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Herein, we provide a non-exhaustive selection of the main clinical trials presented in 2023-2024 related to radiation-oncology used in the treatment of urological cancers including prostate cancer (radiotherapy of localized prostate cancer, post-prostatectomy irradiation, reirradiation, biochemical recurrence following local treatment, radiotherapy for metastatic cancer), muscle invasive bladder cancer and primary kidney cancer., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To study the risk for eye diseases in individuals with Ulcerative Colitis (UC), and to assess whether silica dust-exposure could contribute to the development of inflammatory eye diseases., Methods: A case-control study was conducted using a patient register processed by the National Board of Health and Welfare (NBHW) and Statistics Sweden. Cases were diagnosed with UC between 2007 and 2016. Matching was done with two random controls having the same age, sex and county of residence, without a systemic inflammatory disease. Using a job-exposure matrix, cases and controls were assessed for work-related silica dust exposure. The risk for eye disease was estimated by Cox regression analysis with calculation of Hazard Ratio (HR)., Results: A total of 58 989 individuals were included, comprising 19 663 cases and 39 326 controls. The sex distribution was similar. Overall, individuals with UC had an increased risk for eye disease, specified in ICD 10 chapter VII (H00-H59) with HR 1.25 (CI 1.20-1.32). The highest HR on block-level for cases was 1.52 (CI 1.36-1.70), (H15-H22), which includes episcleritis, keratitis and anterior uveitis. The risk for ocular disease was higher in silica dust-exposed than non-exposed with a HR of 1.44 (CI 1.16-1.78) and 1.25 (CI 1.19-1.31), respectively. Among cases, the risk for iridocyclitis (H20) was further elevated by silica dust exposure, with HR of 3.84 (CI 1.64-8.97) in exposed compared to 1.94 (1.57-2.41) in non-exposed., Conclusion: UC is associated with an increased risk for eye diseases, including inflammatory conditions. Our findings highlight that silica dust-exposure may be of importance in the pathogenesis of uveitis., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Trichloramine is a disinfection by-product in chlorinated swimming pools. It can evaporate into the air and irritate eyes and airways among swimmers and pool workers. This study aimed to evaluate airborne concentrations of trichloramine in different types of indoor swimming pools. Altogether, 72 swimming pools across Sweden were included; 36 exercise pools, 16 instruction pools, seven adventure pools, and 13 rehabilitation pools. In total, 167 sampling sessions were performed with the majority ( N  = 91) conducted in public exercise pools. Repeated sampling sessions on different days were performed within all pool categories. Airborne trichloramine was measured stationary by the poolside using active sampling on quartz filters. In total, 434 air samples were collected. The geometric mean (GM) concentration of trichloramine for the exercise pools was 0.12 mg/m 3 (range GM pool : 0.02-0.29 mg/m 3 ) and for about 30% the GM pool exceeded the Swedish public health guideline value (0.2 mg/m 3 ). The geometric mean for instruction pools was 0.18 mg/m 3 and for adventure pools 0.20 mg/m 3 . Trichloramine concentrations were statistically significantly lower in rehabilitation pools (GM: 0.03 mg/m 3 ) compared with the other pool categories. A statistically significant effect of time of the day for sampling was found for the exercise and instruction pools, with higher trichloramine levels during evenings compared with mornings and afternoons. For the rehabilitation pools, trichloramine was significantly higher during the cold season compared with the warm season. Variability in trichloramine concentrations was attributed to between-pool as well as within-pool variances. The within-pool variability encourages a repeated sampling strategy to capture the variation between different days. These findings have implications for exposure assessment in epidemiological studies as well as for indoor air quality monitoring. Trichloramine can cause acute irritative effects at elevated levels, and since trichloramine concentrations may differ depending on the time of the day it is recommended that full-day stationary measurements are supplemented with short-term samplings to capture these variations.

Increased focus on renovating and maintaining the existing building stock is an integral part of the circular economy, however this might pose challenges to workers health. The aim of this study was to assess the renovation workers' exposure to inhalable dust, thoracic dust, respirable dust, and respirable crystalline silica (RCS). Personal aerosol samples were collected as full shift samples from 92 workers to a total of 407 samples. Fourteen locations around Oslo, Norway was visited for multiple days with repeated measurements of the same individual. Particulate matter from 3 aerosol fractions, respirable, thoracic, and inhalable, were analyzed gravimetrically, and the respirable fraction was analyzed for RCS by NIOSH 7500 method for X-ray diffraction (XRD) with low temperature plasma ashing sample preparation. The total measured concentrations of respirable dust (n = 192) had a geometric mean (GM) of 0.88 mg/m3, RCS concentrations (n = 182) had a GM of 0.040 mg/m3, thoracic dust (n = 131) had GM 2.4 mg/m3, and inhalable dust (n = 84) had a GM of 8.5 mg/m3. The maximum measured concentrations were 29 mg/m3, 3.2 mg/m3, 65 mg/m3, and 163 mg/m3, respectively. Workdays involving tasks such as mechanical demolition and clearing out demolished materials led to the highest exposure levels of both dust and RCS. However, other workers at the renovation sites were indirectly exposed to a considerable amount of RCS. This study revealed substantial exposure to both RCS and dust during renovation, and protective measures are warranted to reduce exposure levels in the industry., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: In the food manufacturing industry, exposure to inhalable aerosols contributes to respiratory illnesses such as occupational asthma and rhinitis. However, there is a lack of comprehensive exposure assessment studies. This study evaluated occupational exposure to inhalable aerosols in an instant powdered food manufacturing plant during work operations involving dried food and powders., Methods: In total, 50 workers from an instant powdered food manufacturing plant were recruited. Personal inhalable aerosol exposure measurements were taken for both full-shift and task-based activities. The concentrations of inhalable aerosols were analyzed to identify any variation within and across departments, as well as between seasons, handedness, and sex., Results: In total, 134 personal air samples were collected, and the particulate mass was determined gravimetrically. The concentrations of inhalable aerosols ranged from 0.1 to 27 mg/m 3 for full-shift exposure measurements and 3.1 to 73 mg/m 3 for task-based measurements. Statistically significant differences in mean aerosol concentrations were found across departments (A:B p  < 0.001, A:C p  < 0.05, B:C p  < 0.001) and between seasons ( p  < 0.001)., Conclusion: This study revealed high exposure to inhalable aerosols among workers, particularly those involved in manual weighing, mixing, and adding powders. The significant differences between departments highlight the specific activities contributing to increased inhalable aerosol concentrations. Seasonal variations were also evident, with autumn showing higher concentrations of inhalable aerosols in all departments compared with summer. These findings emphasize the importance of understanding the distribution of aerosol concentrations across different work tasks and departments, particularly during different seasons., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency.)

Human activities alter biomass, nutrient availability, and species dominance in grasslands, impacting their richness, composition, and biomass production. Stability (invariability in time or space) can inform the predictability of plant communities in response to human activities. However, this measure has been simplistically analyzed for temporal (interannual) changes in live biomass, disregarding their spatial stability and the temporal stability of other plant community attributes. Moreover, the simultaneous analysis of temporal and spatial stabilities of plant communities has been scarcely assessed. Here, we test how biomass removal and nutrient addition simultaneously modify the temporal and spatial stabilities of plant richness (α diversity), composition dissimilarity (β diversity), aboveground live biomass, and the role of plant species dominance in the stability responses. We conducted a factorial experiment of biomass removal (grazing, mowing, or intact -no removal-) and nutrient addition (unfertilized or fertilized with nitrogen, phosphorus, and potassium) in a temperate grassland of Argentina, South America. We replicated the experiment in 6 blocks over 10 years to estimate the temporal and spatial stabilities of the plant community. The spatiotemporal stability of plant richness and composition dissimilarity decreased in the intact grassland, while the temporal stability of live biomass increased, compared to the grazed and mowed grasslands. Nutrient addition reduced the spatiotemporal stability of live biomass and the spatial stability of plant richness. The stabilities of species richness as well as that of composition dissimilarity were negatively associated with plant dominance, while the live biomass stability was not. Our results suggest that simplifying the effect of biomass removal and nutrient addition on grassland stability is not feasible, as plant diversity stability responses are not surrogates for biomass stability. The contrasting spatiotemporal stability responses of plant diversity and biomass represent a step forward in predicting human activities' impact over time and across space in temperate grasslands., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hand-arm vibration is a common occupational exposure that causes neurological impairment, myalgia, and vibration-induced Raynaud's phenomena or vibration white fingers (VWF). The pathological mechanism is largely unknown, though several mechanisms have been proposed, involving both immunological vascular damage and defective neural responses. The aim of this study was to test whether the substances interleukin-33 (IL-33), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), endothelin-1 (ET-1), C-C motif chemokine ligand 20 (CCL20), calcitonin, and thromboxane (TXA 2 ) changed before and after occupational hand-arm vibration exposure. 38 full-time shift workers exposed to hand-arm vibration were recruited. All the participants underwent medical examinations regarding symptoms of Raynaud's phenomena. In 29 of the participants, the concentration of IL-33, MDC, IL-10, ET-1, CCL20, calcitonin, and TXA 2 was measured before and after a workday. There was a significant increase in ET-1 and calcitonin concentration and a decrease in the CCL20 concentration after the work shift in all participants. In the group suffering from VWF, but not in the non-VWF group, MDC was statistically significantly lower before the work shift ( p = .023). The VWF group also showed a significant increase in MDC after the work shift. Exposure to occupational hand-arm vibration is associated with changes in ET-1, calcitonin, and MDC concentration in subjects suffering from vibration white fingers, suggesting a role of these biomarkers in the pathophysiology of this condition., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated., Material and Methods: The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost., Results: A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both)., Conclusion: External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses., (Copyright © 2024 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The development of atopic dermatitis in infancy, and subsequent allergies, such as asthma in later childhood, is known as the atopic march. The mechanism is largely unknown, however the course of disease indicates an inter-epithelial crosstalk, through the onset of inflammation in the skin and progression to other mucosal epithelia. In this study, we investigated if and how skin-lung epithelial crosstalk contributes to the development of the atopic march. First, we emulated inter-epithelial crosstalk through indirect coculture of bioengineered atopic-like skin disease models and three-dimensional bronchial epithelial models triggering an asthma-like phenotype in the latter. A subsequent secretome analysis identified thrombospondin-1, CD44, complement factor C3, fibronectin, and syndecan-4 as potentially relevant skin-derived mediators. Because these mediators are extracellular matrix-related proteins, we then studied the involvement of the extracellular matrix, unveiling distinct proteomic, transcriptomic, and ultrastructural differences in atopic samples. The latter indicated extracellular matrix remodeling triggering the release of the above-mentioned mediators. In vivo mouse data showed that exposure to these mediators dysregulated activated circadian clock genes which are increasingly discussed in the context of atopic diseases and asthma development. Our data point toward the existence of a skin-lung axis that could contribute to the atopic march driven by skin extracellular matrix remodeling., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This cross-sectional study aims to obtain knowledge about workers' exposure to airborne dust, bacterial and fungal species, endotoxin, biofilm formation, and hydrogen sulfide (H2S) in drilling waste treatment plants. In total, 408 full-shift personal samples, 66 work areas, 40 drilling waste, and reference (outdoor air and seawater) samples were analyzed. Some workers were exposed to high levels of endotoxin (207 EU/m3), bacteria (3.8 × 104 colony forming units (CFU)/m3 and 9.8 × 104 DNA copies/m3), or fungi (1.4 × 107 CFU/m3 and 3,600 copies/m3). The exposure levels to endotoxin, bacteria, and peaks of H2S were dependent on the treatment technique. All types of drilling waste contained large concentrations of bacteria compared to the seawater references. Elevated concentrations of airborne bacteria were found close to drilling waste basins. In total, 116, 146, and 112 different bacterial species were found in workers' exposure, work areas, and the drilling waste, respectively. An overlap in bacterial species found in the drilling waste and air (personal and work area) samples was found. Of the bacterial species found, 49 are classified as human pathogens such as Escherichia coli, Enterobacter cloacae, and Klebsiella oxytoca. In total, 44 fungal species were found in the working environment, and 6 of these are classified as human pathogens such as Aspergillus fumigatus. In conclusion, across the drilling waste treatment plants, human pathogens were present in the drilling waste, and workers' exposure was affected by the drilling waste treated at the plants with elevated exposure to endotoxin and bacteria. Elevated exposure was related to working as apprentices or chemical engineers, and working with cleaning, or slop water, and working in the daytime., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Introduction: It is of upmost importance to contribute to fill the knowledge gap concerning the characterization of the occupational exposure to microbial agents in the waste sorting setting (automated and manual sorting)., Methods: This study intends to apply a comprehensive field sampling and laboratory protocol (culture based-methods and molecular tools), assess fungal azole resistance, as well as to elucidate on potential exposure related health effects (cytotoxicity analyses). Skin-biota samples (eSwabs) were performed on workers and controls to identify other exposure routes., Results: In personal filter samples the guidelines in one automated industry surpassed the guidelines for fungi. Seasonal influence on viable microbial contamination including fungi with reduced susceptibility to the tested azoles was observed, besides the observed reduced susceptibility of pathogens of critical priority (Mucorales and Fusarium sp.). Aspergillus sections with potential toxigenic effect and with clinical relevance were also detected in all the sampling methods., Discussion: The results regarding skin-biota in both controls´ and workers´ hands claim attention for the possible exposure due to hand to face/mouth contact. This study allowed concluding that working in automated and manual waste sorting plants imply high exposure to microbial agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Viegas, Eriksen, Gomes, Dias, Cervantes, Pena, Carolino, Twarużek, Caetano, Viegas, Graff, Afanou and Straumfors.)

Left ventricular assist device therapy for advanced heart failure is contraindicated if a patient lives in an unsafe environment and recent guidelines declare that "legal history is pertinent for determining personal constraints or financial responsibilities due to parole requirements, pending charges, and possible imprisonment," implying that incarceration would be a contraindication. International guidelines and precedent in the United States establish that medical care for incarcerated persons should match access in the community. We present a case example and practical considerations for advanced heart failure programs faced with the challenge of partnering with patients with heart failure who may be incarcerated and their correctional health systems in the care of their chronic condition. We encourage the heart failure community to not let incarceration be a contraindication to left ventricular assist device therapy., Competing Interests: Conflict of Interest The authors have no relevant conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although the use of asbestos fibres in building materials has been prohibited in Norway since 1985, asbestos-containing materials (ACMs) are still found in many buildings. Lack of knowledge and awareness of these materials may lead to exposure during refurbishing. The aim of this study was to investigate the airborne fibre concentration and classify fibres found during the abatement of various ACMs. The release of fibres during short-term work tasks, such as drilling and sawing, was also investigated. Parallel air samples were collected during asbestos abetment of different building materials and analysed with scanning electron microscope (SEM) and phase-contrast microscope (PCM), respectively. Material samples were analysed with SEM. A real-time fibre monitor was used to measure asbestos during short-term work. The highest fibre concentrations were measured for samples collected during the removal of asbestos insulating boards (1.5-4.5 fibres/cm3 [f/cm3]), and the numbers were relatively similar for SEM and PCM. A large difference in asbestos concentrations was found between SEM and PCM when analysing floor materials, which were probably caused by a high number of gypsum fibres that the PCM operator counted. Thin fibres (<0.2 µm in width) were included in the SEM count and constituted up to 50% of the total fibre concentration for the asbestos cement materials. The presence of other inorganic and organic fibres on these samples probably led to similar results between SEM and PCM. Short-term work led to peak concentrations above 30 f/cm3., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Purpose: Occupational exposure to bioaerosols during waste handling remains a health concern for exposed workers. However, exposure-related health effects and underlying immunological mechanisms are still poorly described., Methods: The present study assessed the inflammatory potential of work-air samples (n = 56) in vitro and investigated biomarker expression in exposed workers (n = 69) compared to unexposed controls (n = 25). These quantitative results were compared to self-reported health conditions., Results: Personal air samples provoked an activation of TLR2 and TLR4 HEK reporter cells in one-third of all samples, indicating that the work environment contained ligands capable of inducing an immune response in vitro. Monocyte levels, as well as plasma biomarker levels, such as IL-1Ra, IL-18 and TNFα were significantly higher in exposed workers, compared to the control group when confounding factors such as BMI, sex, age and smoking habits were accounted for. Furthermore, a significant exposure-related increase in midweek IL-8 levels was measured among exposed workers. Tendencies of increased prevalence of health effects of the respiratory tract were identified in exposed workers., Conclusion: Inhalable dust provoked TLR activation in vitro, indicating that an exposure-related immune response may be expected in susceptible workers. However, despite significant differences in inflammatory plasma biomarker levels between exposed and unexposed workers, prevalence of self-reported health effects did not differ between the groups. This may be due to the healthy worker effect, or other factors such as adequate use of personal protective respiratory devices or adaptation to the work environment with reduced activation of the immune system., (© 2023. The Author(s).)

Introduction: Disinfection by-products are produced in water disinfected with chlorine-based products. One such group is trihalomethanes, and chloroform is the most abundant trihalomethane in swimming pool areas. Chloroform can be absorbed by inhalation, ingestion, and dermal absorption, and is classified as possibly carcinogenic., Aim: To investigate if chloroform concentrations in air and water affect the chloroform concentration in urine samples of exposed swimming pool workers., Methods: Workers from 5 adventure indoor swimming pools carried personal chloroform air samplers and provided up to 4 urine samples during one workday. Chloroform concentrations were analyzed with a linear mixed model analysis to investigate a possible correlation between air and urine concentrations., Results: The geometric mean chloroform concentration was 11 μg/m3 in air and 0.009 µg/g creatinine in urine among individuals with ≤2 h at work, 0.023 µg/g creatinine among those with >2-5 working hours, and 0.026 µg/g creatinine in the group with >5-10 working hours. A risk of higher levels of chloroform in urine was associated with longer hours at work (≤2 h versus >5-10 h, odds ratio [OR] 2.04, 95% confidence interval [CI] 1.25-3.34), personal chloroform concentrations in air (≤17.00 µg/m3 versus >28.00 µg/m3, OR 9.23, 95% CI 3.68-23.13) and working at least half the working day near the swimming pools (OR 3.16, 95% CI 1.33-7.55). Executing work tasks in the swimming pool water was not associated with higher chloroform concentrations in urine compared to only working on land (OR 0.82, 95% CI 0.27-2.45)., Conclusion: There is an accumulation of chloroform concentrations in urine during a workday and a correlation between personal air and urine concentrations of chloroform among workers in Swedish indoor swimming pools., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

This study assessed microorganisms in personal inhalable work air samples aiming to identify potential human pathogens, and correlate exposure to adverse health outcomes in waste workers. Full-shift personal exposure was measured in six different waste sorting plants. Microbial concentrations in inhalable air samples were analysed using MALDI-TOF MS for cultivable, and next generation sequencing (NGS) for non-cultivable microorganisms. Concentrations of bacterial and fungal CFUs varied substantially within and between waste sorting plants, ranging from no identifiable organisms to a maximum concentration in the order of 10 5  CFU/m 3 . Bacillus and Staphylococcus were among the most abundant bacterial genera, whilst fungal genera were dominated by Aspergillus and Penicillium. Approximately 15% of all identified species were human pathogens classified in risk group 2, whereas 7% belonged to risk group 1. Furthermore, significant correlations between concentrations of fungi in risk group 1 and self-reported adverse symptoms, such as wheezing were identified in exposed workers. The combination of culture-based methods and NGS facilitated the investigation of infectious microbial species with potential pathophysiological properties as well as non-infectious biological agents in inhalable work air samples and thereby contributed to the risk assessment of occupational exposure in waste sorting., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Vibration exposure from handheld tools can affect the hands with neurological symptoms and vibration-induced Raynaud's phenomenon (VRP). The underlying pathophysiological mechanisms are not fully known, however, changes in the composition of blood parameters may contribute to VRP with an increase in blood viscosity and inflammatory response. The aim of this study was to examine the effect on blood parameters in capillary blood from fingers that had been exposed to a vibrating hand-held tool. This study involved nine healthy participants who had been exposed to vibration and an unexposed control group of six participants. Capillary blood samples were collected before and after vibration exposure for the exposed group, and repeated samples also from the control group. The exposed groups were exposed to vibration for a 15-min period or until they reached a 5.0 m/s 2 vibration dose. Analysis of blood status and differential counting of leucocytes was performed on the capillary blood samples. The results of the blood samples showed an increase in mean value for erythrocyte volume fraction (EVF), hemoglobin, red blood cell count, white blood cell count and neutrophils, as well as a decrease of mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration. The increase of EVF and neutrophils was statistically significant for samples taken from the index finger but not the little finger. Even though the study was small it showed that an acute vibration exposure to the hands might increase EVF and neutrophilic granulocytes levels in the capillary blood taken from index fingers.

When the U.S. COVID-19 public health emergency declaration expires on May 11, 2023, national reporting of certain categories of COVID-19 public health surveillance data will be transitioned to other data sources or will be discontinued; COVID-19 hospitalization data will be the only data source available at the county level (1). In anticipation of the transition, national COVID-19 surveillance data sources and indicators were evaluated for purposes of ongoing monitoring. The timeliness and correlations among surveillance indicators were analyzed to assess the usefulness of COVID-19-associated hospital admission rates as a primary indicator for monitoring COVID-19 trends, as well as the suitability of other replacement data sources. During April 2022-March 2023, COVID-19 hospital admission rates from the National Healthcare Safety Network (NHSN) † lagged 1 day behind case rates and 4 days behind percentages of positive test results and COVID-19 emergency department (ED) visits from the National Syndromic Surveillance Program (NSSP). In the same analysis, National Vital Statistics System (NVSS) trends in the percentage of deaths that were COVID-19-associated, which is tracked by date of death rather than by report date, were observable 13 days earlier than those from aggregate death count data, which will be discontinued (1). During October 2020-March 2023, strong correlations were observed between NVSS and aggregate death data (0.78) and between the percentage of positive SARS-CoV-2 test results from the National Respiratory and Enteric Viruses Surveillance System (NREVSS) and COVID-19 electronic laboratory reporting (CELR) (0.79), which will also be discontinued (1). Weekly COVID-19 Community Levels (CCLs) will be replaced with levels of COVID-19 hospital admission rates (low, medium, or high) which demonstrated >99% concordance by county during February 2022-March 2023. COVID-19-associated hospital admission levels are a suitable primary metric for monitoring COVID-19 trends, the percentage of COVID-19 deaths is a timely disease severity indicator, and the percentages of positive SARS-CoV-2 test results from NREVSS and ED visits serve as early indicators for COVID-19 monitoring. Collectively, these surveillance data sources and indicators can support monitoring of the impact of COVID-19 and related prevention and control strategies as ongoing public health priorities., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

This manuscript presents the results of an exploratory study on the relationships between NF-κB response through Toll-like receptor (TLR) activation by dust characterized by fungal spore concentrations and species diversity. Personal total dust samples were collected from Norwegian waste sorting plants and then characterized for fungal spores and fungal species diversity, as well as for other bioaerosol components, including endotoxins and actinobacteria. The ability of the dust to induce an NF-κB response by activating TLR2 and TLR4 in vitro was evaluated, as well as the relationship between such responses and quantifiable bioaerosol components. The average concentrations of bioaerosols were 7.23 mg total dust m -3 , 4.49 × 10 5 fungal spores m -3 , 814 endotoxin units m -3 , and 0.6 × 10 5 actinobacteria m -3 . The mean diversity measurements were 326, 0.59, and 3.39 for fungal richness, evenness, and Shannon index, respectively. Overall, fungal operational taxonomic units (OTUs) belonging to the Ascomycota phylum were most abundant (55%), followed by Basidiomycota (33%) and Mucoromycota (3%). All samples induced significant NF-κB responses through TLR2 and TLR4 activation. While fungal spore levels were positively associated with TLR2 and TLR4 activation, there was a trend that fungal species richness was negatively associated with the activation of these receptors. This observation supports the existence of divergent immunological response relationships between TLR activation and fungal spore levels on one hand and between TLR activation and fungal species diversity on the other. Such relationships seem to be described for the first time for dust from waste facilities. IMPORTANCE This manuscript presents results on multifactorial characterization of bioaerosol exposure in Norwegian waste sorting plants and the potential of such airborne dust to induce NF-κB reactions through TLR2 and TLR4 activations in an in vitro reporter cell model system. Our data revealed that increasing fungal spore levels in the dust is associated with increased activation of TLR2 and TLR4, whereas increasing fungal OTU richness is associated with decreasing activation of these receptors. The NF-κB-induced responses by the collected dust represent, therefore, effective measures of potential key immunological effects induced by a complex mixture of hazardous components, including characterized factors such as endotoxins, fungal spores, bacteria, and many other uncharacterized components. The key immunological events reported here are suggested as holistic alternatives to today's bioaerosol exposure characterization approaches for epidemiological studies in the future.

Occupational exposure during waste sorting is associated with several health outcomes. This study obtained knowledge about the impact of work in fully automated waste sorting plants (AWSP; n = 3) vs manual waste sorting plants (MWSP; n = 3) on personal exposure (n = 71) to bioaerosols and exposure-related health effects. Personal full-shift air samples were collected using various filter-based active sampling devices that were placed in the workers' breathing zone. Personal exposure to inhalable and thoracic dust, endotoxin and microorganisms varied considerably between and within types of waste sorting plants (WSP). Workers at AWSP were on average exposed to 0.34 mg/m 3 inhalable dust, 0.15 mg/m 3 thoracic dust, and 51 EU/m 3 endotoxins (geometric mean (GM) levels), whereas GM exposure levels at MWSP were 0.66 mg/m 3 for inhalable dust, 0.44 mg/m 3 for thoracic dust, and 32 EU/m 3 for endotoxins. Exposure to submicronic fungal fragments did not differ between types of plants and ranged from levels below the detection limit (limit of detection, LOD) to levels in the order of 10 6 fragments/m 3 . Higher levels of fungal fragments and fungal spores were found at AWSP compared to MWSP with a GM of 2.1 × 10 5 spores/m 3 and with a GM of 1.2 × 10 5 spores/m 3 , respectively. Actinobacterial spores were found in samples from AWSP only, with exposure levels ranging from 1.9 × 10 4 to 1.1 × 10 7 spores/m 3 . Exposure to microbial DNA varied within and between WSP and was on average in the order of 10 4 copies/m 3 for fungi and 10 5 copies/m 3 for bacteria. Health symptoms, such as sneezing, congested nose and runny nose were significantly more common among exposed workers compared to the unexposed control group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Contamination of the environment with nano-and microplastic particles (NMPs) and its putative adverse effects on organisms, ecosystems, and human health is gaining increasing scientific and public attention. Various studies show that NMPs occur abundantly within the environment, leading to a high likelihood of human exposure to NMPs. Here, different exposure scenarios can occur. The most notable exposure routes of NMPs into the human body are via the airways and gastrointestinal tract (GIT) through inhalation or ingestion, but also via the skin due to the use of personal care products (PCPs) containing NMPs. Once NMPs have entered the human body, it is possible that they are translocated from the exposed organ to other body compartments. In our review article, we combine the current knowledge on the (1) exposure routes of NMPs to humans with the basic understanding of the potential (2) translocation mechanisms into human tissues and, consequently, their (3) fate within the human body. Regarding the (1) exposure routes, we reviewed the current knowledge on the occurrence of NMPs in food, beverages, personal care products and the air (focusing on indoors and workplaces) and found that the studies suggest an abundant presence of MPs within the exposure scenarios. The overall abundance of MPs in exposure matrices relevant to humans highlights the importance of understanding whether NMPs have the potential for tissue translocation. Therefore, we describe the current knowledge on the potential (2) translocation pathways of NMPs from the skin, GIT and respiratory systems to other body compartments. Here, particular attention was paid to how likely NMPs can translocate from the primary exposed organs to secondary organs due to naturally occurring defence mechanisms against tissue translocation. Based on the current understanding, we conclude that a dermal translocation of NMPs is rather unlikely. In contrast, small MPs and NPs can generally translocate from the GIT and respiratory system to other tissues. Thus, we reviewed the existing literature on the (3) fate of NMPs within the human body. Based on the current knowledge of the contamination of human exposure routes and the potential translocation mechanisms, we critically discuss the size of the detected particles reported in the fate studies. In some cases, the particles detected in human tissue samples exceed the size of a particle to overcome biological barriers allowing particle translocation into tissues. Therefore, we emphasize the importance of critically reading and discussing the presented results of NMP in human tissue samples., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive., Methods: Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used to validate ex vivo results., Results: We provide evidence that alveolar ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus. Instead, ex vivo infected human lungs and COVID-19 autopsy samples showed that alveolar macrophages were frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake and a related inflammatory and anti-viral activation, especially in "inflammatory alveolar macrophages", comparable to those induced by SARS-CoV and MERS-CoV, but different from NL63 or influenza virus infection., Conclusions: Collectively, our findings indicate that severe lung injury in COVID-19 probably results from a macrophage-triggered immune activation rather than direct viral damage of the alveolar compartment., Competing Interests: Conflict of interest: J-C. Rückert and H. Radbruch report support from DFG RA 2491/1-1, BMBF (Defeat Pandemics). A.E. Hauser reports support from Charité – Universitätsmedizin Berlin and Deutsches Rheuma-Forschungszentrum Berlin, and grants from Deutsche Forschungsgemeinschaft (HA5354/10-1, TRR130,P17 and C01, HA5354/8-1). T. Wolff reports support from Federal Ministry of Education and Research (BMBF) grant 01K12006F. M. Kessler reports grants from BMBF Organo-Strat, Einstein 3R. M. Dohmen reports contracts with Max-Delbrück Center, Berlin; grants from Gender Equality Fund, Berlin Institute of Health. F. Klauschen reports consulting fees, lecture honoraria, travel support and participation on advisory boards with BMS, Novartis, Roche and Lilly, and is a co-founder of AI-BIH/Charité-Spinoff Aignostics GmbH. F. Heppner reports consulting fees, lecture honoraria, payment for expert testimony and leadership roles at Novartis, AstraZeneca and ThinkHealth Hygiene Solutions. V.M. Corman reports the following patents: 20210190797 (Methods and reagents for diagnosis of SARS-CoV-2 infection); 9841834 (Human recombinant monoclonal antibody against SARS-CoV-2 spike glycoprotein); 9909654 (A pharmaceutical combination comprising an anti-viral protonophore and a serine protease inhibitor). D. Niemeyer reports that Technische Universität Berlin, Freie Universität Berlin and Charité – Universitätsmedizin have filed a patent application for siRNAs inhibiting SARS-CoV-2 replication with D. Niemeyer as coauthor. M.A. Müller reports the following patents: 20210190797 (Methods and reagents for diagnosis of SARS-CoV-2 infection); 9841834 (Human recombinant monoclonal antibody against SARS-CoV-2 spike glycoprotein); 9909654 (A pharmaceutical combination comprising an anti-viral protonophore and a serine protease inhibitor); and has participated on an advisory board for ECDC/WHO. S. Ludwig reports consulting fees from Atriva Therapeutics GmbH, Biontec SE; and has patent PCT/EP2021/063485 pending. M. Witzenrath reports grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Stiftung, Capnetz Stiftung, International Max Planck Research School, Quark Pharma, Takeda Pharma, Noxxon, Pantherna, Silence Therapeutics, Vaxxilon, Actelion, Bayer Health Care, Biotest and Boehringer Ingelheim; consulting fees from Noxxon, Pantherna, Silence Therapeutics, Vaxxilon, Aptarion, GlaxoSmithKline, Sinoxa and Biotest; lecture honoraria from AstraZeneca, Berlin Chemie, Chiesi, Novartis, Teva, Actelion, Boehringer Ingelheim, GlaxoSmithKline, Biotest, Bayer Health Care; and has the following patents issued: EPO 12181535.1 (IL-27 for modulation of immune response in acute lung injury), WO/2010/094491 (Means for inhibiting the expression of Ang-2), DE 102020116249.9 (Camostat/Niclosamide cotreatment in SARS-CoV-2 infected human lung cells). All other authors have nothing to disclose., (Copyright ©The authors 2022.)

Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive. Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify "gray areas" pertinent to the indication for PORT in this clinical setting. Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios. There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In 1998, an editorial from the International Journal of Radiation Oncology - Biology - Physics (IJROBP) on the occasion of the publication of Phase I by Zelefsky et al. on 3D radiotherapy dose escalation asked the question: "will more prove better?". More than 20 years later, several prospective studies have supported the authors' conclusions, making dose escalation a new standard in prostate cancer. The data from prospective randomized studies were ultimately disappointing in that they failed to show an overall survival benefit from dose escalation. However, there is a clear and consistent benefit in biochemical recurrence-free survival, which must be weighed on an individual patient basis against the potential additional toxicity of dose escalation. Techniques and concepts have become more and more precise, such as intensity modulated irradiation, simultaneous integrated boost, hypofractionated dose-escalation, pelvic irradiation with involved node boost or focal dose-escalation on gross recurrence after prostatectomy. The objective here was to summarize the prospective data on dose escalation in prostate cancer and in particular on recent advances in the field. In 2022, can we finally say that more has proven better?, (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objectives. This study aimed to investigate whether introducing a digital risk assessment tool, the Swedish National Vibration Database, would increase the number of risk assessments on hand-arm and whole-body vibration. Employer and safety representatives from companies where vibration exposure is common were invited. Methods. Of the 2953 invited companies, 1916 were selected for educational intervention and the remaining 1037 companies served as a control group with no intervention. For the educational intervention, participating companies were further divided into two groups (group A, n  = 26; group B, n  = 47) that both received information regarding risk assessment, but group B was also informed about the digital tool. Both groups answered a questionnaire on risk assessment before the intervention and at the follow-up, 6 months later; the control group received the same questionnaire but no education (group C, n  = 22). Results . Of the invited companies, only 2% chose to participate and 7% at follow-up. Seventy-eight percent of the participants had made some kind of risk assessment of vibration at follow-up. Conclusion. Due to the low participation rate among invited companies, this study is not able to draw any conclusions on whether the digital tool can be used to increase the number of risk assessments.

Ecological models predict that the effects of mammalian herbivore exclusion on plant diversity depend on resource availability and plant exposure to ungulate grazing over evolutionary time. Using an experiment replicated in 57 grasslands on six continents, with contrasting evolutionary history of grazing, we tested how resources (mean annual precipitation and soil nutrients) determine herbivore exclusion effects on plant diversity, richness and evenness. Here we show that at sites with a long history of ungulate grazing, herbivore exclusion reduced plant diversity by reducing both richness and evenness and the responses of richness and diversity to herbivore exclusion decreased with mean annual precipitation. At sites with a short history of grazing, the effects of herbivore exclusion were not related to precipitation but differed for native and exotic plant richness. Thus, plant species' evolutionary history of grazing continues to shape the response of the world's grasslands to changing mammalian herbivory., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Laser cutting is used in many industrial settings to achieve precise cuts of metal sheets. Laser operators may be exposed to particles formed during cutting when opening the cabinet or when metal sheets are exchanged. To characterise the potential exposure, particles formed during laser cutting were studied with scanning electron microscopy equipped with an energy dispersive X-ray detector and an energy backscatter diffraction detector. The total concentration of particles (11-615 nm) was determined online with a scanning mobility particle sizer. The chemical composition of the particles formed during the cutting of the different metal sheets was determined by inductively coupled plasma mass spectrometry (ICP-MS). X-ray diffraction was applied to determine the phase composition. The occupational exposure was assessed gravimetrically and by ICP-MS for five laser operators handling different laser cutters, and materials and were found to be low. Agglomerates and aggregates of condensation particles were formed during laser cutting, independent of the sheet type. Iron, present as both magnetite and α-Fe, was the main element found in the particles formed when cutting steel sheets. The size of the particles generated was mainly below 300 nm. Open laser cutters may lead to higher metal exposures, which is especially relevant when cutting metal sheets containing heavy metals.

Background and Purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group., Materials and Methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two., Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines., Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Parkinson's disease (PD) is a progressive neurodegenerative disease, whose main neuropathological finding is pars compacta degeneration due to the accumulation of Lewy bodies and Lewy neurites, and subsequent dopamine depletion. This leads to an increase in the activity of the subthalamic nucleus (STN) and the internal globus pallidus (GPi). Understanding functional anatomy is the key to understanding and developing new targets and new technologies that could potentially improve motor and non-motor symptoms in PD. Currently, the classical targets are insufficient to improve the entire wide spectrum of symptoms in PD (especially non-dopaminergic ones) and none are free of the side effects which are not only associated with the procedure, but with the targets themselves. The objective of this narrative review is to show new targets in DBS surgery as well as new technologies that are under study and have shown promising results to date. The aim is to give an overview of these new targets, as well as their limitations, and describe the current studies in this research field in order to review ongoing research that will probably become effective and routine treatments for PD in the near future.

Human skin equivalents emerged as novel tools in preclinical dermatological research. It is being claimed that they may bridge the translational gap between preclinical and clinical research, yet only a few studies have investigated their suitability for preclinical drug testing so far. Therefore, we investigated if inflammatory skin equivalents, which emulate hallmarks of atopic dermatitis (AD), are suitable to assess the anti-inflammatory effects of dexamethasone (DXM) in a cream formulation or loaded onto dendritic core-multishell nanoparticles. Topical DXM application resulted in significantly decreased expression of the proinflammatory cytokine TSLP, increased expression of the skin barrier protein involucrin, and facilitated glucocorticoid receptor translocation in a dose-dependent manner. Further, DXM treatment inhibited gene expression of extracellular matrix components, potentially indicative of the known skin atrophy-inducing side effects of glucocorticoids. Overall, we were able to successfully assess the anti-inflammatory effects of DXM and the superiority of the nanoparticle formulation. Nevertheless the identification of robust readout parameters proved challenging and requires careful study design.

Since the development of new radiotherapy techniques that have improved healthy tissue sparing, reirradiation (reRT) has become possible. The selection of patients eligible for reRT is complex given that it can induce severe or even fatal side effects. The first step should therefore be to assess, in the context of multidisciplinary staff meeting, the patient's physical status, the presence of sequelae resulting from the first irradiation and the best treatment option available. ReRT can be performed either curatively or palliatively to treat a cancer-related symptom that is detrimental to the patient's quality of life. The selected techniques for reRT should provide the best protection of healthy tissue. The construction of target volumes and the evaluation of constraints regarding the doses that can be used in this context have not yet been fully codified. These points raised in the literature suggest that randomized studies should be undertaken to answer pending questions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO)., Material and Methods: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire., Results: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only., Conclusions: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: To study occupational exposure totrichloramine and endotoxins in air at adventure and rehabilitation swimming pool facilities from an adverse health effects perspective., Methods: Air concentrations of trichloramine and endotoxins were measured in five adventure and 10 rehabilitation facilities. Respiratory and ocular symptoms were self-reported, and spirometry and fraction of exhaled nitric oxide (FEno) were measured., Results: Compared to rehabilitation facilities, the mean trichloramine concentrations in the adventure facilities were higher, both personal (80 μg/m3 (n  = 41) vs 19 μg/m3 (n = 21)) and stationary (183 μg/m3 (n = 51) vs 23 μg/m3 (n = 32)), with higher frequency of ocular and respiratory symptoms. Low stationary endotoxin levels (<0.64 to 25 EU/m3) were found, compared to the reference value (90 EU/m3)., Conclusions: Higher trichloramine concentrations in air and more ocular and respiratory symptoms in adventure facilities call for adequate occupational exposure limits., Competing Interests: Westerlund, Bryngelsson, Fornander, Löfstedt, and Graff have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even if level 1 evidence is lacking. However, BT remains a strong competitor, especially for young patients, as series with 10-15 years of median follow-up have proven its efficacy over time. SBRT will thus have to confirm its effectiveness over the long-term as well. SBRT has the advantage over BT of less acute urinary toxicity and, more hypothetically, less sexual impairment. Data are limited regarding SBRT for high-risk disease while BT, as a boost after EBRT, has demonstrated superiority against EBRT alone in randomized trials. However, patients should be informed of significant urinary toxicity. SBRT is under investigation in strategies of treatment intensification such as combination of EBRT plus SBRT boost or focal dose escalation to the tumor site within the prostate. Our goal was to examine respective levels of evidence of SBRT and BT for the treatment of localized prostate cancer in terms of oncologic outcomes, toxicity and quality of life, and to discuss strategies of treatment intensification.

Objective: To investigate the increased risk for carpal tunnel syndrome (CTS) in men and women with hand-arm vibration (HAV) exposure., Design: Case-control study of CTS where 4396 cases was obtained from National Outpatient Register between 2005 through 2016. Cases were matched to controls and exposure was estimated using a job exposure matrix., Results: Exposure to HAV increased the risk of CTS with an OR of 1.61 (95% CI 1.46-1.77). The risk was highest in men <30 years of age and among women <30 years no increased risk was observed. The risk increased with a mean year exposure above 2.5 m/s2 to OR 1.84 (95% CI 1.38-2.46)., Conclusions: HAV exposure increase the risk of CTS in both genders, with highest risk increase in younger men. This emphasize identification of HAV exposure in patients with CTS., Competing Interests: Vihlborg, Pettersson, Makdoumi, Wikström, Bryngelsson, Selander, and Graff have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background: The global shift toward greener societies demands new technologies and work operations in the waste-management sector. However, progressive industrial methods do not necessarily consider workers' health. This study characterized workers' exposure to bioaerosols and investigated the bioaerosols' potential to engage the immune system in vitro ., Methods: Full shift personal aerosol sampling was conducted over three consecutive days. Dust load was analyzed by gravimetry, fungal and actinobacterial spores were analyzed by scanning electron microscopy, and endotoxin by limulus amebocyte lysate (LAL) assay. In vitro exposure of HEK cells to airborne dust samples was used to investigate the potential of inducing an inflammatory reaction., Results: The total dust exposure level exceeded the recommended occupational exposure limit (OEL) of 5.0 mg/m 3 in 3 out of 15 samples. The inhalable endotoxin level exceeded the recommended exposure level by a 7-fold, whereas the fungal spore level exceeded the recommended exposure level by an 11-fold. Actinobacterial spores were identified in 8 out of 14 samples. In vitro experiments revealed significant TLR2 activation in 9 out of 14 samples vs. significant TLR4 activation in all samples., Conclusion: The present study showed that the dust samples contained potentially health-impairing endotoxin, fungi, and actinobacterial levels. Furthermore, the sampled dust contained microbial components capable of inducing TLR activation and thus have the potential to evoke an inflammatory response in exposed individuals., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, was first clinically identified in the United States on December 1, 2021, and spread rapidly. By late December, it became the predominant strain, and by January 15, 2022, it represented 99.5% of sequenced specimens in the United States* (1). The Omicron variant has been shown to be more transmissible and less virulent than previously circulating variants (2,3). To better understand the severity of disease and health care utilization associated with the emergence of the Omicron variant in the United States, CDC examined data from three surveillance systems and a large health care database to assess multiple indicators across three high-COVID-19 transmission periods: December 1, 2020-February 28, 2021 (winter 2020-21); July 15-October 31, 2021 (SARS-CoV-2 B.1.617.2 [Delta] predominance); and December 19, 2021-January 15, 2022 (Omicron predominance). The highest daily 7-day moving average to date of cases (798,976 daily cases during January 9-15, 2022), emergency department (ED) visits (48,238), and admissions (21,586) were reported during the Omicron period, however, the highest daily 7-day moving average of deaths (1,854) was lower than during previous periods. During the Omicron period, a maximum of 20.6% of staffed inpatient beds were in use for COVID-19 patients, 3.4 and 7.2 percentage points higher than during the winter 2020-21 and Delta periods, respectively. However, intensive care unit (ICU) bed use did not increase to the same degree: 30.4% of staffed ICU beds were in use for COVID-19 patients during the Omicron period, 0.5 percentage points lower than during the winter 2020-21 period and 1.2 percentage points higher than during the Delta period. The ratio of peak ED visits to cases (event-to-case ratios) (87 per 1,000 cases), hospital admissions (27 per 1,000 cases), and deaths (nine per 1,000 cases [lagged by 3 weeks]) during the Omicron period were lower than those observed during the winter 2020-21 (92, 68, and 16 respectively) and Delta (167, 78, and 13, respectively) periods. Further, among hospitalized COVID-19 patients from 199 U.S. hospitals, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital were lower during the Omicron period than during previous periods. COVID-19 disease severity appears to be lower during the Omicron period than during previous periods of high transmission, likely related to higher vaccination coverage, † which reduces disease severity (4), lower virulence of the Omicron variant (3,5,6), and infection-acquired immunity (3,7). Although disease severity appears lower with the Omicron variant, the high volume of ED visits and hospitalizations can strain local health care systems in the United States, and the average daily number of deaths remains substantial. § This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccination and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Vikas Gupta reports stock option holdings in Becton, Dickinson and Company, his employer. No other potential conflicts of interest were disclosed.

Polymeric nanogels are promising nonirritating nanocarriers for topical delivery applications. However, conventional hydrophilic networks limit encapsulation of hydrophobic therapeutics and hinder tailored interactions with the amphiphilic skin barrier. To address these limitations, we present amphiphilic nanogels containing hydrophilic networks with hydrophobic domains. Two competing factors determine favorable nanogel-skin interactions and need to be balanced through network composition: suitable surface hydrophobicity and low network rigidity (through physical hydrophobic cross-links). To ensure comparability in such investigations, we prepared a library of nanogels with increasing hydrophobic cholesteryl amounts but similar colloidal features. By combining mechanical and surface hydrophobicity tests (atomic force microscopy (AFM)) with dermal delivery experiments on excised human skin, we can correlate an increased delivery efficacy of Nile red to the viable epidermis with a specific network composition, i.e., 20-30 mol % cholesterol. Thus, our nanogel library identifies a specific balance between surface amphiphilicity and network rigidity to guide developments of advanced dermal delivery vehicles.

The genus Paracles Walker, 1855 is one of the most diverse genera present in Arctiinae and some species have larvae with aquatic habits. Several larvae were found swimming in flooded areas in different grasslands and were bred to adults to identify the species: Paracles vulpina (Hbner, [1825]). The current knowledge of immature stages of this species is not useful to identify and discriminate from other species of Paracles. For this reason, we proposed to redescribe adults of P. vulpina, showing for the first time the male and female genitalia, and improve the information on the immature stages and their habits. The adults can be recognized by the whitish paler brown band in the costal area in the forewing and whitish paler brown antenna. The final larval stage of P. vulpina can be differentiated from other species because it shows a body with a black pubescence except for a ferruginous subventral pubescence, blue dorsal verrucae, red lateral verrucae, and dorsal plastron with longest white setae. Because of its polyphagous feeding habit on aquatic and non aquatic plants we consider the aquatic larval habit is not a necessary strategy and could depend on the ground topography or weather of the locality.

Objective: Rheumatoid arthritis (RA) is an inflammatory disease with unknown etiology. This study examines if silica dust exposure increases the risk for seropositive and seronegative RA., Methods: A nationwide registry case-control study was conducted that included all cases of RA in Sweden between 2005 and 2016. In total, 31,139 cases with two matched controls were included. A JEM was used to estimate exposure., Results: Silica dust exposure was associated with a statistically significant increase in odds ratio (OR) for seropositive (OR 1.22, 95% CI 1.05 to 1.40) and seronegative (OR 1.23, 95% CI 1.04 to 1.46) RA among men., Conclusion: This study found an increased OR for RA in silica-exposed men. The OR was equal for seropositive and seronegative RA. These findings further support the hypothesis that silica dust may be a trigger for RA., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

In many countries, the management of household waste has recently changed with an increased focus upon waste sorting resulting in lower collection frequency for some waste fractions. A consequence of this is the potential for increased growth of microorganisms in the waste before collection, which can lead to an increased exposure via inhalation for waste collection workers. Through a review of the literature, we aimed to evaluate risks caused by waste collecting workers' exposure to bioaerosols and to illuminate potential measures to reduce the exposure. Across countries and waste types, median exposure to fungi, bacteria, and endotoxin were typically around 10 4 colony forming units (cfu)/m 3 , 10 4 cfu/m 3 , and 10 EU/m 3 , respectively. However, some studies found 10-20+ times higher or lower median exposure levels. It was not clear how different types of waste influence the occupational exposure levels. Factors such as high loading, ventilation in and cleaning of drivers' cabs, increased collection frequency, waste in sealed sacks, and use of hand sanitizer reduce exposure. Incidences of gastrointestinal problems, irritation of the eye and skin and symptoms of organic dust toxic syndrome have been reported in workers engaged in waste collection. Several studies reported a correlation between bioaerosol exposure level and reduced lung function as either a short or a long term effect; exposure to fungi and endotoxin is often associated with an inflammatory response in exposed workers. However, a better understanding of the effect of specific microbial species on health outcomes is needed to proceed to more reliable risk assessments. Due to the increasing recycling effort and to the effects of global warming, exposure to biological agents in this working sector is expected to increase. Therefore, it is important to look ahead and plan future measures as well as improve methods to prevent long and short-term health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Exposure to metalworking fluid has been shown to cause health problems among workers. The aim of this study was to compare health outcomes and levels of exposure among workers exposed to metalworking fluid before and after the implementation of preventive measures. The frequencies of self-reported symptoms, as well as the concentrations of measured substances were lower after the implementation of preventive measures. Logistic regression showed statistically significant differences in the report of irritations, a stuffy or runny nose, eye irritation, a hoarse or dry throat, and a cough with odds ratios of 0.31 (95% confidence interval [CI] 0.21 to 0.47), 0.12 (95% CI 0.05 to 0.29), 0.13 (95% CI 0.06 to 0.28), and 0.24 (95% CI 0.12 to 0.46), respectively. This confirms the efficiency of the performed intervention and highlights the importance of eliminating the recirculation of contaminated air., Competing Interests: Declaration of interest: The authors declare that they have no conflict of interest, whether commercial or non-commercial. E.N. and H.J. work in companies that uses metalworking fluids in their production, but do not produce or sell metalworking fluids., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Still an emerging approach a few years ago, stereotactic body radiation therapy (SBRT) has ranked as a valid option for the treatment of localized prostate cancer. Inherent properties of prostatic adenocarcinoma (low α/β) make it the perfect candidate. We propose a critical review of the literature trying to put results into perspective to identify their strengths, limits and axes of development. Technically sophisticated, the stereotactic irradiation of the prostate is well tolerated. Despite the fact that median follow-up of published data is still limited, ultra-hypofractionated radiotherapy seems very efficient for the treatment of low and intermediate risk prostate cancers. Data seem satisfying for high-risk cancers as well. New developments are being studied with a main interest in treatment intensification for unfavorable intermediate risk and high-risk cancers. Advantage is taken of the sharp dose gradient of stereotactic radiotherapy to offer safe reirradiation to patients with local recurrence in a previously irradiated area., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The use of metal additive manufacturing (AM) is steadily increasing and is an emerging concern regarding occupational exposure. In this study, non-invasive sampled nasal lavage fluid (NLF) from the upper airways was collected from metal AM operators at the beginning and end of a workweek during two consecutive years with preventive interventions in the occupational setting in-between (n = 5 year 1, n = 9 year 2). During year one, NLF was also collected from welders (n = 6) from the same company to get a comparison with a traditional manufacturing technique with known exposure and health risks. The samples were investigated using untargeted proteomics, as well as using multi-immunoassay to analyze a panel of 71 inflammatory protein markers. NLF in AM operators from year 1 showed decreased levels of Immunoglobulin J and WAP four-disulfide core domain protein 2 and increased levels of Golgi membrane protein 1, Uteroglobin and Protein S100-A6 at the end of the workweek. At year two, after preventive interventions, there were no significant differences at the end of the workweek. In welders, Annexin A1 and Protein S100-A6 were increased at the end of the workweek. The analysis of 71 inflammatory biomarkers showed no significant differences between the beginning and the end of workweek year 1 in AM operators. We identified several proteins of interest in the AM operators that could serve as possible markers for exposure in future studies with a larger cohort for validation., Competing Interests: The authors have declared that no competing interests exist.

Vibration white finger (VWF) is a complication from exposure to hand-arm vibrations. Poor knowledge of the pathophysiology of VWF means that making an accurate prognosis is difficult. Thus, a better understanding of VWF's pathophysiology is of importance.The purpose of this study was to investigate whether there were arterial abnormalities in the hands in patients with VWF and a positive Allen's test, using ultrasound and MRA imaging.This was a case series where arterial abnormalities in the hands were investigated in ten participants with VWF and using prolonged Allen's test (> 5 s). The participants had an average vibration exposure of 22 years and underwent Doppler ultrasound and Magnetic Resonance Angiography (MRA) to check for arterial abnormalities.The participants had VWF classified as 1-3 on the Stockholm workshop scale. Ultrasound and MRA identified vascular abnormalities in all participants, the predominant finding was missing or incomplete superficial arch. Also, stenosis was identified in four participants.This study reveals a high proportion of arterial stenosis and abnormalities in patients with VWF and a prolonged Allen's test., (© 2021. The Author(s).)

Introduction: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps., Material and Methods: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance., Results: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown., Conclusion: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mucosal surfaces pose a challenging environment for efficient drug delivery. Various delivery strategies such as nanoparticles have been employed so far; yet, still yielding limited success. To address the need of efficient transmucosal drug delivery, this report presents the synthesis of novel disulfide-containing dendritic polyglycerol (dPG)-based nanogels and their preclinical testing. A bifunctional disulfide-containing linker is coupled to dPG to act as a macromolecular crosslinker for poly-N-isopropylacrylamide (PNIPAM) and poly-N-isopropylmethacrylamide (PNIPMAM) in a precipitation polymerization process. A systematic analysis of the polymerization reveals the importance of a careful polymer choice to yield mucus-degradable nanogels with diameters between 100 and 200 nm, low polydispersity, and intact disulfide linkers. Absorption studies in porcine intestinal tissue and human bronchial epithelial models demonstrate that disulfide-containing nanogels are highly efficient in overcoming mucosal barriers. The nanogels efficiently degrade and deliver the anti-inflammatory biomacromolecule etanercept into epithelial tissues yielding local anti-inflammatory effects. Over the course of this work, several problems are encountered due to a limited availability of valid test systems for mucosal drug-delivery systems. Hence, this study also emphasizes how critical a combined and multifaceted approach is for the preclinical testing of mucosal drug-delivery systems, discusses potential pitfalls, and provides suggestions for solutions., (© 2021 Wiley-VCH GmbH.)