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To examine the effect of night shift on salivary cortisol at awakening (C1), 30 min later (C2), and on the cortisol awakening response (CAR, the difference between C2 and C1). We compared shift and non-shift workers with a focus on the impact of worker chronotype. Our study included 66 shift-working females (mean age = 37.3 years, SD = 10.2) and 21 non-shift working females (mean age = 47.0 years, SD = 8.9). The shift workers collected their saliva samples at C1 and C2 on each two consecutive day shifts and night shifts. Non-shift workers collected their samples on two consecutive day shifts. We applied linear mixed-effects models (LMM) to determine the effect of night shift on CAR and log-transformed C1 and C2 levels. LMMs were stratified by chronotype group. Compared to non-shift workers, shift workers before day shifts (i.e. after night sleep) showed lower cortisol at C1 (exp ( β ^ ) =0.58, 95% CI 0.42, 0.81) but not at C2. In shift workers, the CARs after night shifts (i.e. after day sleep) were lower compared to CARs before day shifts ( β ^ = − 11.07, 95% CI − 15.64, − 6.50). This effect was most pronounced in early chronotypes (early: β ^ = − 16.61, 95% CI − 27.87, − 5.35; intermediate: β ^ = − 11.82, 95% CI − 18.35, − 5.29; late: β ^ = − 6.27, 95% CI − 14.28, 1.74). Chronotype did not modify the association between night shift and CAR. In our population of shift workers, there was a mismatch between time of waking up and their natural cortisol peak at waking up (CAR) both during day and night shift duties.

We compared psychomotor vigilance in female shift workers of the Bergmannsheil University Hospital in Bochum, Germany (N = 74, 94% nurses) after day and night shifts. Participants performed a 3-minute Psychomotor Vigilance Task (PVT) test bout at the end of two consecutive day and three consecutive night shifts, respectively. Psychomotor vigilance was analyzed with respect to mean reaction time, percentage of lapses and false starts, and throughput as an overall performance score, combining reaction time and error frequencies. We also determined the reaction time coefficient of variation (RTCV) to assess relative reaction time variability after day and night shifts. Further, we examined the influence of shift type (night vs. day) by mixed linear models with associated 95% confidence intervals (CI), adjusted for age, chronotype, study day, season, and the presence of obstructive sleep apnea (OSA). At the end of a night shift, reaction times were increased (β = 7.64; 95% CI 0.94; 14.35) and the number of lapses higher compared to day shifts (exp(β) = 1.55; 95% CI 1.16-2.08). By contrast, we did not observe differences in the number of false starts between day and night shifts. Throughput was reduced after night shifts (β = -15.52; 95% CI -27.49; -3.46). Reaction times improved across consecutive day and night shifts, whereas the frequency of lapses decreased after the third night. RTCV remained unaffected by both, night shifts and consecutive shift blocks. Our results add to the growing body of literature demonstrating that night-shift work is associated with decreased psychomotor vigilance. As the analysis of RTCV suggests, performance deficits may selectively be driven by few slow reactions at the lower end of the reaction time distribution function. Comparing intra-individual PVT-performances over three consecutive night and two consecutive day shifts, we observed performance improvements after the third night shift. Although a training effect cannot be ruled out, this finding may suggest better adaptation to the night schedule if avoiding fast-changing shift schedules.

Objective Malignant mesothelioma is an aggressive cancer of the serous membranes. For the detection of the tumor at early stages non- or minimally-invasive biomarkers are needed. The circulating biomarkers miR-132-3p, miR-126-3p, and miR-103a-3p were analyzed in a nested case–control study using plasma samples from 17 prediagnostic mesothelioma cases and 34 matched asbestos-exposed controls without a malignant disease. Results Using prediagnostic plasma samples collected in median 8.9 months prior the clinical diagnosis miR-132-3p, miR-126-3p, and miR-103a-3p revealed 0% sensitivity on a defined specificity of 98%. Thus, the analyzed miRNAs failed to detect the cancer in prediagnostic samples, showing that they are not feasible for the early detection of malignant mesothelioma. However, the miRNAs might still serve as possible markers for prognosis and response to therapy, but this needs to be analyzed in appropriate studies.

Night shift work can have a serious impact on health. Here, we assess whether and how night shift work influences the metabolite profiles, specifically with respect to different chronotype classes. We have recruited 100 women including 68 nurses working both, day shift and night shifts for up to 5 consecutive days and collected 3640 spontaneous urine samples. About 424 waking-up urine samples were measured using a targeted metabolomics approach. To account for urine dilution, we applied three methods to normalize the metabolite values: creatinine-, osmolality- and regression-based normalization. Based on linear mixed effect models, we found 31 metabolites significantly (false discovery rate <0.05) affected in nurses working in night shifts. One metabolite, acylcarnitine C10:2, was consistently identified with all three normalization methods. We further observed 11 and 4 metabolites significantly associated with night shift in early and late chronotype classes, respectively. Increased levels of medium- and long chain acylcarnitines indicate a strong impairment of the fatty acid oxidation. Our results show that night shift work influences acylcarnitines and BCAAs, particularly in nurses in the early chronotype class. Women with intermediate and late chronotypes appear to be less affected by night shift work.

ObjectiveNight-shift work is known to disrupt circadian rhythms, potentially leading to adverse health effects. This study investigated the relationship between sleep timing and cortisol secretion profiles among female hospital employees.Material and Methods89 female hospital workers (68 shift workers, 21 non-shift workers) were included in this cross-sectional study. Shift workers worked rotating shifts, including night shifts, whereas non-shift workers maintained regular day shifts. Shift workers provided salivary cortisol samples collected at multiple time points during two consecutive day shifts and three consecutive night shifts. Non-shift workers collected their samples across two consecutive day shifts. Sleep timing was assessed through polysomnography and sleep diaries. Using generalized additive mixed models, we estimated shift-specific cortisol curves, considering the non-linear relationship between time since waking up and logarithmized cortisol levels, adjusted for age, chronotype, menopausal status, contraceptive use, stress load, smoking status. Each cortisol curve was summarized by cortisol awakening response (CAR), peak-to-bed slope, and total cortisol output.ResultsShift workers on night shifts showed a flattened U-shaped cortisol profile after the post-awakening peak, with peak-to-bed slope close to zero (-0.02, 95%-CI = -0.82, 0.78). In the same women, a normal diurnal cortisol profile with a steep negative peak-to-bed slope after the post-awakening peak (-2.57, 95%-CI = -3.17, -1.98) was observed on day shifts. Day-shift cortisol curves were similar in shape for both, shift workers and non-shift workers, showing differences in mean cortisol levels at waking up (-0.41 log(nmol/L), 95%-CI = -0.79, -0.02) and in CAR (0.37 log(nmol/L), 95%-CI = 0.10, 0.63).ConclusionThis study in female shift workers showed night-work associated circadian misalignment between timing of sleep and cortisol rhythm. These findings highlight the importance of considering circadian biology in occupational health, particularly for professions requiring night work.

Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools – like minimally-invasive biomarkers – are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.

Purpose Malignant pleural mesothelioma (MPM) is a highly lethal cancer caused by exposure to asbestos. Currently, the diagnosis is a challenge, carried out by means of invasive methods of limited sensitivity. This is a case–control study to evaluate the individual and combined performance of minimally invasive biomarkers for the diagnosis of MPM. Method A study of 166 incident cases of MPM and 378 population controls of Mestizo-Mexican ethnicity was conducted. Mesothelin, calretinin, and megakaryocyte potentiating factor (MPF) were quantified in plasma by ELISA. The samples were collected from 2011 to 2016. Results Based on ROC analysis and a preset specificity of 95%, the combination of the three biomarkers reached an AUC of 0.944 and a sensitivity of 82% in men. In women, an AUC of 0.937 and a sensitivity of 87% were reached. In nonconditional logistic regression models, the adjusted ORs in men were 7.92 (95% CI 3.02–20.78) for mesothelin, 20.44 (95% CI 8.90–46.94) for calretinin, and 4.37 (95% CI 1.60–11.94) for MPF. The ORs for women were 28.89 (95% CI 7.32–113.99), 17.89 (95% CI 3.93–81.49), and 2.77 (95% CI 0.47–16.21), respectively. Conclusions To our knowledge, this is the first study evaluating a combination of mesothelin, calretinin, and MPF, and demonstrating a sex effect for calretinin. The biomarker panel showed a good performance in a Mestizo-Mexican population, with high sensitivity and specificity for the diagnosis of MPM.

Objective Calretinin is a well-known immunohistochemical tissue marker in the diagnosis of malignant mesothelioma. Promising results also indicate the use in early detection. In the present cross-sectional survey, correlations of calretinin plasma levels with clinical features were investigated. Plasma samples of 60 patients with malignant pleural mesothelioma (MPM) and 111 cancer-free controls formerly exposed to asbestos were compared. Calretinin concentrations were determined in plasma using an enzyme-linked immunosorbent assay (ELISA). Results The median concentration was higher in MPM patients than in controls (0.79 vs. 0.23 ng/ml; p  < 0.0001). Patients with epithelioid MPM or biphasic MPM had higher calretinin plasma levels than patients with sarcomatoid MPM. Strong expression of calretinin in the tumor tissue was associated with higher plasma levels. Preoperative patients showed higher levels of calretinin than patients after thoracic surgery (1.20 vs. 0.67 ng/ml; p  = 0.096). The suitability of plasma calretinin has been confirmed as a tumor marker in the differential diagnosis of epithelioid MPM. The value of plasma calretinin for therapy monitoring or as a prognostic marker should be further investigated.

Background For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers. Methods Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls. Results GAS5 (growth arrest-specific transcript 5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel’s sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status. Conclusions GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.

Invasive fungal infections pose significant challenges in the management of immunocompromised patients, particularly those undergoing treatment for hematologic malignancies. is a rare but severe cause of invasive trichosporonosis, associated with mortality rates. Effective management is complicated by its resistance to echinocandins and reduced susceptibility to polyenes, necessitating azole-based therapy. This paper aims to illustrate the diagnostic challenges associated with Trichosporon infections, analyze the complexities of treatment, review and synthesize known risk factors, and highlight the need for improved clinical management. It addresses the clinical and therapeutic difficulties involved in diagnosing and treating Trichosporon asahii infections in pediatric and adult hemato-oncologic patients. We present the first case of a 14-year-old female with T-cell acute lymphoblastic leukemia who developed a disseminated infection during chemotherapy in Central and Eastern Europe. Initial symptoms included joint pain, fever, and neutropenia. The diagnosis was confirmed through synovial fluid and urine cultures. Despite initial treatment with voriconazole (70 days) and liposomal amphotericin B (309 days), the infection progressed, involving the lungs, liver, kidneys, and spleen. The patient transitioned to isavuconazole (232 days intravenous then orally), along with extensive supportive care, which eventually controlled the infection. However, the patient experienced significant complications, including joint contractures and prolonged hospitalization. Maintenance therapy was carefully adjusted to minimize adverse effects while ensuring disease control. The patient was followed monthly through September 2024, resulting in a successful outcome. A literature review highlighted neutropenia, antibiotic use, central venous catheters, and corticosteroid therapy as significant risk factors for invasive trichosporonosis. The diagnostic challenge stems from its resemblance to and other yeasts, necessitating advanced methods like matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for accurate identification. Voriconazole remains the first-line treatment, with combination therapy using liposomal amphotericin B as a salvage approach. This case underscores the critical importance of early recognition and targeted management of Trichosporon infections in immunocompromised patients. Enhanced diagnostic techniques and tailored antifungal strategies are imperative to improve outcomes. This case provides new insight for pediatric hematology practice by demonstrating that early use of advanced diagnostic methods and timely adjustment to azole-focused antifungal therapy are critical for controlling disseminated Trichosporon asahii infections, even in severely immunocompromised children.