Chronic Toxoplasma gondii Infection Modulates Hearing Ability across the Adult Life Span.

While several studies have shown associations between hearing disorders and congenital toxoplasmosis, the present study investigated the impact of chronic, latent Toxoplasma gondii (T. gondii) infection on hearing loss. We used a regression analysis to explore whether latent T. gondii infection modulates changes in hearing thresholds over an age range from 20 to 70 years. We analyzed audiometric data of 162 T. gondii IgG-positive and 430 T. gondii-negative participants, collected in the Dortmund Vital Study (DVS, ClinicalTrials.gov Identifier: NCT05155397), a prospective study on healthy cognitive aging. The regression analysis indicated that latent toxoplasmosis was associated with an accelerated development in hearing loss over the observed age range. Hearing loss was less frequent in IgG-positive than in IgG-negative participants up to the age of about 40 for a low (0.125-1 kHz)-frequency range. For high (2-8 kHz) frequencies, this pattern reversed for ages above 65 years. We discuss these findings on hearing function in the context of a recently proposed model, suggesting that latent toxoplasmosis can differentially affect brain functions across a lifespan.

From Immunosenescence to Aging Types-Establishing Reference Intervals for Immune Age Biomarkers by Centile Estimation.

Immunological aging type definition requires establishing reference intervals from the distribution of immunosenescence biomarkers conditional on age. For 1605 individuals (18-97 years), we determined the comprehensive immune age index IMMAX from flow-cytometry-based blood cell sub-populations and identified age-specific centiles by fitting generalized additive models for location, scale, and shape. The centiles were uncorrelated with age and facilitated the categorization of individuals as immunologically slow or fast aging types. Using its 50th percentile as a reference, we rescaled the IMMAX to equivalent years of life (EYOL) and computed the immunological age gap as the difference between EYOL and chronological age. Applied to preliminary baseline and follow-up measurements from 53 participants of the Dortmund Vital Study (Clinical-Trials.gov Identifier: NCT05155397), the averaged changes in the IMMAX and EYOL conformed to the 5-year follow-up period, whereas no significant changes occurred concerning IMMAX centiles and age gap. This suggested that the participants immunologically adapted to aging and kept their relative positions within the cohort. Sex was non-significant. Methodical comparisons indicated that future confirmatory analyses with the completed follow-up examinations could rely on percentile curves estimated by simple linear quantile regression, while the selection of the immunosenescence biomarker will greatly influence the outcome, with IMMAX representing the preferable choice.

Early expansion of activated adaptive but also exhausted NK cells during acute severe SARS-CoV-2 infection.

The analysis of immunological parameters during the course of a SARS-CoV-2 infection is of great importance, both to identify diagnostic markers for the risk of a severe course of COVID-19, and to better understand the role of the immune system during the infection. By using multicolor flow cytometry we compared the phenotype of Natural Killer (NK) cells from hospitalized COVID-19 patients during early SARS-CoV-2 infection with samples from recovered and SARS-CoV-2 naïve subjects. Unsupervised high-dimensional analysis of 28-color flow cytometric data revealed a strong enrichment of NKG2C expressing NK cells in response to the acute viral infection. In addition, we found an overrepresentation of highly activated NK cell subsets with an exhausted phenotype. Moreover, our data show long-lasting phenotypic changes within the NK cell compartment that did not completely reverse up to 2 months after recovery. This demonstrates that NK cells are involved in the early innate immune response against SARS-CoV-2.

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.

A Systematic Analysis of Biological, Sociodemographic, Psychosocial, and Lifestyle Factors Contributing to Work Ability Across the Working Life Span: Cross-sectional Study.

BACKGROUND: As employees age, their physical and mental abilities decline and work ability decreases, enhancing the risk for long-term sick leave or even premature retirement. However, the relative impact of biological and environmental determinants on work ability with increasing age is poorly understood in terms of their complexity. OBJECTIVE: Previous research has shown relationships between work ability and job and individual resources, as well as specific demographic and lifestyle-related variables. However, other potentially important predictors of work ability remain unexplored, such as personality traits and biological determinants, including cardiovascular, metabolic, immunological, and cognitive abilities or psychosocial factors. Our aim was to systematically evaluate a wide range of factors to extract the most crucial predictors of low and high work ability across the working life span. METHODS: As part of the Dortmund Vital Study, 494 participants from different occupational sectors, aged between 20 and 69 years, completed the Work Ability Index (WAI) assessing employee's mental and physical resources. A total of 30 sociodemographic variables were grouped into 4 categories (social relationships, nutrition and stimulants, education and lifestyle, and work related), and 80 biological and environmental variables were grouped into 8 domains (anthropometric, cardiovascular, metabolic, immunologic, personality, cognitive, stress related, and quality of life) and have been related to the WAI. RESULTS: Using the analyses, we extracted important sociodemographic factors influencing work ability, such as education, social activities, or sleep quality, and identified age-dependent and age-independent determinants of work ability. Regression models explained up to 52% of the WAI variance. Negative predictors of work ability were chronological and immunological age, immunological inefficiency, BMI, neuroticism, psychosocial stress, emotional exhaustion, demands from work, daily cognitive failures, subclinical depression, and burnout symptoms. Positive predictors were maximum heart rate during ergometry, normal blood pressure, hemoglobin and monocyte concentration, weekly physical activity, commitment to the company, pressure to succeed, and good quality of life. CONCLUSIONS: The identified biological and environmental risk factors allowed us to evaluate work ability in its complexity. Policy makers, employers, and occupational safety and health personnel should consider the modifiable risk factors we identified to promote healthy aging at work through focused physical, dietary, cognitive, and stress-reduced preventive programs, in addition to well-balanced working conditions. This may also increase the quality of life, commitment to the job, and motivation to succeed, which are important factors to maintain or even enhance work ability in the aging workforce and to prevent early retirement. TRIAL REGISTRATION: ClinicalTrials.gov NCT05155397; https://clinicaltrials.gov/ct2/show/NCT05155397. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32352.

A modelling framework for local thermal comfort assessment related to bicycle helmet use.

Thermal discomfort due to accumulated sweat increasing head skin wettedness may contribute to low wearing rates of bicycle helmets. Using curated data on human head sweating and helmet thermal properties, a modelling framework for the thermal comfort assessment of bicycle helmet use is proposed. Local sweat rates (LSR) at the head were predicted as the ratio to the gross sweat rate (GSR) of the whole body or by sudomotor sensitivity (SUD), the change in LSR per change in body core temperature (Δtre). Combining those local models with Δtre and GSR output from thermoregulation models, we simulated head sweating depending on the characteristics of the thermal environment, clothing, activity, and exposure duration. Local thermal comfort thresholds for head skin wettedness were derived in relation to thermal properties of bicycle helmets. The modelling framework was supplemented by regression equations predicting the wind-related reductions in thermal insulation and evaporative resistance of the headgear and boundary air layer, respectively. Comparing the predictions of local models coupled with different thermoregulation models to LSR measured at the frontal, lateral and medial head under bicycle helmet use revealed a large spread in LSR predictions predominantly determined by the local models and the considered head region. SUD tended to overestimate frontal LSR but performed better for lateral and medial head regions, whereas predictions by LSR/GSR ratios were lower and agreed better with measured frontal LSR. However, even for the best models root mean squared prediction errors exceeded experimental SD by 18-30%. From the high correlation (R > 0.9) of skin wettedness comfort thresholds with local sweating sensitivity reported for different body regions, we derived a threshold value of 0.37 for head skin wettedness. We illustrate the application of the modelling framework using a commuter-cycling scenario, and discuss its potential as well as the needs for further research.

Calibrating a Comprehensive Immune Age Metric to Analyze the Cross Sectional Age-Related Decline in Cardiorespiratory Fitness.

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging, as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20-70 years from the 'Dortmund Vital Study' (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age, while adjusting our analysis for the influence of sex, obesity, and the level of regular physical activity, by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

Indicators to assess physiological heat strain - Part 1: Systematic review.

In a series of three companion papers published in this Journal, we identify and validate the available thermal stress indicators (TSIs). In this first paper of the series, we conducted a systematic review (registration: INPLASY202090088) to identify all TSIs and provide reliable information regarding their use (funded by EU Horizon 2020; HEAT-SHIELD). Eight databases (PubMed, Agricultural and Environmental Science Collection, Web of Science, Scopus, Embase, Russian Science Citation Index, MEDLINE, and Google Scholar) were searched from database inception to 15 April 2020. No restrictions on language or study design were applied. Of the 879 publications identified, 232 records were considered for further analysis. This search identified 340 instruments and indicators developed between 200 BC and 2019 AD. Of these, 153 are nomograms, instruments, and/or require detailed non-meteorological information, while 187 can be mathematically calculated utilizing only meteorological data. Of these meteorology-based TSIs, 127 were developed for people who are physically active, and 61 of those are eligible for use in occupational settings. Information regarding the equation, operating range, interpretation categories, required input data, as well as a free software to calculate all 187 meteorology-based TSIs is provided. The information presented in this systematic review should be adopted by those interested in performing on-site monitoring and/or big data analytics for climate services to ensure appropriate use of the meteorology-based TSIs. Studies two and three in this series of companion papers present guidance on the application and validation of these TSIs, to guide end users of these indicators for more effective use.

Indicators to assess physiological heat strain - Part 2: Delphi exercise.

In a series of three companion papers published in this Journal, we identify and validate the available thermal stress indicators (TSIs). In this second paper of the series, we identified the criteria to consider when adopting a TSI to protect individuals who work in the heat, and we weighed their relative importance using a Delphi exercise with 20 experts. Two Delphi iterations were adequate to reach consensus within the expert panel (Cronbach's α = 0.86) for a set of 17 criteria with varying weights that should be considered when adopting a TSI to protect individuals who work in the heat. These criteria considered physiological parameters such as core/skin/mean body temperature, heart rate, and hydration status, as well as practicality, cost effectiveness, and health guidance issues. The 17 criteria were distributed across three occupational health-and-safety pillars: (i) contribution to improving occupational health (55% of total importance), (ii) mitigation of worker physiological strain (35.5% of total importance), and (iii) cost-effectiveness (9.5% of total importance). Three criteria [(i) relationship of a TSI with core temperature, (ii) having categories indicating the level of heat stress experienced by workers, and (iii) using its heat stress categories to provide recommendations for occupational safety and health] were considered significantly more important when selecting a TSI for protecting individuals who work in the heat, accumulating 37.2 percentage points. These 17 criteria allow the validation and comparison of TSIs that presently exist as well as those that may be developed in the coming years.

Impact of Biological and Lifestyle Factors on Cognitive Aging and Work Ability in the Dortmund Vital Study: Protocol of an Interdisciplinary, Cross-sectional, and Longitudinal Study.

BACKGROUND: Previous research revealed several biological and environmental factors modulating cognitive functioning over a human's lifespan. However, the relationships and interactions between biological factors (eg, genetic polymorphisms, immunological parameters, metabolic products, or infectious diseases) and environmental factors (eg, lifestyle, physical activity, nutrition, and work type or stress at work) as well as their impact on cognitive functions across the lifespan are still poorly understood with respect to their complexity. OBJECTIVE: The goal of the Dortmund Vital Study is to validate previous hypotheses as well as generate and validate new hypotheses about the relationships among aging, working conditions, genetic makeup, stress, metabolic functions, the cardiovascular system, the immune system, and mental performance over the human lifespan with a focus on healthy working adults. The Dortmund Vital Study is a multidisciplinary study involving the Departments of Ergonomics, Immunology, Psychology and Neurosciences, and Toxicology at the Leibniz Research Centre for Working Environment and Human Factors at the Technical University of Dortmund (IfADo) in Germany, as well as several national and international partners. METHODS: The Dortmund Vital Study is designed as a combined cross-sectional and longitudinal study. Approximately 600 healthy subjects aged between 20 and 70 years will participate. A wide range of demographic, psychological, behavioral, sensory, cardiovascular, immunological, and biochemical data, a comprehensive electroencephalography (EEG)-based cognitive test battery as well as structural and functional magnetic resonance imaging (MRI) have been included in the study. RESULTS: The study was approved by the Ethics Committee of IfADo in October 2015. The baseline testing was conducted between 2016 and 2021 and will be repeated every 5 years (3 follow-up measures until 2035). As of March 2020 (until the outbreak of the COVID-19 pandemic), 593 participants have been enrolled. Some results from the cross-sectional part of the study were already published, further results will be published soon. Longitudinal data will be analyzed and published by 2025. CONCLUSIONS: We anticipate that the study will shed light on sources of interindividual differences in the alterations of cognitive functioning with increasing age and reveal biological and lifestyle markers contributing to work ability, longevity, and healthy aging on the one hand, and to risk factors for cognitive decline, mild cognitive impairment, or even dementia on the other hand. TRIAL REGISTRATION: ClinicalTrials.gov NCT05155397; https://clinicaltrials.gov/ct2/show/NCT05155397. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32352.

Neutralizing antibody responses 300 days after SARS-CoV-2 infection and induction of high antibody titers after vaccination.

Neutralizing antibodies against SARS-CoV-2 are important to protect against infection and/or disease. Using an assay to detect antibodies directed against the receptor binding domain (RBD) of SARS-CoV-2 Spike, we identified individuals with SARS-CoV-2 infection after an outbreak at a local health institution. All but one COVID-19 patient developed detectable anti-RBD antibodies and 77% had virus neutralizing antibody titers of >1:25. Antibody levels declined slightly over time. However, we still detected virus neutralizing antibody titers in 64% of the COVID-19 patients at >300 days after infection, demonstrating durability of neutralizing antibody levels after infection. Importantly, full COVID-19 vaccination of these individuals resulted in higher antibody titers compared to fully vaccinated individuals in the absence of prior infection. These data demonstrate long-lived antibody-mediated immunity after SARS-CoV-2 infection, and a clear benefit of two vaccine doses for recovered individuals.

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.

Results of the Optimune trial: A randomized controlled trial evaluating a novel Internet intervention for breast cancer survivors.

INTRODUCTION: After the acute treatment phase, breast cancer patients often experience low quality of life and impaired mental health, which could potentially be improved by offering cognitive behavioural therapy (CBT) and addressing exercise and dietary habits. However, CBT and other behavioural interventions are rarely available beyond the acute treatment phase. Internet-based interventions could bridge such treatment gaps, given their flexibility and scalability. In this randomized controlled trial (RCT), we investigated the effects of such an intervention ("Optimune") over three months. METHODS: This RCT included 363 female breast cancer survivors (age range = 30-70), recruited from the community, who had completed the active treatment phase. Inclusion criteria were: breast cancer diagnosis less than 5 years ago and acute treatment completion at least 1 month ago. Participants were randomly assigned to (1) an intervention group (n = 181), in which they received care as usual (CAU) plus 12-month access to Optimune immediately after randomization, or (2) a control group (n = 182), in which they received CAU and Optimune after a delay of 3 months. Primary endpoints were quality of life (QoL), physical activity, and dietary habits at three months. We hypothesized that intervention group participants would report better QoL, more physical activity, and improved dietary habits after 3 months. RESULTS: Intention-to-treat (ITT) analyses revealed significant effects on QoL (d = 0.27, 95% CI: 0.07-0.48) and dietary habits (d = 0.36, 95% CI: 0.15-0.56), but the effect on physical exercise was not significant (d = 0.30; 95% CI: 0.10-0.51). DISCUSSION: These findings suggest the effectiveness of Optimune, a new CBT-based Internet intervention for breast cancer survivors, in facilitating improvements in quality of life and dietary habits. Efforts to disseminate this intervention more broadly may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03643640. Registered August 23rd 2018, https://clinicaltrials.gov/ct2/show/NCT03643640.

Low self-reported stress despite immune-physiological changes in paramedics during rescue operations.

Despite the high stress levels, paramedics seem to ignore or even negate the stress. This can be detrimental and lead to stress-related diseases. Therefore, we investigated the divergence between physiological and psychological stress responses of paramedics. Participants were 16 paramedics and 17 white-collar workers. We assessed psychological stress parameters, cortisol awakening response (CAR), and quantified immune parameters. In paramedics, electrocardiogram (ECG) was measured during one complete 24-hour shift. Our results revealed that CAR was higher in paramedics compared to controls. An alteration of immune parameters was observed even during days of free time. Also, ECG recordings showed acute stress in paramedics during rescue situations. Questionnaires revealed that rescue-service specific stressors affect psychological outcomes. However, paramedics reported significantly less mental stress and higher levels of depersonalization than controls. Taken together, our results suggest higher stress in paramedics compared to controls. However, paramedics negate their daily stress. Our findings underline therefore the importance to develop stress-management interventions for paramedics including sensitization for their stress reactions.

Impact of biometeorological conditions and air pollution on influenza-like illnesses incidence in Warsaw.

In order to assess the influence of atmospheric conditions and particulate matter (PM) on the seasonally varying incidence of influenza-like illnesses (ILI) in the capital of Poland-Warsaw, we analysed time series of ILI reported for the about 1.75 million residents in total and for different age groups in 288 approximately weekly periods, covering 6 years 2013-2018. Using Poisson regression, we predicted ILI by the Universal Thermal Climate Index (UTCI) as biometeorological indicator, and by PM2.5 and PM10, respectively, as air quality measures accounting for lagged effects spanning up to 3 weeks. Excess ILI incidence after adjusting for seasonal and annual trends was calculated by fitting generalized additive models. ILI morbidity increased with rising PM concentrations, for both PM2.5 and PM10, and with cooler atmospheric conditions as indicated by decreasing UTCI. While the PM effect focused on the actual reporting period, the atmospheric influence exhibited a more evenly distributed lagged effect pattern over the considered 3-week period. Though ILI incidence adjusted for population size significantly declined with age, age did not significantly modify the effect sizes of both PM and UTCI. These findings contribute to better understanding environmental conditionings of influenza seasonality in a temperate climate. This will be beneficial to forecasting future dynamics of ILI and to planning clinical and public health resources under climate change scenarios.

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-1ß 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.

Long Term Adaptation to Heat Stress: Shifts in the Minimum Mortality Temperature in the Netherlands.

It is essentially unknown how humans adapt or will adapt to heat stress caused by climate change over a long-term interval. A possible indicator of adaptation may be the minimum mortality temperature (MMT), which is defined as the mean daily temperature at which the lowest mortality occurs. Another possible indicator may be the heat sensitivity, i.e., the percentage change in mortality per 1°C above the MMT threshold, or heat attributable fraction (AF), i.e., the percentage relative excess mortality above MMT. We estimated MMT and heat sensitivity/AF over a period of 23 years for older adults (≥65 years) in the Netherlands using three commonly used methods. These methods are segmented Poisson regression (SEG), constrained segmented distributed lag models (CSDL), and distributed lag non-linear models (DLNM). The mean ambient temperature increased by 0.03°C/year over the 23 year period. The calculated mean MMT over the 23-year period differed considerably between methods [16.4 ± 1.2°C (SE) (SEG), 18.9 ± 0.5°C (CSDL), and 15.3 ± 0.4°C DLNM]. MMT increased during the observed period according to CSDL (0.11 ± 0.05°C/year) and DLNM (0.15 ± 0.02°C/year), but not with SEG. The heat sensitivity, however, decreased for the latter method (0.06%/°C/year) and did not change for CSDL. Heat AF was calculated for the DLNM method and decreased with 0.07%/year. Based on these results we conclude that the susceptibility of humans to heat decreases over time, regardless which method was used, because human adaptation is shown by either an increase in MMT (CSDL and DLNM) or a decrease in heat sensitivity for unchanged MMT (SEG). Future studies should focus on what factors (e.g., physiological, behavioral, technological, or infrastructural adaptations) influence human adaptation the most, so it can be promoted through adaptation policies. Furthermore, future studies should keep in mind that the employed method influences the calculated MMT, which hampers comparability between studies.

Quantitative analysis of human NK cell reactivity using latex beads coated with defined amounts of antibodies.

Natural Killer (NK) cell responses are regulated by a variety of different surface receptors. While we can determine the overall positive or negative effect of a given receptor on NK cell functions, investigating NK cell regulation in a quantitative way is challenging. To quantitatively investigate individual receptors for their effect on NK cell activation, we chose to functionalize latex beads that have approximately the same size as lymphocytes with defined amounts of specific antibodies directed against distinct activating receptors. This enabled us to investigate NK cell reactivity in a defined, clean, and controllable system. Only CD16 and NKp30 could activate the degranulation of resting human NK cells. CD16, NKG2D, NKp30, NKp44, and NKp46 were able to activate cultured NK cells. NK cell activation resulted in the induction of polyfunctional cells that degranulated and produced IFN-γ and MIP-1ß. Interestingly, polyfunctional NK cells were only induced by triggering ITAM-coupled receptors. NKp44 showed a very sensitive response pattern, where a small increase in receptor stimulation caused maximal NK cell activity. In contrast, stimulation of 2B4 induced very little NK cell degranulation, while providing sufficient signal for NK cell adhesion. Our data demonstrate that activating receptors differ in their effectiveness to stimulate NK cells.

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.