Association of shift work with mood disorders and sleep problems according to chronotype: a 17-year cohort study

Both evening chronotype and shift work are associated with depressive symptoms. This study examined whether the association between shift work and mood disorders and sleep problems varies by chronotype. The study population included 10637 participants from the Finnish Hospital Personnel Cohort Study. Work schedule was assessed using repeated questionnaires between 2000 and 2017. Chronotype, assessed using a single item from the Diurnal Type Scale, was categorized into definite morning, somewhat morning, somewhat evening, and definite evening types. The presence of mood disorders was identified by the 12-item General Health Questionnaire. Sleep problems were assessed by self-reported frequency of difficulty falling asleep and maintaining asleep. Longitudinal fixed effects models were used to examine the associations between shift work and the presence of mood disorders and sleep problems, stratified by chronotype. We found that fixed night work was associated with mood disorders among somewhat evening (adjusted odds ratio [OR] 1.91, 95% CI 1.09-3.34) and definite evening-type workers (adjusted OR 2.05, 95% CI 1.06-3.98). Shift work with night shifts was associated with mood disorders among definite evening-type workers (adjusted OR 1.75, 95% CI 1.18-2.60). Similarly, fixed night work was associated with difficulty maintaining sleep only among evening-type workers. In conclusion, evening chronotype increase the vulnerability to mood disorders and sleep disturbances related to night work

Luminescence stability improvement in liposome-based homogeneous luminescence resonance energy transfer

A stable liposome-based time-resolved luminescence resonance energy transfer (TR-LRET) assay was developed based on the interaction of biotinylated lipids and streptavidin. Eu ion chelated to 4,4,4-trifluoro-1-(2- naphthalenyl)-1,3-butanedione and trioctylphosphine oxide was incorporated into liposomes. Acceptor-labeled streptavidin bound to biotinylated lipids of the liposomes enables TR-LRET. A stable assay performance was achieved by optimization. High Eu signal and stability, low variation, and sensitivity below 100 pM for free biotin was achieved by incorporating the chelate into liposomes containing cholesterol in a carbonate buffer. Potentially, the stable assay compared with the assay without cholesterol offers an improved platform to liposome-based detection systems. © 2013 Elsevier Inc

Predicting long-term sickness absence with employee questionnaires and administrative records: a prospective cohort study of hospital employees

Objective: This study aimed to compare the utility of risk estimation derived from questionnaires and administrative records in predicting long-term sickness absence among shift workers. Methods This prospective cohort study comprised 3197 shift-working hospital employees (mean age 44.5 years, 88.0% women) who responded to a brief 8-item questionnaire on work disability risk factors and were linked to 28 variables on their working hour and workplace characteristics obtained from administrative registries at study baseline. The primary outcome was the first sickness absence lasting ≥90 days during a 4-year follow-up. Results The C-index of 0.73 [95% confidence interval (CI) 0.70–0.77] for a questionnaire-only based prediction model, 0.71 (95% CI 0.67–0.75) for an administrative records-only model, and 0.79 (95% CI 0.76–0.82) for a model combining variables from both data sources indicated good discriminatory ability. For a 5%-estimated risk as a threshold for positive test results, the detection rates were 76%, 74%, and 75% and the false positive rates were 40%, 45% and 34% for the three models. For a 20%-risk threshold, the corresponding detection rates were 14%, 8%, and 27% and the false positive rates were 2%, 2%, and 4%. To detect one true positive case with these models, the number of false positive cases accompanied varied between 7 and 10 using the 5%-estimated risk, and between 2 and 3 using the 20%-estimated risk cut-off. The pattern of results was similar using 30-day sickness absence as the outcome. Conclusions The best predictive performance was reached with a model including both questionnaire responses and administrative records. Prediction was almost as accurate with models using only variables from one of these data sources. Further research is needed to examine the generalizability of these findings

Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery

Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.Peer reviewe

Quantification of Dynamic Morphological Drug Responses in 3D Organotypic Cell Cultures by Automated Image Analysis

Glandular epithelial cells differentiate into complex multicellular or acinar structures, when embedded in three-dimensional (3D) extracellular matrix. The spectrum of different multicellular morphologies formed in 3D is a sensitive indicator for the differentiation potential of normal, non-transformed cells compared to different stages of malignant progression. In addition, single cells or cell aggregates may actively invade the matrix, utilizing epithelial, mesenchymal or mixed modes of motility. Dynamic phenotypic changes involved in 3D tumor cell invasion are sensitive to specific small-molecule inhibitors that target the actin cytoskeleton. We have used a panel of inhibitors to demonstrate the power of automated image analysis as a phenotypic or morphometric readout in cell-based assays. We introduce a streamlined stand-alone software solution that supports large-scale high-content screens, based on complex and organotypic cultures. AMIDA (Automated Morphometric Image Data Analysis) allows quantitative measurements of large numbers of images and structures, with a multitude of different spheroid shapes, sizes, and textures. AMIDA supports an automated workflow, and can be combined with quality control and statistical tools for data interpretation and visualization. We have used a representative panel of 12 prostate and breast cancer lines that display a broad spectrum of different spheroid morphologies and modes of invasion, challenged by a library of 19 direct or indirect modulators of the actin cytoskeleton which induce systematic changes in spheroid morphology and differentiation versus invasion. These results were independently validated by 2D proliferation, apoptosis and cell motility assays. We identified three drugs that primarily attenuated the invasion and formation of invasive processes in 3D, without affecting proliferation or apoptosis. Two of these compounds block Rac signalling, one affects cellular cAMP/cGMP accumulation. Our approach supports the growing needs for user-friendly, straightforward solutions that facilitate large-scale, cell-based 3D assays in basic research, drug discovery, and target validation.</p

Toward universal protein post-translational modification detection in high throughput format

Post-translational modification (PTM) of proteins plays essential regulatory roles in a variety of pathological conditions. Reliable and practical assays are required to accelerate the discovery of inhibitors and activators for PTM related diseases. Today, methodologies are based on specific or group-specific PTM recognition of e.g. phosphate for kinase activity without extending to other type of PTMs. Here we have established a universal time-resolved luminescence assay on a peptide-break platform for the direct detection of wide variety of PTMs. The developed assay is based on the leucine zipper concept wherein a europium-chelate labeled detection peptide and a non-labeled peptide substrate form a highly luminescent dimer. As an active PTM enzyme at sub or low nanomolar concentration modifies the substrate peptide, the luminescent signal of the detached detection peptide is quenched in the presence of soluble quenchers. The functionality of this universal assay technique has been demonstrated for the monitoring of phosphorylation, dephosphorylation, deacetylation, and citrullination with high applicability also to other PTMs in a high throughput format

Associations between shift work and use of prescribed medications for the treatment of hypertension, diabetes, and dyslipidemia: a prospective cohort study

Objective This study examined the associations between shift work and use of antihypertensive, lipid-lowering, and antidiabetic medications.Methods Survey data from two cohorts of Finnish men (N=11998) and women (N=49 944) working in multiple occupations where shift work was used were linked to national Drug Prescription Register data, with up to 11 years of follow-up. In each cohort, age-stratified Cox proportional hazard regression models were computed to examine any incident use of prescription medication for each of the three medical conditions, separately comparing each of two groups of rotating shift workers (those whose schedules included night shifts. and those whose schedules did not include night shifts) with day workers who worked in a similar range of occupations.Results In the larger cohort, among participants aged 40-49 at baseline, shift work without night shifts was associated with increased use of type-2 diabetes medication after adjustments for sex, occupational status, marital status, alcohol consumption, smoking, and physical activity [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.62], while shift work with night shifts was associated with increased use of dyslipidemia medication after adjustments (HR 1.33, 95% CI 1.12-1.57). There were no such associations among younger and older shift workers. Also in the larger cohort, among those aged Conclusions There was mixed evidence regarding the use of medications for cardiovascular risk factors by shift workers. Selection effects may have affected the associations.</p

Nanomolar Protein-Protein Interaction Monitoring with a Label-Free Protein-Probe Technique

Protein-protein interactions (PPIs) are an essential part of correct cellular functionality, making them increasingly interesting drug targets. While Forster resonance energy transfer-based methods have traditionally been widely used for PPI studies, label-free techniques have recently drawn significant attention. These methods are ideal for studying PPIs, most importantly as there is no need for labeling of either interaction partner, reducing potential interferences and overall costs. Already, several different label-free methods are available, such as differential scanning calorimetry and surface plasmon resonance, but these biophysical methods suffer from low to medium throughput, which reduces suitability for high-throughput screening (HTS) of PPI inhibitors. Differential scanning fluorimetry, utilizing external fluorescent probes, is an HTS compatible technique, but high protein concentration is needed for experiments. To improve the current concepts, we have developed a method based on time-resolved luminescence, enabling PPI monitoring even at low nanomolar protein concentrations. This method, called the protein probe technique, is based on a peptide conjugated with Eu3+ chelate, and it has already been applied to monitor protein structural changes and small molecule interactions at elevated temperatures. Here, the applicability of the protein probe technique was demonstrated by monitoring single-protein pairing and multiprotein complexes at room and elevated temperatures. The concept functionality was proven by using both artificial and multiple natural protein pairs, such as KRAS and eIF4A together with their binding partners, and C-reactive protein in a complex with its antibody

Oro-facial pain experience among symphony orchestra musicians in Finland is associated with reported stress, sleep bruxism and disrupted sleep-Independent of the instrument group

Background To evaluate whether oro-facial pain experience was related to the type of musical instrument and to learn more about the roles of sleep and sleep-related issues in the pain among professional musicians. Objectives A standard questionnaire was sent to all Finnish symphony orchestras (n = 19), with altogether 1005 professional musicians and other personnel. Methods The questionnaire covered descriptive data, instrument group, items on perceived quality of sleep, possible sleep bruxism, stress experience and oro-facial pain experience during the past 30 days. Results In the present study, which included the musicians only, the response rate was 58.7% (n = 488). All orchestras participated in the study, and there was no significant difference in the response rate between the orchestras. The mean age of men (52.3%) was 47.7 (SD 10.3) and of women (47.7%) was 43.4 (SD 9.8) years (P <0.001). Overall, current pain in the oro-facial area was reported by 28.9%, frequent bruxism by 12.1% and frequent stress by 20.8%. According to Somers' d, there were statistically significant but moderate correlations between overall pain reports in the oro-facial area and disrupted sleep (d = 0.127, P = 0.001), sleep bruxism (d = 0.241, P <0.001) and stress experiences (d = 0.193, P <0.001). Logistic regression revealed, independent of the instrument group (string, woodwind, brass wind, percussion), that current oro-facial pain experience was significantly associated with disrupted sleep (P = 0.001), frequent sleep bruxism (P <0.001) and frequent stress (P = 0.002) experiences. Conclusions Among symphony orchestra musicians, oro-facial pain experience seems to be related to perceptions of stress, sleep bruxism and disrupted sleep rather than the instrument group.Peer reviewe

A comparison of acoustic and linguistics methodologies for Alzheimer’s dementia recognition

In the light of the current COVID-19 pandemic, the need for remote digital health assessment tools is greater than ever. This statement is especially pertinent for elderly and vulnerable populations. In this regard, the INTERSPEECH 2020 Alzheimer’s Dementia Recognition through Spontaneous Speech (ADReSS) Challenge offers competitors the opportunity to develop speech and language-based systems for the task of Alzheimer’s Dementia (AD) recognition. The challenge data consists of speech recordings and their transcripts, the work presented herein is an assessment of different contemporary approaches on these modalities. Specifically, we compared a hierarchical neural network with an attention mechanism trained on linguistic features with three acoustic-based systems: (i) Bag-of-Audio-Words (BoAW) quantising different low-level descriptors, (ii) a Siamese Network trained on log-Mel spectrograms, and (iii) a Convolutional Neural Network (CNN) end-to-end system trained on raw waveforms. Key results indicate the strength of the linguistic approach over the acoustics systems. Our strongest test-set result was achieved using a late fusion combination of BoAW, End-to-End CNN, and hierarchical-attention networks, which outperformed the challenge baseline in both the classification and regression tasks