Validity of self-reported exposure to shift work

OBJECTIVE: To evaluate the validity of widely used questionnaire items on work schedule using objective registry data as reference. METHOD: A cohort study of hospital employees who responded to a self-administered questionnaire on work schedule in 2008, 2012 and 2014 and were linked to individual-level pay-roll-based records on work shifts. For predictive validity, leisure-time fatigue was assessed. RESULTS: According to the survey data in 2014 (n=8896), 55% of the day workers had at least 1 year of earlier shift work experience. 8% of the night shift workers changed to day work during the follow-up. Using pay-roll data as reference, questions on ‘shift work with night shifts’ and ‘permanent night work’ showed high sensitivity (96% and 90%) and specificity (92% and 97%). Self-reported ‘regular day work’ showed moderate sensitivity (73%), but high specificity (99%) and ‘shift work without night shifts’ showed low sensitivity (62%) and moderate specificity (87%). In multivariate logistic regression analysis, the age-adjusted, sex-adjusted and baseline fatigue-adjusted association between ‘shift work without night shifts’ and leisure-time fatigue was lower for self-reported compared with objective assessment (1.30, 95% CI 0.94 to 1.82, n=1707 vs 1.89, 95% CI 1.06 to 3.39, n=1627). In contrast, shift work with night shifts, compared with permanent day work, was similarly associated with fatigue in the two assessments (2.04, 95% CI 1.62 to 2.57, n=2311 vs 1.82, 95% CI 1.28 to 2.58, n=1804). CONCLUSIONS: The validity of self-reported assessment of shift work varies between work schedules. Exposure misclassification in self-reported data may contribute to bias towards the null in shift work without night shifts

Prediction of bullying at work: A data-driven analysis of the Finnish public sector cohort study

AIM: To determine the extent to which change in (i.e., start and end of) workplace bullying can be predicted by employee responses to standard workplace surveys. METHODS: Responses to an 87-item survey from 48,537 Finnish public sector employees at T1 (2017–2018) and T2 (2019–2020) were analyzed with least-absolute-shrinkage-and-selection-operator (LASSO) regression. The predictors were modelled both at the individual- and the work unit level. Outcomes included both the start and the end of bullying. Predictive performance was evaluated with C-indices and density plots. RESULTS: The model with best predictive ability predicted the start of bullying with individual-level predictors, had a C-index of 0.68 and included 25 variables, of which 6 remained in a more parsimonious model: discrimination at work unit, unreasonably high workload, threat that some work tasks will be terminated, working in a work unit where everyone did not feel they are understood and accepted, having a supervisor who was not highly trusted, and a shorter time in current position. Other models performed even worse, either from the point of view of predictive performance, or practical useability. DISCUSSION: While many bivariate associations between socioeconomic characteristics, work characteristics, leadership, team climate, and job satisfaction were observed, reliable individualized detection of individuals at risk of becoming bullied at workplace was not successful. The predictive performance of the developed risk scores was suboptimal, and we do not recommend their use as an individual-level risk prediction tool. However, they might be useful tool to inform decision-making when planning the contents of interventions to prevent bullying at an organizational level

Tumour inflammatory infiltrate predicts survival following curative resection for node-negative colorectal cancer

<b>Background</b>: A pronounced tumour inflammatory infiltrate is known to confer a good outcome in colorectal cancer. Klintrup and colleagues reported a structured assessment of the inflammatory reaction at the invasive margin scoring low grade or high grade. The aim of the present study was to examine the prognostic value of tumour inflammatory infiltrate in node-negative colorectal cancer. <b>Methods</b>: Two hundred patients had undergone surgery for node-negative colorectal cancer between 1997 and 2004. Specimens were scored with Jass’ and Klintrup’s criteria for peritumoural infiltrate. Pathological data were taken from the reports at that time. <b>Results</b>: Low-grade inflammatory infiltrate assessed using Klintrup’s criteria was an independent prognostic factor in node-negative disease. In patients with a low-risk Petersen Index (n = 179), low-grade infiltrate carried a threefold increased risk of cancer death. Low-grade infiltrate was related to increasing T stage and an infiltrating margin. <b>Conclusion</b>: Assessment of inflammatory infiltrate using Klintrup’s criteria provides independent prognostic information on node-negative colorectal cancer. A high-grade local inflammatory response may represent effective host immune responses impeding tumour growth

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

BACKGROUND: Obliterative bronchiolitis after lung transplantation is characterized by chronic airway inflammation leading to the obliteration of small airways. Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular responses to hypoxia and inflammation. The Von Hippel-Lindau protein (pVHL) drives the degradation of oxygen-sensitive subunit HIF-1 alpha that controls the activity of HIF-1. We investigated the effect of myeloid cell targeted gene deletion of HIF-1 alpha or its negative regulator pVHL on the development of obliterative airway disease (OAD) in the recipients of tracheal allografts, a mouse model for obliterative bronchiolitis after lung transplantation. METHODS: Tracheal allografts were heterotopically transplanted from BALB/c donor mice to fully major histocompatibility complex mismatched recipient mice with HIF-1 alpha or VHL gene deletion in myeloid cells. The recipients were left non-immunosuppressed or received tacrolimus daily. Histologic, immunohistochemical, and real-time reverse transcription polymerase chain reaction analyses were performed at 3, 10, and 30 days. RESULTS: In the absence of immunosuppression, myeloid cell-specific VHL deficiency of the recipient mice improved epithelial recovery, decreased inflammatory cell infiltration and expression of pro-inflammatory cytokines, increased regulatory forkhead box P3 messenger RNA expression, and reduced OAD development in tracheal allografts. In the presence of tacrolimus immunosuppression, loss of HIF-1 alpha activity in myeloid cells of the recipient by HIF-1 alpha gene deletion accelerated OAD development in mouse tracheal allografts. CONCLUSIONS: Activity of the HIF-pathway affects the development of allograft rejection, and our results suggest that myeloid cell-specific VHL-deficiency that potentially increases HIF-activity decreases allograft inflammation and the subsequent development of OAD in mouse tracheal allografts. (C) 2016 International Society for Heart and Lung Transplantation. All rights reserved.Peer reviewe

Search for the active ingredients from a 2-aminothiazole DMSO stock solution with antimalarial activity

Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme Pf IspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from. Solvent- and temperature-dependent studies using HRMS and NMR spectroscopy to monitor the decomposition led to the isolation and in vitro evaluation of several fractions against Pf IspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised compounds using SFC purification and correlated the observed activities to them. Due to the unstable nature of the two isolates, it is likely that they undergo further decomposition contributing to the overall instability of the compound

High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug Suspensions

Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydro- philic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers, thus, for the first time a versatile platform for stable general-use stabilizing agents of drug suspensions.Peer reviewe

Self-Assembly of Amphiphilic Janus Dendrimers into Mechanically Robust Supramolecular Hydrogels for Sustained Drug Release

Peer reviewe