Search

With the recent advent of smart wearable sensors for monitoring brain activities in real-time, the scopes for using Electroencephalograms (EEGs) and Magnetoencephalography (MEG) in mobile and dynamic environments have become more relevant. However, their application in dynamic and open environments, typical of mobile wearable use, poses challenges. Presently, there is limited clinical data on using EEG/MEG as wearables. To advance these technologies at a time when large-scale clinical trials are not feasible, many researchers have turned to realistic phantom heads to further explore EEG and MEG capabilities. However, to achieve translational results, such phantom heads should have matching geometric features and electrical properties. Here, we have designed and fabricated multilayer chopped carbon fiber–PDMS reinforced composites to represent phantom head tissues. Two types of phantom layers are fabricated, namely seven-layer and four-layer systems with a goal to achieve matching electrical conductivities in each layer. Desired electrical conductivities are obtained by varying the weight fraction of the carbon fibers in PDMS. Then, the prototype system was calibrated and tested with a 32-electrode EEG cap. The test results demonstrated that the phantom effectively generates a variety of scalp potential patterns, achieved through a finite number of internal dipole generators within the phantom sample. This innovative design holds potential as a valuable test platform for assessing wearable EEG technology as well as developing an EEG analysis process.

Objectives To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine acceptance among patients with rheumatic diseases (RMD). Methods All rheumatology patients attending a large suburban health network were invited to participate in an anonymized online survey. The primary outcome of interest was SARS-COV-2 vaccine acceptance. Results The mean (SD) age of respondents (n = 641) was 52.7 (15.1) years and 74.4% (n = 474) were female. Sixty-five percent were willing to have a SARS-COV-2 vaccine, while 34.4% were vaccine-hesitant (unwilling or undecided). On multivariate analysis, vaccine acceptance was associated with smoking (OR: 2.25 [95% CI: 1.22–4.15; p = .009]), history of malignancy (OR: 2.51 [95% CI: 1.19–5.26; p = .015]), influenza or pneumococcal vaccination in the preceding year (OR: 2.69 [95% CI: 1.78–4.05; p

The evaluation of a literary work is a continuous, multifaceted process, which takes place through a wide range of diverse individual actions and social and institutional activities. The complexity of this process has deepened with the transition to the information society, and many forms of evaluation have been transferred from the material to the digital realm. In this paper, I am particularly interested in some of those aspects of valuation which, due to the mediatisation of the literary field, as well as the dictates of market logic, can characterise highly institutionalised forms of evaluation or legitimation practices in the literary field, and which we can also observe in the field of Slovenian literature. Thus, alongside the author’s primary evaluation, it is necessary today to take into account the author’s secondary evaluation of his or her own work, and, more generally, to recognise the mechanisms of mediatisation (e.g. eventisation, personalisation, scandalisation) and the consequences that the mediatisation of society has on the literary field: the imposition of the evaluative criterion of media efficiency instead of quality (and consequently the pursuit of visibility, success rather than quality), the media evaluation of works and/or the focus of media attention on authors, the hyperproduction of events, the elimination of the space and means for in-depth reflection on literary production in the mass media and the relocation of this reflection to specialised online media with a narrower readership, the tabloid coverage of literary events. As a direct consequence of the profound mediatisation of society, the formerly unified reading public is being segmented and differentiated, and more or less close (digital) reading communities are being formed; because the media connect very different social fields, the reception of literary works is becoming more heterogeneous, which multiplies and at the same time disperses the factors influencing the evaluation of literary works.

Background: Bisphenol A (BPA; or 4,4′-isopropylidenediphenol) is an endocrine disrupting chemical. It was widely used in a variety of plastic-based manufactured products for several years. The European Food Safety Authority (EFSA) recently reduced the Tolerable Daily Intake (TDI) for BPA by 20,000 times due to concerns about immune-toxicity. Objective: We used human biomonitoring (HBM) data to investigate the general level of BPA exposure from 2007 to 2014 of European women aged 18–73 years (n = 4,226) and its determinants. Methods: Fifteen studies from 12 countries (Austria, Belgium, Denmark, France, Germany, Greece, Israel, Luxembourg, Slovenia, Spain, Sweden, and the United Kingdom) were included in the BPA Study protocol developed within the European Joint Programme HBM4EU. Seventy variables related to the BPA exposure were collected through a rigorous post-harmonization process. Linear mixed regression models were used to investigate the determinants of total urine BPA in the combined population. Results: Total BPA was quantified in 85–100 % of women in 14 out of 15 contributing studies. Only the Austrian PBAT study (Western Europe), which had a limit of quantification 2.5 to 25-fold higher than the other studies (LOQ=2.5 µg/L), found total BPA in less than 5 % of the urine samples analyzed. The geometric mean (GM) of total urine BPA ranged from 0.77 to 2.47 µg/L among the contributing studies. The lowest GM of total BPA was observed in France (Western Europe) from the ELFE subset (GM=0.77 µg/L (0.98 µg/g creatinine), n = 1741), and the highest levels were found in Belgium (Western Europe) and Greece (Southern Europe), from DEMOCOPHES (GM=2.47 µg/L (2.26 µg/g creatinine), n = 129) and HELIX-RHEA (GM=2.47 µg/L (2.44 µg/g creatinine), n = 194) subsets, respectively. One hundred percent of women in 14 out of 15 data collections in this study exceeded the health-based human biomonitoring guidance value for the general population (HBM-GVGenPop) of 0.0115 µg total BPA/L urine derived from the updated EFSA’s BPA TDI. Variables related to the measurement of total urine BPA and those related to the main socio-demographic characteristics (age, height, weight, education, smoking status) were collected in almost all studies, while several variables related to BPA exposure factors were not gathered in most of the original studies (consumption of beverages contained in plastic bottles, consumption of canned food or beverages, consumption of food in contact with plastic packaging, use of plastic film or plastic containers for food, having a plastic floor covering in the house, use of thermal paper…). No clear determinants of total urine BPA concentrations among European women were found. A broader range of data planned for collection in the original questionnaires of the contributing studies would have resulted in a more thorough investigation of the determinants of BPA exposure in European women. Conclusion: This study highlights the urgent need for action to further reduce exposure to BPA to protect the population, as is already the case in the European Union. The study also underscores the importance of pre-harmonizing HBM design and data for producing comparable data and interpretable results at a European-wide level, and to increase HBM uptake by regulatory agencies.

Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. Results: In children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs

Background The way the nursing profession is perceived plays a pivotal role in shaping the public's attitude toward its members, primarily influenced by interactions with nurses and media representation. However, it can be significantly impacted by historical and traditional stereotypes, coupled with enduring gender bias and other preconceived notions. Objectives The study aimed to examined how the title “nurse” reflects the profession's identity, perception as a female occupation, and status as a healthcare activity. It also assessed awareness of nurses’ roles, education and public presence, comparing general population and patients’ opinions in the Republic of Croatia. Methods Conducted as a cross-sectional study, this research employed a structured questionnaire and a convenience sampling approach. It encompassed both the general population and patients from Croatia, with data collection spanning from February 15, 2023, to March 16, 2023, and resulting in a total sample size of 624 participants. Statistical analysis included both descriptive and inferential techniques, and significance was set at p

The close interconnection of plants with rhizosphere- and root-associated microorganisms is well recognized, and high expectations are raised for considering their symbioses in the breeding of future crop varieties. However, it is unclear how consistently plant-mediated selection, a potential target in crop breeding, influences microbiome members compared to selection imposed by the agricultural environment. Landraces may have traits shaping their microbiome, which were lost during the breeding of modern varieties, but knowledge about this is scarce. We investigated prokaryotic community composition along the radial root axis of two European maize (Zea mays L.) landraces. A sampling gradient included bulk soil, a distal and proximal rhizosphere fraction, and the root compartment. Our study was replicated at two field locations with differing edaphic and climatic conditions. Further, we tested for differences between two plant developmental stages and two precipitation treatments. Community data were generated by metabarcoding of the V4 SSU rRNA region. While communities were generally distinct between field sites, the effects of landrace variety, developmental stage, and precipitation treatment were comparatively weak and not statistically significant. Under all conditions, patterns in community composition corresponded strongly to the distance to the root. Changes in α- and β-diversity, as well as abundance shifts of many taxa along this gradient, were similar for both landraces and field locations. Most affected taxa belonged to a core microbiome present in all investigated samples. Remarkably, we observed consistent enrichment of Actinobacteriota (particularly Streptomyces, Lechevalieria) and Pseudomonadota (particularly Sphingobium) toward the root. Further, we report a depletion of ammonia-oxidizers along this axis at both field sites. We identified clear enrichment and depletion patterns in microbiome composition along the radial root axis of Z. mays. Many of these were consistent across two distinct field locations, plant developmental stages, precipitation treatments, and for both landraces. This suggests a considerable influence of plant-mediated effects on the microbiome. We propose that the affected taxa have key roles in the rhizosphere and root microbiome of Z. mays. Understanding the functions of these taxa appears highly relevant for the development of methods aiming to promote microbiome services for crops.

Bacterial overgrowth, also known as dysbiosis, is a common concomitant of canine atopic dermatitis. Microbial diversity is decreased and coagulase-positive staphylococci are more abundant in dogs with canine atopic dermatitis compared to healthy dogs. Antimicrobial therapy restores the diversity of the skin microbiome; however, this effect can diminish after treatment is discontinued. Therapies for skin dysbiosis have traditionally included antibiotics and antiseptic medications. Due to increasing microbial resistance to antibiotics, the era of novel antimicrobial agents for the treatment of skin infections has already begun. Recent research highlights potential new treatment options, of which one of the most promising appears to be the use of bacteriophages. Bacteriophages are viruses that can infect and kill bacteria without having negative effects on human or animal cells. This article provides an update on human and veterinary research on phage therapy as a potential approach for the treatment of bacterial infections, with a focus on the treatment of skin dysbiosis in atopic dogs. The clear clinical potential of phage therapy, its advantages and disadvantages, and the legal, biological, technical, and economic challenges it faces for its further implementation and wider application are outlined.

Many efforts to improve crop yields in water-limited environments have been directed towards identifying genotypes capable of restricting their transpiration rate (TR) at high vapor pressure deficit (VPD). This has proven challenging due to the dependence of the TR-VPD relationship on environmental conditions. In this context, however, the impact of edaphic properties on the TR response to VPD has largely been overlooked as experiments investigating the TR-VPD relationship are usually performed in wet soil conditions. Hence, the soil is not expected to be limiting the water supply to the canopy at high VPD. Nonetheless, soil (hydraulic) properties are known to shape plant growth and the development of the plant hydraulic system. Thereby, they might indirectly affect plant water use during rising VPD, even in wet soils. To test the soil dependency of the TR-VPD relation, we measured the TR response of genotypes of three important C4 cereals - maize, sorghum, and pearl millet - to increasing VPD in two soil textural classes (sandy loam vs. clay loam). We show that the TR response to rising VPD differed among soil textures in wet conditions. Plants grown in sandy loam exhibited a higher initial slope in TR during increasing VPD (slope1), a restriction in TR at lower VPD (VPDBP), and a greater difference in TR before and after the VPDBP (slopediff.), compared to plants grown in clay loam. Additionally, plants grown in more conductive soils (i.e., sandy loam) systematically exhibited higher maximum canopy conductance (i.e., slope1) and restricted their transpiration rate at lower VPD levels (VPDBP), resulting in a greater reduction in transpiration. This aligns with a hydraulic mechanism underpinning TR response to VPD. We advocate that considering soil texture is valuable in breeding for water conservation based on TR restriction under increasing VPD.

Izhodišče: Okužbe sečil se pri novorojenčkih pojavljajo bolj pogosto kot pri starejših otrocih. V raziskavi smo želeli analizirati klinično sliko in povezavo s strukturnimi nepravilnostmi sečil ter pridobiti pregled nad povzročitelji in njihovo občutljivostjo za antibiotike. Metode: V retrospektivno raziskavo smo vključili novorojenčke, ki so bili zaradi okužbe sečil hospitalizirani na Kliničnem oddelku za neonatologijo Pediatrične klinike med letoma 2013 in 2021. Podat-ke smo pridobili s pomočjo bolnišničnega informacijskega sistema Clinical. Rezultati: V raziskavo je bilo vključenih 274 novorojenčkov, od tega 69 % dečkov. Delež bolnikov s pridruženimi nepravilnostmi sečil je znašal 39,8 %. Klinični znaki ob sprejemu so bili nespecifični, najpogosteje so se pojavljali vročina (37,1 %), slabše hranjenje (21,5 %) in razdražljivost oziroma neutolažljiv jok (17,1 %). Najpogosteje dokazani povzročitelj okužbe je bila Escherichia coli (60,4 %). Antibiotično zdravljenje je večinoma potekalo v parenteralni obliki (74,8 %) in je v povprečju trajalo 9,6 dneva (mediana 7 dni). Najpogosteje izbrano empirično antibiotično zdravljenje je bilo zdravljenje z ampicilinom in gentamicinom (61,3 %). V 36,5 % je bila osamljena bakterija odporna proti enemu od testiranih antibiotikov. Escherichia coli je bila najpogosteje (36,7 %) odporna proti ampicilinu in v 1,8 % proti gentamicinu. Zaključek: Okužbe sečil se pri novorojenčkih lahko kažejo z nespecifičnimi znaki. Velik delež novorojenčkov ima pridružene nepravilnosti sečil – ti običajno zbolevajo bolj zgodaj kot novorojenčki z zdravimi sečili. Pri tej skupini bolnikov je najpogostejši povzročitelj okužbe prav tako Escherichia coli, a v manjšem deležu, in je v tretjini primerov odporna proti ampicilinu in le redko proti gentamicinu.

Background: Urinary tract infections occur more often in newborns than older children. With our research, we wanted to analyze the clinical picture and the connection with structural abnormalities of the urinary tract and create an overview of the disease agents and their sensitivity to antibiotics. Methods: The retrospective study included hospitalized newborns due to urinary tract infections at the Clinical Department for Neonatology of the Paediatric Clinic between 2013 and 2021. Data were obtained using the Clinical Information System. Results: This research included 274 newborns, of which 69% were boys. The percentage of patients with associated urinary tract anomalies was 39,8%. Clinical signs upon admission were nonspecific; the most common were fever (37.1%), poor feeding (21.5%) and irritation or inconsolable weeping (17.1%). The most commonly discovered pathogen was Escherichia coli (E. coli) (60.4%). Antibiotic treatment was primarily given in the parenteral form (74.8%) and lasted, on average, 9,6 days, with a median of 7 days. The most commonly chosen empiric antibiotic therapy was therapy with ampicillin and gentamicin (61.3%). In 36.5%, the isolated bacteria were resistant to one of the tested antibiotics: Escherichia coli was most often resistant to ampicillin (36.7%) and in 1.8% to gentamicin. Conclusion: Clinical signs of urinary tract infection in neonates are nonspecific. A high percentage of newborns have associated urinary tract anomalies. The average age at the onset of the first signs of the disease is lower in newborns with congenital urinary tract anomalies. In this group of patients, Escherichia coli, as the most commonly isolated pathogen, occurs in a lower percentage and is resistant to ampicillin in a third of the cases and rarely to gentamicin.

Abstract Epidemiological and experimental evidence indicated that processed meat consumption is associated with colorectal cancer risks. Several studies suggest the involvement of nitrite or nitrate additives via N-nitroso-compound formation (NOCs). Compared to the reference level (120 mg/kg of ham), sodium nitrite removal and reduction (90 mg/kg) similarly decreased preneoplastic lesions in F344 rats, but only reduction had an inhibitory effect on Listeria monocytogenes growth comparable to that obtained using the reference nitrite level and an effective lipid peroxidation control. Among the three nitrite salt alternatives tested, none of them led to a significant gain when compared to the reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions in rats despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions in rats but the concomitant presence of nitrosyl iron in feces. Except the vegetable stock, other alternatives were less efficient than sodium nitrite in reducing L. monocytogenes growth.

The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.

Background: Per- and polyfluoroalkyl substances (PFAS) are heat and stain resisting chemicals. They are persistent, bioaccumulating and spread ubiquitously. Many hotspots where humans are exposed to high levels of PFAS have been reported. A few small observational studies in humans suggest that treatment with an Anion Exchange Resin (AER) decreases serum PFAS. This first clinical controlled crossover study aimed to assess whether AER decreases perfluorooctanesulfonic acid (PFOS) in highly exposed adults. Methods: An open label 1:1 randomized treatment sequence crossover study with allocation to oral AER (cholestyramine 4 g three times daily) or observation for 12 weeks was conducted among citizens from a PFAS hotspot. Main inclusion criteria was serum PFOS > 21 ng/mL. Primary endpoint was change in serum PFOS levels between treatment and observational period. Results: In total, 45 participants were included with a mean age of 50 years (SD 13). Serum PFOS baseline median was 191 ng/mL (IQR: 129–229) and decreased with a mean of 115 ng/mL (95 % CI: 89–140) on treatment, and 4.3 ng/mL in observation period corresponding to a decrease of 60 % (95 % CI: 53–67; p

Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

BackgroundThe demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. ObjectiveThis study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. MethodsThe stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. ResultsOverall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. ConclusionsThrough the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

Abstract Background Perfluoroalkyl substances (PFAS) are persistent chemicals used in everyday consumer products leading to ubiquitous human exposure. Findings of impaired neurodevelopment after prenatal exposure to PFAS are contradictory and few studies have assessed the impact of postnatal PFAS exposure. Language development is a good early marker of neurodevelopment but only few studies have investigated this outcome separately. We therefore investigated the association between prenatal and early postnatal PFAS exposure and delayed language development in 18 to 36-month-old Danish children. Methods The Odense Child Cohort is a large prospective cohort. From 2010 to 2012 all newly pregnant women residing in the Municipality of Odense, Denmark was invited to participate. Concentration of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were assessed in maternal serum collected in the 1st trimester of pregnancy and in child serum at 18 months. Parents responded to the Danish adaption of the MacArthur-Bates Communicative Development Inventories (MB-CDI) when their child was between 18 and 36 months. Language scores were converted into sex and age specific percentile scores and dichotomized to represent language scores above or below the 15th percentile. We applied Multiple Imputation by Chained Equation and conducted logistic regressions investigating the association between prenatal and early postnatal PFAS exposure and language development adjusting for maternal age, pre-pregnancy BMI, education and respectively fish intake in pregnancy or childhood and duration of breastfeeding in early postnatal PFAS exposure models. Results We found no significant associations between neither prenatal nor early postnatal PFAS exposure and language development among 999 mother-child pairs. Conclusion In this low-exposed cohort the finding of no association between early postnatal PFAS exposure and language development should be interpreted with caution as we were unable to separate the potential adverse effect of PFAS exposure from the well documented positive effect of breastfeeding on neurodevelopment. We, therefore, recommend assessment of child serum PFAS at an older age as development of the brain proceeds through childhood and even a small impact of PFAS on neurodevelopment would be of public health concern at population level due to the ubiquitous human exposure.

Introduction: Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. Objectives: To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. Methods: In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010–2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 881) and/or at age 18 months (n = 668) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. Results: Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of 18-month exposure to PFNA or PFOS, BMD Z-scores were lowered by −0.10 (95 % CI −0.19;-0.00) and −0.08 (-0.17;-0.00), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. Discussion: Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Background: Phthalates are endocrine disrupting chemicals used in everyday consumer products. Several epidemiological studies have examined the association between prenatal phthalate concentration and Attention-Deficit Hyperactivity Disorder (ADHD) in offspring, but the findings have been inconclusive. Objectives: To investigate the association between maternal urinary concentrations of phthalate metabolites during pregnancy and ADHD related symptoms in children at 2 to 4 years in a large prospective cohort. Methods: In the Odense Child Cohort from Denmark were women recruited in early pregnancy from 2010 to 2012. Phthalate concentrations were measured in urine samples collected in 3rd trimester and separated into low and high weight phthalates. Parents filled in the Child Behavior Checklist for ages 1.5 to 5 years (CBCL/1½-5), including a 6-item ADHD symptom scale at children aged 2 to 4 years. Data were analysed by use of adjusted negative binomial regression. Results: A total of 658 mother–child pairs were included. Urinary phthalate metabolite concentrations were generally low compared to previous cohorts. A doubling in maternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with lower ADHD symptoms score in children (IRR: 0.95 (95 % CI 0.91–0.98)), strongest in girls (IRR: 0.92 (0.87–0.98)). Sex differences were observed. High maternal phthalate metabolite concentrations were associated with lower ADHD symptom score in girls, significant trends across tertile of MCPP and MnBP (p = 0.018, p = 0.038, respectively). In boys, maternal concentrations of high-molecular-weight phthalates (MBzP, ∑DiNP and ∑DEHP) were associated with an almost significantly higher ADHD symptom score (IRR for a doubling in concentration: 1.04 (95 % CI: 0.99–1.10), IRR: 1.05 (95 % CI: 0.97–1.13), IRR: 1.04 (95 % CI: 0.99–1.10), respectively). Conclusion: Maternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with a lower ADHD symptom score in children, strongest in girls. Maternal concentrations of high-molecular-weight phthalates were associated with non-significant increase in ADHD symptom score in boys.

Prispevek analizira dve kabinetni žanrski sliki iz druge polovice 18. stoletja, ki sta do konca druge svetovne vojne viseli v dvorcu Podsmreka pri Višnji Gori, danes pa sta v zasebni lasti v Ljubljani. Na podlagi pečatov in oznak na hrbtiščih ju zanesljivo povezuje z zbirko, ki jo je na Dunaju zasnoval Isidor vitez Klarwill (1842–1898), del njegove zbirke pa je ob nakupu posesti Podsmreka na Slovensko pripeljal njegov vnuk Peter Klarwill. Na podlagi študija arhivskih virov razkriva doslej neznane okoliščine prenosa dela rodbinske zbirke v Podsmreko leta 1935, prodajo dvorca Antonu Verovšku leta 1939 ter usodo zbirke in grajske opreme, ki sta ob prodaji dvorca državi po Verovškovi smrti prešli v javno last. Z zapuščino Klarwillov prvič povezuje tudi posamezne umetnine in kose opreme, ki so bili ob prodaji dvorca državi leta 1948 dodeljeni javnim muzejskim zbirkam.

Abstract Motivation Compound structure identification is using increasingly more sophisticated computational tools, among which machine learning tools are a recent addition that quickly gains in importance. These tools, of which the method titled Compound Structure Identification:Input Output Kernel Regression (CSI:IOKR) is an excellent example, have been used to elucidate compound structure from mass spectral (MS) data with significant accuracy, confidence and speed. They have, however, largely focused on data coming from liquid chromatography coupled to tandem mass spectrometry (LC–MS). Gas chromatography coupled to mass spectrometry (GC–MS) is an alternative which offers several advantages as compared to LC–MS, including higher data reproducibility. Of special importance is the substantial compound coverage offered by GC–MS, further expanded by derivatization procedures, such as silylation, which can improve the volatility, thermal stability and chromatographic peak shape of semi-volatile analytes. Despite these advantages and the increasing size of compound databases and MS libraries, GC–MS data have not yet been used by machine learning approaches to compound structure identification. Results This study presents a successful application of the CSI:IOKR machine learning method for the identification of environmental contaminants from GC–MS spectra. We use CSI:IOKR as an alternative to exhaustive search of MS libraries, independent of instrumental platform and data processing software. We use a comprehensive dataset of GC–MS spectra of trimethylsilyl derivatives and their molecular structures, derived from a large commercially available MS library, to train a model that maps between spectra and molecular structures. We test the learned model on a different dataset of GC–MS spectra of trimethylsilyl derivatives of environmental contaminants, generated in-house and made publicly available. The results show that 37% (resp. 50%) of the tested compounds are correctly ranked among the top 10 (resp. 20) candidate compounds suggested by the model. Even though spectral comparisons with reference standards or de novo structural elucidations are neccessary to validate the predictions, machine learning provides efficient candidate prioritization and reduction of the time spent for compound annotation.

In the field of environment and health studies, recent trends have focused on the identification of contaminants of emerging concern (CEC). This is a complex, challenging task, as resources, such as compound databases (DBs) and mass spectral libraries (MSLs) concerning these compounds are very poor. This is particularly true for semi polar organic contaminants that have to be derivatized prior to gas chromatography-mass spectrometry (GC-MS) analysis with electron impact ionization (EI), for which it is barely possible to find any records. In particular, there is a severe lack of datasets of GC-EI-MS spectra generated and made publicly available for the purpose of development, validation and performance evaluation of cheminformatics-assisted compound structure identification (CSI) approaches, including novel cutting-edge machine learning (ML)-based approaches [1].We set out to fill this gap and support the machine learning-assisted compound identification, thus aiding cheminformatics-assisted identification of silylated derivatives in GC-MS laboratories working in the field of environment and health. To this end, we have generated 12 datasets of GC-EI-MS spectra, six of which contain GC-EI-MS spectra of trimethylsilyl (TMS) and six GC-EI-MS spectra of tert-butyldimethylsilyl (TBDMS) derivatives. Four of these datasets, named testing datasets, contain mass spectra acquired by the authors. They are available in full, together with corresponding metadata. Eight datasets, named training datasets, were derived from mass spectra in the NIST 17 Mass Spectral Library. For these, we have only made the metadata publicly available, due to licensing reasons.For each type of derivative, two testing datasets are generated by acquiring and processing GC-EI-MS spectra, such that they include raw and processed GC-EI-MS spectra of TMS and TBDMS derivatives of CECs, along with their corresponding metadata. The metadata contains IUPAC name, exact mass, molecular formula, InChI, InChIKey, SMILES and PubChemID, of each CEC and CEC-TMS or CEC-TBDMS derivative, where available. Eight GC-EI-MS training datasets are generated by using the National Institute of Standards and Technology (NIST)/U.S. Environmental Protection Agency (EPA)/National Institute of Health (NIH) 17 Mass Spectral Library. For each derivative type (TMS and TBDMS), four datasets are given, each corresponding to an original dataset obtained from NIST/EPA/NIH 17 and three variants thereof, obtained after each of the filtering steps of the procedure described below. Only the metadata about the training datasets are available, describing the corresponding NIST/EPA/NIH 17 entires: These include the compound name, CAS Registry number, InChIKey, exact mass, Mw, NIST number and ID number.The datasets we present here were used to train and test predictive models for identification of silylated derivatives built with ML approaches [4]. The models were built by using data curated from the NIST Mass Spectral Library 17 [2] and the machine learning approach of CSI:Output Kernel Regression (CSI:OKR) [2]. Data from the NIST Mass Spectral Library 17 are commercially available from the National Institute of Standards and Technology (NIST)/U.S. Environmental Protection Agency (EPA)/National Institute of Health (NIH) and thus cannot be made publicly available. This highlights the need for publicly available GC-EI-MS spectra, which we address by releasing in full the four testing datasets.

Objectives We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.Design Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.Setting 352 community family practices across 4 Canadian provinces between March 2017 and September 2020.Participants 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.Intervention Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.Primary and secondary outcome measures Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.Results At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p

Background Obstructive fibrinous pseudomembrane tracheitis (OFPT) is a rare complication of endotracheal intubation. Case We describe the case of a 73-year-old woman who underwent short-term intubation for video-assisted thoracoscopic surgery and developed an acute life-threatening stridor two days after extubation. The patient required an emergency tracheostomy to maintain airway patency and a microscopic direct laryngoscopy procedure was performed thereafter with removal of the obstructive pseudomembrane. Subsequently, the patient also suffered a non-ST-elevation myocardial infarction. The patient successfully recovered, and the tracheostomy was subsequently decannulated two months later. Histological examination revealed mucosal ulcerations and inflammatory changes. Conclusions OFPT is an uncommon cause of life-threatening airway obstruction after extubation that is not often recognized immediately but can usually be treated with early bronchoscopic intervention or microscopic direct laryngoscopy.

In the world of intense usage of antibiotics, the emergence of antimicrobial resistance necessitates research on alternative forms of antibiotics, antimicrobial peptides (AMPs), which are least known to induce resistance. The partial sequence of bacteriocin BaCf3, produced by marine Bacillus amyloliquefaciens BTSS3, derived from Matrix Assisted Laser Desorption Ionisation - Time of Flight Tandem Mass Spectroscopy (MALDI-ToF MS/MS) data was analyzed for amino acid composition and modelled in silico using TrRosetta. The mechanism of action of BaCf3 was studied in vitro on B. circulans NCIM2107 cell wall using microscopic techniques, such as confocal laser scanning microscopy, scanning electron microscopy, and high resolution transmission electron microscopy. Docking studies with cancer markers, glucose transporter protein, and mesenchymal-epithelial transition factor (MET) receptor tyrosine kinase were also conducted. BaCf3 was found to be rich in glycine and hydrophobic in nature, a characteristic property of cell wall acting AMPs. The structure of BaCf3 obtained from TrRosetta had antiparallel b-sheets resembling Laterosporulin. The bacteriocin BaCf3 has been found to act on the cell membrane of opportunistic pathogen Bacillus circulans, causing permeabilization and pore formation by dissipating the membrane potential. The microscopic examination also proved the mode of action of BaCf3 as cell wall acting. In silico docking studies with anticancer target proved that bacteriocin BaCf3 is also a possible anticancer drug candidate. In vitro anticancer assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and acridine orange/ethidium bromide dual staining on lung carcinorma cell line A549 further prove the anticancer activity of the bacteriocin.

Membranous lupus nephritis associated with anti-GBM antibodies is a rare entity, particularly in lupus nephritis patients who are serologically negative for ANA and anti-dsDNA with normal complement levels. We present an unusual case of a patient initially diagnosed with anti-GBM disease whose repeat biopsy demonstrated combined focal proliferative and membranous lupus nephritis (III + V). The first biopsy showed a granular linear pattern, and the second biopsy had multiple electron dense deposits in the subendothelial, epithelial, and mesangial regions along with podocyte effacement. Experimental research suggests that the sequential histopathological transition observed may reflect the action of immunological rearrangement and epitope spreading.

IntroductionData are lacking on the pharmacokinetic profile and safety of levobupivacaine (LB) used for regional anesthesia of the maxilla and mandibles in dogs.MethodsInfraorbital block (n = 10), inferior alveolar block (n = 10) or both infraorbital and inferior alveolar blocks (n = 10) were administered to dogs undergoing dental surgery under isoflurane anesthesia. The dose of LB was calculated as 0.11 ml/kg2/3 for the infraorbital block and 0.18 ml/kg2/3 for the inferior alveolar block. Blood samples were collected before and immediately after administration of the oral blocks, and 3, 4, 7, 12, 17, 32, 47, 62, 92, and 122 min thereafter. Quantification of LB in plasma was performed by LC-MS/MS.Results and discussionThe results are presented as median and interquartile range. In dogs in which all four quadrants of the oral cavity were desensitized with LB, the Cmax was 1,335 (1,030–1,929) ng/ml, the Tmax was 7 (4–9.5) min, and the AUC(0 → 120) was 57,976 (44,954–96,224) ng min/ml. Plasma concentrations of LB were several times lower than the reported toxic concentrations, and no signs of cardiovascular depression or neurotoxicity were observed in any of the dogs, suggesting that the occurrence of severe adverse effects after administration of LB at the doses used in this study is unlikely.

Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which is responsible for the degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, the enzyme is involved in many other homeostatic, toxic and cancer-related mechanisms. In this review, we first summarize the importance of HO-1 in physiology and pathophysiology with a focus on the digestive system. We then detail its structure and function, followed by a section on the regulatory mechanisms that control HO-1 expression and activity. Moreover, HO-2 as important further HO isoform is discussed, highlighting the similarities and differences with regard to HO-1. Subsequently, we describe the direct and indirect cytoprotective functions of HO-1 and its breakdown products carbon monoxide and biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, we address the role of HO-1 in cancer with a particular focus on colorectal cancer. Here, relevant pathways and mechanisms are presented, through which HO-1 impacts tumor induction and tumor progression. These include oxidative stress and DNA damage, ferroptosis, cell cycle progression and apoptosis as well as migration, proliferation, and epithelial-mesenchymal transition.

The knowledge of the effects of organophosphate flame retardants on children’s neurodevelopment is limited. The purpose of the present research is to evaluate the association between exposure to organophosphate flame retardants and children’s neurodevelopment in two European cohorts involved in the Human Biomonitoring Initiative Aligned Studies. The participants were school-aged children belonging to the Odense Child Cohort (Denmark) and the PCB cohort (Slovakia). In each cohort, the children’s neurodevelopment was assessed through the Full-Scale Intelligence Quotient score of the Wechsler Intelligence Scale for Children, using two different editions. The children’s urine samples, collected at one point in time, were analyzed for several metabolites of organophosphate flame retardants. The association between neurodevelopment and each organophosphate flame retardant metabolite was explored by applying separate multiple linear regressions based on the approach of MM-estimation in each cohort. In the Danish cohort, the mean ± standard deviation for the neurodevelopment score was 98 ± 12; the geometric mean (95% confidence interval (95% CI)) of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) standardized by creatinine (crt) was 0.52 µg/g crt (95% CI = 0.49; 0.60), while that of diphenyl phosphate (DPHP) standardized by crt was 1.44 µg/g crt (95% CI = 1.31; 1.58). The neurodevelopment score showed a small, negative, statistically imprecise trend with BDCIPP standardized by crt (β = −1.30; 95%CI = −2.72; 0.11; p-value = 0.07) and no clear association with DPHP standardized by crt (β = −0.98; 95%CI = −2.96; 0.99; p-value = 0.33). The neurodevelopment score showed a negative trend with BDCIPP (β = −1.42; 95% CI = −2.70; −0.06; p-value = 0.04) and no clear association with DPHP (β = −1.09; 95% CI = −2.87; 0.68; p-value = 0.23). In the Slovakian cohort, the mean ± standard deviation for the neurodevelopment score was 81 ± 15; the geometric mean of BDCIPP standardized by crt was 0.18 µg/g crt (95% CI = 0.16; 0.20), while that of DPHP standardized by crt was 2.24 µg/g crt (95% CI = 2.00; 3.52). The association of the neurodevelopment score with BDCIPP standardized by crt was −0.49 (95%CI = −1.85; 0.87; p-value = 0.48), and with DPHP standardized by crt it was −0.35 (95%CI = −1.90; 1.20; p-value = 0.66). No clear associations were observed between the neurodevelopment score and BDCIPP/DPHP concentrations that were not standardized by crt. No clear associations were observed with bis(1-chloro-2-propyl) phosphate (BCIPP) in either cohort, due to the low detection frequency of this compound. In conclusion, this study provides only limited evidence of an inverse association between neurodevelopment and exposure to BDCIPP and DPHP. The timing of exposure and effect modification of other organophosphate flame retardant metabolites and other substances should be the subject of further investigations that address this scientific hypothesis.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

Price shocks that propagate through the financial system present a significant risk to financial system stability. This study was an evaluation of the vulnerability of South African banks’ portfolios to pricemediated contagion in the last decade. Using longitudinal data of balance sheet positions of the 10 largest banks from 2010 to 2020, the stress tests were triggered by price shocks on one marketable asset held by all banks: South African government bonds. Overall, the study found that second-order feedback effects from bank deleveraging are muted and that the concentrated structure of the South African banking system has a positive effect on shock absorption. However, a gradual trend towards more similar asset portfolios in the past 10 years has gradually increased exposure to the price-mediated contagion channel. Significance: • The paper presents a novel modelling framework to study feedback price-effects in stress tests conducted on the South African banking system. • A new data set shows the evolution of South African banks’ portfolio structure and vulnerability by computing two fragility metrics and a portfolio similarity measure. • Using this data set, the relationship between banking sector vulnerability and portfolio similarity is tested empirically and it is shown how common asset holdings aggravate systemic risk to pricemediated contagion.

Abstract Background Exposure to perfluoroalkyl substances (PFASs) has been associated with changes in body mass index and adiposity, but evidence is inconsistent as study design, population age, follow-up periods and exposure levels vary between studies. We investigated associations between PFAS exposure and body fat in a cross-sectional study of healthy boys. Methods In 109 boys (10–14 years old), magnetic resonance imaging and dual-energy X-ray absorptiometry were performed to evaluate abdominal, visceral fat, total body, android, gynoid, android/gynoid ratio, and total fat percentage standard deviation score. Serum was analysed for perfluorooctanoic acid, perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid, perfluorononanoic acid, and perfluorodecanoic acid using liquid chromatography and triple quadrupole mass spectrometry. Data were analysed by multivariate linear regression. Results Serum concentrations of PFASs were low. Generally, no clear associations between PFAS exposure and body fat measures were found; however, PFOS was negatively associated with abdominal fat (β = -0.18, P = 0.046), android fat (β = -0.34, P = 0.022), android/gynoid ratio (β = -0.21, P = 0.004), as well as total body fat (β = -0.21, P = 0.079) when adjusting for Tanner stage. Conclusions Overall, we found no consistent associations between PFAS exposure and body fat. This could be due to our cross-sectional study design. Furthermore, we assessed PFAS exposure in adolescence and not in utero, which is considered a more vulnerable time window of exposure.

Abstract Background Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive. Objective To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children. Method In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score. Results BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03). Conclusion Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.

Abstract Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications in Drosophila models of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Among these, dlp mRNA, which encodes the glypican Dally like protein (Dlp)/GPC6, a wingless (Wg/Wnt) signaling regulator is insolubilized both in flies and patient tissues with TDP-43 pathology. While Dlp/GPC6 forms puncta in the Drosophila neuropil and ALS spinal cords, it is reduced at the neuromuscular synapse in flies suggesting compartment specific effects of TDP-43 proteinopathy. These findings together with genetic interaction data show that Dlp/GPC6 is a novel, physiologically relevant target of TDP-43 proteinopathy.

Objective: Calculating the free testosterone level has gained increasing interest and different indirect algorithms have been suggested. The objective was to compare free androgen index (FAI), free testosterone estimated using the linear binding model (Vermeulen: cFTV) and the binding framework accounting for allosterically coupled SHBG monomers (Zakharov: cFTZ) in relation to cardiometabolic condit ions. Design: A prospective cohort study including 5350 men, aged 30–70 years, participating in population-based surveys (MONICA I–III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters and vital status. Results: Using age-standardized hormone levels, FAI was higher among men with baseline cardiometabolic conditions, whereas cFTV and cFTZ levels were lower compared to men without these conditions as also seen for total testoste rone. Men in highest quartiles of cFTV or cFTZ had lower risk of developing type 2 d iabetes (cFTV: HR = 0.74 (0.49–1.10), cFTZ: HR = 0.59 (0.39–0.91)) than men in lowest quartile. In contrast, me n with highest levels of FAI had a 74% (1.17–2.59) increased risk of developing type 2 diabetes compared to men in lowest quartile. Conclusion: The association of estimated free testosterone and the studied outcomes differ depending on algorithm used. cFTV and cFTZ showed similar assoc iations to baseline and long-term cardiometabolic parameters. In contrast, an empiric r atio, FAI, showed opposite associations to several of the examined parameters and may refle ct limited clinical utility.

Abstract Background Prenatal phthalate exposure has been suggested to alter immune responses and increase the risk of asthma, eczema and rhinitis. However, few studies have examined the effects in prospective cohorts and only one examined rhinitis. We therefore studied associations between maternal urinary concentrations of phthalate metabolites and asthma, eczema and rhinitis in offspring aged 5 years. Methods From 552 pregnant women in the Odense Child Cohort, we quantified urinary concentrations of 12 phthalate metabolites in third trimester. We assessed asthma, rhinitis and eczema in their offspring at age 5 years with a questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC), and conducted logistic regression adjusting for relevant confounders. Results 7.4% of the children had asthma, 11.7% eczema and 9.2% rhinitis. Phthalate exposure was low compared to previous cohorts. No significant associations between prenatal phthalate exposure and asthma were found. Odds ratios (ORs) of child rhinitis with a doubling in ΣDiNPm and di-2-ethylhexyl phthalate metabolite (ΣDEHPm) concentrations were, respectively, 1.15 (95% confidence interval (CI) 0.97,1.36) and 1.21 (CI 0.93,1.58). The OR of eczema when doubling ΣDiNPm was 1.24 (CI 1.00,1.55), whereas the OR of using medicine against eczema when doubling a di-ethyl phthalate (DEP) metabolite was 0.81 (CI 0.68,0.96). Conclusion The lack of association between maternal phthalate exposure and asthma in the offspring may be due to low exposure and difficulties in determining asthma in 5-year-olds. The higher odds of rhinitis may raise public concern but further research in larger cohorts of older children is warranted.

Imatinib is a selective tyrosine kinase inhibitor used to treat chronic myeloid leukemia. It enters the environment by excretion from the body through urine and feces and is transferred with wastewater to a wastewater treatment plant. There, it can be degraded by activated sludge, forming a number of biotransformation products. Presence of imatinib and its potential transformation products in the environment can impose a high risk to aquatic organisms and human health, therefore it is important to obtain knowledge of its environmental fate. The data presented here is a result of a simulated biodegradation of imatinib at two levels of activated sludge using a batch biotransformation setup, with and without carbon source. The data was acquired with UHPLC-HRMS/MS and processed by MzMine2.36 [1]. The dataset presents a table of [M+H]+ features with retention times and corresponding MS/MS data. With development of new data mining tools this data can be used to identify new transformation products of imatinib and with it fully understand its environmental fate and the risk associated with its presence in the environment.

Objectives To evaluate the association of paternal intake of antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, selective serotonin reuptake inhibitors (SSRIs) and (benzo)diazepines during the development of fertilising sperm with birth defects in offspring.Design Prospective registry-based cohort study.Setting Total Danish birth cohort 1997–2016 using Danish national registries.Participants All 1 201 119 Danish liveborn singletons born 1997–2016 were eligible, 39 803 (3.3%) of whom had at least one major birth defect.Exposure Offspring were considered exposed if their father had filled at least one prescription in the relevant drug category during development of fertilising sperm (the 3 months prior to conception).Primary and secondary outcome measures Primary outcome was the diagnosis, in the first year of life, of at least one major birth defect as categorised in the EUROCAT guidelines. Secondary outcome was the diagnosis, in the first year of life, of at least one major birth defect in any of the EUROCAT subcategories. Adjusted ORs (AORs) were calculated, along with their 95% CIs, adjusted for year, education, smoking status and age of the mother, and education, disposable income and age of the father.Results This study found weak or null associations between birth defects and selected drugs. Specifically, antidepressants (17 827 exposed births) gave 3.5% birth defects (AOR 0.97 (0.89 to 1.05)). Diazepines, oxazepines, thiazepines and oxepines (as antipsychotics, 1633 offspring) gave 4.7% birth defects (AOR 1.22 (0.97 to 1.54)), attenuated to 1.13 when excluding by mothers’ prescriptions. The study was well powered assuming 100% therapy adherence, while assuming 50% therapy adherence, the study remained well powered for the largest groups (SSRIs and antidepressants overall).Conclusions Antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, SSRIs and benzodiazepine-derived anxiolytics, when taken by the father during development of fertilising sperm, are generally safe with regard to birth defects.

Single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYPs) and UDP-glucuronosyltransferase (UGTs) genes have been proposed to influence phthalates and 1,2-cyclo-hexanedicarboxylic acid diisononyl ester (DINCH) biotransformation but have not been investigated on a populational level.We investigated the role of SNPs in CYP2C9, CYP2C19, CYP2D6, UGT2B15, and UGT1A7 genes in the biotransformation of phthalates (DEHP, DEP, DiBP, DnBP, BBzP, DiNP, DidP) and DINCH by determining their urine metabolites.From the Slovenian study population of 274 men and 289 lactating primiparous women we obtained data on phthalate and DINCH urine metabolite levels (MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, MEP, MiBP, MnBP, MBzP, cx-MINP, OH-MiDP, MCHP, MnPeP, MnOP, 5OH-MINCH, 5oxo-MINCH), SNP genotypes (rs1057910 = CYP2C9*3, rs1799853 = CYP2C9*2, rs4244285 = CYP2C19*2, rs12248560 = CYP2C19*17, rs3892097 = CYP2D6*4, rs1902023 = UGT2B15*2, and rs11692021 = UGT1A7*3) and questionnaires. Associations of SNPs with levels of metabolites and their ratios were assessed by multiple linear regression and ordinary logistic regression analyses.Significant associations were observed for CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs. The most pronounced was the influence of CYP2C9*2 and *3 on the reduced DEHP biotransformation, with lower levels of metabolites and their ratios in men and women. In contrast, carriers of CYP2C19*17 showed higher urine levels of DEHP metabolites in both genders, and in women also in higher DiNP, DiDP, and DINCH metabolite levels. The presence of UGT1A7*3 was associated with increased metabolite levels of DINCH in men and of DiBP and DBzP in women. Statistical models explained up to 27% of variability in metabolite levels or their ratios.Our observations confirm the effect of CYP2C9*2 and *3 SNPs towards reduced DEHP biotransformation. We show that CYP2C9*2, CYP2C9*3, CYP2C19*17, and UGT1A7*3 SNPs might represent biomarkers of susceptibility or resilience in phthalates and DINCH exposure that have been so far unrecognised.

Background: The quality of life (QoL) of dogs with canine atopic dermatitis (CAD) treated with allergen-specific immunotherapy (ASIT) was studied to determine whether the QoL of dogs treated with ASIT (AG) improved compared with dogs not treated with ASIT (CG). Methods: The power of the study was calculated in advance assuming that the AG would assess QoL 20% better than the CG. The CG consisted of 21 dogs with CAD and the AG of 46 dogs with CAD. Validated QoL1 (pre-treatment) and QoL2 (post-treatment) questionnaires were emailed to owners. Results: AG dogs were significantly less disturbed during mealtimes (i.e., had better appetites and scratched less during mealtimes) and caused significantly less physical discomfort to their owners (due to unpleasant odor, the impression of a dirty apartment) than CG dogs. Owners of dogs treated with ASIT were able to significantly improve their daily activities (leisure, vacation, walks, work, hunting), significantly reduce their expenses (treatment costs, veterinary costs), feel significantly less emotional distress (less guilt, powerlessness, sadness, regret, fear, anger, disgust, rage, frustration), and experience less influence on relationships with family members and friends compared to owners of dogs not treated with ASIT. Conclusions: According to our results, the quality of life of dogs treated with ASIT and their owners seemed to improve significantly.

The Covid-19 pandemic, with its concomitant "stay at home" catchphrase, has certainly made living together as neighbours in a constitutional dispensation more tangible. Conflicts between neighbours will inevitably increase, especially in a time when citizens from different social, cultural, customary or religious backgrounds and with different rights and interests are restricted to the boundaries of their properties as a result of the Covid-19 pandemic. The pandemic has provided us with the impetus to reflect upon the notion of "reasonableness" in neighbour law, particularly nuisance law in the narrow sense. In this context the role of neighbour law is ordinarily to regulate the relationship between neighbours. Therefore, neighbour law is crucial in that it resolves conflicts that arise between neighbours due to their everyday use of their properties. Whether the nuisance is objectively reasonable or goes beyond that which can be reasonably tolerable under the circumstances requires weighing up various factors dependant on the prevailing circumstances, rights, interests, values and obligations of the neighbours and the community. In the constitutional dispensation, based on the values of human dignity, equality, and freedom, this may inadvertently require courts to balance out and reconcile often opposing constitutional rights. To this end the underlying principle of nuisance law encapsulated in the phrases "give and take" and "live and let live" arguably already encapsulates the notion of balancing respective rights (constitutional or otherwise) and interests given the context of each case. However, courts do not always correctly apply the reasonableness test in a principled and coherent fashion, as illustrated in Ellaurie v Madrasah Taleemuddeen Islamic Institute 2021 2 SA 163 (KZD). This may lead to the conclusion that constitutional rights are ignored when the reasonableness test for nuisance law is applied. It is necessary to reconceptualise the reasonableness test in order to ensure that the common law is infused with constitutional values. There are numerous ways in which the ideals and values of the Constitution of the Republic of South Africa, 1996 (and even specific constitutional rights other than property rights) could be advanced if courts were more willing (not being held back by conservatism) and able (equipped with the necessary vocabulary) to apply the common law in line with the Constitution. It is pivotal that courts apply the reasonableness test correctly, considering all the relevant circumstances of the case, including the broader constitutional values and ideals such as ubuntu. It is arguable that if this were done, nuisance law would have a greater potential to incorporate a wider range of rights, interests and values so that the outcomes would be fairer and more equitable, which is, after all, the goal of the reasonableness standard in neighbour law.