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Abstract Background Older adults in Indonesia are mostly living at home with their families. Informal care provided by family caregivers is essential to prevent older adults from getting pressure injuries (PIs). The objectives of this study were to examine the knowledge, attitude and practice of family caregivers regarding PI prevention among community-dwelling older adults in Indonesia. Methods A cross-sectional survey was conducted involving 267 family caregivers randomly selected from a population list provided by municipalities in Bandung, West Java, Indonesia. The study utilized the paper-based Knowledge, Attitude, and Practice on Pressure Injury (KAP-PI) questionnaire. Descriptive analyses (i.e. percentage, mean and standard deviation) were used to present participants’ scores in each domain based on their characteristics or categories and scores in every single item of questions or statements. Bivariate comparison analyses were conducted using independent t-test or ANOVA test to compare scores and a Chi-square was run to check correlations between knowledge, attitude and practice domains. Results This study show that more than half of the participants (61.0%) had insufficient knowledge about PI prevention, but nearly all participants (94.4%) had a positive attitude toward PI prevention for their older relatives. Still, 41.2% of the participants had inadequate practice on PI prevention. A correlation analysis revealed that having sufficient knowledge and a positive attitude towards PI prevention were positively correlated with practice (p

Abstract Background Dutch adolescents predominantly purchase unhealthy snacks in supermarkets, which negatively influence their health. The aim of this study was to investigate the short- and longer-term effects of a nutrition peer-education intervention in supermarkets on food purchases and determinants of food purchase behaviour among adolescents of different education levels. Methods We performed a quasi-experimental study in three supermarkets (two intervention and one comparison school) in Amsterdam, the Netherlands. The intervention schools received a 45-min peer-education workshop in the supermarket near their school, and the comparison school received no intervention. The workshops also included a 2-week ‘healthy snacking challenge’ and were led by two young supermarket employees. Measurements were performed 2 weeks before the intervention (T0) 2 weeks after (T1) and 3 months (T2) after the intervention. Cash receipts were used to examine food purchases (n = 458) and questionnaires to examine determinants of food purchase behaviour (n = 463). Results The nutrition peer-education intervention did not improve food purchases but did improve several determinants of food purchase behaviour. Adolescents from the intervention schools reported improved nutritional knowledge (β = 0.38, 95% CI: 0.04–0.72) at T1, more favourable attitudes (β = 0.21, 95% CI: 0.00–0.42) and stronger social support (β = 0.27, 95% CI: 0.02–0.53) for healthy food purchases at T2 compared to those from the comparison schools. Adolescents with a low level of education reported more short- and longer-term improvements of determinants of food purchase behaviour compared to those with a higher level of education. Conclusions While nutrition peer education in supermarkets did not improve adolescents’ food purchases in the supermarket, determinants of food purchase behaviour did improve. The intervention was especially effective among adolescents with a low level of education. Nevertheless, to promote healthy food purchases of adolescents in supermarkets, more efforts are needed.

Abstract Natural regeneration of Amazon forests offers a promising strategy to mitigate forest loss and advance the goals of the UN Decade on Ecosystem Restoration. However, the vast variability in regeneration rates across environmental gradients and over time poses considerable challenges for assessing regeneration success and ecosystem services provision in human-modified landscapes. Here we compiled 448 plots from forest regeneration in the Amazon to investigate the drivers of regrowth capacity and identify robust ecological indicators. By modeling optimal successional trajectories, we estimated reference values for vegetation structure, diversity, and functioning. After 20 years, successful regeneration should reach a minimum basal area of 14 m². ha−¹, at least 34 tree species per 100 individuals, a structural heterogeneity index of 0.27, and 123 Mg.ha−¹ of aboveground biomass. These straightforward indicators and reference values provide a foundational framework for governments and practitioners to assess success and establish targets for Amazon restoration efforts.

Abstract Objectives This study aimed to investigate the impact of pregnancy and pre-existing comorbidities on COVID-19 infections and associated complications of hospitalisation and mortality in women of reproductive age (WRA). The study also compared the risk of severe COVID-19 complications between pregnant women (PW) and non-pregnant women (NPW) with and without pre-existing comorbidities. Special focus was placed on some understudied comorbidities of immunosuppression, chronic renal disease and chronic obstructive pulmonary disease (COPD). Methods The study utilized anonymized patient-related information for a population of 7,342,869 WRA from the Mexican Ministry of Health data repository on COVID-19. Descriptive variables were characterized using frequencies, percentages, means, and standard deviations. Adjusted odds ratios (aORs) were used to assess the associations between risk factors and outcomes of hospitalisation and mortality. The study covered the entire COVID-19 pandemic period from January 30, 2020, to May 5, 2023. Results The findings revealed that PW were not more likely to get COVID-19 infections than NPW. PW with COVID-19 infections were more likely to require hospital admission, intubation treatments, and ICU admission compared to NPW with COVID-19. PW with immunosuppression had an increased odds ratio (aOR) of getting COVID-19 infections compared to NPW (PW: aOR = 1.0396; NPW: aOR = 0.8373). NPW with immunosuppression had higher risk of mortality (all-cause death: aOR = 1.7084; COVID-19-associated death: aOR = 1.4079) and hospitalisation (all-cause hospitalisation: aOR = 4.1328; COVID-19-associated hospitalisation: aOR = 3.0451) than NPW without immunosuppression. Renal disease was identified as a concerning pre-existing condition that increased the risks of COVID-19 associated mortality/hospitalizations and all-cause mortality/hospitalizations for both PW and NPW. NPW with renal disease had much higher odds ratio (aOR) of either COVID-19-associated-hospitalisations (NPW: aOR = 8.639; PW: aOR = 1.7603) or all-cause hospitalisations (NPW: aOR = 8.8594; PW: aOR = 1.786) than PW with renal disease. Conclusions This study provides valuable insights into the impact of pregnancy and pre-existing comorbidities on COVID-19 outcomes in WRA. The findings underscore the importance of considering demographic factors and pre-existing comorbidities in the management of PW with COVID-19. The study also highlights the need for further research to understand the unique impacts of different comorbidities, particularly immunosuppression and renal disease, on COVID-19 outcomes in WRA.

Abstract Background Mucormycosis is a severe and fatal fungal infection in patients with coronavirus disease 2019 caused by Mucorales. Here we present a case of a 63-year-old man with coronavirus disease 2019 infection, along with rhinosinusitis mucormycosis caused by Rhizopus delemar. Case presentation A 63-year-old Iranian man suffering from a coronavirus disease 2019 infection with symptoms of cough, shortness of breath, and generalized body pain. On the basis of the clinical manifestations, such as headache, a history of black nasal discharge, nasal hypoesthesia, facial swelling, numbness, nasal obstruction, presence of necrotic lesions on the nasal passages on physical examination, and abnormal computed tomography scans of paranasal sinuses, the patient underwent surgical debridement. Direct microscopy of specimens obtained from the paranasal sinuses, and subsequent isolation and identification, revealed a rhinosinusitis mucormycosis caused by R. delemar. Despite therapeutic measures, such as sinus debridement surgery and antifungal therapy with amphotericin B injection (50 mg/day), the patient died after 35 days of hospitalization. Conclusion In this report, we present the first documented case of human infection with R. delemar in a patient with coronavirus disease 2019 infection, who also exhibited rhinosinusitis mucormycosis. R. delemar appears to be an emerging agent of rhinosinusitis mucormycosis in this region. Furthermore, prompt diagnosis and the exploration of alternative antifungal treatments, beyond amphotericin B, may be crucial for effectively managing patients with R. delemar infections.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

Abstract Human biomonitoring (HBM) data indicate that exposure to pyrethroids is widespread in Europe, with significantly higher exposure observed in children compared to adults. Epidemiological, toxicological, and mechanistic studies raise concerns for potential human health effects, particularly, behavioral effects such as attention deficit hyperactivity disorder (ADHD) in children at low levels of exposure. Based on an exposure-response function from a single European study and on available quality-assured and harmonized HBM data collected in France, Germany, Iceland, Switzerland, and Israel, a preliminary estimate of the environmental burden of disease for ADHD associated with pyrethroid exposure was made for individuals aged 0–19 years. The estimated annual number of prevalence-based disability-adjusted life years (DALYs) per million inhabitants were 27 DALYs for Israel, 21 DALYs for France, 12 DALYs for both Switzerland and Iceland, and 3 DALYs for Germany; while the annual ADHD cases per million inhabitants attributable to pyrethroids were 2189 for Israel, 1710 for France, 969 for Iceland, 944 for Switzerland, and 209 for Germany. Direct health costs related to ADHD ranged between 0.3 and 2.5 million EUR yearly per million inhabitants for the five countries. Additionally, a substantial number of ADHD cases, on average 18%, were associated with pyrethroid exposure. Yet, these figures should be interpreted with caution given the uncertainty of the estimation. A sensitivity analysis showed that by applying a different exposure-response function from outside the EU, the population attributable fraction decreased from an average of 18 to 7%. To ensure more robust disease burden estimates and adequate follow-up of policy measures, more HBM studies are needed, along with increased efforts to harmonize the design of epidemiological studies upfront to guarantee meta-analysis of exposure-response functions. This is particularly important for pyrethroids as evidence of potential adverse health effects is continuously emerging.

Abstract The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue formation, making them ideal as synthetic grafts. This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction. In this regard, clinically relevant topics such as ceramic-based biomaterials, graft/scaffold characteristics (macro/micro-features), material extrusion-based 3D printing, and the step-by-step workflow to engineer personalized bioceramic grafts are discussed. Importantly, in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior. Lastly, we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.

Abstract Fungal pathogens exhibit extensive strain heterogeneity, including variation in virulence. Whether closely related non-pathogenic species also exhibit strain heterogeneity remains unknown. Here, we comprehensively characterized the pathogenic potentials (i.e., the ability to cause morbidity and mortality) of 16 diverse strains of Aspergillus fischeri, a non-pathogenic close relative of the major pathogen Aspergillus fumigatus. In vitro immune response assays and in vivo virulence assays using a mouse model of pulmonary aspergillosis showed that A. fischeri strains varied widely in their pathogenic potential. Furthermore, pangenome analyses suggest that A. fischeri genomic and phenotypic diversity is even greater. Genomic, transcriptomic, and metabolic profiling identified several pathways and secondary metabolites associated with variation in virulence. Notably, strain virulence was associated with the simultaneous presence of the secondary metabolites hexadehydroastechrome and gliotoxin. We submit that examining the pathogenic potentials of non-pathogenic close relatives is key for understanding the origins of fungal pathogenicity.

Abstract During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

Abstract Many insects utilise optical information in linearly polarised light for navigation, with the degree of linear polarisation (DoLP) determining whether the ‘visibility’ of such optical information is available to them. However, changes in degree of linear polarisation in response to increased atmospheric levels of fine particulate matter (PM2.5) are poorly understood. We present analyses based on both ground-based monitoring and particulate matter modelling, establishing a quantitative relationship between PM2.5 mass concentration and the DoLP. We apply this relationship to a global PM2.5 projection for 2050 and estimate the increase in number and spatial extent of low visibility days for honeybees. We find an increase by up to 20% in the geographical extent of low visibility days in 2050, with an augmented frequency of low visibility days across an area exceeding 0.75 million km2 in India and 2 million km2 in China. More frequent and widespread low visibility conditions can reduce the ability of insects to navigate, especially in hotspot regions.

The phyllosphere microbiome can positively or negatively impact plant health and growth, but we currently lack the tools to control microbiome composition. Contributing to a growing collection of bacteriophages (phages) targeting bacteria living in the wheat phyllosphere, we here isolate and sequence eight novel phages targeting common phyllosphere Erwinia and Pseudomonas strains, including two jumbo phages. We characterize genomic, phylogenetic, and morphological traits from these phages and argue for establishing four novel viral genera. We also search the genomes for anti-defense systems and investigate DNA modifications using Nanopore sequencing. In Pseudomonas phage Rembedalsseter we find evidence of 13 motif-associated single-stranded DNA breaks. A bioinformatics search revealed that 60 related Pseudomonas phages are enriched in the same motif, suggesting these single-stranded nicks may be widely distributed in this family of phages. Finally, we also search the Sequence Read Archive for similar phages in public metagenomes. We find close hits to the Erwinia jumbo-phage Kaldavass in a wide variety of plant, food, and wastewater metagenomes including a near-perfect hit from a Spanish spinach sample, illustrating how interconnected geographically distant phages can be.

Background: The global prevalence of older adults with diabetes has increased, and family caregivers in Indonesia play a critical role in managing diabetes and providing personal care. However, caregiving can be complex and challenging, often negatively affecting caregivers' quality of life (QoL). Objective: This study aimed to develop and test a hypothesized causal model of QoL among Indonesian family caregivers who care for dependent older persons with type 2 diabetes mellitus (T2DM) in 2024. Methods: A cross-sectional, correlational study was conducted with 270 family caregivers recruited from five Community Health Centers. Data were collected using various scales: the Center for Epidemiologic Studies Depression Scale, the Zarit Burden Interview, the Duke University Religion Index, the Perceived Knowledge on T2DM Care Scale, the Family-Carer Diabetes Management Self-Efficacy Scale, the Multidimensional Scale of Perceived Social Support, and the Quality-of-Life Index. Descriptive statistics and Partial Least Squares Structural Equation Modeling (PLS-SEM) were used for analysis. Results: The final model explained 89.1% of the variance in the quality of life (QoL) of family caregivers (R² = 0.893, Adjusted R² = 0.891), with 66% predictive relevance. Depression symptoms had the strongest negative direct effect on QoL, followed by caregiver burden. Self-efficacy and perceived knowledge had positive direct effects, while social support showed no significant direct effect. Indirect effects revealed that social support and self-efficacy positively influenced QoL through depression symptoms. The total effect (TE) analysis confirmed that depression symptoms had the strongest negative effect on QoL (TE = -0.744, p

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of frozen, dried and powder forms of house crickets (Acheta domesticus) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is proposed in three forms: (i) frozen, (ii) dried, (iii) powder. The main components of the NF are protein, fat and dietary fibre (chitin). The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The NF has a protein content that ranges between 19.7 and 20.9 g/100 g in the frozen form and 61.7–68.6 g/100 g in the dried and powder forms. The Panel acknowledges that the true protein content is overestimated when using the nitrogen‐to‐protein conversion factor of 6.25 due to the presence of non‐protein nitrogen from chitin. The applicant proposed to use the NF as food ingredient in a number of food products. The target population proposed by the applicant is the general population. Considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel notes that no safety concerns arise from the toxicological information on A. domesticus. The Panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The Panel concludes that the NF is safe under the proposed uses and use levels.

Atrial fibrillation (AF) is a prevalent and clinically significant cardiac arrhythmia, with a growing incidence. The primary objectives in AF management are symptom relief, stroke risk reduction, and prevention of tachycardia-induced cardiomyopathy. Two key strategies for rhythm control include antiarrhythmic drug therapy and pulmonary vein isolation (PVI), with PVI being recommended for selected patients. Even though PVI is effective, post procedural health care utilization is high, contributing to emergency department (ED) overcrowding, which is a global healthcare concern. The use of remote rhythm diagnostics, such as a 1-lead ECG device (KM), may mitigate this issue by reducing ED visits and facilitating more plannable AF care.ObjectiveThis study aimed to assess whether providing AF patients with a 1-lead ECG device for 1 year after PVI would reduce ED utilization compared to standard care. Additionally, the study assessed whether this intervention would render AF care more plannable by reducing the incidence of unplanned cardioversions.MethodsA historically controlled, prospective clinical trial was conducted. The intervention group were patients undergoing PVI for AF between September 2018 and August 2020, all patients in this group received a 1-lead ECG device for 1 year for remote rhythm monitoring. The historical control group were patients undergoing PVI between January 2016 and December 2017; these patients did not receive a 1-lead ECG device. Data on ED visits, planned and unplanned cardioversions, and outpatient contacts in the year after the PVI were collected for both groups.ResultsThe study included 204 patients, 123 in the 1-lead ECG group and 81 in the standard care group. There was no statistically significant difference in the number of all-cause ED visits (63 vs 68 per 100 pts, respectively, p = 0.72), ED visits for possible rhythm disorders, or ED visits for definite rhythm disorders between the two groups. However, the 1-lead ECG group demonstrated a higher proportion of planned cardioversions compared to unplanned ones (odds ratio 4.9 [1.57-15.85], p = 0.007).ConclusionProviding patients with AF following PVI with a 1-lead ECG device did not result in a statistically significant reduction in ED visits during the first year. However, it did improve the management of recurrent AF episodes by substituting unplanned cardioversions with scheduled ones. Clinical Trials Registration Number NCT06283654.

Purpose: Frailty and falls are two major health challenges in older adults, but little is known about their levels and interactions in community-dwelling older adults in sub-Saharan Africa. The purpose of this scoping review was to map the literature on frailty and falls with respect to their definitions, measurement methods, associated factors, and interactions in this setting. Methods: A systematic search of eight databases and four other relevant sources was performed with no language restriction using combinations of the keywords ‘frailty’, ‘older adults’, ‘falls’ and ‘Africa’ and their synonyms. Results: Thirty-six studies from nine countries in the sub-region met the inclusion criteria. The average age for participant inclusion in the studies was 50 years. The Frailty Phenotype and the Frailty Index were the primary assessment methods used, yielding frailty prevalence rates ranging from 5.4 % to 17.4 % and 20.6 % to 60.0 %, respectively. Fall prevalence ranged from 20.8 % to 55.1 %, while recurrent falls were reported in 11.0 % to 24.6 % of cases. Comorbidities/multimorbidity and increasing age were the most reported clinical and socio-demographic factors associated with frailty. Low functional status and being female were the primary factors associated with falls. Conclusions and recommendations: In sub-Saharan Africa, there appears to be a high prevalence of frailty and falls in a relatively young cohort of older adults. Future studies should focus on developing frailty definitions and assessment methods that are culturally appropriate in this setting.

Background: The clinical frailty scale (CFS) was used as a triage tool for medical decision making during the COVID-19 pandemic. The CFS has been posed as a suitable risk marker for in-hospital mortality in COVID-19 patients. We evaluated whether the CFS is associated with mortality 24 months after hospitalisation for COVID-19. Methods: The COvid MEdicaTion (COMET) study is an international, multicentre, observational cohort study, including adult patients hospitalised for COVID-19 between March 2020–July 2020. Patients’ characteristics, prescribed medication, clinical characteristics, and CFS were collected at admission, survival data were collected 24 months after hospitalisation. Multivariable cox proportional hazard models stratified by age (

Background: Oxidative stress is thought to be related to many diseases. Furthermore, it is hypothesized that radiofrequency electromagnetic fields (RF-EMF) may induce excessive oxidative stress in various cell types and thereby have the potential to compromise human and animal health. The objective of this systematic review (SR) is to summarize and evaluate the literature on the relation between the exposure to RF-EMF in the frequency range from 100 kHz to 300 GHz and biomarkers of oxidative stress. Methods: The SR framework was developed following the guidelines established in the WHO Handbook for Guideline Development and NTP/OHAT’s Handbook for Conducting a Literature-Based Health Assessment. We used the latter handbook’s methodology for implementing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for environmental health assessments.We searched the following databases up until June 30, 2023: PubMed, Embase, Web of Science Core Collection, Scopus, and the EMF-Portal. The reference lists of included studies and retrieved review articles were also manually searched.We rated Risk of Bias (RoB) using the OHAT RoB Rating Tool and assessed publication bias using funnel plots of included studies. We assessed the certainty of the evidence (high, moderate, low, or very low) for an association between RF-EMF and oxidative stress using an adapted version of the GRADE framework.Data were extracted according to a predefined set of forms developed in DistillerSR.Data were analysed after grouping them first as in vitro or in vivo and then according to outcome category, species category, and exposed tissue. We synthesized study results using a random effects meta-analysis when study characteristics were judged sufficiently similar to be combined and heterogeneity (I2) was lower than 75 %, otherwise we describe the findings narratively. Results: Fifty-six (56) studies, 45 in vivo and 11 in vitro, in which cells (in vitro) or animals (in vivo) were exposed to frequencies in the range 800–2450 MHz, were included in the systematic review after eliminating 12,353 publications because they did not meet the criteria defined in the published protocol (Henschenmacher et al., 2022). Of 56 studies 52 studies with 169 individual results were included in the meta-analysis. Together, these studies examined six human in vitro samples and fifty animal samples, including rodents (mice, rats, hamsters, and guinea pigs, (n = 46)) and rabbits (n = 4). RF-EMF were predominantly applied as continuous wave exposures in these studies. The outcome biomarkers for modified proteins and amino acids were measured in n = 30 studies, for oxidized DNA bases in n = 26 studies, for oxidized lipids in n = 3 studies and hydrogen peroxide production in 2 studies. Outcomes were mostly measured in the brain (n = 22), liver (n = 9), cells (n = 9), blood (n = 6), and testis (n = 2). RoB in studies was high, mainly due to biases in exposure and outcome assessment. In vivo studies: Brain: The effect on biomarkers for oxidized DNA bases in the rodent brain (five studies, n = 98) had an inconsistent effect, varying from a large decrease with a standardized mean difference (SMD) of −3.40 (95 % CI [−5.15, −1.64]) to a large increase with an SMD of 2.2 (95 % CI [0.78, 3.62]). In the brain of rabbits (two studies, n = 44), the effect sizes also varied, from an SMD of −1.06 (95 % CI [−2.13, 0.00]) to an SMD of 5.94 (95 % CI [3.14, 8.73]). The effect on biomarkers for modified proteins and amino acids in the rodent brain (15 studies, n = 328) also varied from a large decrease with an SMD of −6.11 (95 % CI [−8.16, −4.06]) to a large increase with an SMD of 5.33 (95 % CI [2.49, 8.17]).The effect on biomarkers for oxidized lipids in the brain of rodents (one study, n = 56) also varied from a large decrease with SMD = −4.10 (95 % CI [−5.48, −2.73]) to SMD = 1.27 (95 % CI [0.45, 2.10]).Liver: The effect on biomarkers for oxidized DNA bases in the rodent liver (two studies, n = 26) was inconsistent with effect sizes in both directions: SMD = −0.71 (95 % CI [−1.80, 0.38]) and SMD = 1.56 (95 % CI [0.19, 2.92]). The effect on biomarkers for oxidized DNA bases in the rabbits’ liver (two studies, n = 60) was medium with a pooled SMD of 0.39 (95 % CI [−0.79, 1.56]).Biomarkers for modified proteins and amino acids in the liver of rodents (six studies, n = 159) increased with a pooled SMD of 0.55 (95 % CI [0.06, 1.05]).Blood: The effect of RF-EMF on biomarkers for oxidized DNA bases in rodent blood (four studies, n = 104) was inconsistent, with SMDs ranging from −1.14 (95 % CI [−2.23, −0.06]) to 1.71 (95 % CI [−0.10, 3.53]).RF-EMF had no effect on biomarkers for modified proteins and amino acids in rodent blood (three studies, n = 40), with a pooled SMD of −0.08 (95 % CI [−1.32, 1.16]).There was a large increase in biomarkers for oxidized DNA bases in rodent plasma (two studies, n = 38) with a pooled SMD of 2.25 (95 % CI [1.27, 3.24]).Gonads: There was an increase in biomarkers for oxidized DNA bases in the rodent testis (two studies, n = 24) with a pooled SMD of 1.60 (95 % CI [0.62, 2.59]).The effect of RF-EMF on biomarkers for modified proteins and amino acids in the ovary of rodents (two studies, n = 52) was inconsistent with a medium effect, SMD = 0.24 (95 % CI [−0.74, 1.23])) and a large effect (SMD = 2.08 (95 % CI [1.22, 2.94])).Thymus: RF-EMF increased biomarkers for modified proteins and amino acids in the thymus of rodents (one study, n = 42) considerably with a pooled SMD of 6.16 (95 % CI [3.55, 8.76]).Cells: RF-EMF increased oxidized DNA bases in rodent cells with SMD of 2.49 (95 % CI [1.30, 3.67]) (one study, n = 27). There was a medium effect in oxidized lipids (one study, n = 18) but not statistically significant with SMD = 0.34 (95 % CI [−0.62, 1.29]). In vitro studies: In in vitro studies in human cells (three studies, n = 110), there were inconsistent increases in biomarkers for oxidized DNA bases, where the SMDs varied between 0.01 (95 % CI [−0.59, 0.62]) and 7.12 (95% CI [0.06, 14.18]) in 4 results (2 of them statistically significant). In rodent cells (three studies, n = 24), there was a not statistically significant large effect in biomarkers for oxidized DNA bases with SMD = 2.07 (95 % CI [−1.38, 5.52]).The RF-EMF biomarkers for modified proteins and amino acids in human cells (one study, n = 18) showed a large effect with SMD = 1.07 (95 % CI [−0.05, 2.19]). In rodent cells (two studies, n = 24) a medium effect of SMD = 0.56 (95 % CI [−0.29, 1.41]) was observed. Discussion: The evidence on the relation between the exposure to RF-EMF and biomarkers of oxidative stress was of very low certainty, because a majority of the included studies were rated with a high RoB level and provided high heterogeneity. This is due to inaccurate measurements of exposure and/or of measurement of oxidative stress biomarkers and missing information on the blinding of research personnel to exposure conditions or outcome measurements. There may be no or an inconsistent effect of RF-EMF on biomarkers of oxidative stress in the brain, liver, blood, plasma and serum, and in the female reproductive system in animal experiments but the evidence is of very low certainty. There may be an increase in biomarkers of oxidative stress in testes, serum and thymus of rodents but the evidence is of very low certainty. Future studies should improve experimental designs and characterization of exposure systems as well as the use of validated biomarker measurements with positive controls.Other: This review was partially funded by the World Health Organization.The protocol for this review is registered in PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235573) and published in Environment International (https://doi.org/10.1016/j.envint.2021.106932) (Henschenmacher et al., 2022).

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 − 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.

Background Rights-based Respectful Maternity Care (RMC) is crucial for quality of care and improved birth outcomes, yet RMC measurements are rarely included in facility improvement initiatives. We aimed to (i) co-create a routine RMC measurement tool (RMC-T) for congested maternity units in Dar es Salaam, Tanzania, and (ii) assess the RMC-T’s acceptability among women and healthcare stakeholders. Method We employed a participatory approach utilizing multiple mixed methods. This included a scoping review, stakeholder engagement involving postnatal women, healthcare providers, health leadership, and global researchers through interviews, focus groups, and two surveys involving 201 and 838 postnatal women. Cronbach’s alpha and factor analysis were conducted for validation using Stata 15. Theories of social practice and Thematic Framework of Acceptability guided the assessment of stakeholder priorities and tool acceptability. Results The multi-phased iterative co-creation process produced the 25-question RMC-T that measures satisfaction, communication, mistreatment (including physical, verbal, and sexual abuse; neglect; discrimination; lack of privacy; unconsented care; post-birth clean-up; informal payments; and denial of care), supportive care (such as food intake and mobility), birth companionship, post-procedure pain relief, bed-sharing, and newborn respect. The pragmatic validation process prioritized stakeholder feedback over strict statistics, lowering Cronbach’s alpha from 0.70 in version 1 to 0.57 for the RMC-T. Women valued the opportunity to share their experiences. Conclusions The RMC-T is contextualized, validated, and acceptable for measuring women’s experiences of RMC. Routine use in facility-based quality improvement initiatives, along with targeted actions to address gaps, will advance rights-based RMC. Further validation and community-based studies are needed.

Abstract Sarcopenia has been associated with adverse health outcomes, including cognitive dysfunction. However, its specific interrelationship with neurocognitive disorders such as mild cognitive impairment (MCI), Alzheimer's disease (AD) or other types of dementia has not been thoroughly explored. This meta‐analysis aims to summarize the existing evidence on this interrelationship. This systematic review was pre‐registered on PROSPERO (CRD42022366309) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses 2020 guidelines. Databases, including PubMed, Embase, CINAHL, Scopus, Web of Science, PEDro, SPORTDiscus and the Cochrane Central Register of Controlled Trials, and the data registry ClinicalTrials.gov were searched from inception to 8 June 2023. Observational studies (cross‐sectional and cohort) and interventional studies reporting on the association and prevalence of sarcopenia in MCI, AD or other types of dementia in adults ≥50 years were included. For the meta‐analysis, pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of sarcopenia with the neurocognitive disorders using random‐effects/fixed‐effects models. Subgroup analyses were performed to identify potential sources of heterogeneity. A total of 77 studies consisting of 92 058 subjects were finally included in the qualitative analysis (71 cross‐sectional, 4 cohort and 2 interventional studies). Studies were heterogeneous, using different diagnostic criteria to define both sarcopenia and cognitive status. The majority of studies (n = 38) included Asian community‐dwelling older adults. Most studies investigated the association of sarcopenia with AD (33/77) and MCI (32/77). For studies focusing on other forms of dementia, two studies included Lewy body dementia and one study included Parkinson's dementia, whereas the remaining studies did not specify dementia aetiology (n = 21). Three cohort studies explored the association between sarcopenia and incident MCI, whereas only one cohort study explored the association between dementia and incident sarcopenia. Two interventional studies investigated whether an exercise programme could prevent the progression of sarcopenia in older adults with dementia or AD. The information for the meta‐analysis was extracted from 26 studies. Sarcopenia was significantly associated with MCI (pooled OR = 1.58, 95% CI 1.42–1.76) (n = 14), AD (pooled OR = 2.97, 95% CI 2.15–4.08) (n = 3) and non‐AD dementia (pooled OR = 1.68, 95% CI 1.09–2.58) (n = 9). The significance and magnitude of the associations differed in subgroup analyses by study design, population, definition of sarcopenia or used tool to measure cognitive status. This meta‐analysis showed that sarcopenia is significantly associated with MCI, AD and other types of dementia. These findings suggest the importance of early screening and prevention of sarcopenia in older people with cognitive dysfunction, although further longitudinal research is needed to clarify the causal relationship.

Abstract Background Nursing shortages are an ongoing concern for neonatal units, with many struggling to meet recommended nurse to patient ratios. Workforce data underlines the high proportion of neonatal nurses nearing retirement and a reduced number of nurses joining the profession. In order to recommend strategies to increase recruitment and retention to neonatal nursing, we need to understand the current challenges nurses are facing within the profession. The aim of this study is to investigate current job satisfaction, burnout, and intent to stay in neonatal nursing in England and Wales. Methods This study has two parts: (1) a systematic review exploring job satisfaction, burnout and intent to stay in neonatal nursing, and any previous interventions undertaken to enhance nurse retention, (2) an online survey of neonatal nurses in England and Wales exploring job satisfaction, burnout and intent to stay in neonatal nursing. We will measure job satisfaction using the McCloskey Mueller Satisfaction Scale (MMSS), burnout using the Copenhagen Burnout Inventory (CBI) and the Nurse Retention Index (NRI) will be used to measure intent to stay. All nurses working in neonatal units in England and Wales will be eligible to participate in the nursing survey. Discussion Retention of neonatal nurses is a significant issue affecting neonatal units across England and Wales, which can impact the delivery of safe patient care. Exploring job satisfaction and intent to stay will enable the understanding of challenges being faced and how best to support neonatal nurses. Identifying localised initiatives for the geographical areas most at risk of nurses leaving would help to improve nurse retention.

Abstract Background Pharmacotherapy for brain diseases is severely compromised by the blood-brain barrier (BBB). ABCB1 and ABCG2 are drug transporters that restrict drug entry into the brain and their inhibition can be used as a strategy to boost drug delivery and pharmacotherapy for brain diseases. Methods We employed elacridar and tariquidar in mice to explore the conditions for effective inhibition at the BBB. Abcg2;Abcb1a/b knockout (KO), Abcb1a/b KO, Abcg2 KO and wild-type (WT) mice received a 3 h i.p. infusion of a cocktail of 8 typical substrate drugs in combination with elacridar or tariquidar at a range of doses. Abcg2;Abcb1a/b KO mice were used as the reference for complete inhibition, while single KO mice were used to assess the potency to inhibit the remaining transporter. Brain and plasma drug levels were measured by LC-MS/MS. Results Complete inhibition of ABCB1 at the BBB is achieved when the elacridar plasma level reaches 1200 nM, whereas tariquidar requires at least 4000 nM. Inhibition of ABCG2 is more difficult. Elacridar inhibits ABCG2-mediated efflux of weak but not strong ABCG2 substrates. Strikingly, tariquidar does not enhance the brain uptake of any ABCG2-subtrate drug. Similarly, elacridar, but not tariquidar, was able to inhibit its own brain efflux in ABCG2-proficient mice. The plasma protein binding of elacridar and tariquidar was very high but similar in mouse and human plasma, facilitating the translation of mouse data to humans. Conclusions This work shows that elacridar is an effective pharmacokinetic-enhancer for the brain delivery of ABCB1 and weaker ABCG2 substrate drugs when a plasma concentration of 1200 nM is exceeded.

Abstract Background Asymptomatic bacteriuria (ASB) – the presence of bacteria in urine without urinary tract infection (UTI) related signs & symptoms (S&S) – is common in the elderly bladder and is not considered pathogenic for UTI. We hypothesise that colonisation with non-uropathogenic bacteria could protect the bladder from invasion of more harmful bacteria. The exact role and dynamics of bacteriuria in the relation to the development of a UTI is still unknown. We aim to provide insight into the course of bacteriuria in the elderly bladder and its relation to UTI in frail older adults. Methods and analysis A prospective observational cohort study is being conducted in Dutch nursing homes (NHs) between February 2024 and December 2025. Urine samples and case report forms (CRF) on UTI-related S&S will be collected from each consenting NH resident every 3 months for a follow-up period of 18 months. Whenever a UTI-suspicion occurs in between the 3 monthly time points, additional data and a urine sample will be collected. Urine samples undergo several urinalyses (e.g. dipstick and bacterial culture). Additional molecular analysis will be conducted on a selection of cultured Escherichia coli (E. coli) for virulence genes. Primary analyses will be conducted between residents with and without ASB at each time point. The primary outcome is UTI incidence during follow-up. In secondary analyses we will also take into account the low versus high presence of virulence genes of the E. coli. Discussion The combination of high ASB prevalence and a reduced ability of frail older adults to express UTI-related S&S may lead to UTI misdiagnosis and inappropriate antibiotic use. To our knowledge, this is the first study to investigate the dynamics and role of bacteriuria in the elderly bladder and their potential protective effect on the development of UTI. The study findings with comprehensive analysis of epidemiological, clinical and molecular data could set the fundamental base for future guidelines and studies, and contribute to improving prevention, diagnosis and treatment of UTI in frail older adults, in addition to contributing to antibiotic stewardship in NHs.

Abstract Background High rates of labour augmentation with oxytocin have been found in some low- and lower-middle-income countries, causing potential perinatal harm. It is critical to understand the reasons for this overuse. Aim was to explore factors that shape practices around using oxytocin for labour augmentation in a high-volume labour ward in Dar es Salaam, Tanzania. Methods Mixed-methods data collection was conducted from March 2021 to February 2022, including structured observations of 234 births, 220 h of unstructured labour ward observations and 13 individual in-depth interviews with birth attendants. Thematic network analysis and descriptive statistics were used to analyse data. We used a time-lens to understand practices of oxytocin for labour augmentation in time-pressured labour wards. Results Birth attendants constantly had to prioritise certain care practices over others in response to time pressure. This led to overuse of oxytocin for augmentation to ensure faster labour progression and decongestion of the, often overburdened, ward. Simultaneously, birth attendants had little time to monitor foetal and maternal condition. Surprisingly, while oxytocin was used in 146 out of 234 (62.4%) structured labour observations, only 9/234 (4.2%) women had active labour lasting more than 12 h. Correspondingly, 21/48 (43.8%) women who were augmented with oxytocin in the first stage of labour had uncomplicated labour progression at the start of augmentation. While the partograph was often not used for decision-making, timing of starting oxytocin often correlated with natural cycles of ward-rounds and shift-turnovers instead of individual women’s labour progression. This resulted in co-existence of ‘too early’ and ‘too late’ use of oxytocin. Liberal use of oxytocin for labour augmentation was facilitated by an underlying fear of prolonged labour and low alertness of oxytocin-related risks. Conclusions Time scarcity in the labour ward often made birth attendants deviate from clinical guidelines for labour augmentation with oxytocin. Efforts to navigate time pressure resulted in too many women with uncomplicated labour progression receiving oxytocin with little monitoring of labour. Fear of prolonged labour and low alertness to oxytocin-mediated risks were crucial drivers. These findings call for research into safety and benefits of oxytocin in low-resource settings and interventions to address congestion in labour wards to prevent using oxytocin as a time-management tool.

Abstract Objectives This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict ‘brain age’ and ‘brain predicted age difference’ (BPAD = brain age–chronological age) for every subject. Results MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p

Abstract Geological evidence indicates that a supernova within 100 parsecs of Earth occurs around once per million years. Such nearby supernovas can produce an intense gamma-ray burst and a 100-fold increase of cosmic rays, lasting several centuries. We find that the effect of a short burst of gamma rays is small since they are strongly attenuated before reaching the lower stratosphere. Intense cosmic radiation affects stratospheric ozone but, due to compensating effects in catalytic chemical cycles, ozone depletion is moderate and comparable to that from current anthropogenic emissions. This also holds for the low-oxygen atmosphere during early evolution of terrestrial life. We estimate the increase in aerosol and clouds from a 100-fold increase of cosmic rays exerts a radiative forcing comparable in magnitude but opposite in sign to current anthropogenic climate forcing. We conclude that Earth’s atmosphere is effective at shielding the biosphere from nearby supernovae.

Abstract Background Physicians and associate (non-physician) clinicians conduct cesarean sections in Tanzania and Malawi. Urogenital fistulas may occur as complications of cesarean section. Location and circumstances can indicate iatrogenic origin as opposed to ischemic injury following prolonged, obstructed labor. Methods This retrospective review assessed the frequency of iatrogenic urogenital fistulas following cesarean sections conducted by either associate clinicians or physicians in Tanzania and Malawi. It focuses on 325 women with iatrogenic fistulas among 1290 women who had fistulas after cesarean birth in Tanzania and Malawi between 1994 and 2017. An equivalence test compared the proportion of iatrogenic fistulas after cesarean sections performed by associate clinicians and physicians (equivalence margin = 0.135). Logistic regression was used to model the occurrence of iatrogenic fistula after cesarean section, controlling for cadre, date, maternal age, previous abdominal surgery and parity. Results Associate clinicians attended 1119/1290 (86.7%) cesarean births leading to fistulas, while physicians attended 171/1290 (13.3%). Iatrogenic fistulas occurred in 275/1119 (24.6%) cesarean births by associate clinicians and in 50/171 (29.2%) cesarean births by physicians. The risk difference and 90% confidence interval were entirely contained within an equivalence margin of 13.5%, supporting a conclusion of equivalence between the two cadres. The odds of iatrogenic fistula after cesarean section were not statistically significantly different between associate clinicians and physicians (aOR 0.90; 95% CI 0.61–1.33). Conclusions Associate clinicians appear equivalent to physicians performing cesarean sections in terms of iatrogenic fistula risk. Lower iatrogenic proportions for associate clinicians could reflect different caseloads. The occurrence of iatrogenic fistulas illustrates the importance of appropriate labor management and cesarean section decision-making, irrespective of health provider cadre. Given the noninferior performance and lower costs of employing associate clinicians, other countries with insufficient and/or unequally distributed health workforces could consider task-shifting cesarean sections to associate clinicians.

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Tiger nuts (Cyperus esculentus) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tiger nuts (C. esculentus) is an edible tuber with history of consumption as food. The NF is the oil obtained from the nuts through cold pressing of the seeds flour. Oleic acid is the major component, representing 65%–69% of the oil's total fatty acids. The applicant proposed to use the NF as an ingredient in several food categories, and as a cooking oil or added as a condiment. The Panel notes that there are no safety concerns regarding stability if the NF complies with the proposed specification limits during its entire shelf‐life. Taking into consideration the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel considers that, based on the production process, composition of the NF, history of use of and composition of the source, no toxicological studies are required on the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

Background The applicability of quantitative flow ratio (QFR), a nonhyperemic, invasive coronary angiography‐derived computation of fractional flow reserve (FFR), has not been studied in coronary artery bypass grafts. We sought to explore the correlation and diagnostic agreement between QFR and FFR in saphenous vein grafts (SVGs). Methods and Results A total of 129 prospectively included patients (mean age 73±8 years, 84% male) with prior coronary artery bypass grafting underwent invasive coronary angiography and pressure‐derived functional assessment in 150 nonoccluded SVGs. QFR dedicated angiography images of the SVGs were acquired and used for offline QFR computation. The diagnostic performance of QFR was compared with 2‐dimensional quantitative coronary angiography, using FFR as a reference. A threshold of ≤0.80 was used to define functional significance. QFR was successfully computed in 140 (93%) SVGs. We found a significant correlation between QFR and FFR (r=0.72, P

Background: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. Therefore, we assessed women's DCIS knowledge in association with socio-demographic and clinical characteristics. Methods: LORD-PPT participants (N = 376) completed a questionnaire assessing socio-demographic and clinical characteristics, risk perception, treatment choice and DCIS knowledge after being informed about their diagnosis and treatment options. Results: 66 % of participants had poor knowledge (i.e., answered ≤3 out of 7 knowledge items correctly). Most incorrect answers involved overestimating the safety of AS and misunderstanding of DCIS prognostic risks. Overall, women with higher DCIS knowledge score perceived their risk of developing IBC as being somewhat higher than women with poorer knowledge (p = 0.049). Women with better DCIS knowledge more often chose surgery whilst most women with poorer knowledge chose active surveillance (p = 0.049). Discussion: Our findings show that there is room for improvement of information provision to patients. Decision support tools for patients and clinicians could help to stimulate effective shared decision-making about DCIS management.

BackgroundVacuum bell (VB) is a technique to treat pectus excavatum in children. Its effectiveness and influencing factors, however, remain under investigated. The aim of this study was to examine the therapeutic effect and its influencing factors of VB in children with pectus excavatum.MethodsA cross-sectional observational study was conducted. Parents of children with pectus excavatum who underwent treatment with a VB between January 2018 and December 2019 were recruited. A survey was designed based on previously related studies and delivered to the parents in September–October 2021. The therapeutic effect was analyzed using subjective experiences by parents. Factors related to effectiveness were analyzed through univariate analysis and multivariate logistic regression.ResultsOf the 77 surveys distributed, 65 (84%) were returned. The mean duration of VB was 23.20 (SD 9.86) months. Caregivers rated the effect of VB treatment as moderate (41.5%), good (46.2%), excellent (12.3%). There were 39 children (60%) who had at least one pause of using VB for more than two weeks. Univariate analysis showed no significant difference between age, height, weight, duration of VB (months) and the effectiveness of VB therapy as defined by caregivers (p > 0.05) and significant difference were observed of the variables “complication of petechiae” (p = 0.034) and “device returned to manufacturer for repair” (p = 0.011). The multivariate logistic regression showed that the occurrence of complication petechiae (p = 0.046) was an influential factor for the effectiveness of VB.ConclusionsThe evaluations reported by the parents suggested that the VB treatment was effective, although with varying degrees. The complication of petechiae seems an influencing factor to successful VB treatment in children with pectus excavatum. Further studies are needed to assess the long-term outcome and effect of VB and to improve the device and to reduce complications in order to enhance compliance and improve effectiveness.

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of oil from Schizochytrium limacinum (strain FCC‐3204) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in protein products at a maximum use level of 1 g of docosahexaenoic acid (DHA) in 100 g of product. The Panel considers that the information provided on the composition and the production process is sufficiently described and does not raise safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided demonstrated the absence of viable cells in the NF. Under the proposed extension of use, the highest intake estimate (at the 95th percentile) of DHA from the NF in protein products is 6.3 mg DHA/kg bw per day for adolescents. The Panel notes that the exposure to DHA from the new intended use of the NF in protein products is very low compared to the exposure to DHA from the already authorised food categories (excluding food supplements). The Panel concludes that the NF (oil from S. limacinum (FCC‐3204)) is safe under the new intended use.

Objective: No established definition for early-stage knee osteoarthritis (KOA) is available, nor classification criteria. Identifying the characteristics of individuals presenting with early-stage KOA symptoms can enhance diagnosis to prevent progression. This study aimed to describe clinical and structural features of individuals presenting with knee complaints within two years after their first consultation, while exploring differences in the duration of knee complaints. Method: Baseline data was used from the LITE randomized controlled trial, assessing the effectiveness of a lifestyle intervention for individuals with knee complaints and overweight in primary care. Baseline assessments included questionnaires, clinical assessment, and MRI of the most symptomatic knee. Differences between groups with varying durations of knee complaints (

Background: Prospective, trial-based data comparing health-related quality of life (HRQoL) in patients surviving out-of-hospital cardiac arrest (OHCA) through extracorporeal cardiopulmonary resuscitation (ECPR) or conventional CPR (CCPR) are scarce. We aimed to determine HRQoL during 1-year after refractory OHCA in patients treated with ECPR and CCPR. Methods: We present a secondary analysis of the multicenter INCEPTION-trial, which studied the effectiveness of ECPR versus CCPR in patients with refractory OHCA. HRQoL was prospectively assessed using the EQ-5D-5L questionnaire. Poor HRQoL was pragmatically defined as an EQ-5D-5L health utility index (HUI) > 1 SD below the age-adjusted norm. We used mixed linear models to assess the difference in HRQoL over time and univariable analyses to assess factors potentially associated with poor HRQoL. Results: A total of 134 patients were enrolled, and hospital survival was 20% (27 patients). EQ-5D-5L data were available for 25 patients (5 ECPR and 20 CCPR). One year after OHCA, the estimated mean HUI was 0.73 (0.05) in all patients, 0.84 (0.12) in ECPR survivors, and 0.71 (0.05) in CCPR survivors (p-value 0.31). Eight (32%) survivors had a poor HRQoL. HRQoL was good in 17 (68%) patients, with 100% in ECPR survivors versus 60% in CCPR survivors (p-value 0.14). Conclusion: One year after refractory OHCA, 68% of the survivors had a good HRQoL. We found no statistically significant difference in HRQoL one year after OHCA in patients treated with ECPR compared to CCPR. However, numerical differences may be clinically relevant in favor of ECPR.

Soil organic carbon (SOC) is central to the functioning of terrestrial ecosystems, has climate mitigation potential and provides several benefits for soil health. Understanding the spatial distribution of SOC can help formulate sustainable soil management practices. Digital soil mapping (DSM) uses advanced statistical and geostatistical methods to estimate soil properties across large areas. DSM integrates climate data, topographic features, geology, legacy soil maps, land management and remote sensing data. Bare soil spectra may reflect the presence of particular soil components, making satellite derived spectra suitable predictors of SOC. Bare soil spectra derived from Sentinel-2 were used to estimate SOC concentration (SOC%) and granulometric fractions in the plough layer (0–30 cm) of agricultural parcels in northern Belgium. Thereafter, the estimation performance of SOC% was compared for three DSM models: one with bare soil spectra, one with environmental covariates (topography, granulometry and vegetation), and a combined model with bare soil spectra and environmental covariates. The estimation performance of sand, silt and clay fractions using bare soil spectra from the spring seedbed (R2: 0.53–0.74; RPD: 1.49–2.05; RPIQ: 1.52–2.39) was higher than that of SOC% (R2: 0.16; RPD: 1.08; RPIQ: 1.32). The highest estimation performance of SOC% was obtained for a DSM model including all covariates (R2: 0.28; RPD: 1.18; RPIQ: 1.44), but the contribution of spring seedbed spectra to a model containing environmental covariates was small. The results provide valuable insights for refining soil property estimation using DSM with spectral and environmental covariates.

Biomonitoring has been widely used in assessing exposures in both occupational and public health complementing chemical risk assessments because it measures the concentrations of chemical substances in human body fluids (e.g., urine and blood). Biomonitoring considers all routes and sources of exposure. An occupational biomonitoring guidance document has been elaborated (OECD Occupational Biomonitoring Guidance) within the OECD framework and specifically, the Working Parties on Exposure and Hazard Assessment by scientific experts from 40 institutes and organizations representing 15 countries. The guidance provides practical information for assessing chemical exposures in occupational settings including the three common routes of exposure: inhalation, skin absorption and ingestion due to hand to mouth contact. The elaborated stepwise approach for conducting biomonitoring is tailored for occupational health professionals, scientists, risk assessors, and regulators. It includes methods for selecting appropriate biomarkers, devising sampling strategies, and assessing laboratories for validated analytical methods for the biomarker of interest, and ensuring timely feedback of results. Furthermore, it describes procedures for setting up efficient biomonitoring programs based on the Similar Exposure Group (SEG) approaches. Derived health-based human exposure biomarker assessment values called Occupational Biomonitoring Levels (OBLs) are proposed for use in occupational exposure and risk assessment. It also helps with the interpretation of biomonitoring results routinely collected and procedures for communicating biomonitoring results at individual, collective, and workplace levels. Ethical considerations associated with biomonitoring are also discussed. The ultimate goal of this biomonitoring approach is to promote harmonized application and interpretation of biomarkers as well as evidence-based occupational risk management measures.

The root parasitic weed Striga hermonthica has a devastating effect on sorghum and other cereal crops in Sub-Saharan Africa. Available Striga management strategies are rarely sufficient or not widely accessible or affordable. Identification of soil- or plant-associated microorganisms that interfere in the Striga infection cycle holds potential for development of complementary biological control measures. Such inoculants should be preferably based on microbes native to the regions of their application. We developed a method to assess microbiome-based soil suppressiveness to Striga with a minimal amount of field-collected soil. We previously used this method to identify the mechanisms of microbe-mediated suppression of Striga infection and to test individual microbial strains. Here, we present protocols to assess the functional potential of the soil microbiome and individual bacterial taxa that adversely affect Striga parasitism in sorghum via three major known suppression mechanisms. These methods can be further extended to other Striga hosts and other root parasitic weeds.

Abstract Histone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven replication fork degradation is elicited by suppressing CtIP-mediated fork protection. As a result, H2AX loss restores replication fork stability and increases chemoresistance in BRCA1/2-deficient tumour cells without restoring homology-directed DNA repair, as highlighted by the lack of DNA damage-induced RAD51 foci. Furthermore, in the attempt to discover acquired genetic vulnerabilities, we find that ATM but not ATR inhibition overcomes PARP inhibitor (PARPi) resistance in H2AX-deficient tumours by interfering with CtIP-mediated fork protection. In summary, our results demonstrate a role for H2AX in replication fork biology in BRCA-deficient tumours and establish a function of H2AX separable from its classical role in DNA damage signalling and DSB repair.

Abstract Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, “Biology in Space and Analogue Environments”, focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: “How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?” The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed.

Abstract The fire crises in the Amazon continues to increase the risk of large-scale forest dieback, threatening regional biodiversity and global climate. This issue gained international attention in 2019 when fires in the Brazilian Amazon led to a fire ban imposition. Despite the uncertainty of its impact, the fire ban was reenacted in subsequent years. Here we assess the effectiveness of each fire ban by comparing observed fire counts with climate-driven predictions of fire for 2019–2021. While the 2019 ban likely reduced the number of fires to expected levels, it was largely ineffective in the years that followed. Four years later in 2023 under a different political dynamic, the Brazilian Amazon faced another fire crisis. Resolving this recurrent issue requires interventions that target the underlying causes of fire and extend beyond emergency measures, including long-term strategies focused on landscape management, public awareness and education, and engagement with local communities and stakeholders.

Plant domestication and breeding not only resulted in multiple phenotypic changes but also impacted the agricultural ecosystems in which our current crops are cultivated. Most crops to date rely on the extensive use of fertilizers and pesticides to support crop growth and health. To minimize the environmental impact of these management practices, the plant microbiome has gained renewed attention as a large yet untapped resource of microorganisms with beneficial effects on plant growth and health. In the past decade, it has become evident that the microbiome of plants plays a key role in nutrient acquisition, plant development, and tolerance to diverse abiotic and biotic stresses. Here, we review past and present knowledge of the microbiome of tomato as a model for unraveling the functional potential of plant microbiomes, the impact of domestication, and the underlying genetics of microbiome assembly and activity. We also provide perspectives on how this knowledge can be adopted to enhance crop productivity and strengthen the sustainability of agricultural management practices. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Abstract Background Research into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer’s disease (AD) dementia. Methods The study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 μg roflumilast, and 100 μg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants’ performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants. Discussion The outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders. Trial registration The Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NL ) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1 ) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.

Abstract Bacteria have an extensive adaptive ability to live in close association with eukaryotic hosts, exhibiting detrimental, neutral or beneficial effects on host growth and health. However, the genes involved in niche adaptation are mostly unknown and their functions poorly characterized. Here, we present bacLIFE ( https://github.com/Carrion-lab/bacLIFE ) a streamlined computational workflow for genome annotation, large-scale comparative genomics, and prediction of lifestyle-associated genes (LAGs). As a proof of concept, we analyzed 16,846 genomes from the Burkholderia/Paraburkholderia and Pseudomonas genera, which led to the identification of hundreds of genes potentially associated with a plant pathogenic lifestyle. Site-directed mutagenesis of 14 of these predicted LAGs of unknown function, followed by plant bioassays, showed that 6 predicted LAGs are indeed involved in the phytopathogenic lifestyle of Burkholderia plantarii and Pseudomonas syringae pv. phaseolicola. These 6 LAGs encompassed a glycosyltransferase, extracellular binding proteins, homoserine dehydrogenases and hypothetical proteins. Collectively, our results highlight bacLIFE as an effective computational tool for prediction of LAGs and the generation of hypotheses for a better understanding of bacteria-host interactions.

Abstract Background Inpatient falls in hospitals are an acknowledged indicator of quality of care. International comparisons could highlight quality improvement potential and enable cross-national learning. Key to fair cross-national comparison is the availability of a risk adjustment model validated in an international context. This study aimed to 1) ascertain that the variables of the inpatient fall risk adjustment model do not interact with country and thus can be used for risk adjustment, 2) compare the risk of falling in hospitals between Switzerland and Austria after risk adjustment. Methods The data on inpatient falls from Swiss and Austrian acute care hospitals were collected on a single measurement day in 2017, 2018 and 2019 as part of an international multicentre cross-sectional study. Multilevel logistic regression models were used to screen for interaction effects between the patient-related fall risk factors and the countries. The risks of falling in hospital in Switzerland and in Austria were compared after applying the risk-adjustment model. Results Data from 176 hospitals and 43,984 patients revealed an inpatient fall rate of 3.4% in Switzerland and 3.9% in Austria. Two of 15 patient-related fall risk variables showed an interaction effect with country: Patients who had fallen in the last 12 months (OR 1.49, 95% CI 1.10–2.01, p = 0.009) or had taken sedatives/psychotropic medication (OR 1.40, 95% CI 1.05–1.87, p = 0.022) had higher odds of falling in Austrian hospitals. Significantly higher odds of falling were observed in Austrian (OR 1.38, 95% CI 1.13–1.68, p = 0.002) compared to Swiss hospitals after applying the risk-adjustment model. Conclusions Almost all patient-related fall risk factors in the model are suitable for a risk-adjusted cross-country comparison, as they do not interact with the countries. Further model validation with additional countries is warranted, particularly to assess the interaction of risk factors “fall in the last 12 months” and “sedatives/psychotropic medication intake” with country variable. The study underscores the crucial role of an appropriate risk-adjustment model in ensuring fair international comparisons of inpatient falls, as the risk-adjusted, as opposed to the non-risk-adjusted country comparison, indicated significantly higher odds of falling in Austrian compared to Swiss hospitals.

Abstract Attaining complete anomeric control is still one of the biggest challenges in carbohydrate chemistry. Glycosyl cations such as oxocarbenium and dioxanium ions are key intermediates of glycosylation reactions. Characterizing these highly-reactive intermediates and understanding their glycosylation mechanisms are essential to the stereoselective synthesis of complex carbohydrates. Although C-2 acyl neighbouring-group participation has been well-studied, the reactive intermediates in more remote participation remain elusive and are challenging to study. Herein, we report a workflow that is utilized to characterize rhamnosyl 1,3-bridged dioxanium ions derived from C-3 p-anisoyl esterified donors. First, we use a combination of quantum-chemical calculations and infrared ion spectroscopy to determine the structure of the cationic glycosylation intermediate in the gas-phase. In addition, we establish the structure and exchange kinetics of highly-reactive, low-abundance species in the solution-phase using chemical exchange saturation transfer, exchange spectroscopy, correlation spectroscopy, heteronuclear single-quantum correlation, and heteronuclear multiple-bond correlation nuclear magnetic resonance spectroscopy. Finally, we apply C-3 acyl neighbouring-group participation to the synthesis of complex bacterial oligosaccharides. This combined approach of finding answers to fundamental physical-chemical questions and their application in organic synthesis provides a robust basis for elucidating highly-reactive intermediates in glycosylation reactions.

Abstract Background Dementia is often associated with Neuropsychiatric Symptoms (NPS) such as agitation, depression, hallucinations, anxiety, that can cause distress for the resident with dementia in long-term care settings and can impose emotional burden on the environment. NPS are often treated with psychotropic drugs, which, however, frequently cause side effects. Alternatively, non-pharmacological interventions can improve well-being and maintain an optimal quality of life (QoL) of those living with dementia. Other QoL related outcomes, such as pain, discomfort and sleep disruption are relevant outcomes in music trials as well. Music therapy is a non-pharmacological intervention that can reduce NPS and improve well-being, and its associated symptoms in dementia. Methods The research will be conducted at eight nursing home facilities of a health care organization in the Netherlands. A sample size of 30 in each group (experimental and control group) is required, totalling 60 residents increased to 80 when considering expected drop out to follow up. The participants in the intervention group receive 30 min of individual music therapy (MT) in their own room by a music therapist twice a week for 12 weeks. The participants in the control group will receive 30 min of individual attention in their own room by a volunteer twice a week for 12 weeks. Assessments will be done at baseline, 6 weeks and 12 weeks. An independent observer, blinded for the intervention or control condition, will assess directly observed well-being (primary outcome) and pain (secondary outcome) before and after the sessions. Nurses will assess other secondary outcomes unblinded, i.e., perceived quality of life and NPS, both assessed with validated scales. The sleep duration will be indirectly assessed by a wrist device called MotionWatch. Information about psychotropic drug use will be derived from electronic medical chart review. Discussion The main purpose of this study is to assess the effects of individual music therapy on directly observed well-being controlled for individual attention in nursing home residents with dementia with NPS. The outcomes refer to both short-term and long-term effects consistent with therapeutic goals of care for a longer term. We hope to overcome limitations of previous study designs such as not blinded designs and music facilitators that were not only music therapists but also occupational therapists and nurses. This study should lead to more focused recommendations for practice and further research into non-pharmacological interventions in dementia such as music therapy. Trial registration The trial is registered at the International Clinical Trials Registry Platform (ICTRP) search portal in the Netherlands Trial Registration number NL7708, registration date 04-05-2019.

The exploration of new pharmacological compounds from endophytic fungi offers infinite possibilities. The aim of this study was to evaluate the antibacterial and antioxidant activities of extracts from the leaves of Ziziphus lotus and five of its endophytic fungi and investigate the chemical diversity of the secondary metabolites produced. Isolated, purified, and molecularly identified endophytes and plant leaves were subjected to ethyl acetate extraction. The antibacterial potential of the extracts was assessed by the disc diffusion method against five bacterial strains: Staphylococcus aureus ATCC 25923; Staphylococcus aureus MU50; Enterococcus faecalis WDCM00009; Escherichia coli ATCC 25922; and Pseudomonas aeruginosa ATCC 27853. DPPH and reducing power tests were performed to assess antioxidant potential. GC–MS analysis was used to identify volatile compounds in extracts. Fungal endophytes were identified as Aspergillus cavernicola, Aspergillus persii, Alternaria alternata, Cladosporium asperlatum, and Fusarium incarnatum–equiseti complex, with respective accession numbers DTO 412-G6, DTO 412-I5, DTO 413-E7, DTO 412-G4, and DTO 414-I2. GC–MS analysis revealed a large number of bioactive compounds. All extracts showed antibacterial activity against at least two of the bacteria tested, and most showed antioxidant activity. The Aspergillus cavernicola extract stood out for its higher phenolic content and higher antioxidant and antibacterial activities in all tests.

ObjectiveTo assess the efficacy of continuous contactless vital signs monitoring with an automated Early Warning System (EWS) in detecting clinical deterioration among patients in general wards.MethodsA prospective observational cohort study was conducted in the medical unit of a tertiary care hospital in India, involving 706 patients over 84,448 monitoring hours. The study used a contactless ballistocardiography system (Dozee system) to continuously monitor heart rate, respiratory rate, and blood pressure. The study assessed total, mean, and median alerts at 24, 48, 72, 96, 120 h, and length of stay (LOS) before patient deterioration or discharge. It analyzed alert sensitivity and specificity, average time from initial alert to deterioration, and healthcare practitioners (HCP) activity. Study was registered with the Clinical Trials Registry-India CTRI/2022/10/046404.ResultsOut of 706 patients, 33 (5%) experienced clinical deterioration, while 673 (95%) did not. The deterioration group consistently had a higher number of alerts compared to those who were discharged normally, across all time-points. On average, the time between the initial alert and clinical deterioration was 16 h within the last 24 h preceding the event. The sensitivity of the Dozee-EWS varied between 67% and 94%. HCP spend 10% of their time on vital signs check and documentation.ConclusionsThis study suggests that utilizing contactless continuous vital signs monitoring with Dozee-EWS in general ward holds promise for enhancing the early detection of clinical deterioration. Further research is essential to evaluate the effectiveness across a wider range of clinical settings.