Effects of heat and personal protective equipment on thermal strain in healthcare workers: part B-application of wearable sensors to observe heat strain among healthcare workers under controlled conditions.

PURPOSE: As climate change accelerates, healthcare workers (HCW) are expected to be more frequently exposed to heat at work. Heat stress can be exacerbated by physical activity and unfavorable working requirements, such as wearing personal protective equipment (PPE). Thus, understanding its potential negative effects on HCW´s health and working performance is becoming crucial. Using wearable sensors, this study investigated the physiological effects of heat stress due to HCW-related activities. METHODS: Eighteen participants performed four experimental sessions in a controlled climatic environment following a standardized protocol. The conditions were (a) 22 °C, (b) 22 °C and PPE, (c) 27 °C and (d) 27 °C and PPE. An ear sensor (body temperature, heart rate) and a skin sensor (skin temperature) were used to record the participants´ physiological parameters. RESULTS: Heat and PPE had a significant effect on the measured physiological parameters. When wearing PPE, the median participants' body temperature was 0.1 °C higher compared to not wearing PPE. At 27 °C, the median body temperature was 0.5 °C higher than at 22 °C. For median skin temperature, wearing PPE resulted in a 0.4 °C increase and higher temperatures in a 1.0 °C increase. An increase in median heart rate was also observed for PPE (+ 2/min) and heat (+ 3/min). CONCLUSION: Long-term health and productivity risks can be further aggravated by the predicted temperature rise due to climate change. Further physiological studies with a well-designed intervention are needed to strengthen the evidence for developing comprehensive policies to protect workers in the healthcare sector.

Evaluation of long-term data on surface contamination by antineoplastic drugs in pharmacies.

PURPOSE: The handling of antineoplastic drugs represents an occupational health risk for employees in pharmacies. To minimize exposure and to evaluate cleaning efficacy, wipe sampling was used to analyze antineoplastic drugs on surfaces. In 2009, guidance values were suggested to facilitate the interpretation of results, leading to a decrease in surface contamination. The goal of this follow-up was to evaluate the time trend of surface contamination, to identify critical antineoplastic drugs and sampling locations and to reassess guidance values. METHODS: Platinum, 5-fluorouracil, cyclophosphamide, ifosfamide, gemcitabine, methotrexate, docetaxel and paclitaxel were analyzed in more than 17,000 wipe samples from 2000 to 2021. Statistical analysis was performed to describe and interpret the data. RESULTS: Surface contaminations were generally relatively low. The median concentration for most antineoplastic drugs was below the limit of detection except for platinum (0.3 pg/cm2). Only platinum and 5-fluorouracil showed decreasing levels over time. Most exceedances of guidance values were observed for platinum (26.9%), cyclophosphamide (18.5%) and gemcitabine (16.6%). The most affected wipe sampling locations were isolators (24.4%), storage areas (17.6%) and laminar flow hoods (16.6%). However, areas with no direct contact to antineoplastic drugs were also frequently contaminated (8.9%). CONCLUSION: Overall, the surface contaminations with antineoplastic drugs continue to decrease or were generally at a low level. Therefore, we adjusted guidance values according to the available data. The identification of critical sampling locations may help pharmacies to further improve cleaning procedure and reduce the risk of occupational exposure to antineoplastic drugs.

Blood lead levels in 2018/2019 compared to 1987/1988 in the German population-based KORA study.

INTRODUCTION: Lead exposure remains of continuing concern due to its known and suspected impacts on human health and has been designated as a priority substance for investigation in human biomonitoring studies by the EU. The aims of this study were to measure blood lead levels (BLL) in a population based cohort of middle-aged individuals without major current exposures to lead, and to compare these to historical blood lead levels obtained thirty years earlier. METHODS: The population-based KORA study from 1984 to 2001 included inhabitants of the Augsburg Region, Germany. During 2018 to 2019, a subsample of these participants (KORA-Fit) was invited for interview regarding demographic and lifestyle factors, physical examination and blood withdrawal. Blood samples were stored at -80C prior to measurement of BLL via graphite furnace atomic absorption spectroscopy (GF-AAS). Descriptive and multivariable analyses were performed. RESULTS: BLLs were measured in 3033 eligible persons aged 54 to 73, establishing a geometric mean (GM) BLL of 24.8 µg/l in 2018/19. Of these, 555 (18%) had BLL above proposed 95th percentile reference values of the German Environment Agency. Only small differences were found in BLL stratified by sociodemographic categories, however regular smokers had higher GM BLL (26.1 µg/l) compared to never smokers (23.7 µg/l), and an increasing BLL with increased wine consumption was noted. For 556 individuals, BLLs (GM: 54.0 µg/l) reduced by 35% in men and 50% in women compared to levels in 1987/88 with only 1.4% of individuals having an unchanged or increased BLL. DISCUSSION: KORA-Fit provided contemporary normative data for BLL in a Western European population without major current sources of lead exposure. Mean BLLs have fallen since the 1980s using historical BLL data which is likely linked to the ban of leaded gasoline. Nevertheless, BLLs in this population remain elevated at levels associated with morbidity and mortality.

Effect of experimental exposures to 3-D printer emissions on nasal allergen responses and lung diffusing capacity for inhaled carbon monoxide/nitric oxide in subjects with seasonal allergic rhinitis.

3-D printers are widely used. Based on previous findings, we hypothesized that their emissions could enhance allergen responsiveness and reduce lung diffusing capacity. Using a cross-over design, 28 young subjects with seasonal allergic rhinitis were exposed to 3-D printer emissions, either from polylactic acid (PLA) or from acrylonitrile butadiene styrene copolymer (ABS), for 2 h each. Ninety minutes later, nasal allergen challenges were performed, with secretions sampled after 1.5 h. Besides nasal functional and inflammatory responses, assessments included diffusing capacity. There was also an inclusion day without exposure. The exposures elicited slight reductions in lung diffusing capacity for inhaled nitric oxide (DLNO ) that were similar for PLA and ABS. Rhinomanometry showed the same allergen responses after both exposures. In nasal secretions, concentrations of interleukin 6 and tumor necrosis factor were slightly reduced after ABS exposure versus inclusion day, while that of interleukin 5 was slightly increased after PLA exposure versus inclusion.

Exposure to cisplatin in the operating room during hyperthermic intrathoracic chemotherapy.

PURPOSE: Hyperthermic intrathoracic chemotherapy (HITOC) is an additive, intraoperative treatment for selected malignant pleural tumors. To improve local tumor control, the thoracic cavity is perfused with a cisplatin-containing solution after surgical cytoreduction. Since cisplatin is probably carcinogenic to humans, potential contamination of surfaces and pathways of exposure should be systematically investigated to enable risk assessments for medical staff and thus derive specific recommendations for occupational safety. METHODS: Wipe sampling was performed at pre-selected locations during and after ten HITOC procedures, including on the surgeon's gloves, for the quantitation of surface contaminations with cisplatin. After extraction of the samples with hydrochloric acid, platinum was determined as a marker for cisplatin by voltammetry. RESULTS: High median concentrations of cytostatic drugs were detected on the surgeons' (1.73 pg Cis-Pt/cm2, IQR: 9.36 pg Cis-Pt/cm2) and perfusionists' (0.69 pg Cis-Pt/cm2, IQR: 1.73 pg Cis-Pt/cm2) gloves. The display of the perfusion device showed partially elevated levels of cisplatin up to 4.92 pg Cis-Pt/cm2 and thus could represent an origin of cross-contamination. In contrast, cisplatin levels on the floor surfaces in the area of the surgeon and the perfusion device or in the endobronchial tube were relatively low. CONCLUSION: With a correct use of personal protective equipment and careful handling, intraoperative HITOC appears to be safe to perform with a low risk of occupational exposure to cisplatin.

Mercury biomonitoring in German adults using volumetric absorptive microsampling.

Mercury (Hg) is a global pollutant and a danger to human health. Human biomonitoring of Hg using a dried blood matrix instead of venous blood sampling for exposure assessment is of growing interest. This study aims to develop, validate, and evaluate the application of volumetric absorptive microsampling (VAMS) for Hg biomonitoring in humans. Sampling, drying, and storage conditions were evaluated during method development. Storage in pre-cleaned glass vials after drying for 2 h in a desiccator ensured analyte stability for at least 4 weeks. Sixty-eight paired capillary VAMS and venous blood samples from volunteers in Munich, Germany, were used for method validation. Hg levels in VAMS and venous blood samples were determined by direct mercury analysis. The limits of detection and quantitation for VAMS were 0.18 and 0.61 µg/l, respectively. However, sensitivity could be improved by using two microsamples for analysis instead of one. Hg levels in VAMS samples correlated very well with Hg levels in venous blood samples (R2 = 0.958). Furthermore, VAMS showed a high accuracy (median recovery: 117%) and precision (median relative standard deviation: 8.7%), especially for Hg concentrations above 1.0 µg/l. In fact, accuracy and precision of VAMS improved with increasing Hg concentrations. In conclusion, VAMS in combination with direct mercury analysis is an accurate and viable alternative for human biomonitoring of Hg.

Advanced glycation end products in human diabetic lens capsules.

Advanced glycation end products (AGEs) accumulate with age in human lens capsules. AGEs in lens capsules potentiate the transforming growth factor beta-2-mediated mesenchymal transition of lens epithelial cells, which suggests that they play a role in posterior capsule opacification after cataract surgery. We measured AGEs by liquid chromatography-mass spectrometry in capsulorhexis specimens obtained during cataract surgery from nondiabetic and diabetic patients with and without established retinopathy. Our data showed that the levels of most AGEs (12 out of 13 measured) were unaltered in diabetic patients and diabetic patients with retinopathy compared to nondiabetic patients. There was one exception: glucosepane, which was significantly higher in diabetic patients, both with (6.85 pmol/µmol OH-proline) and without retinopathy (8.32 pmol/µmol OH-proline), than in nondiabetic patients (4.01 pmol/µmol OH-proline). Our study provides an explanation for the similar incidence of posterior capsule opacification between nondiabetic and diabetic cataract patients observed in several studies.

Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro.

Proteins in the eye lens have negligible turnover and therefore progressively accumulate chemical modifications during aging. Carbonyls and oxidative stresses, which are intricately linked to one another, predominantly drive such modifications. Oxidative stress leads to the loss of glutathione (GSH) and ascorbate degradation; this in turn leads to the formation of highly reactive dicarbonyl compounds that react with proteins to form advanced glycation end products (AGEs). The formation of AGEs leads to the crosslinking and aggregation of proteins contributing to lens aging and cataract formation. To inhibit AGE formation, we developed a disulfide compound linking GSH diester and mercaptoethylguanidine, and we named it carboxitin. Bovine lens organ cultured with carboxitin showed higher levels of GSH and mercaptoethylguanidine in the lens nucleus. Carboxitin inhibited erythrulose-mediated mouse lens protein crosslinking, AGE formation and the formation of 3-deoxythreosone, a major ascorbate-derived AGE precursor in the human lens. Carboxitin inhibited the glycation-mediated increase in stiffness in organ-cultured mouse lenses measured using compressive mechanical strain. Delivery of carboxitin into the lens increases GSH levels, traps dicarbonyl compounds and inhibits AGE formation. These properties of carboxitin could be exploited to develop a therapy against the formation of AGEs and the increase in stiffness that causes presbyopia in aging lenses.

Implementation of mercury biomonitoring in German adults using dried blood spot sampling in combination with direct mercury analysis.

Venous blood is a preferred matrix for the determination of total mercury (Hg) in human biomonitoring but has some drawbacks such as the requirement for an uninterrupted cold chain for transport and storage and the need of medical personnel for sample collection. Therefore, we tested and implemented a simpler and less expensive method for measuring Hg in human blood using dried blood spots (DBS). For method development, we investigated the influence of different storage conditions (temperature, storage vessel, time) on DBS samples. For method validation, we compared DBS and venous blood and investigated whether DBS sampling is suitable for measuring Hg in the general population in countries with low Hg exposure such as Germany. Based on our results, we found that pre-cleaned glass tubes were most suitable for storage of DBS samples, as this allowed the samples to remain stable for at least 4 weeks even at high temperatures (40 °C). When comparing venous blood and DBS, a very good correlation (r = 0.95, p < 0.01, Spearman-Rho) and high precision of DBS (mean relative standard deviation 8.2% vs. 7.2% in venous blood samples) were observed. Comparing the recoveries of both matrices in different concentration ranges, the variation of the recoveries decreases with increasing Hg concentration. The mean recoveries also decreased with increasing Hg concentration. Overall, we found comparable results for DBS and venous blood using direct Hg analysis. Furthermore, we demonstrated that DBS are suitable for Hg biomonitoring in the general population in Germany and improved the storage conditions for the DBS.

Lysine malonylation and propionylation are prevalent in human lens proteins.

Acylated lysine residues represent major chemical modifications in proteins. We investigated the malonylation and propionylation of lysine residues (MalK, PropK) in the proteins of aging human lenses. Western blot results showed that the two modifications are present in human lens proteins. Liquid chromatography-mass spectrometry (LC-MS/MS) results showed 4-18 and 4-32 pmol/mg protein of MalK and PropK, respectively, in human lens proteins with no apparent changes related to aging. Mass spectrometry results revealed that MalK- and PropK-modified lysine residues are present in all major crystallins, other cytosolic proteins, and membrane and cytoskeletal proteins of the lens. Several mitochondrial and cytosolic proteins in cultured human lens epithelial cells showed MalK and PropK modifications. Sirtuin 3 (SIRT3) and sirtuin 5 (SIRT5) were present in human lens epithelial and fiber cells. Moreover, lens epithelial cell lysate deacylated propionylated and malonylated lysozyme. The absence of SIRT3 and SIRT5 led to higher PropK and MalK levels in mouse lenses. Together, these data suggest that MalK and PropK are widespread modifications in lens and SIRT3 and SIRT5 could regulate their levels in lens epithelial cells.

Health-related quality of life (EQ-5D + C) among people living in artisanal and small-scale gold mining areas in Zimbabwe: a cross-sectional study.

BACKGROUND: In Zimbabwe, an estimated 500,000 people work in the sector of artisanal and small-scale gold mining (ASGM). Two million Zimbabweans are dependent on this sector. Using mercury is common to extract gold from ore. Long term exposure to mercury can cause various adverse health conditions including chronic mercury intoxication. The influence of these adverse health effects on the health-related quality of life (HRQoL) is still unknown. The aim of this study is to assess the HRQoL of people who identify themselves as miners, and to analyze potential influencing factors, such as age, years of working with mercury and health conditions caused by mercury exposure. METHODS: This cross-sectional study assessed the HRQoL using the standardized EQ-5D + C (3 L) questionnaire and collected human specimens (blood, urine) of people living and possibly working in ASGM areas in Zimbabwe. Factors such as age, years of working with mercury and adverse health conditions possibly caused by mercury exposure were analyzed with regards to their influence on the HRQoL. RESULTS: The 207 participants (82% male, mean age 38 years) reported 40 different health states. Of the study participants 42.5% reported to be in complete good health while 57.5% reported being unwell in different ways. Nine participants (4.3%) were identified with chronic mercury intoxication, whereas 92 participants (33.3%) had mercury levels above the "Alert" threshold in at least one specimen. Having chronic mercury intoxication has a significant negative influence on the HRQoL, when taking into account age, gender and years of working with mercury. Cognitive problems were the most reported in the questionnaire, however, the association between this domain separately and the HRQoL was not verified. CONCLUSION: This study shows that adverse health effects caused by chronic exposure to mercury, have a negative influence on the HRQoL among people living in ASGM areas.

Exposure assessment of toxic metals and organochlorine pesticides among employees of a natural history museum.

Chemical compounds such as arsenic, mercury and organochlorine pesticides have been extensively used as preventive and curative conservation treatments for cultural and biological collections to protect them from pest and mold infestations. Most of the aforementioned compounds have been classified as carcinogenic, mutagenic and teratogenic and represent a health risk for members of staff exposed to contaminated objects. The present study addresses the internal exposure of 28 museum employees in Museum für Naturkunde Berlin by measuring arsenic species and mercury in urine as well as hexachlorocyclohexane isomers (α-HCH, ß-HCH, γ-HCH), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (4,4'-DDT) and its main metabolite, dichlorodiphenyldichloroethylene (4,4'-DDE), and pentachlorophenol (PCP) in blood serum. This study was carried out in order to assess the internal exposure of Natural History Museum staff members to toxic metals and organochlorine pesticides. During a working week, two blood samples and five urine samples were taken from each participant, involving 8 women and 20 men. Information about work activity and exposure related factors such as dust development through work, use of personal protective equipment, as well as a nutrition diary were obtained through a questionnaire. Information on fish and seafood intakes as well as amalgam fillings was also available. The results of the study showed that the museum staff members had quantified concentrations of arsenic (median of 6.4 µg/l; maximum of 339 µg/l), mercury (median of 0.20 µg/l; max of 2.6 µg/l), ß-HCH (median of 0.12 µg/l; max of 0.39 µg/l) and 4,4'-DDT (median of 0.050 µg/l; max of 0.82 µg/l). Despite that all the concentrations were below the established reference values, multivariate regression models were able to show that museum staff members are currently exposed to the aforementioned compounds while handling museum objects. To validate our findings, further studies are required.

Artisanal and small-scale gold mining: A cross-sectional assessment of occupational mercury exposure and exposure risk factors in Kadoma and Shurugwi, Zimbabwe.

In artisanal and small-scale gold mining (ASGM) the toxic metal mercury is used for gold extraction. The objective of this cross-sectional study was to assess mercury concentrations in urine and blood and mercury-related symptoms of participants identifying themselves as miners from Kadoma and Shurugwi, Zimbabwe. Moreover, we aimed to explore possible risk factors influencing mercury body burden. In 2019, urine and blood samples of 207 participants were collected and analyzed for mercury using atomic absorption spectroscopy. All participants answered questions regarding their exposure risks. The median urine mercury value was 4.75 µg/L with a maximum of 612 µg/L. Median mercury concentration in creatinine corrected urine values was 3.98 µg/g with a maximum value of 478 µg/g. The median blood mercury value was 2.70 µg/L with a maximum of 167 µg/L. Correlations between exposure risks factors such as the lack of retort use and elevated mercury values were demonstrated. ASGM is very common in Zimbabwe. Thus, mercury exposure is a major occupational health risk for miners. Moreover, this study emphasizes the impact of exposure risk factors on the mercury body burden.

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

BACKGROUND: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury. METHODS: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts. RESULTS: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury. CONCLUSION: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose.

Succinylation Is a Gain-of-Function Modification in Human Lens αB-Crystallin.

Acylation of lysine residues is a common post-translational modification of cellular proteins. Here, we show that lysine succinylation, a type of acylation, occurs in human lens proteins. All of the major crystallins exhibited Nε-succinyllysine (SuccK) residues. Quantification of SuccK in human lens proteins (from donors between the ages of 20 and 73 years) by LC-MS/MS showed a range between 1.2 and 14.3 pmol/mg lens protein. The total SuccK levels were slightly reduced in aged lenses (age > 60 years) relative to young lenses (age < 30 years). Immunohistochemical analyses revealed that SuccK was present in epithelium and fiber cells. Western blotting and immunoprecipitation experiments revealed that SuccK is particularly prominent in αB-crystallin, and succinylation in vitro revealed that αB-crystallin is more prone to succinylation than αA-crystallin. Mass spectrometric analyses showed succinylation at K72, K90, K92, K166, K175, and potentially K174 in human lens αB-crystallin. We detected succinylation at K72, K82, K90, K92, K103, K121, K150, K166, K175, and potentially K174 by mass spectrometry in mildly succinylated αB-crystallin. Mild succinylation improved the chaperone activity of αB-crystallin along with minor perturbation in tertiary and quaternary structure of the protein. These observations imply that succinylation is beneficial to αB-crystallin by improving its chaperone activity with only mild conformational alterations.

Identification of Kynoxazine, a Novel Fluorescent Product of the Reaction between 3-Hydroxykynurenine and Erythrulose in the Human Lens, and Its Role in Protein Modification.

Kynurenine pathway metabolites and ascorbate degradation products are present in human lenses. In this study, we showed that erythrulose, a major ascorbate degradation product, reacts spontaneously with 3-hydroxykynurenine to form a fluorescent product. Structural characterization of the product revealed it to be 2-amino-4-(2-hydroxy-3-(2-hydroxyethyl)-2H-benzo[b][1,4]oxazin-5-yl)-4-oxobutanoic acid, which we named kynoxazine. Unlike 3-hydroxykynurenine, 3-hydroxykynurenine glucoside and kynurenine were unable to form a kynoxazine-like compound, which suggested that the aminophenol moiety in 3-hydroxykynurenine is essential for the formation of kynoxazine. This reasoning was confirmed using a model compound, 1-(2-amino-3-hydroxyphenyl)ethan-1-one, which is an aminophenol lacking the amino acid moiety of 3-hydroxykynurenine. Ultra-performance liquid chromatography-tandem mass spectrometry analyses showed that kynoxazine is present in the human lens at levels ranging from 0 to 64 pmol/mg lens. Kynoxazine as well as erythrulose degraded under physiological conditions to generate 3-deoxythreosone, which modified and cross-linked proteins through the formation of an arginine adduct, 3-deoxythreosone-derived hydroimidazolone, and a lysine-arginine cross-linking adduct, 3-deoxythreosone-derived hydroimidazolimine cross-link. Ultra-performance liquid chromatography-tandem mass spectrometry quantification showed that 32-169 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolone and 1.1-11.2 pmol/mg protein of 3-deoxythreosone-derived hydroimidazolimine cross-link occurred in aging lenses. Taken together, these results demonstrate a novel biochemical mechanism by which ascorbate oxidation and the kynurenine pathway intertwine, which could promote protein modification and cross-linking in aging human lenses.

Biomonitoring of lead in blood of children living in a former mining area in Lower Saxony, Germany.

Environmental exposure to lead substantially decreased over the past decades. However, soil of former mining areas still contains high lead levels. We therefore performed a biomonitoring study among children living in two former mining communities in Lower Saxony, Germany. In these communities, soil contains lead levels of 1000 to 30,000 mg/kg. Overall, 75 children (6-10 years of age) attending the two primary schools of the study area took part in the study. Parents completed a short questionnaire on sociodemographics, and children provided capillary whole blood samples. We analysed lead using inductively coupled plasma tandem mass spectrometer. We compared the results to current German (20 µg/l for boys, 15 µg/l for girls) and US (35 µg/l) reference values. Potential associations between questionnaire information and lead results were tested using lead as continuous outcome and using lead dichotomized at the reference values. Finally, we analysed spatial patterns of elevated biomonitoring results. Of all children, 48% exceeded the German reference values for lead (5% expected) and 8% the US reference value (2.5% expected). Children 6-8 years of age were more likely to exceed German reference values (63%) than 9-10 year old children were (32%; pFisher = 0.01). No other questionnaire information was statistically significantly associated with biomonitoring results. Additionally, we did not find any indication of spatial clustering. In conclusion, we observed elevated blood lead levels in primary school children living in a former mining area. In the next step, exposure pathways need to be identified to implement effective public health measures.

Assessment of subjective well-being of healthcare workers in response to heat and personal protective equipment under controlled conditions using a standardized protocol.

BACKGROUND: Due to climate change, the increasing frequency of hot summer days and heat waves can result in occupational heat strain, especially in non-air-conditioned workplaces. Healthcare workers (HCW) engaged in patient care are particularly affected, as they are additionally exposed to physical stress. The use of personal protective equipment (PPE) can aggravate heat strain in HCW. This study aimed to examine the subjective well-being of HCW when exposed to heat and PPE under controlled conditions. METHODS: This study was designed as a randomized crossover trial. Participants performed standardized healthcare tasks in a climatic chamber for approximately 3.5 h at different indoor temperatures (22 °C and 27 °C) and varied working conditions (with or without PPE). The effects on participants' subjective well-being, encompassing thermal, physiological and psychological stress were assessed using a customized questionnaire. RESULTS: Heat had a greater effect than PPE on thermal, physical and psychological stress. Conversely, PPE had a greater effect on physical demand and effort. For the majority of outcomes, combined exposure to heat and PPE resulted in the highest perceived discomfort. Furthermore, the participants reported increased sweating and other discomforts when working at elevated temperatures or with PPE. CONCLUSIONS: In this study, heat and PPE, but particularly the combination of both factors, were identified as unfavorable working environments. Although the trials were conducted in a controlled environment, the outcomes provide valuable information about the effect of heat and PPE on HCW in a real-life setting. Furthermore, the design used in this study can be beneficial in evaluating the effect of mitigation strategies.

Serum heat shock protein concentrations are not associated with amyotrophic lateral sclerosis risk or survival in three European populations.

Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (in Germany, Ireland, and Italy). Serum HSP concentrations were determined using enzyme-linked immunosorbent assay. Descriptive statistics, generalized logistic regression, and Cox proportional hazards models were used to model associations between log serum HSP concentrations and ALS risk. Results: In total, 251 ALS patients and 184 healthy volunteers were included. Logistic regression models failed to find associations between ALS risk and log serum concentration of HSP70 (OR 0.43, 95% CI: 0.10-1.78, p = 0.242), HSP90 (OR 0.95, 95% CI: 0.39-2.37, p = 0.904), or DNAJC7 (OR 1.55, 95% CI: 0.90-2.68, p = 0.118). Survival of ALS patients was not associated with log serum concentration of HSP HSP70 (HR1.06, 95% CI: 0.36-3.14, p = 0.916), HSP90 (HR 1.17, 95% CI: 0.67-2.02, p = 0.584), or DNAJC7 (HR 0.83, 95% CI: 0.57-1.21, p = 0.337). Discussion: We did not replicate previous findings that serum HSP70 and HSP90 concentrations were associated with risk of ALS. DNAJC7 was not associated with ALS risk, and there were no obvious longitudinal patterns in log serum concentrations of HSP70, HSP90, or DNAJC7. In addition, serum HSP concentrations were not associated with ALS survival.

The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy.

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.