Saltwater intrusion and human health risks for coastal populations under 2050 climate scenarios.

Populations consuming saline drinking water are at greater risk of high blood pressure and potentially other adverse health outcomes. We modelled data and used available datasets to identify countries of higher vulnerability to future saltwater intrusion associated with climate change in 2050 under Representative Concentration Pathways (RCP)4.5 and RCP8.5. We developed three vulnerability criteria to capture geographies with: (1) any coastal areas with projected inland saltwater intrusion of ≥ 1 km inland, (2) > 50% of the population in coastal secondary administrative areas with reliance on groundwater for drinking water, and 3) high national average sodium urinary excretion (i.e., > 3 g/day). We identified 41 nations across all continents (except Antarctica) with ≥ 1 km of inland saltwater intrusion by 2050. Seven low- and middle-income countries of higher vulnerability were all concentrated in South/Southeast Asia. Based on these initial findings, future research should study geological nuances at the local level in higher-risk areas and co-produce with local communities contextually appropriate solutions to secure equitable access to clean drinking water.

Sex-Specific Association of Ambient Temperature With Urine Biomarkers in Southwest Coastal Bangladesh.

Introduction: Men are vulnerable to ambient heat-related kidney disease burden; however, limited evidence exists on how vulnerable women are when exposed to high ambient heat. We evaluated the sex-specific association between ambient temperature and urine electrolytes, and 24-hour urine total protein, and volume. Methods: We pooled a longitudinal 5624 person-visits data of 1175 participants' concentration and 24-hour excretion of urine electrolytes and other biomarkers (24-hour urine total protein and volume) from southwest coastal Bangladesh (Khulna, Satkhira, and Mongla districts) during November 2016 to April 2017. We then spatiotemporally linked ambient temperature data from local weather stations to participants' health outcomes. For evaluating the relationships between average ambient temperature and urine electrolytes and other biomarkers, we plotted confounder-adjusted restricted cubic spline (RCS) plots using participant-level, household-level, and community-level random intercepts. We then used piece-wise linear mixed-effects models for different ambient temperature segments determined by inflection points in RCS plots and reported the maximum likelihood estimates and cluster robust standard errors. By applying interaction terms for sex and ambient temperature, we determined the overall significance using the Wald test. Bonferroni correction was used for multiple comparisons. Results: The RCS plots demonstrated nonlinear associations between ambient heat and urine biomarkers for males and females. Piecewise linear mixed-effects models suggested that sex did not modify the relationship of ambient temperature with any of the urine parameters after Bonferroni correction (P < 0.004). Conclusion: Our findings suggest that women are as susceptible to the effects of high ambient temperature exposure as men.

Progression of multiple vertebral fractures after Denosumab discontinuation under treatment with Romosozumab. A case-report.

INTRODUCTION: Denosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon. CASE PRESENTATION: We present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed. DISCUSSION: Our clinical case illustrates the effectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option.

Temporal trends of cancer incidence rates for the most frequent cancer sites in Cyprus (2004-2017).

BACKGROUND: Cancer is one of the leading causes of morbidity and mortality, worldwide. Little information is available for the temporal trends of cancer in the Mediterranean region, including Cyprus. AIMS: We aimed to analyze cancer incidence trends overall and by sex for the period 2004-2017 regarding the five most common cancer sites for the population of Cyprus. METHODS AND RESULTS: Data were obtained from the nationwide cancer registry dataset that included 27 017 total cancer cases in Cyprus (2004-2017). We estimated the crude, sex-, and age-specific, as well as age-standardized (ASR) cancer incidence rates and we analyzed the time trends of ASR using the joinpoint regression program. For the general population (0-85+ years of age), the most common cancer sites in descending order, were breast, prostate, lung, colorectal, and thyroid cancer. During the study period, breast and thyroid cancer ASR presented a significant (p < .05) increasing temporal trend. Lung cancer ASRs seemed to stabilize (no increase or decrease) during the more recent years (2009 onwards) for both sexes; a similar pattern was observed for colorectal cancer in males. The ASRs of prostate cancer in men were in steady decline from 2012 onwards and the same was observed for the female ASRs of colorectal cancer from 2007 onwards. The colorectal cancer ASR temporal patterns overall, during the whole study period appeared unchanged. CONCLUSION: This temporal analysis would feed into cancer surveillance and control programs that focus on prevention, early detection, and treatment, particularly for cancer sites of higher mortality rates or those with temporally increasing trends.

Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives.

BACKGROUND: Vitamin D, acknowledged since the 1930s for its role in preventing rickets, gained additional prominence in relation to fragility fracture prevention in the late 1980s. From the early 2000s, connections between vitamin D deficiency and extra-skeletal pathologies emerged, alongside increased awareness of widespread deficits. This prompted crucial debates on optimal serum concentrations, expected to conclude when the outcomes of high-dose supplementation randomized controlled trials were available. Skepticism arose with inconclusive results from these trials. CONTENT: This review begins with an exploration of vitamin D metabolism, followed by a detailed description of the measurement of vitamin D metabolites and the crucial role of standardization. Subsequent sections focus on the association of vitamin D with bone health and explore the extra-skeletal effects. The review concludes with a comprehensive discussion on the definition of vitamin D status and its implications for supplementation. SUMMARY: Despite standardization efforts, assay variations and challenges still exist, especially in specific patient groups. Vitamin D supplementation has a significant impact on bone metabolism and optimal vitamin D status improves the efficacy of antiresorptive drugs such as bisphosphonates. The extra-skeletal effects of vitamin D remain debated, but may include potential benefits in conditions such as respiratory infections and cancer mortality, particularly in deficient individuals. The definition of vitamin D sufficiency is nuanced, especially when variations in population groups and analytical methods are taken into account. Despite ongoing debates and recent mega-trials tempering enthusiasm, vitamin D remains a complex and essential element in human health. Further research is needed to clarify its role in various health outcomes and guide supplementation strategies.

Temporal dynamics of drinking water sodium levels in coastal areas, Cyprus 2009-2020.

Around the world, groundwater salinity levels are increasing in coastal areas, as a result of its systematic overexploitation for domestic, agricultural and industrial demand and potentially due to climate change manifestations (such as, sea level rise). We hypothesized that the groundwater quality of many Mediterranean coastal areas is already being perturbed, especially for water salinity, depending on the groundwater distance from the seafront. The objectives of this study were: i) to evaluate the magnitude and temporal variance of drinking water sodium (Na) as a metric of salt intake used for public health purposes using drinking water data in Cyprus; and ii) to examine the degree of Na enrichment in drinking water as defined by the seawater coastline distance of each sampling point. Open access governmental data of drinking water Na (n = 3304), daily max ambient air temperature and total rainfall were obtained for the period of 2009-2020 from governmental repositories. Linear mixed-effect regression models of drinking water Na with unsupervised covariance matrix were used. After adjusting for temperature and rainfall data, there was a significant annual increase in drinking water Na levels over time (beta = 0.01; 95 % CI: 0.00, 0.02; p = 0.02) for the coastal areas (<10 km from coastline, cutoff used by the EU Environment Agency), but this was not the case for non-coastal areas (>10 km distance from coastline). The distance of each sampling point from the coastline in Cyprus was negatively associated with drinking water Na in coastal areas (beta = -0.04, 95%CI: -0.06, -0.01; p = 0.002); this was not the case for non-coastal areas. More research is warranted to better understand the impacts of global environmental change on water quality in association with the burden of disease in coastal areas.

The Need for an Alternative Health Claim Process for Foods Based on Both Nutrient and Contaminant Profiles.

Most authorized health claims on foods have been established on the basis of single dietary components, mainly micronutrients, such as vitamins, minerals, and possibly bioactives. Failure to sufficiently define and characterize the nutritional profile of a food product is one of the main reasons for rejection or incomplete status for thousands of health claim applications, whereas the food's contaminant profile is simply not accounted for. The objective of this work was to highlight the accumulating scientific evidence supporting a reform of the health claim evaluation process for foods toward more holistic approaches. This would entail the characterization of multiple nutrient-contaminant pairs and contaminant mixture profiles at contaminant levels currently considered "safe," including their interactions that would impact human health outcome(s) in a net positive or negative direction. The notion of a stable nutritional profile in food commodities has been challenged by studies reporting a variable food contaminant content and a declining content of proteins/micronutrients in crops due to anthropogenic greenhouse gas emissions. A holistic approach in the health claim process for foods would entail the incorporation of cumulative risk assessment and/or risk-benefit protocols that effectively combine health risks and benefits associated with multiple nutritional and contaminant attributes of the food/diet under evaluation.

An anti-inflammatory response of an organic food intervention by reducing pesticide exposures in children of Cyprus: A cluster-randomized crossover trial.

Organic food consumption in children has been shown to reduce the body burden of chemical pesticides. However, there is little evidence of human health benefits associated with the consumption of organic foods. The objectives were to i) determine the effectiveness of an organic food intervention treatment in reducing the magnitude of an inflammation biomarker (C-reactive protein, CRP) in children (10-12 years) and ii) assess the association between the urinary biomarkers of exposure to pesticides and CRP. This work was part of the ORGANIKO cluster-randomized cross-over trial entailing a 40-day organic food treatment in healthy children. Urinary biomarkers of exposure to pesticides and inflammation (CRP) were measured using tandem mass spectrometry and ELISA immunoassay, respectively. Linear mixed-effect regression models of CRP were used to account for the effect and duration of organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. Results supported an anti-inflammatory effect of organic food treatment in children, albeit with mixed results, depending on the creatinine adjustment method; biomarker levels were divided by urinary creatinine (method a1), or urinary creatinine was used as a fixed effect variable (a2). In the a1 method, a time-dependent reduction for creatinine-adjusted CRP (ß = -0.019; 95% CI: -0.031, -0.006; q = 0.045) was observed during the organic food intervention period. A statistically significant association (ß = 0.104; 95% CI: 0.035, 0.173; q = 0.045) was found between the biomarker of pyrethroids exposure (3-PBA) and CRP inflammatory biomarker, but not for 6-CN. In the a2 method, similar trend of time-dependent reduction for creatinine-adjusted CRP (ß = -0.008; 95% CI: -0.021, 0.004; p = 0.197) was observed during the organic food intervention period, but did not reach statistical significance (q > 0.05); the associations of pyrethroid and neonicotinoid biomarkers with CRP were not statistically significant (q > 0.05). More studies are warranted to sufficiently understand the potential anti-inflammatory response of an organic food treatment.

Decoding the exposome: data science methodologies and implications in exposome-wide association studies (ExWASs).

This paper explores the exposome concept and its role in elucidating the interplay between environmental exposures and human health. We introduce two key concepts critical for exposomics research. Firstly, we discuss the joint impact of genetics and environment on phenotypes, emphasizing the variance attributable to shared and nonshared environmental factors, underscoring the complexity of quantifying the exposome's influence on health outcomes. Secondly, we introduce the importance of advanced data-driven methods in large cohort studies for exposomic measurements. Here, we introduce the exposome-wide association study (ExWAS), an approach designed for systematic discovery of relationships between phenotypes and various exposures, identifying significant associations while controlling for multiple comparisons. We advocate for the standardized use of the term "exposome-wide association study, ExWAS," to facilitate clear communication and literature retrieval in this field. The paper aims to guide future health researchers in understanding and evaluating exposomic studies. Our discussion extends to emerging topics, such as FAIR Data Principles, biobanked healthcare datasets, and the functional exposome, outlining the future directions in exposomic research. This abstract provides a succinct overview of our comprehensive approach to understanding the complex dynamics of the exposome and its significant implications for human health.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.

Assessing the status of European laboratories in evaluating biomarkers for chronic kidney diseases (CKD) and recommendations for improvement: insights from the 2022 EFLM Task Group on CKD survey.

OBJECTIVES: Chronic kidney disease (CKD) is a global health issue, ranking as the third leading cause of death worldwide. CKD diagnosis and management depend on clinical laboratory tests, necessitating consistency for precise patient care. Global harmonization of CKD testing through clinical practice guidelines (CPGs) is recommended. Prior to CPG development, assessing the current CKD testing landscape is crucial. In 2022, the European Federation of Laboratory Medicine (EFLM) conducted an online survey among European laboratories associated with EFLM, evaluating CKD testing practices, including new glomerular filtration rate (GFR) estimation methods. This report summarizes the 2022 survey findings and offers recommendations for improving CKD test standardization. METHODS: An online survey was conducted in November 2022 using a questionnaire hosted on LimeSurvey sent to European laboratories affiliated with the EFLM. The survey results were recorded in Excel files and analysed. RESULTS: The results highlight significant discrepancies among countries in unit expression, methods, cystatin C use, and GFR calculation equations. Additionally, limited attention to pediatric renal biology specifics, varied proteinuria and albuminuria result expressions, and limited awareness of GFR measurement methods through iohexol clearance are noted. CONCLUSIONS: In an effort to enhance the standardization of crucial biomarkers utilized in nephrology for evaluating renal function and diagnosing kidney injuries, the EFLM Task Group on CKD suggests nine practical recommendations tailored for European laboratories. The group is confident that implementing these measures will minimize result expression discrepancies, ultimately leading to enhanced patient care.

Objectively measured cognitive dysfunction in patients with primary hyperparathyroidism improves after parathyroidectomy.

BACKGROUND: A relationship between primary hyperparathyroidism (PHPT) and decreased quality of life has been shown using patient-reported outcome measures, including Pasieka's Parathyroid Assessment of Symptoms, SF-36, and PROMIS. Despite this, there remains a paucity of objectively measured data demonstrating cognitive dysfunction in patients with PHPT. We assessed whether parathyroidectomy resulted in quantifiable cognitive improvement. METHODS: We examined 59 consecutive patients with PHPT who underwent parathyroidectomy at a single institution between 2019 and 2021. We used BrainCheck, a clinically validated objective measure of neurocognition, to assess pre- and postoperative neurocognitive changes and evaluated associations between BrainCheck scores and parathyroidectomy using the Wilcoxon signed-rank test. RESULTS: Of the 59 patients with PHPT who underwent parathyroidectomy and rapid cognitive assessment with BrainCheck, 72.9% were female, 49.2% were White, and 30.5% were African American. A total of 44.1% of patients preoperatively showed neurocognitive dysfunction relative to the general population compared to 22% postoperatively, representing an improvement in 53% of the cohort. Postoperative scores for the entire cohort were significantly higher than preoperative scores (Z =2.85, P = .004). This association remained significant when the cohort was stratified by sex, as both males (Z =2.02, P = .044) and females (Z =2.09, P = .037) had a significant increase in scores. Domain sub-analysis demonstrated a significant association between parathyroidectomy and improved executive function (P < .01). CONCLUSION: Patients with PHPT experience objectively measurable cognitive changes associated with PHPT that can be reversed by parathyroidectomy, with improvements observed as early as 2 weeks after surgery. Further research with a larger cohort is needed to corroborate our findings.

Glucose-dependent insulinotropic polypeptide regulates body weight and food intake via GABAergic neurons in mice.

The development of single-molecule co-agonists for the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) is considered a breakthrough in the treatment of obesity and type 2 diabetes. But although GIPR-GLP-1R co-agonism decreases body weight with superior efficacy relative to GLP-1R agonism alone in preclinical1-3 and clinical studies4,5, the role of GIP in regulating energy metabolism remains enigmatic. Increasing evidence suggests that long-acting GIPR agonists act in the brain to decrease body weight through the inhibition of food intake3,6-8; however, the mechanisms and neuronal populations through which GIP affects metabolism remain to be identified. Here, we report that long-acting GIPR agonists and GIPR-GLP-1R co-agonists decrease body weight and food intake via inhibitory GABAergic neurons. We show that acyl-GIP decreases body weight and food intake in male diet-induced obese wild-type mice, but not in mice with deletion of Gipr in Vgat(also known as Slc32a1)-expressing GABAergic neurons (Vgat-Gipr knockout). Whereas the GIPR-GLP-1R co-agonist MAR709 leads, in male diet-induced obese wild-type mice, to greater weight loss and further inhibition of food intake relative to a pharmacokinetically matched acyl-GLP-1 control, this superiority over GLP-1 vanishes in Vgat-Gipr knockout mice. Our data demonstrate that long-acting GIPR agonists crucially depend on GIPR signaling in inhibitory GABAergic neurons to decrease body weight and food intake.

High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling.

Oxytocin-expressing paraventricular hypothalamic neurons (PVNOT neurons) integrate afferent signals from the gut, including cholecystokinin (CCK), to adjust whole-body energy homeostasis. However, the molecular underpinnings by which PVNOT neurons orchestrate gut-to-brain feeding control remain unclear. Here, we show that mice undergoing selective ablation of PVNOT neurons fail to reduce food intake in response to CCK and develop hyperphagic obesity on a chow diet. Notably, exposing wild-type mice to a high-fat/high-sugar (HFHS) diet recapitulates this insensitivity toward CCK, which is linked to diet-induced transcriptional and electrophysiological aberrations specifically in PVNOT neurons. Restoring OT pathways in diet-induced obese (DIO) mice via chemogenetics or polypharmacology sufficiently re-establishes CCK's anorexigenic effects. Last, by single-cell profiling, we identify a specialized PVNOT neuronal subpopulation with increased κ-opioid signaling under an HFHS diet, which restrains their CCK-evoked activation. In sum, we document a (patho)mechanism by which PVNOT signaling uncouples a gut-brain satiation pathway under obesogenic conditions.

A comparative study between low- and high-tech methods for the detection and mitigation of illicit connections in stormwater systems.

Illicit connections of wastewater to stormwater systems are the main drawback of separate sewer systems, as they lead to a direct discharge of untreated wastewater to the aquatic environment. Consequently, several inspection methods have been developed for detecting illicit connections. This study simultaneously applied several low- and high-tech methods for the detection of illicit connections in the same catchment (De Heuvel, the Netherlands). The methods included mesh wire screens for capturing coarse contamination, measurements of electroconductivity and temperature, sampling and quantification of Escherichia coli and extended-spectrum ß-lactamase-producing E. coli (ESBL-EC), DNA analysis via quantitative polymerase chain reaction for human-, dog-, and bird-specific fecal indicators, and distributed temperature sensing. Significant illicit connections could be identified using all methods. Nonetheless, hydraulic conditions and, predominantly, the sewage volume determine whether a misconnection can be detected by especially the low-tech methods. Using these results, the identified misconnections were repaired and biological and DNA analyses were repeated. Our results demonstrate that there were no changes in E. coli or ESBL-EC before and after mitigation, suggesting that these common markers of fecal contamination are not specific enough to evaluate the performance of mitigation efforts. However, a marked decrease in human wastewater markers (HF183) was observed.

Optical vortices shape optical tornados.

We demonstrate that by seeding an accelerating ring-Airy beam with a finite number of off-axis optical vortices, it transforms into a tornado wave (ToW) upon propagation. Using numerical simulations, we show that both the spiraling high-intensity lobes and the optical vortices exhibit angular acceleration and follow interwinding braid-like trajectories. Likewise, we study the effect of the number, position, and topological charge of the vortices on the propagation dynamics and reveal the connection between optical vortices and optical tornados.

Prevalence and sociodemographic determinants of selected noncommunicable diseases among the general population of Cyprus: A large population-based cross-sectional study.

Background: Noncommunicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. The aim of this study was to determine the prevalence of NCDs among the population of Cyprus and to identify the distribution of the socioeconomic and demographic determinants among individuals with the most frequent NCDs. Methods: A cross-sectional study was conducted using stratified sampling. Socioeconomic and demographic characteristics and the presence of NCDs were collected through a standardized questionnaire. The diseases were classified using the 10th revision of the International Classification of Diseases (ICD-10). Results: In total, 1140 individuals participated in the study, among whom 590 (51.7%) had at least one chronic disease. The most prevalent NCDs were hyperlipidemia (17.4%), hypertension (12.9%), and thyroid diseases (8.4%). We identified more males than females with hyperlipidemia aged 25-44 years old and >65 years old (p = 0.024), more males compared to females with hypertension (p = 0.001) and more females compared to males with thyroid diseases (p < 0.001). Individuals with hypertension and hyperlipidemia were more likely to be married, to have completed a higher education, and to have a high annual income. Discussion: In Cyprus, the majority of the general population had at least one NCD. Hyperlipidemia, hypertension, and thyroid disease are relatively common, even at younger ages, highlighting the need for the development of public health programs aimed at addressing and preventing NCDs.

Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

Clinical Performance Evaluation of Continuous Glucose Monitoring Systems: A Scoping Review and Recommendations for Reporting.

The use of different approaches for design and results presentation of studies for the clinical performance evaluation of continuous glucose monitoring (CGM) systems has long been recognized as a major challenge in comparing their results. However, a comprehensive characterization of the variability in study designs is currently unavailable. This article presents a scoping review of clinical CGM performance evaluations published between 2002 and 2022. Specifically, this review quantifies the prevalence of numerous options associated with various aspects of study design, including subject population, comparator (reference) method selection, testing procedures, and statistical accuracy evaluation. We found that there is a large variability in nearly all of those aspects and, in particular, in the characteristics of the comparator measurements. Furthermore, these characteristics as well as other crucial aspects of study design are often not reported in sufficient detail to allow an informed interpretation of study results. We therefore provide recommendations for reporting the general study design, CGM system use, comparator measurement approach, testing procedures, and data analysis/statistical performance evaluation. Additionally, this review aims to serve as a foundation for the development of a standardized CGM performance evaluation procedure, thereby supporting the goals and objectives of the Working Group on CGM established by the Scientific Division of the International Federation of Clinical Chemistry and Laboratory Medicine.

Chrono-modulated effects of external stressors on oxidative stress and damage in humans: A scoping review on night shift work.

BACKGROUND: Oxidative stress and tissue damage (OSD) play a pivotal role as an early-stage process in chronic disease pathogenesis. However, there has been little research to better understand the temporal (χρόνος[chronos]) dimensions of OSD process associated with environmental (non-genetic, including behaviors/lifestyle) and/or occupational stressors, like night shift work. OSD processes have recently attracted attention in relation to time-resolved external stressor trajectories in personalized medicine (prevention) initiatives, as they seem to interact with circadian clock systems towards the improved delineation of the early stages of (chronic) disease process. OBJECTIVES: This work critically reviewed human studies targeting the temporal dynamics of OSD and circadian clock system's activity in response to environmental/occupational stressors; the case of night shift work was examined. METHODS: Being a key stressor influencing OSD processes and circadian rhythm, night shift work was evaluated as part of a scoping review of research in OSD, including inflammatory and metabolic processes to determine the extent of OSD research undertaken in human populations, methodologies, tools and biomarkers used and the extent that the temporal dimensions of exposure and biological effect(s) were accounted for. Online databases were searched for papers published from 2000 onwards, resulting in the selection of 53 original publications. RESULTS AND DISCUSSION: The majority of studies (n = 41) took place in occupational settings, while the rest were conducted in the general population or patient groups. Most occupational studies targeted outcomes of oxidative stress/damage (n = 19), followed by the combination of OSD with inflammatory response (n = 10), and studies focused on metabolic outcomes (n = 12). Only a minor fraction of the studies measured biomarkers related to circadian rhythm, such as, melatonin, its metabolite, or cortisol. Night shift work was associated with select biomarkers of OSD and inflammation, albeit with mixed results. Although much progress in delineating the biological mechanisms of OSD process has been made, an equally thorough investigation on the temporal trajectory of OSD processes as triggered by environmental/occupational stressors in human studies has yet to fully evolve.