Prevention of occupational diseases in Turkey : deriving lessons from journey of surveillance

Introduction: To prevent and manage the societal and economic burden of occupational diseases (ODs), countries should develop strong prevention policies, health surveillance and registry systems. This study aims to contribute to the improvement of OD surveillance at national level as well as to identify priority actions in Turkey. Methods: The history and current status of occupational health studies were considered from the perspective of OD surveillance. Interpretative research was done through literature review on occupational health at national, regional and international level. Analyses were focused on countries' experiences in policy development and practice, roles and responsibilities of institutions, multidisciplinary and intersectoral collaboration. OD surveillance models of Turkey, Belgium and the Netherlands were examined through exchange visits. Face-to-face interviews were conducted to explore the peculiarities of legislative and institutional structures, the best and worst practices, and approach principles. Results: Some countries are more focused on exploring OD trends through effective and cost-efficient researches, with particular attention to new and emerging ODs. Other countries try to reach every single case of OD for compensation and rehabilitation. Each practice has advantages and shortcomings, but they are not mutually exclusive, and thus an effective combination is possible. Conclusion: Effective surveillance and registry approaches play a key role in the prevention of ODs. A well-designed system enables monitoring and assessment of OD prevalence and trends, and adoption of preventive measures while improving the effectiveness of redressing and compensation. A robust surveillance does not only provide protection of workers' health but also advances prevention of economic losses

A 15-million-year surface- and subsurface-integrated TEX86 temperature record from the eastern equatorial Atlantic

TEX86 is a paleothermometer based on Thaumarcheotal glycerol dialkyl glycerol tetraether (GDGT) lipids and is one of the most frequently used proxies for sea-surface temperature (SST) in warmer-than-present climates. However, GDGTs are not exclusively produced in and exported from the mixed layer, so sedimentary GDGTs may contain a depth-integrated signal that is also sensitive to local subsurface temperature variability. In addition, the correlation between TEX86 and SST is not significantly stronger than that to depth-integrated mixed-layer to subsurface temperatures. The calibration of TEX86 to SST is therefore controversial. Here we assess the influence of subsurface temperature variability on TEX86 using a downcore approach. We present a 15 Myr TEX86 record from Ocean Drilling Program Site 959 in the Gulf of Guinea and use additional proxies to elucidate the source of the recorded TEX86 variability. Relatively high GDGT[2/3] ratio values from 13.6 Ma indicate that sedimentary GDGTs were partly sourced from deeper (> 200 m) waters. Moreover, late Pliocene TEX86 variability is highly sensitive to glacial–interglacial cyclicity, as is also recorded by benthic δ18O, while the variability within dinoflagellate assemblages and surface/thermocline temperature records (Uk370 and Mg/Ca) is not primarily explained by glacial–interglacial cyclicity. Combined, these observations are best explained by TEX86 sensitivity to sub-thermocline temperature variability. We conclude that TEX86 represents a depth-integrated signal that incorporates a SST and a deeper component, which is compatible with the present-day depth distribution of Thaumarchaeota and with the GDGT[2/3] distribution in core tops. The depth-integrated TEX86 record can potentially be used to infer SST variability, because subsurface temperature variability is generally tightly linked to SST variability. Using a subsurface calibration with peak calibration weight between 100 and 350 m, we estimate that east equatorial Atlantic SST cooled by ∼ 5◦C between the Late Miocene and Pleistocene. On shorter timescales, we use the TEX86 record as a proxy for South Atlantic Central Water (SACW), which originates from surface waters in the South Atlantic Gyre and mixes at depth with Antarctic Intermediate Water (AAIW). Leads and lags around the Pliocene M2 glacial (∼ 3.3 Ma) in our record, combined with published information, suggest that the M2 glacial was marked by SACW cooling during an austral summer insolation minimum and that decreasing CO2 levels were a feedback, not the initiator, of glacial expansion

Education and Training: Key Factors in Global Occupational and Environmental Health

Introduction: Education and training in Occupational and Environmental Health (OEH) play an important role in building global capacity and contribute to safer working conditions. The shortage of occupational health professionals, the lack of knowledge and a high number of occupational accidents and diseases stress the demand for providing further education and training in OEH. This need is especially urgent in low and middle-income countries. Three international courses on OEH provide valuable insights on how to develop successful trainings in the field and how to contribute to the creation of healthy and safe workplaces. Methodology and Results: The courses "Global Occupational and Environmental Determinants of Diseases: a multidisciplinary and multicultural approach for prevention" (University of Brescia, Italy), "Advanced International Training Course in OEH" (Chulabhorn Research Institute, Bangkok, Thailand) and "Teaching interventions crossing borders" (Ludwig-Maximillians-Universitat, Munich, Germany) offer a unique networking opportunity for health professionals from low-, middle- and high-income countries. Three main characteristics of learning were identified as successful for adult learning in OEH: Interdisciplinary learning allows exchanging skills and knowledge and therefore closes gaps between the several disciplines within OEH. Experiential learning enables participants to reflect on their personal experiences, e.g. through workplace visits. Finally, active learning empowers the learner to take the leading role in the learning process using e.g. problem- or project-based learning approaches. Conclusion: Training and education in OEH should become a higher priority by including it in the standard public health and medical curricula. For this, train the trainer approaches are essential in many countries. Any OEH training should follow the interdisciplinary, experiential and interactive learning approach and should be accessible to participants from all regions

Genetic susceptibility loci for cardiovascular disease and their impact on atherosclerotic plaques

Background: Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke and coronary artery disease. However, deciphering their underlying mechanisms are challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for large artery ischemic stroke and coronary artery disease relate to plaque characteristics is thus far unknown but may point to novel mechanisms. Methods: We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in 2 independent biobanks, Biobank of Karolinska Endarterectomy and Stockholm Atherosclerosis Gene Expression. Results: A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, P=5.09×10−6 after correction for multiple testing. We further characterized this 7q22 Locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood and provide data from public resources showing an association with decreased LDL (low-density lipoprotein) and increase HDL (high-density lipoprotein) in the blood. Conclusions: Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics

Plasma Lipoprotein Lipase Is Associated with Risk of Future Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy

Introduction: Carotid plaque intraplaque haemorrhage (IPH) is associated with future cardiovascular events. It was hypothesised that plasma proteins associated with carotid plaque IPH are also likely to be associated with major adverse cardiovascular events (MACE) after carotid endarterectomy (CEA). Methods: In pre-operative blood samples from patients undergoing CEA within the Athero-Express biobank, proteins involved in cardiovascular disease were measured using three OLINK proteomics immunoassays. The association between proteins and IPH was analysed using logistic regression analyses. Subsequently, the association between the IPH associated plasma proteins and the three year post-operative risk of MACE (including stroke, myocardial infarction, or cardiovascular death) was analysed. Results: Within the three year follow up, 130 patients (18.9%) of 688 symptomatic and asymptomatic patients undergoing CEA developed MACE. Six of 276 plasma proteins were found to be significantly associated with IPH, from which only lipoprotein lipase (LPL) was associated with the post-operative risk of MACE undergoing CEA. Within the 30 day peri-operative period, high plasma LPL was independently associated with an increased risk of MACE (adjusted hazard ratio [HR] per standard deviation [SD] 1.60, 1.10 – 2.30), p = .014). From 30 days to three years, however, high LPL was associated with a lower risk of MACE (adjusted HR per SD 0.80, 0.65 – 0.99, p= .036). Conclusion: High LPL concentrations were found to be associated with a higher risk of MACE in the first 30 post-operative days but with a lower risk MACE between 30 days and three years, meaning that LPL has different hazards at different time points

An automatic entropy method to efficiently mask histology whole-slide images

Tissue segmentation of histology whole-slide images (WSI) remains a critical task in automated digital pathology workflows for both accurate disease diagnosis and deep phenotyping for research purposes. This is especially challenging when the tissue structure of biospecimens is relatively porous and heterogeneous, such as for atherosclerotic plaques. In this study, we developed a unique approach called 'EntropyMasker' based on image entropy to tackle the fore- and background segmentation (masking) task in histology WSI. We evaluated our method on 97 high-resolution WSI of human carotid atherosclerotic plaques in the Athero-Express Biobank Study, constituting hematoxylin and eosin and 8 other staining types. Using multiple benchmarking metrics, we compared our method with four widely used segmentation methods: Otsu's method, Adaptive mean, Adaptive Gaussian and slideMask and observed that our method had the highest sensitivity and Jaccard similarity index. We envision EntropyMasker to fill an important gap in WSI preprocessing, machine learning image analysis pipelines, and enable disease phenotyping beyond the field of atherosclerosis

Characteristics of peripheral blood cells are independently related to major adverse cardiovascular events after carotid endarterectomy

BACKGROUND AND AIMS: Patients who underwent carotid endarterectomy (CEA) still have a residual risk of 13% of developing a major adverse cardiovascular event (MACE) within 3 years. Inflammatory processes leading up to MACE are not fully understood. Therefore, we examined blood cell characteristics (BCCs), possibly reflecting inflammatory processes, in relation to MACE to identify BCCs that may contribute to an increased risk. METHODS: We analyzed 75 pretreatment BCCs from the Sapphire analyzer, and clinical data from the Athero-Express biobank in relation to MACE after CEA using Random Survival Forests, and a Generalized Additive Survival Model. To understand biological mechanisms, we related the identified variables to intraplaque hemorrhage (IPH). RESULTS: Of 783 patients, 97 (12%) developed MACE within 3 years after CEA. Red blood cell distribution width (RDW) (HR 1.23 [1.02, 1.68], p = 0.022), CV of lymphocyte size (LACV) (HR 0.78 [0.63, 0.99], p = 0.043), neutrophil complexity of the intracellular structure (NIMN) (HR 0.80 [0.64, 0.98], p = 0.033), mean neutrophil size (NAMN) (HR 0.67 [0.55, 0.83], p < 0.001), mean corpuscular volume (MCV) (HR 1.35 [1.09, 1.66], p = 0.005), eGFR (HR 0.65 [0.52, 0.80], p < 0.001); and HDL-cholesterol (HR 0.62 [0.45, 0.85], p = 0.003) were related to MACE. NAMN was related to IPH (OR 0.83 [0.71-0.98], p = 0.02). CONCLUSIONS: This is the first study to present a higher RDW and MCV and lower LACV, NIMN and NAMN as biomarkers reflecting inflammatory processes that may contribute to an increased risk of MACE after CEA

Development of a GIS-based knowledge hub for contaminants of emerging concern in South African water resources using open-source software : lessons learnt

SUPPLEMENTARY INFORMATION : The development of the CEC Knowledge Hub.DATA AVAILABILITY STATEMENT : Data will be made available on request.With population growth and dwindling freshwater sources, protecting such sources has come to the forefront of water resource management. Historically, society’s response to a problem is based on funding availability, current threat, and public outcry. Achieving this is largely dependent on the knowledge of the factors that are resulting in compromised water sources. These factors are constantly changing as novel contaminants are introduced into surface water sources. As we are in the information age, the interest in contaminants of emerging concern (CEC) is gaining ground. Whilst research is being conducted to identify contaminants in South African water sources, the research outputs and available information is not collated and presented to the science community and stakeholders in readily available formats and platforms. Current research outcomes need to be made known to regulators in order to develop environmental laws. By using fourth industrial revolution technology, we were able to collate available data in literature and display these in a user-friendly online format to regulatory bodies as well as researchers. A standardized excel spreadsheet was developed and uploaded to a PostgreSQL, running a PostGIS extension and was then processed in the GeoServer to allow for visualization on an interactive map which can be continuously updated. The near real-time access to information will reduce the possibility of duplication of research efforts, enhance collaboration in the discipline, and act as a CEC early warning system.Water Research Commissionhttps://www.cell.com/heliyon/homePlant Production and Soil Scienc

X chromosome inactivation skewing is common in advanced carotid atherosclerotic lesions in females and predicts secondary peripheral artery events

BACKGROUND AND AIM: Sex differences in atherosclerosis have been described with female plaques being mostly perceived as stable and fibrous. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men have been linked to cardiovascular health. In women, X-linked mechanisms such as X chromosome inactivation (XCI) skewing is common in several tissues. Yet, information on the role of XCI in female atherosclerotic plaques is lacking. Here, we investigated the presence of XCI skewing in advanced atherosclerotic lesions and its association with cardiovascular risk factors, histological plaque data, and clinical data. METHODS: XCI skewing was quantified in 154 atherosclerotic plaque and 55 blood DNA samples of women included in the Athero-Express study. The skewing status was determined performing the HUMARA assay. Then, we studied the relationship of XCI skewing in female plaque and cardiovascular risk factors using regression models. In addition, we studied if plaque XCI predicted plaque composition, and adverse events during 3-years follow-up using Cox proportional hazard models. RESULTS: XCI skewing was detected in 76 of 154 (49.4%) plaques and in 27 of 55 (67%) blood samples. None of the clinical risk factors were associated with plaque skewing. Plaque skewing was more often detected in plaques with a plaque hemorrhage (OR [95% CI]: 1.44 [1.06-1.98], P = 0.02). Moreover, skewed plaques were not associated with a higher incidence of composite and major events but were specifically associated with peripheral artery events during a 3-year follow-up period in a multivariate model (HR [95%CI]: 1.46 [1.09-1.97]; P = 0.007). CONCLUSIONS: XCI skewing is common in carotid plaques of females and is predictive for the occurrence of peripheral artery events within 3 years after carotid endarterectomy

Human extrahepatic and intrahepatic cholangiocyte organoids show region-specific differentiation potential and model cystic fibrosis-related bile duct disease

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis