A systematic review and meta-analysis of human population studies on the association between exposure to toxic environmental chemicals and left ventricular dysfunction (LVD).

BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.

Comparing survival rates for clusters of depressive symptoms found by Network analysis' community detection algorithms: Results from a prospective population-based study among 9774 cancer survivors from the PROFILES-registry.

OBJECTIVES: Previous studies have shown that depression is associated with mortality in patients with cancer. Depression is however a heterogeneous construct and it may be more helpful to look at different (clusters) of depressive symptoms than to look at depression as a discrete condition. The aim of the present study is to investigate whether clusters of depressive symptoms can be identified using advanced statistics and to investigate how these symptom clusters are associated with all-cause mortality in a large group of patients with cancer. METHOD: Data from a large population-based cohort study (PROFILES) including various cancer types were used. Eligible patients completed self-report questionnaires (i.e. Fatigue assessment scale, Hospital anxiety and depression scale, EORTC QOL-C30) after diagnosis. Survival status was determined on 31 January 2022. RESULTS: In total, 9744 patients were included. Network analyses combining different community detection algorithms showed that clusters of depressive symptoms could be detected that correspond with motivational anhedonia, consummatory anhedonia and negative affect. Survival analyses using the variables that represented these clusters best showed that motivational and consummatory anhedonia were associated with survival. Even after controlling for clinical and sociodemographic variables items assessing motivational anhedonia were significantly associated with mortality over time. CONCLUSION: Separate clusters of symptoms that correspond with motivational and consummatory anhedonia and negative affect can be distinguished and anhedonia may be associated with mortality more than negative affect. Looking at particular (clusters of) depressive symptoms may be more informative and clinically relevant than using depression as a single construct (i.e. syndrome).

Modeling the migration of chemicals from food contact materials to food: The MERLIN-expo/VERMEER toolbox.

Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficients and FCM-Food partition coefficients. The aim of the present study was to evaluate the performance of these operational models in the prediction of a chemical's concentration in food in contact with a plastic monolayer FCM. A comparison to experimental migration values reported in literature was conducted. Deterministic simulations showed a good match between predicted and experimental values. The tested models can be used to provide insights in the amount and the type of toxicological data that are needed for the safety evaluation of the FCM substance. Uncertainty in QPPRs used for describing the processes of both diffusion in FCM and partition at the FCM-Food interface was included in the analysis. Combining uncertainty in QPPR predictions, it was shown that the third quartile (75th percentile) derived from probabilistic calculations can be used as a conservative value in the prediction of chemical concentration in food, with reasonable safety factors.

Emergency Heart failure Mortality Risk Grade may help to reduce heart failure admissions.

INTRODUCTION: Hospital admissions for heart failure (HF) are frequent and pose a heavy burden on health care resources. Currently, the decision to hospitalise is based on clinical judgement rather than on prognostic risk stratification. The Emergency Heart failure Mortality Risk Grade (EHMRG) was recently developed to identify high-risk HF patients in the emergency department (ED). OBJECTIVE: To assess the ability of the EHMRG to predict 30-day mortality in Dutch HF patients visiting the ED and to evaluate whether the EHMRG could help to reduce the number of hospital admissions for decompensated HF. METHODS: Patients visiting the ED for decompensated HF were included. The decision to hospitalise or discharge was based on clinical judgement. The EHMRG was calculated retrospectively. Based on their EHMRG, patients were stratified as very low risk, low risk, intermediate risk, high risk and very high risk. RESULTS: In 227 patients (age 73 ± 12 years, 69% male) 30-day mortality was 11%. Mortality differed significantly among the EHMRG risk groups at 7­day (p = 0.012) and 30-day follow-up (p < 0.01). Based on clinical judgement, 76% of patients were hospitalised. If decision-making had been based on EHMRG, the hospitalisation rate could have been reduced to 66% (p < 0.01), particularly by reducing hospitalisations in patients at low risk of death. Mortality in discharged patients, whether the decision was based on EHMRG or clinical judgement, was 0%. CONCLUSION: The EHMRG accurately differentiates between high- and low-risk decompensated HF patients visiting the ED, making it a promising tool to safely reduce the number of HF admissions.

Occurrence of (suspected) genotoxic flavoring substances in Belgian alcohol-free beers.

The regulatory landscape of flavorings is evolving, thereby putting pressure on control laboratories to develop analytical methods for a wide range of compounds in various types of food and drinks. In order to improve the monitoring of flavoring substances, a versatile and accurate analytical method using the solvent-assisted flavor evaporation (SAFE) technique coupled to GC-MS(SIM) was developed and validated. Focus was put on authorized flavoring substances requiring specific attention due to a genotoxic concern based on information from European risks assessment reports. Thirty-seven (suspected) genotoxic flavoring substances were analyzed in a selection of ten alcohol-free beers. Five suspected genotoxic compounds (i.e. 1-(2-furyl)-2-propanone, 2-acetylfuran, 2-acetyl-5-methylfuran, 2-acetyl-3,5-dimethylfuran, hex-2-eno-1,4-lactone) as well as two confirmed genotoxic flavoring substances (p-mentha-1,8-dien-7-al, 2,4-pentanedione) were identified and quantified among the selected samples. Low concentrations and natural occurrences of the identified compounds suggested that these were not added as such but rather originated from heat-treatments or from plant-based extracts.

Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays.

Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.

Myocardial infarction patients referred to the primary care physician after 1­year treatment according to a guideline-based protocol have a good prognosis.

INTRODUCTION: Identifying ST-elevation myocardial infarction (STEMI) patients who can be referred back to the general practitioner (GP) can improve patient-tailored care. However, the long-term prognosis of patients who are returned to the care of their GP is unknown. Therefore, the aim of this study was to assess the long-term prognosis of patients referred back to the GP after treatment in accordance with a 1-year institutional guideline-based protocol. METHODS: All consecutive patients treated between February 2004 up to May 2013 who completed the 1­year institutional MISSION! Myocardial Infarction (MI) follow-up and who were referred to the GP were evaluated. After 1 year of protocolised monitoring, asymptomatic patients with a left ventricular ejection fraction >45% on echocardiography were referred to the GP. Long-term prognosis was assessed with Kaplan-Meier curves and Cox proportional hazards analysis was used to identify independent predictors for 5­year all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: In total, 922 STEMI patients were included in this study. Mean age was 61.6 ± 11.7 years and 74.4% were male. Median follow-up duration after the 1­year MISSION! MI follow-up was 4.55 years (interquartile range [IQR] 2.28-5.00). The event-free survival was 93.2%. After multivariable analysis, age, not using an angiotensin-converting enzyme (ACE) inhibitor/angiotensin-II (AT2) antagonist and impaired left ventricular function remained statistically significant predictors for 5­year all-cause mortality. Kaplan-Meier curves revealed that 80.3% remained event-free for MACE after 5 years. Multivariable predictors for MACE were current smoking and a mitral regurgitation grade ≥2. CONCLUSION: STEMI patients who are referred back to their GP have an excellent prognosis after being treated according to the 1­year institutional MISSION! MI protocol.

Identification and validation of two peptide markers for the recognition of Clostridioides difficile MLST-1 and MLST-11 by MALDI-MS.

OBJECTIVES: Clostridioides difficile infection (CDI) has become the main cause of nosocomial infective diarrhoea. To survey and control the spread of different C. difficile strains, there is a need for suitable rapid tests. The aim of this study was to identify peptide/protein markers for the rapid recognition of C. difficile strains by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). METHODS: We analysed 44 well-characterized strains, belonging to eight different multi-locus sequence types (MLST), using ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS. The amino acid sequence of two peptide markers specific for MLST-1 and MLST-11 strains was elucidated by MALDI-TOF-MS/MS. The investigation of 2689 C. difficile genomes allowed the determination of the sensitivity and specificity of these markers. C18-solid-phased extraction was used to enrich the MLST-1 marker. RESULTS: Two peptide markers (m/z 4927.81 and m/z 5001.84) were identified and characterized for MLST-1 and MLST-11 strains, respectively. The MLST-1 marker was found in 786 genomes of which three did not belong to MLST-1. The MLST-11 marker was found in 319 genomes, of which 14 did not belong to MLST-11. Importantly, all MLST-1 and MLST-11 genomes were positive for their respective marker. Furthermore, a peptide marker (m/z 5015.86) specific for MLST-15 was found in 59 genomes. We translated our findings into a fast and simple method that allowed the unambiguous identification of the MLST-1 marker on a MALDI-TOF-MS platform. CONCLUSIONS: MALDI-FTICR MS-based peptide profiling resulted in the identification of peptide markers for C. difficile MLST-1 and MLST-11.

Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis.

This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM) proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017) [1].

[Multidose drug dispensing: what does it really involve?] / Medicatie op rol, wat komt er bij kijken?

- Multidose drug dispensing (MDD) systems are individualised forms of distribution that give structure to medication use. - Starting to use a multidose drug dispensing system must be initiated in joint discussion with the patient, once alternatives such as dosing schemes or automatic repeat-prescription services have been considered. The patient's autonomy and self-management are central.- Studies have shown positive effects of individualised forms of distribution on intermediary outcome measures such as HbA1c, LDL cholesterol, blood pressure and adherence. - Changes in medication should preferably be implemented when the pharmacist orders a new multidose drug dispensing system. It is difficult for the pharmacist to determine whether an immediate change is necessary if the indication and other possible reasons for change are not known. - The prescriber should preferably enquire whether the patient has a multidose dispensing system and should state the moment or the reason for the change on the prescription.- Pharmacotherapy in patients using a multidose drug dispensing system should be reviewed annually.

Bakers' cyst and tibiofemoral abnormalities are more distinctive MRI features of symptomatic osteoarthritis than patellofemoral abnormalities.

OBJECTIVE: To investigate which structural MR abnormalities discriminate symptomatic knee osteoarthritis (OA), taking co-occurrence of abnormalities in all compartments into account. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45-65 years. In 1285 participants (median age 56 years, 55% women, median body mass index (BMI) 30 kg/m(2)), MRI of the right knee were obtained. Structural abnormalities (osteophytes, cartilage loss, bone marrow lesions (BMLs), subchondral cysts, meniscal abnormalities, effusion, Baker's cyst) at 9 patellofemoral and tibiofemoral locations were scored following the knee OA scoring system. Symptomatic OA in the imaged knee was defined following the American College of Rheumatology criteria. Logistic ridge regression analyses were used to investigate which structural abnormalities discriminate best between individuals with and without symptomatic OA, crude and adjusted for age, sex and BMI. RESULTS: Symptomatic knee OA was present in 177 individuals. Structural MR abnormalities were highly frequent both in individuals with OA and in those without. Baker's cysts showed the highest adjusted regression coefficient (0.293) for presence of symptomatic OA, followed by osteophytes and BMLs in the medial tibiofemoral compartment (0.185-0.279), osteophytes in the medial trochlear facet (0.262) and effusion (0.197). CONCLUSIONS: Baker's cysts discriminate best between individuals with and without symptomatic knee OA. Structural MR abnormalities, especially in the medial side of the tibiofemoral joint and effusion, add further in discriminating symptomatic OA. Baker's cysts may present as a target for treatment.

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium.

BACKGROUND: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. OBJECTIVES: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. METHODS: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). RESULTS: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. DISCUSSION AND CONCLUSION: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.

[Implementation of the influenza vaccination recommendation in nursing homes in Germany : results of a survey as part of the national influenza immunization campaign]. / Umsetzung der Influenzaimpfempfehlung in Alten- und Pflegeheimen : Ergebnisse einer Erhebung im Rahmen der nationalen Influenza-Impfaufklärungskampagne.

Residents and staff of nursing homes are important target groups for influenza vaccination in Germany. The aim of this study was to gain the first insights into whether nursing homes organize activities with respect to vaccination against influenza and whether there is a demand for further information. In the context of the national influenza immunization campaign-which is jointly carried out by the Robert Koch Institute (RKI) and the Federal Centre for Health Education (BZgA) on an annual basis-influenza information kits were sent to the management of 10,700 nursing homes in September 2013. Along with the information material, the institutions also received a questionnaire to which they were able to respond via mail, fax, or online. Data from 988 homes were included in the analysis. The majority of institutions informed both residents (88.9 %) and nursing staff (81.2 %) about influenza vaccination. However, only 64.7 % of nursing homes carried out specific immunization activities for their residents and only half (49.3 %) offered a flu shot to their staff. When asked why the institutions do not provide influenza-specific information and vaccination to their staff, the majority had the opinion that this is the responsibility of each individual's general practitioner. Overall, only 4.9 % of nursing homes assessed influenza vaccination coverage among their staff annually. A third of all surveyed institutions (33.6 %) expressed a demand for additional influenza vaccine-related information. In conclusion, improved health education is needed to raise awareness about the importance of influenza vaccination among residents and employees of nursing homes in Germany so as to prevent influenza-associated morbidity and mortality in this risk group.

Case-controlled identification of colorectal cancer based on proteomic profiles and the potential for screening.

AIM: Colorectal cancer (CRC) screening programmes detect early cancers but unfortunately have limited sensitivity and specificity. Mass spectrometry-based determination of serum peptide and protein profiles provides a new approach for improved screening. METHOD: Serum samples were obtained from 126 CRC patients before treatment and 277 control individuals. An additional group of samples from 50 CRC patients and 82 controls was used for validation. Peptide and protein enrichments were carried out using reverse-phase C18 and weak-cation exchange magnetic beads in an automated solid-phase extraction and spotting procedure. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight system. Discriminant rules using logistic regression were calibrated for the peptide and protein signatures separately, followed by combining the classifications to obtain double cross-validated predicted class probabilities. Results were validated on an identical patient set. RESULTS: A discriminative power was found for patients with CRC representative for all histopathological stages compared with controls with an area under the curve of 0.95 in the test set (0.93 for the validation set) and with a high specificity (94-95%). CONCLUSION: The study has shown that a serum peptide and protein biomarker signature can be used to distinguish CRC patients from healthy controls with high discriminative power. This relatively simple and cheap test is promising for CRC screening.

Acrylonitrile exposure in the general population following a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On Saturday May 4, 2013, a train transporting chemicals derailed in the village of Wetteren (Belgium) and caused a leak of acrylonitrile (ACN). OBJECTIVES: To assess the human exposure to acrylonitrile in the local population with the highest suspected exposure. METHODS: Between May 18-25, 242 residents participated in the study. N-2-cyanoethylvaline (CEV), a biomarker that is highly specific for ACN exposure, was measured in the blood. To account for potential influence by smoking, cotinine was determined in the urine. Participants also filled in a short questionnaire. RESULTS: In the evacuated zone, 37.3% of the non-smokers and 40.0% of the smokers had CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively, at the time of the train accident. Spatial mapping of the CEV concentrations depending on the residential address showed a distribution pattern following the sewage system. DISCUSSION AND CONCLUSION: The train derailment resulted in a highly atypical sequence-of-events. In addition to exposure in the direct vicinity of the site of the train derailment, exposure also occurred via the sewage system, into which acrylonitrile had entered shortly after the accident.

Acrylonitrile exposure assessment in the emergency responders of a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On May 4, 2013, a train transporting chemicals derailed in Wetteren, Belgium. Several tanks loaded with acrylonitrile (ACN) exploded, resulting in a fire and a leakage of ACN. OBJECTIVES: To determine exposure to ACN and to assess discriminating factors for ACN exposure in the emergency responders involved in the on-site management of the train accident. METHODS: The study population consisted of 841 emergency responders. Between May 21 and June 28, they gave blood for the determination of N-2-cyanoethylvaline (CEV) hemoglobin adducts and urine for the measurement of cotinine. They also filled in a short questionnaire. RESULTS: 163 (26%) non-smokers and 55 (27%) smokers showed CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively. The 95th percentile in the non-smokers was 73 pmol/g globin and the maximum was 452 pmol/g globin. ACN exposure among the non-smokers was predicted by (1) the distance to the accident, (2) the duration of exposure, and (3) the occupational function. DISCUSSION AND CONCLUSION: Emergency responders involved in the on-site management of the train accident were clearly exposed to ACN from the accident. However, the extent of exposure remained relatively moderate with CEV concentrations staying within the ranges described in literature as background for a smoking population. Moreover, the exposure was less pronounced in the emergency responders as compared to that in the local population.

[Knowledge, attitude, and practice concerning measles vaccination. Approaches for national vaccination education]. / Wissen, Einstellung und Verhalten zur Masernimpfung. Ansätze für eine nationale Impfaufklärung.

Achievement of the goal to eliminate measles by 2015 set by the European region of the World Health Organization (WHO) necessitates an increase in the willingness of German nationals to get vaccinated. To identify influential factors on vaccination behavior as the basis for communication measures specific to target groups, the Federal Centre for Health Education (BZgA) has conducted two representative surveys on attitude, knowledge, and practice concerning vaccination among parents of children between 0 and 13 years as well as among adolescents and adults. The parents' survey (n = 3,002) revealed that more than one-third see measles as a harmless disease. The survey of adolescents and adults (n = 4,483, 16-85 years) also shows that about one-quarter of the interviewees between 16 and 44 years regarded vaccination against measles as not very important. Moreover, 81 % of adults born after 1970 without sufficient existing vaccine protection were not aware of the new measles vaccination recommendation for this age group. Personal consultation with the physician was regarded as the major source of vaccination information in both surveys. About half of all persons interviewed intended to obtain information about vaccinations on the Internet. The results of these studies were used for the development of a nationwide multilevel BZgA campaign on vaccination protection against measles, its goal being to support medical professionals with comprehensive information and to enable adolescents and young adults via different communication measures to make well-informed vaccination decisions.

Investigation into the genotoxicity of water extracts from Hypoxis species and a commercially available Hypoxis preparation.

We performed an in vitro evaluation of the genotoxic potential of water extracts from four Hypoxis species (Hypoxis hemerocallidea, H. colchicifolia, H. rigidula, H. acuminata) and a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.