcting for this bias the accuracy was 10–15% as stipulated by the standard. Thus, methods correcting for the thermal component of heart rate, e.g. by introducing intermittent resting periods of sufficient length of at least five min when investigating heat stress at workplaces, should become a mandatory element in the ongoing revision of the relevant standards

Heat Acclimation Does Not Modify Q10 and Thermal Cardiac Reactivity

Heat acclimation (HA) is an essential modifier of physiological strain when working or exercising in the heat. It is unknown whether HA influences the increase of energy expenditure (Q10 effect) or heart rate (thermal cardiac reactivity TCR) due to increased body temperature. Therefore, we studied these effects using a heat strain database of climatic chamber experiments performed by five semi-nude young males in either non-acclimated or acclimated state. Measured oxygen consumption rate (VO2), heart rate (HR), and rectal temperature (Tre) averaged over the third hour of exposure were obtained from 273 trials in total. While workload (walking 4 km/h on level) was constant, heat stress conditions varied widely with air temperature 25–55°C, vapor pressure 0.5–5.3 kPa, and air velocity 0.3–2 m/s. HA was induced by repeated heat exposures over a minimum of 3 weeks. Non-acclimated experiments took place in wintertime with a maximum of two exposures per week. The influence of Tre and HA on VO2 and HR was analyzed separately with mixed model ANCOVA. Rising Tre significantly (p &lt; 0.01) increased both VO2 (by about 7% per degree increase of Tre) and HR (by 39–41 bpm per degree Tre); neither slope nor intercept depended significantly on HA (p &gt; 0.4). The effects of Tre in this study agree with former outcomes for VO2 (7%/°C increase corresponding to Q10 = 2) and for HR (TCR of 33 bpm/°C in ISO 9886). Our results indicate that both relations are independent of HA with implications for heat stress assessment at workplaces and for modeling heat balance