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Introduction: Patients being on immunosuppressive treatment of any reason, along with other risk factors such as smoking and obesity, are vulnerable to be infected from SARS-CoV2. Aim of this report is to describe a case of a female patient under Rituximab therapy who experienced episodes of lung infection due to Severe Acute Coronavirus 2 (SARS-CoV-2) invasion although fully vaccinated. Case report: A 50-year-old woman, with a past medical history of lupus nephritis on rituximab was diagnosed with lung infection due to SARS-CoV-2. Eight months later, following her last infusion of Rituximab (RTX), she developed moderate Coronavirus Disease 2019 (COVID-19). After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and a decision was made to restart rituximab. Conclusions: This case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus in a patient with SLE and Rituximab therapy. We emphasize a precise consideration of management of patients with autoimmune disorders during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Altered meal timing patterns can disrupt the circadian system and affect metabolism. Our aim was to describe sex-specific chrono-nutritional patterns, assess their association with body mass index (BMI) and investigate the role of sleep in this relationship., Methods: We used the 2018 questionnaire data from the population-based Genomes for Life (GCAT) (n = 7074) cohort of adults aged 40-65 in Catalonia, Spain, for cross-sectional analysis and its follow-up questionnaire data in 2023 (n = 3128) for longitudinal analysis. We conducted multivariate linear regressions to explore the association between mutually adjusted meal-timing variables (time of first meal, number of eating occasions, nighttime fasting duration) and BMI, accounting for sleep duration and quality, and additional relevant confounders including adherence to a Mediterranean diet. Finally, cluster analysis was performed to identify chrono-nutritional patterns, separately for men and women, and sociodemographic and lifestyle characteristics were compared across clusters and analyzed for associations with BMI., Results: In the cross-sectional analysis, a later time of first meal (β 1 h increase = 0.32, 95% CI 0.18, 0.47) and more eating occasions (only in women, β 1 more eating occasion = 0.25, 95% CI 0.00, 0.51) were associated with a higher BMI, while longer nighttime fasting duration with a lower BMI (β 1 h increase=-0.27, 95% CI -0.41, -0.13). These associations were particularly evident in premenopausal women. Longitudinal analyses corroborated the associations with time of first meal and nighttime fasting duration, particularly in men. Finally, we obtained 3 sex-specific clusters, that mostly differed in number of eating occasions and time of first meal. Clusters defined by a late first meal displayed lower education and higher unemployment in men, as well as higher BMI for both sexes. A clear "breakfast skipping" pattern was identified only in the smallest cluster in men., Conclusions: In a population-based cohort of adults in Catalonia, we found that a later time of first meal was associated with higher BMI, while longer nighttime fasting duration associated with a lower BMI, both in cross-sectional and longitudinal analyses., (© 2024. The Author(s).)

Background: COVID-19 related syndromes are not yet well described and understood. Multisystem inflammatory syndrome of the adults (MIS-A) is a recently characterized syndrome affecting multiple organs of young adults, causing serious complications, even shock and death., Objectives: To determine the clinical characteristics, course, and complications of MIS-A in a systematic way and summarize currently used treatments., Methods: Literature search in March 2023 in PubMed and Scopus databases. Case reports and case-series that fulfilled the CDC criteria for MIS-A were eligible for inclusion., Results: A total of 71 patients from 60 reports were included. 66% of the patients were male and the mean age of the synthetic cohort was 32.9 years old. The majority (70.4%) of the enrolled cases had no significant medical history. MIS-A was diagnosed after a median of 4 weeks period. All but two patients presented with cardiac symptoms, while the most common secondary diagnostic criterion was abdominal pain, vomiting or diarrhea followed by shock or hypotension. Heart failure therapy and immunomodulation were used as therapeutic options. Although more than half of the cohort was admitted to the Intensive Care Unit (ICU) (n=39) only 4 deaths were reported., Conclusion: MIS-A can affect patients independently of age, sex, and co-morbidity status, resulting in serious complications, often including severe cardiac disease, shock, acute kidney injury and sometimes death. It can occur immediately after SARS-CoV-2 acute infection until two months later, usually manifesting four weeks after acute disease., Competing Interests: Conflicts of interest: The authors declare that there are not any conflicts of interest.

We investigated the association between outdoor artificial light-at-night (ALAN) exposure and cardiometabolic risk in the GCAT study. We included 9,752 participants from Barcelona (59% women). We used satellite images (30m resolution) and estimated photopic illuminance and the circadian-regulation relevant melanopic illuminance (melanopic EDI). We explored the association between ALAN exposure and prevalent obesity, hypertension, and diabetes with logistic regressions. We assessed the relationship with incident cardiometabolic diseases ascertained through electronic health records (mean follow-up 6.5 years) with Cox proportional hazards regressions. We observed an association between photopic illuminance and melanopic EDI and prevalent hypertension, Odds ratio (OR) = 1.09 (95% CI, 1.01-1.16) and 1.08 (1.01-1.14) per interquartile range increase (0.59 and 0.16 lux, respectively). Both ALAN indicators were linked to incident obesity (hazard ratio [HR] = 1.29, 1.11-1.48 and 1.19, 1.05-1.34) and haemorrhagic stroke (HR = 1.73, 1.00-3.02 and 1.51, 0.99-2.29). Photopic illuminance was associated with incident hypercholesterolemia in all participants (HR = 1.17, 1.05-1.31) and with angina pectoris only in women (HR = 1.55, 1.03-2.33). Further research in this area and increased awareness on the health impacts of light pollution are needed. Results should be interpreted carefully since satellite-based ALAN data do not estimate total individual exposure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Pancreatic stone protein (PSP) is an acute-phase reactant mainly produced in response to stress. Its diagnostic and prognostic accuracy for several types of infection has been studied in several clinical settings. The aim of the current review was to assess all studies examining a possible connection of pancreatic stone protein levels with the severity and possible complications of patients diagnosed with infection. We performed a systematic search in PubMed, Scopus, the Cochrane Library and Clinicaltrials.gov to identify original clinical studies assessing the role of pancreatic stone protein in the diagnosis and prognosis of infectious diseases. We identified 22 eligible studies. Ten of them provided diagnostic aspects, ten studies provided prognostic aspects, and another two studies provided both diagnostic and prognostic information. The majority of the studies were performed in an intensive care unit (ICU) setting, five studies were on patients who visited the emergency department (ED), and three studies were on burn-injury patients. According to the literature, pancreatic stone protein has been utilized in patients with different sites of infection, including pneumonia, soft tissue infections, intra-abdominal infections, urinary tract infections, and sepsis. In conclusion, PSP appears to be a useful point-of-care biomarker for the ED and ICU due to its ability to recognize bacterial infections and sepsis early. Further studies are required to examine PSP's kinetics and utility in specific populations and conditions.

It is a general assumption that the prospective cohort study design is the gold standard approach and is superior to the case-control study design in epidemiology. However, there may be exceptions if the exposure is complex and requires collection of detailed information on many different aspects. Night-shift work, which impairs circadian rhythms, is an example of such a complex occupational exposure and may increase the risks of breast, prostate, and colorectal cancer. So far, for logistical reasons, investigators in cohort studies have assessed shift work rather crudely, lacking information on full occupational history and relevant shift-work metrics, and have presented mostly null findings. On the other hand, most cancer case-control studies have assessed the lifetime occupational histories of participants, including collection of detailed night-shift work metrics (e.g., type, duration, intensity), and tend to show positive associations. In this commentary, we debate why cohort studies with weak exposure assessment and other limitations might not necessarily be the preferred or less biased approach in assessing the carcinogenicity of night-shift work. Furthermore, we propose that risk-of-bias assessment and comparison of associations between studies with low versus high risks of bias be considered in future synthesis of the evidence., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In view of the recent revival of interest in circadian biology and circadian epidemiology at the Medical University of Vienna, it seems appropriate to highlight the rich and pioneering history of circadian research in Austria. Among the forefathers of circadian research in Vienna are Otto Marburg (1874-1948), who discovered important elements of the pineal gland physiology, Robert Hofstätter (1883-1970), who used pineal gland extract in obstetrics/gynecology, and Paul Engel (1907-1997), who discovered that the pineal gland was controlled by light. More recently, Vera Lapin (1920-2007) showed that surgical removal of the pineal gland increased tumor growth, while Franz Waldhauser (*1946) investigated melatonin in conjunction with night work. Michael Kundi (*1950) and his team conducted among the first studies demonstrating differences in rhythms of night workers and early evidence for health impairments among them. Furthermore, Vienna-born Erhard Haus (1926-2013) pioneered the discovery of the role and importance of melatonin in relation to numerous diseases. This rich pioneering contribution of scientists in Vienna or with roots in Vienna is continued today by a new generation of chronobiologists, epidemiologists and clinicians in Vienna whose new insights contribute to the rapidly developing field of circadian rhythms research. Current topics and contributions relate to the impact of circadian rhythm disruption on health, and the application of chronotherapeutic approaches in clinical and preventive settings., (© 2023. The Author(s).)

Night shift work has been associated with breast, prostate, and colorectal cancer, but evidence on other types of cancer is limited. We prospectively evaluated the association of rotating night shift work, sleep duration, and sleep difficulty with thyroid cancer risk in the Nurses' Health Study 2 (NHS2). We assessed rotating night shift work duration (years) at baseline and throughout follow-up (1989-2015) and sleep characteristics in 2001. Cox proportional hazard models, adjusted for potential confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for (a) shift work duration, (b) sleep duration, and (c) difficulty falling or staying asleep. We stratified the analyses of night shift work by sleep duration and sleep difficulty. Over 26 years of follow-up, 588 incident cases were identified among 114,534 women in the NHS2 cohort. We observed no association between night shift work and the risk of thyroid cancer. Difficulty falling or staying asleep was suggestively associated with a higher incidence of thyroid cancer when reported sometimes (HR 1.26, 95% CI 0.95, 1.66) and all or most of the time (HR 1.35, 95% CI 1.00, 1.81). Night shift workers (10+ years) with sleep difficulty all or most of the time (HR 1.47; 0.58-3.73) or with >7 h of sleep duration (HR 2.17; 95% CI, 1.21-3.92) had a higher risk of thyroid cancer. We found modest evidence for an increased risk of thyroid cancer in relation to sleep difficulty, which was more pronounced among night shift workers.

Background: The Pancreatic Stone Protein (PSP) is an acute-phase protein that is mainly secreted by pancreatic cells in response to stress. The current literature supports its use as a predictor of sepsis. Its prognostic role has recently been evaluated in a point-of-care setting, mostly in high-risk patients. We conducted a prospective observational cohort study to evaluate its utility in the prognosis of patients admitted to the hospital with a diagnosis of intra-abdominal infection., Methods: Adult patients consecutively admitted to the Internal Medicine Department of the University Hospital of Patras, Greece, with a diagnosis of intra-abdominal infection were enrolled. PSP levels were measured within 24 h of admission in whole blood., Results: a total of 40 patients were included after being diagnosed with IAI. PSP was used as an independent predictive factor for sepsis after adjusting for age with OR = 7.888 (95% CI: 1.247-49.890). PSP also predicted readmission and the need for treatment escalation ( p : <0.01) and was an excellent prognostic factor regarding these outcomes (AUC = 0.899, 95% CI: 0.794-1.0, and AUC = 0.862, 95% CI: 0.748-0.976, respectively). PSP also proved superior to CRP, ferritin, and fibrinogen in sepsis diagnosis, treatment escalation, and readmission prediction with an AUC of 0.862, 0.698, and 0.899, respectively., Conclusions: PSP can predict unfavorable outcomes, such as sepsis development, readmission, and the need for treatment escalation among patients with intra-abdominal infections.

Social restriction measures (SRM) implemented during the COVID-19 pandemic led to a reduction in time spent outdoors (TSO). The aim of this study was to describe TSO and evaluate its association with sleep outcomes, optimism, happiness and health-status before and during SRM. Two online surveys were conducted in 2017 (N = 1004) and 2020, during SRM (N = 1010), in samples representative of the age, sex and region of the Austrian population. Information on the duration of TSO, sleep, optimism, happiness and health-status was collected. Multivariable-adjusted logistic regression models were used to study the association of TSO with chronic insomnia, short sleep, late chronotype, optimism, happiness and self-rated health-status. The mean TSO was 3.6 h (SD: 2.18) in 2017 and 2.6 h (SD: 1.87) during times of SRM. Men and participants who were older, married or in a partnership and lived in a rural area reported longer TSO. Participants who spent less time outdoors were more likely to report short sleep or a late chronotype in both surveys and, in 2020, also chronic insomnia. Less TSO was associated with lower happiness and optimism levels and poor health-status. Our findings suggest that TSO may be a protective factor for sleep, mood and health, particularly during stressful and uncertain times.

Purpose: This study aimed at describing meal-timing patterns using cluster analysis and explore their association with sleep and chronic diseases, before and during COVID-19 mitigation measures in Austria., Methods: Information was collected in two surveys in 2017 (N = 1004) and 2020 (N = 1010) in representative samples of the Austrian population. Timing of main meals, nighttime fasting interval, last-meal-to-bed time, breakfast skipping and eating midpoint were calculated using self-reported information. Cluster analysis was applied to identify meal-timing clusters. Multivariable-adjusted logistic regression models were used to study the association of meal-timing clusters with prevalence of chronic insomnia, depression, diabetes, hypertension, obesity and self-rated bad health status., Results: In both surveys, median breakfast, lunch and dinner times on weekdays were 7:30, 12:30 and 18:30. One out of four participants skipped breakfast and the median number of eating occasions was 3 in both samples. We observed correlation between the different meal-timing variables. Cluster analysis resulted in the definition of two clusters in each sample (A17 and B17 in 2017, and A20 and B20 in 2020). Clusters A comprised most respondents, with fasting duration of 12-13 h and median eating midpoint between 13:00 and 13:30. Clusters B comprised participants reporting longer fasting intervals and later mealtimes, and a high proportion of breakfast skippers. Chronic insomnia, depression, obesity and self-rated bad health-status were more prevalent in clusters B., Conclusions: Austrians reported long fasting intervals and low eating frequency. Meal-timing habits were similar before and during the COVID-19-pandemic. Besides individual characteristics of meal-timing, behavioural patterns need to be evaluated in chrono-nutrition epidemiological studies., (© 2023. The Author(s).)

Breast cancer is highly prevalent yet a more complete understanding of the interplay between genes and probable environmental risk factors, such as night work, remains lagging. Using a discordant twin pair design, we examined the association between night shift work and breast cancer risk, controlling for familial confounding. Shift work pattern was prospectively assessed by mailed questionnaires among 5,781 female twins from the Older Finnish Twin Cohort. Over the study period (1990-2018), 407 incident breast cancer cases were recorded using the Finnish Cancer Registry. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for potential confounders. Within-pair co-twin analyses were employed in 57 pairs to account for potential familial confounding. Compared to women who worked days only, women with shift work that included night shifts had a 1.58-fold higher risk of breast cancer (HR = 1.58; 95%CI, 1.16-2.15, highest among the youngest women i.e. born 1950-1957, HR = 2.08; 95%CI, 1.32-3.28), whereas 2-shift workers not including night shifts, did not (HR = 0.84; 95%CI, 0.59-1.21). Women with longer sleep (average sleep duration > 8 h/night) appeared at greatest risk of breast cancer if they worked night shifts (HR = 2.91; 95%CI, 1.55-5.46; P intx =0.32). Results did not vary by chronotype (P intx =0.74). Co-twin analyses, though with limited power, suggested that night work may be associated with breast cancer risk independent of early environmental and genetic factors. These results confirm a previously described association between night shift work and breast cancer risk. Genetic influences only partially explain these associations., (© 2023. The Author(s).)

Gastrointestinal (GI) bleeding (GIB) in athletes has previously been reported in several studies, as an important factor of underperformance in competitive sports events. Yet it is still underreported, partly because it is usually occult and self-limited soon after the effort. It can originate in either the upper or the lower GI tract and can be proportionally related to the amount and duration of effort. Key pathophysiological factors seem to include splanchnic hypoperfusion, mechanical trauma of the GI wall, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Appropriate nutrition, hydration and regulation of exercise, along with substances such as arginine and citrulline can relieve upper and lower GI symptoms, including nausea, vomiting, cramping, diarrhea, and possibly hemorrhage. Cessation of NSAIDs, use of proton pump inhibitors and H 2 -receptor-antagonists, as well as "training" the gut, also seem to be effective in reducing the incidence of GIB in athletes. Maintenance of hemodynamic stability and identification of the source of bleeding are key elements in the management of this condition. Endoscopy might be necessary for both. GIB should not be immediately attributed to endurance exercise, and endoscopy should always be performed to rule out other existing pathology., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Ambient air pollution has been associated with COVID-19 disease severity and antibody response induced by infection., Objectives: We examined the association between long-term exposure to air pollution and vaccine-induced antibody response., Methods: This study was nested in an ongoing population-based cohort, COVICAT, the GCAT-Genomes for Life cohort, in Catalonia, Spain, with multiple follow-ups. We drew blood samples in 2021 from 1,090 participants of 2,404 who provided samples in 2020, and we included 927 participants in this analysis. We measured immunoglobulin M (IgM), IgG, and IgA antibodies against five viral-target antigens, including receptor-binding domain (RBD), spike-protein (S), and segment spike-protein (S2) triggered by vaccines available in Spain. We estimated prepandemic (2018-2019) exposure to fine particulate matter [PM ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 )], nitrogen dioxide ( NO 2 ), black carbon (BC), and ozone ( O 3 ) using Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) models. We adjusted estimates for individual- and area-level covariates, time since vaccination, and vaccine doses and type and stratified by infection status. We used generalized additive models to explore the relationship between air pollution and antibodies according to days since vaccination., Results: Among vaccinated persons not infected by SARS-CoV-2 ( n = 632 ), higher prepandemic air pollution levels were associated with a lower vaccine antibody response for IgM (1 month post vaccination) and IgG. Percentage change in geometric mean IgG levels per interquartile range of PM 2.5 ( 1.7   μ g / m 3 ) were - 8.1 (95% CI: - 15.9 , 0.4) for RBD, - 9.9 ( - 16.2 , - 3.1 ) for S, and - 8.4 ( - 13.5 , - 3.0 ) for S2. We observed a similar pattern for NO 2 and BC and an inverse pattern for O 3 . Differences in IgG levels by air pollution levels persisted with time since vaccination. We did not observe an association of air pollution with vaccine antibody response among participants with prior infection ( n = 295 )., Discussion: Exposure to air pollution was associated with lower COVID-19 vaccine antibody response. The implications of this association on the risk of breakthrough infections require further investigation. https://doi.org/10.1289/EHP11989.

Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.

Bladder cancer is the sixth most common cancer in the United States. Night shift work has previously been linked with cancer risk. Whether there is an association between rotating night shift work and bladder cancer in women has not been studied previously. Eligible participants in the Nurses' Health Study (NHS, n = 82,147, 1988-2016) and Nurses' Health Study II (NHSII, n = 113,630, 1989-2015) were prospectively followed and a total of 620 and 122 incident bladder cancer cases were documented during the follow-up of NHS and NHSII, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for bladder cancer incidence. We observed a significantly increased risk of bladder cancer among women with >5 years of night shift work history compared with women who never worked rotating night shifts in NHS (HR = 1.24; 95%CI = 1.01-1.54, p for trend = 0.06), but not in the pooled NHS and NHS II (HR = 1.18; 95%CI = 0.97-1.43, p for trend = 0.08). Secondary analyses stratified by smoking status showed no significant interaction ( p = 0.89) between the duration of rotating night shift work and smoking status. In conclusion, our results did not provide strong evidence for an association between rotating night shift work and bladder cancer risk.

Background: Burnout is increasingly being recognized as a major concern, affecting the physical and mental well-being of Healthcare workers (HCWs)., Objective: The aim of the study was to investigate the incidence of occupational exhaustion in healthcare workers (doctors, nurses, paramedics, assistants, administrative staff) and possible contributing factors during the COVID-19 pandemic., Methods: This study was conducted from March to September 2022 in seven (7) hospitals in Western Greece. It was carried out using an anonymous questionnaire. The questionnaire was designed based on results of previously published studies and consisted of 22 multiple-choice questions., Results: There were 259 (60.2%) female and 178 (39.8%) male participants enrolled in the study. The majority of the respondents were nurses (n=207, 48.1%), followed by doctors (n+ 178, 41.4%). There was a marked increase in emotional exhaustion, depersonalization, personal fulfillment and pandemic-related total burnout in participants older than 61 years old (40,05±2,2, 27,16±1,0, 21,11±4,1, 88,32±4,3, respectively). Widow/ers healthcare workers were mostly affected from pandemic related burnout compared to married, unmarried, and divorced healthcare workers. Respondents without postgraduate education demonstrated significantly greater prevalence of emotional exhaustion, depersonalization and pandemic-related total burnout in comparison to those with doctoral/master degree. The prevalence of personal and work-related burnout among paramedics and administrative staff was higher than that seen in doctors and nurses(32,82±3,8 vs32,08±5,0/29,11±4,7 22,33±4,0 vs21,57±3,1/18,89±5,4 19,60±3,9 vs17,26±2,8/15,24±3,7 74,76±10,4 vs70,92±9,5/63,23±12,1).The prevalence of emotional exhaustion and work-related total burnout was significantly higher among doctors, nurses, paramedics, and administrative staff working with direct contact with COVID-19 patients than those among healthcare workers working without direct contact with COVID-19 patients., Conclusion: The present study highlights the impact of the COVID-19 pandemic on healthcare workers., Competing Interests: The authors declare no conflicts of interest., (© 2023 Anastasia-Kiriaki Koutsouri, Despoina Gkentzi. Themis Paraskevas, Christos Michailides, Konstantinos Papantoniou, Michalis Kavvousanos, Anastasios Kantanis, Stelios Assimakopoulos, Markos Marangos, Maria Lagadinou.)

Breast and prostate cancers have been associated with circadian disruption. Some previous studies examined associations of sleep duration and breast or prostate cancer risk though findings remain inconsistent. This study examines associations of a range of detailed sleep characteristics and breast and prostate cancer risk in a large-scale population-based case-control study, MCC-Spain. A total of 1738 incident breast cancer cases, 1112 prostate cancer cases and frequency matched controls (n = 1910, and 1493 respectively) were recruited. Detailed data on habitual sleep duration, quality, timing, and daytime napping ("siesta") were collected at recruitment. Additional data on sleep habits during both the previous year and at age 40 years were also subsequently captured. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated. There were no associations of habitual sleep duration (h), timing of sleep, or any or specific sleep problems, and either breast and prostate cancer risk. There was a significant positive association of ever taking habitual siestas at recruitment and breast cancer risk (OR = 1.22, 95% CI 1.06-1.42), which strengthened with increased frequency or duration. There were also significant positive associations observed for both breast and prostate cancer, among those reporting recent sleep problems, but not sleep problems at age 40 years, in a subsequent circadian questionnaire. Adverse associations with siesta and disturbed sleep during the previous year likely reflect symptoms of developing/diagnosed cancer and comorbidities. Overall, there was no clear association between various sleep characteristics and breast or prostate cancer risk observed., (© 2022. The Author(s).)

Mechanistic studies are needed to understand how rotating shift work perturbs metabolic processing. We collected plasma samples (n = 196) from 49 males, rotating car factory shift workers at the beginning and end of a night-shift (22:00-06:00 h) and day-shift (06:00 h-14:00 h). Samples underwent targeted LC-MS/MS metabolomics and concentrations of 130 metabolites were log 2 -transformed and pareto-scaled. An elastic net selected the most influential metabolites for linear mixed models examining within-person variation in metabolite levels at night-shift end (06:00 h) compared to day-shift start (06:00 h). Quantitative enrichment analysis explored differentially enriched biological pathways between sample time points. We included 20 metabolites (amino acids, biogenic amines, acylcarnitines, glycerophospholipids) in mixed models. Night-shift was associated with changes in concentrations of arginine (geometric mean ratio [GMR] 2.30, 95%CI 1.25, 4.23), glutamine (GMR 2.22, 95%CI 1.53, 3.24), kynurenine (GMR 3.22, 95%CI 1.05, 9.87), lysoPC18:2 (GMR 1.86, 95%CI 1.11, 3.11), lysoPC20:3 (GMR 2.48, 95%CI 1.05, 5.83), PCaa34:2 (GMR 2.27, 95%CI 1.16, 4.44), and PCae38:5 (GMR 1.66, 95%CI 1.02, 2.68). Tryptophan metabolism, glutathione metabolism, alanine metabolism, glycine and serine metabolism, and urea cycle were pathways differing between shifts. Night shift work was associated with changes in metabolites and the perturbation of metabolic and biochemical pathways related to a variety of health outcomes.

Background: Heterogeneity of the population in relation to infection, COVID-19 vaccination, and host characteristics is likely reflected in the underlying SARS-CoV-2 antibody responses., Methods: We measured IgM, IgA, and IgG levels against SARS-CoV-2 spike and nucleocapsid antigens in 1076 adults of a cohort study in Catalonia between June and November 2020 and a second time between May and July 2021. Questionnaire data and electronic health records on vaccination and COVID-19 testing were available in both periods. Data on several lifestyle, health-related, and sociodemographic characteristics were also available., Results: Antibody seroreversion occurred in 35.8% of the 64 participants non-vaccinated and infected almost a year ago and was related to asymptomatic infection, age above 60 years, and smoking. Moreover, the analysis on kinetics revealed that among all responses, IgG RBD, IgA RBD, and IgG S2 decreased less within 1 year after infection. Among vaccinated, 2.1% did not present antibodies at the time of testing and approximately 1% had breakthrough infections post-vaccination. In the post-vaccination era, IgM responses and those against nucleoprotein were much less prevalent. In previously infected individuals, vaccination boosted the immune response and there was a slight but statistically significant increase in responses after a 2nd compared to the 1st dose. Infected vaccinated participants had superior antibody levels across time compared to naïve-vaccinated people. mRNA vaccines and, particularly the Spikevax, induced higher antibodies after 1st and 2nd doses compared to Vaxzevria or Janssen COVID-19 vaccines. In multivariable regression analyses, antibody responses after vaccination were predicted by the type of vaccine, infection age, sex, smoking, and mental and cardiovascular diseases., Conclusions: Our data support that infected people would benefit from vaccination. Results also indicate that hybrid immunity results in superior antibody responses and infection-naïve people would need a booster dose earlier than previously infected people. Mental diseases are associated with less efficient responses to vaccination., (© 2022. The Author(s).)

Introduction: Preliminary studies suggest that night shift work is associated with a desynchronization of rhythmic immune markers, possibly explaining the increased risk of infection, cardiometabolic disorders, and cancer in shift workers., Methods: This study included 51 male rotating shift workers from a car industry in Barcelona, Spain, sampled twice toward the end of a 3-week night shift (22:00-06:00 h) and a 3-week day shift (06:00-14:00 h) rotation. We collected four blood samples per worker, at the start and end of each shift. We measured 27 cytokines, chemokines and growth factors in plasma samples by luminex using the Cytokine Human Magnetic 30-Plex Panel LHC6003M and applied linear mixed models to examine within-person associations between shift work and analytes' concentrations, comparing samples taken at 06:00 h on a day and night shift. We also conducted a factor analysis using analyte concentrations from all 4 time points for each individual to identify common factors and determine if these factors were altered by shift work., Results: We observed lower levels of 15 analytes in the night shift compared to the day shift including cytokines (pro-inflammatory TNF-α, IL-2R; anti-inflammatory IL1-RA; Th1 IL-2, Th2 IL-4 and Th17 Il-17), chemokines (IP-10, MIP-1α, MIP-1β, RANTES) and growth factors (EGF, G-CSF, HGF, VEGF, FGF). In a factor analysis, three factors were identified. The main factor (Factor 1), explaining 57% of the variance and including IL-1β, IL-12, IL-15, MIP-1α, MIP-1β, EGF and FGF; and another factor (Factor 3) explaining 10% of the variance and including the Th1 cytokine IL-12, were inversely associated with the night shift (coefficient: -0.17, 95%CI -0.32 to -0.01 and coefficient: -0.22, 95%CI -0.38, -0.06, for Factors 1 and 3, respectively). Our results indicate that night shift disrupts the levels of several immune markers, which could contribute to the increased risk of infections and cancer reported in night shift workers., Conclusion: Night shift is associated with disruption of multiple immune response pathways., Competing Interests: JN, PF and AT work at the Occupational Health service of the car factory, which was the setting of the present study. At the HORMONIT study working group they express their own views and do not represent the company. The remaining 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., (Copyright © 2022 Harding, Aguilar, Espinosa, Castaño-Vinyals, Papantoniou, Navarrete, Such Faro, Torrejón, Dobaño, Moncunill and Kogevinas.)

Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008-2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95-1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01-1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer., 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., (Copyright © 2022 Palomar-Cros, Harding, Espinosa, Papantoniou, Pérez-Gómez, Straif, Ardanaz, Fernández Villa, Amiano, Gómez-Acebo, Moreno, Alguacil, Fernández-Tardón, Molina-Barceló, Marcos-Gragera, Aragonés, Castaño-Vinyals, Guevara, Marcos Delgado, Pollán, Romaguera and Kogevinas.)

Background: Acute upper gastrointestinal bleeding (AUGIB) remains a common medical emergency with considerable morbidity and mortality. The aim of this study was to describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with AUGIB nowadays and compare these with those of patients 15 years ago., Methods: This was a single-center survey of adults (> 16 years) presenting with AUGIB to a tertiary hospital. Data from 401 patients presenting with AUGIB in a tertiary hospital between January 1, 2019 and December 31, 2020 were analyzed and compared with data from 434 patients presenting with AUGIB at the same hospital between January 1, 2004 and December 31, 2005., Results: Nowadays, patients were older, mean age was 69.5 (± 15.4) vs. 66.2 (± 16.0) years, they had more frequently coexisting diseases (83.5% vs. 72.8%), especially cardiovascular diseases (62.3% vs. 52.5%), and more individuals were inpatients at onset of bleeding (8.2% vs. 4.1%). In addition, more patients were under anticoagulants (18.5% vs. 6.2%), but less were under acetylsalicylic acid ± clopidogrel (36.9% vs. 33.9%). Carlson Comorbidity Index was higher nowadays (5.6 ± 6.4 vs. 3.4 ± 2.3). Moreover, a peptic ulcer was less frequently found as the cause of bleeding (38.4% vs. 56.9%), while more often nowadays endoscopy was negative (12.7% vs. 3.5%). In patients with peptic ulcer, active bleeding on endoscopy was less frequent (7.1% vs. 14.2%). Also, bleeding spots requiring hemostasis were less common on endoscopy (39.6% vs. 49.4%) and more patients were without spots of recent bleeding (49.4% vs. 38.9%). Finally, the rate of rebleeding statistically decreased (7.8% vs. 4.2%), while overall mortality remained relatively unchanged (5.0% vs. 6.2%)., Conclusions: AUGIB episodes nowadays are less severe with less peptic ulcer bleeding, but the patients are older and with more comorbidities., Competing Interests: The authors declare that there is no conflict of interest., (Copyright 2022, Sotiropoulos et al.)

Background: The role of patients' metabolic clinical and biochemical profile in NAFLD has not been extensively explored., Aims: The aim of the study was to assess the role of metabolic health in NAFLD patients and to examine liver disease progression in these populations., Methods: The medical charts of 569 patients diagnosed with fatty liver were thoroughly reviewed; 344 patients were excluded because of other chronic liver diseases. Metabolically healthy people were defined as those who met none of the following criteria: blood pressure ≥ 130/85 mmHg or under hypertension treatment, fasting glucose ≥ 100 mg/dl or under diabetes treatment, serum triglycerides > 150 mg/dl, high density lipoprotein-cholesterol <40/50 mg/dl for men/women. Study participants were followed-up over a median period of 22 months., Results: The present observational case-control study included 225 NAFLD patients; 14 (6.2%) were metabolically healthy. Metabolically healthy participants were younger (p = 0.006), had lower age at diagnosis (p = 0.002), lower levels of γ-GT (p = 0.013), fasting glucose (p <0.001) and triglycerides (p <0.001) and higher HDL-cholesterol (p = 0.005) compared to metabolically non-healthy. By the last follow up assessment, 8 metabolically healthy patients had developed dyslipidemia; 1 patient (14.4%) had presented liver disease progression compared to 8 patients (10.5%) from the unhealthy group (p = 0.567). In multivariate analysis, diabetes mellitus (p = 0.017) and hemoglobin levels (p = 0.009) were the sole independent predictors of disease progression. No significant difference was observed in liver disease progression-free survival rates among the two patient groups (p = 0.503)., Conclusions: Metabolically healthy NAFLD patients presented with a favorable biochemical profile; however, they were diagnosed with NAFLD at a younger age and the liver disease progression risk was similar to that of metabolically unhealthy patients. These findings suggest that metabolically healthy NAFLD may not constitute a benign condition and patients could potentially be at increased risk of metabolic syndrome and liver disease progression., Competing Interests: Declaration of 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., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: In aging healthcare professionals, multiple stressors such as night work may affect life and work satisfaction and risk for chronic diseases (e.g. cardiovascular disease [CVD]). In this pilot study we compared workability, quality of life (QoL), and CVD risk markers between night shift and day workers., Methods: We included 70 hospital employees (mean age 52 ± 4 years, 91.4% female): 32 rotating night shift workers (> 3 nights/month) and 38 permanent day workers. In addition to sociodemographic, lifestyle, and sleep characteristics, we assessed i) workability index (WAI), ii) QoL (World Health Organization Quality of Life [WHOQOL-Bref]) and iii) CVD risk markers, i.e. carotid ultrasound measurements, and biomarkers (NTproBNP, CRP, IL‑6, LDL, ferritin, copper, zinc, and selenium). WAI, QoL, and CVD risk markers were compared between night and day workers. In a subgroup of participants (N = 38) with complete data, we used quantile regression analysis to estimate age and multivariate adjusted differences in biomarker levels., Results: We found no differences in the domains of QoL (physical health, psychological, social relationships, and environment) and WAI scores between night and day workers. Night shift workers were less likely to report excellent workability than day workers, although differences were not statistically significant. Night shift workers reported more sleep problems (73.1% vs. 55.6%) and tended to have lower zinc levels and higher inflammatory markers (CRP, IL‑6, ferritin), but differences were not significant after adjusting for potential confounders., Conclusions: Workability, QoL and CVD markers did not significantly differ between rotating night shift and day workers in this small pilot study. Sleep problems and inflammatory marker levels carry implications for occupational health., (© 2021. The Author(s).)

Objective: Data from real world settings on circadian disruption and subsequent hormone-related changes may explain the higher risk of hormone-dependent cancers among night shift workers.The present study examines the melatonin and sex steroid hormone levels among night shift workers., Methods: We included 44 male, rotating shift workers from a car factory in Spain, sampled both at the end of a 3-week night shift (22:00-06:00 hrs) and a 3-week early morning shift (06:00-14:00 hrs). Participants collected all urine voids over 24-hours during each shift. Urinary concentrations of sex steroid hormones (estrogens, androgens and progestogens) and 6-sulfatoxymelatonin (aMT6s, major melatonin metabolite) were determined. Individual cosinor analysis was used to derive the acrophase (peak time) and area under the curve (total production). Linear mixed models examined intraindividual associations between night shift work and log-transformed 24-hour peak time and total production of hormones compared to early morning shift work., Results: The acrophase was delayed during the night shift for aMT6s [geometric mean difference (GMD) 7.53 hrs, 95% confidence interval (CI) 4.46-10.60], androgens (eg, testosterone: GMD 6.83 hrs, 95% CI 0.34-13.32) and progestogens (eg, 17-hydroxyprogesterone: GMD 4.54 hrs, 95% CI 2.92-6.16) compared to the early morning shift. We found a higher production of adrenal androgen 11-oxoandrosterone/11-oxoetiocholanolone [geometric mean ratio (GMR) 1.43, 95% CI 1.12-1.81], and a lower production of adrenal progestogen 16-cysteinylprogesterone (GMR 0.79, 95% CI 0.67-0.93) during the night shift compared to the early morning shift levels., Conclusions: Night shift work was associated with melatonin and sex hormone-related changes in timing and total production, providing insight into the mechanistic path for its association with hormone-dependent cancer.

Objectives: To explore changes in quality of life and perceived productivity, focusing on the effects of working from home during the first COVID-19 50-day mitigation period in Austria., Methods: We conducted an Austrian-representative online survey (N = 1010) of self-reported life- and work-related changes during the first COVID-19 50-day mitigation period (March 16 through May 1 2020) compared to the situation before. We used multinominal logistic regression models to identify correlates of improved/decreased quality of life in the entire sample, and of improved/decreased productivity in a subsample of the working population (N = 686). We also calculated age- and multivariable-adjusted ORs and 95% CIs of an improved/decreased quality of life and an improved/decreased productivity by work from home status., Results: During the COVID-19 mitigation period, quality of life improved in 17.5%, but decreased in 20.7% of the general Austrian population; perceived productivity at work increased in 12.7%, but decreased in 30.2% of the working population. Working from home during the mitigation period was associated with an increased quality of life (vs. none, partially: OR 2.07, 95% CI 1.09-3.91; all the time: 3.69, 1.86-7.29). In contrast, perceived productivity seemed to decrease when people worked from home (vs. none, partially: 1.42, 0.86-2.35; all the time: 1.48, 0.85-2.58). Working from home and related benefits were not equally distributed among gender, age, and educational attainment., Conclusions: A transition to more flexibility of workplace and working hours for employees could have important positive consequences for family and professional life, for stakeholders, for public health, and ultimately for the environment., (© 2021. The Author(s).)

Objective: Birth cohorts collect valuable and under-utilized information on employment and health of parents before and during pregnancy, at birth, and sometimes after birth. In this discussion paper, we examine how these data could be exploited to study the complex relationships and interactions between parenthood, work, and health among parents themselves., Methods: Using a web-based database of birth cohorts, we summarize information on maternal employment and health conditions and other potentially related variables in cohorts spread throughout Europe. This provided information on what data are available and could be used in future studies, and what was missing if specific questions are to be addressed, exploiting the opportunity to explore work-health associations across heterogenous geographical and social contexts., Results: We highlight the many potentialities provided by birth cohorts and identify gaps that need to be addressed to adopt a life-course approach and investigate topics specific to the peri-pregnancy period, such as psychosocial aspects. We address the technical difficulties implied by data harmonization and the ethical challenges related to the repurposing of data, and provide scientific, ecological and economic arguments in favor of improving the value of data already available as a result of a serious investment in human and material resources., Conclusions: There is a hidden treasure in birth cohorts that deserves to be brought out to study the relationships between employment and health among working parents in a time when the boundaries between work and life are being stretched more than ever before.