Development and validation of an UPLC-ESI-MS/MS method for simultaneous quantification of antineoplastic agents and their metabolites in human plasma after unintentional exposure.

Cyclophosphamide, daunorubicin, epirubicin, doxorubicin and paclitaxel are commonly used drugs in cancer treatment. However, there are no methods available enabling simultaneous measurement of these compounds and their metabolites in human plasma. Our aim was to develop and validate a sensitive method for simultaneous quantification of multiple antineoplastic drugs and their major metabolites in plasma. Solid phase extraction with Oasis PRiME HLB cartridges was used for sample clean-up. The samples were separated on an Acquity UPLC BEH C18 column, ionised by electrospray ionisation and detected with tandem mass spectrometry. The method was validated based on selectivity, extraction efficiency, matrix effect, process efficiency, linearity, sensitivity, precision and accuracy. The established LLOQs were 0.05 ng/mL (cyclophosphamide), 30 ng/mL (4-oxo-cyclophosphamide), 0.3 ng/mL (doxorubicin, daunorubicinol), 0.7 ng/mL (epirubicin, epirubicinol, doxorubicinol), 1 ng/mL (daunorubicin and paclitaxel) and 5 ng/mL (6-alpha-hydroxypaclitaxel). Afterwards, the method was tested in a real-life, unintentional exposure setting. Twenty-two plasma samples of matched maternal and cord blood pairs from pregnant cancer patients treated with chemotherapy were analysed. This resulted in two positive samples, with cyclophosphamide concentrations up to 0.37 ng/mL. The validated method is now ready to be applied in the field.

Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.

BACKGROUND: Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic. METHODS: We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results. RESULTS: Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID. CONCLUSION: Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.

Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms. METHODS: A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software. RESULTS: This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and ß1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), ß2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01). CONCLUSION: This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.

Exploring the reasons behind nurses' intentions to leave their hospital or profession: A cross-sectional survey.

Background: Multiple factors can fuel nurses' intention to leave their employing hospital or their profession. Job dissatisfaction and burnout are contributors to this decision. Sociodemographic and work context factors can also play a role in explaining nurses' intention to leave. Objective: To investigate the role of sociodemographic and work context factors, including job resources, job demands, job dissatisfaction, depersonalization, and emotional exhaustion, on nurses' intention to leave their hospital or their profession. Design: Multicentre cross-sectional study. Settings: Eight European hospitals, two per each country, including Belgium, the Netherlands, Italy, and Poland. Participants: From May 16 to September 30, 2022, we collected 1,350 complete responses from nurses working at the selected hospitals (13 % response rate). Methods: The intention to leave was assessed through two 5-Likert scale outcomes, agreeing with the intention to leave the profession and the intention to leave the hospital. Logistic regression models were used for statistical analysis. Results: At the multivariable analysis, a higher intention to leave the hospital was observed for: younger age, having served on the frontline against COVID-19, lack of quipment, living in the Netherlands, emotional exhaustion, dissatisfaction with work prospects, and dissatisfaction with the use of professional abilities. There was a higher intention to leave the profession for: younger age, living in the Netherlands, having work-related health problems, depersonalization, emotional exhaustion, low possibilities of professional development, dissatisfaction with work prospects, lack of use of professional abilities, overall ob issatisfaction, and dissatisfaction with salary. Nurses living in Italy expressed the lowest intention to leave. Conclusion: While confirming the role of job dissatisfaction and burnout, we found higher intention to leave for young nurses, nurses with work-related health problems, and caregivers during the COVID-19 pandemic. Dissatisfaction with work prospects, professional development, and salary also increased the intention to leave. We call for educators, managers, and policymakers to address these factors to retain at-risk nursing categories, implementing strategies to mitigate intentions to leave.

Identifying pain profiles in employees including work-related factors and pain perceptions: a cross-sectional study in Belgian companies.

OBJECTIVES: Studies usually investigate a limited number or a predefined combinations of risk factors for sickness absence in employees with pain. We examined frequently occurring combinations across a wide range of work-related factors and pain perceptions. DESIGN: Cross-sectional study. SETTING: Belgian companies that are under supervision of IDEWE, an external service for prevention and protection at work. PARTICIPANTS: In total, 249 employees experiencing pain for at least 6 weeks were included and filled out an online survey. OUTCOMES: Latent profile analysis was used to differentiate profiles of work-related factors (physical demands, workload, social support and autonomy) and pain perceptions (catastrophising, fear-avoidance beliefs and pain acceptance). Subsequently, profiles were compared on sociodemographics (age, gender, level of education, work arrangement, duration of complaints, multisite pain and sickness absence in the previous year) and predictors of sickness absence (behavioural intention and perceived behavioural control). RESULTS: Four profiles were identified. Profile 1 (38.2%) had favourable scores and profile 4 (14.9%) unfavourable scores across all indicators. Profile 2 (33.3%) had relatively high physical demands, moderate autonomy levels and favourable scores on the other indicators. Profile 3 (13.7%) showed relatively low physical demands, moderate autonomy levels, but unfavourable scores on the other indicators. Predictors of profiles were age (OR 0.93 and 95% CI (0.89 to 0.98)), level of education (OR 0.28 and 95% CI (0.1 to 0.79)) and duration of sickness absence in the previous year (OR 2.29 and 95% CI (0.89 to 5.88)). Significant differences were observed in behavioural intention (χ2=8.92, p=0.030) and perceived behavioural control (χ2=12.37, p=0.006) across the four profiles. CONCLUSION: This study highlights the significance of considering the interplay between work-related factors and pain perceptions in employees. Unfavourable scores on a single work factor might not translate into maladaptive pain perceptions or subsequent sickness absence, if mitigating factors are in place. Special attention must be devoted to employees dealing with unfavourable working conditions along with maladaptive pain perceptions. In this context, social support emerges as an important factor influencing sickness absence.

Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes. Aberrant DNA methylation profiles have been observed in patients with various chronic pain syndromes, correlating with hypersensitivity to painful stimuli, neuronal hyperexcitability, and inflammatory responses. Genome-wide analyses shed light on differentially methylated regions and genes that could serve as potential biomarkers for chronic pain in the epigenetic landscape. The transition from acute to chronic pain is marked by rapid DNA methylation reprogramming, suggesting its potential role in pain chronicity. This review highlights the importance of understanding the temporal dynamics of DNA methylation during this transition to develop targeted therapeutic interventions. Reversing pathological DNA methylation patterns through epigenetic therapies emerges as a promising strategy for pain management.

Undergraduate occupational medicine education in European Medical Schools: better training to meet today's challenges.

BACKGROUND: Occupational medicine (OM) faces considerable challenges today, one of them related to the university training of future physicians considered suboptimal at a global level as it has been pointed out in many studies. The aim of this study is to update the state of OM medical education in European universities. METHODS: Between March and August 2022, an e-mail survey regarding OM training to undergraduate medical students was conducted among OM professors at European universities in 28 countries (n = 347). RESULTS: Of the 347 universities, 53 medical schools from 19 countries responded (response rate = 15.3%). In 89% of cases, OM was taught. The average number of hours per academic year was 24.3, with significant variation within the same country. Lectures were the most popular teaching technique (98%), with a considerable use of modern approaches such as problem-based learning (61%), and e-learning (57%). While occupational diseases and principles of prevention were covered, other subjects such as the environmental impact or collaboration with an OM physician were poorly represented in the educational program. CONCLUSION: According to data, several European medical schools may provide insufficient OM education and training to their students. The education of undergraduate occupational medicine students in European medical schools should be designed to equip them with the knowledge and skills required to meet today's challenges. It is critical that undergraduate OM education in European medical schools be enhanced, harmonized, and standardized.

Relationship between Vitamin D Insufficiency, Lipid Profile and Atherogenic Indices in Healthy Women Aged 18-50 Years.

Although vitamin D insufficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH)D) and atherogenic indices predictive of CVD. This study investigated the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred women aged 18 to 50 years from Meknes were included. Fasting 25(OH)D and lipid concentrations were assayed by a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), non-HDL cholesterol (non-HDL-C), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH)D levels associated with high atherogenic indices. 25(OH) D below 20 ng/mL was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959), 3.637 (2.149-6.158), 3.589 (1.673-7.700), 2.074 (1.215-3.540), and 2.481 (1.481-4.123), respectively. According to the ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/mL, ≤17.5 ng/mL, ≤19.8 ng/mL, ≤20.1 ng/mL, and ≤19.5 ng/mL, respectively, all p < 0.01. Based on the atherogenic indices, this study indicates that vitamin D below 20 ng/mL may increase the risk of cardiovascular disease in adult women. Additional health measures are essential to raise awareness among women and health professionals of preventing and controlling cardiovascular risk factors, particularly among young individuals.

Additive genotoxic effects in cord blood cells upon indirect exposure to chemotherapeutic compounds crossing an in vitro placental barrier.

Prenatal exposure to toxins can adversely affect long-term health outcomes of the offspring. Though chemotherapeutics are now standard of care for treating cancer patients during pregnancy, certain compounds are known to cross the placenta and harm placental tissue. The consequences for the fetus are largely unexplored. Here we examined the responses of newborn cord blood mononuclear cells in tissue culture to two chemotherapeutic drugs, cyclophosphamide and epirubicin, when either directly exposed to these drugs, or indirectly after crossing a placenta trophoblast bilayer barrier. Cord blood mononuclear cells exposed to the conditioned media obtained from cyclophosphamide-exposed trophoblast barriers showed a significant 2.4-fold increase of nuclear ROS levels compared to direct exposure to cyclophosphamide. Indirect exposure to epirubicine-exposed trophoblast barriers not only enhanced nuclear ROS levels but also significantly increased the fraction of cord blood cells with double strand breaks, relative to directly exposed cells. Neither apoptosis nor proliferation markers were affected in cord mononuclear blood cells upon direct or indirect exposure to cyclophosphamide or epirubicin. Our data suggests that trophoblast cells exposed to cyclophosphamide or epirubicine may induce an indirect 'bystander' effect and can aggravate genotoxicity in the fetal compartment.

Burnout and predictive factors among medical students: a cross-sectional survey.

BACKGROUND: Burnout is a growing problem in medical education, and is usually characterised by three dimensions: emotional exhaustion, cynicism, and reduced professional efficacy. Currently, the majority of burnout studies have been conducted in western high-income countries, overshadowing findings from low- and middle-income countries. Our objective is to investigate burnout and its associated predictive factors in Morocco, aiming to guide intervention strategies, while also assessing differences between the preclinical and clinical years. METHODS: A cross-sectional, self-administered online survey assessing burnout dimensions and its main determinants was distributed among medical students at Université Mohammed VI des Sciences et de la Santé (UM6SS, Casablanca, Morocco). Descriptive analyses involved computing mean scores, standard deviations and Pearson correlations. Further, t-tests were performed to check for significant differences in burnout dimensions across the preclinical and clinical learning phase, and stepwise linear regression analyses were conducted using a backward elimination method to estimate the effects of the selected variables on the three burnout dimensions. RESULTS: A t-test assessing the difference in cynicism found a significant difference between students at the preclinical phase and the clinical phase, t(90) = -2.5, p = 0.01. For emotional exhaustion and reduced professional efficacy no significant difference was observed. A linear regression analysis showed that emotional exhaustion was significantly predicted by workload, work-home conflict, social support from peers and neuroticism. Cynicism was predicted by the learning phase, workload, meaningfulness and neuroticism; and reduced professional efficacy by neuroticism only. CONCLUSIONS: Our findings suggest a potential gradual increase in cynicism during medical education in Morocco. Conducting this study in a low- and middle income country has enhanced the scientific understanding of burnout in these regions. Given the identified predictive factors for burnout, such as workload, work-home conflict, support from peers, neuroticism, and meaningfulness, it is necessary to focus on these elements when developing burnout interventions.

Retaining Healing Hands: A Transnational Study on Job Retention Interventions for the Healthcare Workforce.

Healthcare organizations worldwide face challenges in retaining their healthcare workforce, with individual and organizational factors influencing their intentions to leave. This study conducted eight online co-creation workshops and four Delphi sessions to gain qualitative and in-depth insights into job retention interventions, involving healthcare workers, hospital managers, and policymakers. A thematic analysis was conducted, resulting in multiple interventions that were clustered in four pre-defined themes: professional and personal support, education, financial incentives, and regulatory measures. Professional and personal support interventions included regular interprofessional team meetings, leadership training programs, self-scheduling and sabbaticals, support for administrative and non-clinical work, and the provision of psychological counselling. Educational interventions encompassed facilitating development opportunities, periodic evaluations, onboarding, mentorship programs, and peer support groups. Financial incentives included the provision of competitive salaries, adequate infrastructure, extra benefits, transport possibilities, and permanent employment contracts. Regulatory measures addressed the need for complementary legislation across various levels, fixed healthcare worker-to-patient ratio, and instruments to monitor workload. To optimize retention strategies, healthcare organizations should tailor these interventions to address the unique factors influencing their workforce's intentions to leave within their specific context. The study concludes that combining personal and professional support, educational opportunities, financial incentives, and regulatory measures is necessary because there is no one-size-fits-all solution.

SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema.

INTRODUCTION: Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema. METHODS AND ANALYSIS: A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient's own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased. ETHICS AND DISSEMINATION: The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT05064176.

Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.

Success rate and predictors of return to work after implementation of a formal return-to-work trajectory: A retrospective cohort study.

BACKGROUND: Long term sick leave (SL) is increasing in Europe, several countries have legislative initiatives to reduce long-term absenteeism. OBJECTIVE: We evaluated the impact of a legally defined return-to-work (RTW) trajectory on the RTW of employees on sick leave in Belgium. METHODS: This was a retrospective register-based cohort study of employees (n = 1416) who followed an RTW trajectory in 2017. We linked workers' data from a prevention service with social security data. By multinomial logistic regression, we analysed which characteristics predicted the RTW with the same or another employer. RESULTS: One year after their RTW trajectory, 69.2% of the 1416 employees did not RTW; 10.7% returned to work with the same employer and 20.1% with a new employer. Duration of SL was an important predictor for the RTW with both the same employer and another employer. The odds of RTW were lower when the SL duration was >  6 months compared to <  6 months. Marital status, organization-size, and the occupational physician decision had a significant impact on the RTW with the same employer. Age and who initiated the RTW-trajectory were important predictors on the RTW with another employer. CONCLUSIONS: Overall, 30.8% of employees returned to work after their RTW trajectory. A one-size-fits-all approach is not recommended. A stepped approach with an early, informal start of the RTW process is advised. When employees or employers fail to initiate the RTW on their own, a legally defined RTW trajectory could be useful. In particular, RTW with another employer seemed a positive effect of the RTW-trajectory.

The Relationship Between Work-Related Stress and Depression: A Scoping Review.

Objectives: Work-related stress is highly prevalent. Recent systematic reviews concluded on a significant association between common work-related stress measures and depression. Our scoping review aims to explore whether work-related psychosocial stress is generally associated with depression or depressiveness, the extent and methodology of the primary research undertaken on this topic and to elucidate inconsistencies or gaps in knowledge. Methods: We searched for literature in Pubmed, PsycInfo and Web of Science including full reports in seven languages published between 1999 and 2022 and applied the PRISMA statement for scoping reviews criteria. Results: Of 463 primarily identified articles, 125 were retained after abstract and full-text screening. The majority report significant associations between work-related stress and depression. Cross-sectional studies are most prevalent. Sufficient evidence exists only for job strain and effort-reward imbalance. Most studies are from Asia, North America and Europe. The health sector is the most studied. Several research gaps such as the lack of interventional studies were identified. Conclusion: The consistency of most studies on the significant association between work-related stress and depression is remarkable. More studies are needed to improve evidence and to close research gaps.

Level of BPA contamination in resin composites determines BPA release.

OBJECTIVES: Resin composites may release bisphenol A (BPA) due to impurities present in the monomers. However, there is a lack of knowledge regarding the leaching characteristics of BPA from resin composites. Therefore, experimental resin composites were prepared with known amounts of BPA. The objective of this study was (1) to determine which amount of BPA initially present in the material leaches out in the short term and, (2) how this release is influenced by the resin composition. METHODS: BPA (0, 0.001, 0.01, or 0.1 wt%) was added to experimental resin composites containing 60 mol% BisGMA, BisEMA(3), or UDMA, respectively, as base monomer and 40 mol% TEGDMA as diluent monomer. Polymerized samples (n = 5) were immersed at 37 °C for 7 days in 1 mL of water, which was collected and refreshed daily. BPA release was quantified with UPLC-MS/MS after derivatization with pyridine-3-sulfonyl chloride. RESULTS: Between 0.47 to 0.67 mol% of the originally added BPA eluted from the resin composites after 7 days. Similar elution trends were observed irrespective of the base monomer. Two-way ANOVA showed a significant effect of the base monomer on BPA release, but the differences were small and not consistent. SIGNIFICANCE: The released amount of BPA was directly proportional to the quantity of BPA present in the resin composite as an impurity. BPA release was mainly diffusion-based, while polymer composition seemed to play a minor role. Our results underscore the importance for manufacturers only to use monomers of the highest purity in dental resin composites to avoid unnecessary BPA exposure in patients.

Elution from direct composites for provisional restorations.

Purpose To assess elution from direct composite materials for provisional restorations and compare them with elution from direct restorative composites for permanent restorations.Methods Two dual-cure (Integrity Multi-Cure and Tempsmart DC) and two self-curing composites (Protemp 4 and Structur 3) were used, with Essentia serving as a reference. Cylindrical specimens (n=20) were cured according to the manufacturer's instructions; the dual-cure materials were prepared in both self- and dual-curing modes. Elution experiments were performed using water and absolute ethanol. The samples were incubated at 37 °C for either 24 h or four weeks; the extraction solvents were refreshed weekly. The eluted BisEMA (-3 / -6 / -10), BisGMA, CQ, UDMA, and TEGDMA were quantified using UHPLC-MS/MS.Results Monomer elution was detected in all provisional composites at 24 h and four weeks, but the amounts released did not exceed those released by the reference composite. When prepared in self-curing mode, Integrity Multi-Cure exhibited significantly higher elution of BisEMA-3, -6, and -10 in ethanol both after 24 h and cumulatively after four weeks. Self-cured Tempsmart DC released significantly more CQ, TEGDMA, and UDMA in both water and ethanol after immersion for 24 h and four weeks, along with significantly more BisGMA in ethanol both after 24 h and four weeks comparison to dual-cured Tempsmart DC (two-way ANOVA, post-hoc Tukey, P < 0.05).Conclusions Provisional composite materials did not elute higher amounts of monomers than a restorative composite. Dual-cured materials, prepared in the self-curing mode, show a trend towards higher monomer elution.

Hazardous Effects of Pesticides on Human Health.

Pesticides, a major group of biocides, are designed to control harmful and/or unwanted organisms [...].

Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study.

INTRODUCTION: Around 1 in 1000-2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within normal ranges for their age, subtle differences have been identified. Given that chemotherapeutic compounds can cross the placenta, the possibility that prenatal chemotherapy exposure mutates the offspring's genome and/or epigenome, with potential deleterious effects later in life, urges to be investigated. METHODS AND ANALYSES: This multicentric observational study aims to collect cord blood, meconium and neonatal buccal cells at birth, as well as peripheral blood, buccal cells and urine from infants when 6, 18 and/or 36 months of age. Using bulk and single-cell approaches, we will compare samples from chemotherapy-treated pregnant patients with cancer, pregnant patients with cancer not treated with chemotherapy and healthy pregnant women. Potential chemotherapy-related newborn genomic and/or epigenomic alterations, such as single nucleotide variants, copy number variants and DNA-methylation alterations, will be identified in mononuclear and epithelial cells, isolated from blood, buccal swabs and urine. DNA from maternal peripheral blood and paternal buccal cells will be used to determine de novo somatic mutations in the neonatal blood and epithelial cells. Additionally, the accumulated exposure of the fetus, and biological effective dose of alkylating agents, will be assessed in meconium and cord blood via mass spectrometry approaches. ETHICS AND DISSEMINATION: The Ethics Committee Research of UZ/KU Leuven (EC Research) and the Medical Ethical Review Committee of University Medical Center Amsterdam have approved the study. Results of this study will be disseminated via presentations at (inter)national conferences, through peer-reviewed, open-access publications, via social media platforms aimed to inform patients and healthcare workers, and through the website of the International Network on Cancer, Infertility and Pregnancy (www.cancerinpregnancy.org).