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In dit artikel staat de vraag centraal hoe jongvolwassenen die begeleid wonen hun leven ervaren en wat zij vinden van de ondersteuning die ze hierbij krijgen. Naast het perspectief van de jongvolwassenen is ook het perspectief van naasten onderzocht en zijn dossiers bestudeerd. In de resultaten worden vier thema’s besproken die uit het onderzoek naar voren zijn gekomen: (1) Jongvolwassenen ervaren de meeste problemen op het terrein van mentale gezondheid. (2) Jongvolwassenen hebben behoefte aan sociale contacten, maar hebben moeite om de juiste (hoeveelheid) vrienden te vinden. (3) Jongvolwassenen worden vooral op een praktische manier voorbereid op de toekomst en stellen aandacht voor hun lichamelijke gezondheid uit. (4) In de ondersteuning zou meer aandacht moeten zijn voor toekomstvragen van jongvolwassenen die niet alleen praktisch, maar ook existentieel en maatschappelijk van aard zijn.

Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies. This flow-FISH method was employed to isolate CD4+ T cells expressing abortive or elongated HIV-1 transcripts from five ART-naïve PWH for transcriptomic analysis by 3' RNA sequencing. Supervised cluster analysis identified several differentially expressed mitochondrial genes in infected CD4+ T cells with abortive HIV-1 transcripts compared to cells containing elongated HIV-1 transcripts. Notably, enhancing mitochondrial function induced HIV-1 transcription in PBMC from PWH. Our data strongly suggests that cellular metabolism is involved in maintaining HIV-1 latency and show that improving mitochondrial functions induces HIV-1 transcriptional activity in PWH. These findings underline the relevance of metabolic regulation in HIV-1 infection, and support the development of strategies modulating immunometabolism to target viral latency.

There is a lack of acceptance, adoption and sustained use of mobile phones for agricultural purposes by smallholder farmers in Zimbabwe, but the reasons for this have not been critically explored. In this study, the authors used a naturalistic methodology to help uncover the nuances of adoption dynamics among smallholder farmers in Gokwe South District, Zimbabwe. Data was gathered from in-depth interviews and focus groups. The findings suggest that gender, age, land ownership size, farming experience, mobile device ownership, and the period of owning a mobile device are critical precursors to adoption and use. Furthermore, digital proficiency and literacy, affluence, mobile technology services cost and telecommunication infrastructure availability are vital in achieving continuous, sustainable use of mobile technology in the Zimbabwean agricultural sector. This research has practical implications for policy and practice and may inform national legislation encouraging the increased use and affordability of mobile devices in the local agricultural sector. The research also makes a theoretical contribution in terms of unpacking the key factors that inhibit the adoption of mobile technology in marginalised settings.

Abstract In the future, rivers may export more pollutants to coastal waters, driven by socio‐economic development, increased material consumption, and climate change. However, existing scenarios often ignore multi‐pollutant problems. Here, we aim to explore future trends in annual river exports of nutrients (nitrogen and phosphorus), plastics (macro and micro), and emerging contaminants (triclosan and diclofenac) at the sub‐basin scale worldwide. For this, we implement into the process‐based MARINA‐Multi model (Model to Assess River Inputs of pollutaNts to the seAs) two new multi‐pollutant scenarios: “Sustainability‐driven Future” (SD) and “Economy‐driven Future” (ED). In ED, river exports of nutrients and microplastics will double by 2100, globally. In SD, a decrease of up to 83% is projected for river export of all studied pollutants by 2100, globally. Diffuse sources such as fertilizers are largely responsible for increasing nutrient pollution in the two scenarios. Point sources, namely sewage systems, are largely responsible for increasing microplastic pollution in the ED scenario. In both scenarios, the coastal waters of the Indian Ocean will receive up to 400% more pollutants from rivers by 2100 because of growing population, urbanization, and poor waste management in the African and Asian sub‐basins. The situation differs for sub‐basins draining into the Mediterranean Sea and the Pacific Ocean (mainly less future pollution) and the Atlantic Ocean and Arctic Ocean (more or less future pollution depending on sub‐basins and scenarios). From 56% to 78% of the global population are expected to live in more polluted river basins in the future, challenging sustainable development goals for clean waters.

Trace metal contamination is ubiquitous around the world and may affect the health of wildlife. Divalent trace metals, including ions of mercury (Hg) and lead (Pb), have been shown to be immunotoxic to avian species. However, little is known about the immunomodulatory effects of trace metal exposure on viral infections, especially in young birds, who may be more sensitive. Therefore, the objective of the current study is to provide more insights in the causality between trace metal exposure and the effects of exposure on the immune responses in young waterfowls. Pekin duckling was used as an animal model to investigate the effects of inorganic divalent Hg (II) and Pb (II) on avian immune responses upon a viral-like challenge with double-stranded RNA. Our results indicate that Hg (II) altered the immune gene expression 24 h post-challenge, as reflected by induction of pro-inflammatory genes IL-8, iNOS, TLR3 and TLR7, and a significant decrease of microRNA-155. Ducklings exposed to Pb (II) showed lower levels of natural antibodies, reduced white blood cell counts and lower heterophil proportions 24 h post-challenge. Although inorganic divalent Hg (II) and Pb (II) showed specific differential effects on the immune response of Pekin ducklings, the overall adverse immunomodulatory outcomes in both cases point to inflammation, impaired B-cell function, and weaker immunocompetence.

A healthy body mass contributes to a positive quality of life, and for overweight/obese individuals, weight loss of even modest proportions improves health-related outcomes. A novel approach to promoting body mass regulation is to pair exercise with high altitude, thereby upregulating metabolic processes and increasing caloric expenditure. As an added measure of body mass regulation, data suggest that high altitude stimulates the production of the appetite-suppressing hormone leptin. Issues arise, however, given that high altitude compromises aerobic exercise capacity. Whereas exercising at high altitude may compromise exercise intensity and duration, recovering at high altitude retains the integrity of exercise while still potentially conferring the benefits of the low oxygen environment on energy expenditure and energy intake. The purpose of this study was to perform a proof-of-concept pilot test on whether post-exercise exposure to a simulated high altitude influenced acute energy balance. Twelve healthy men and women ran for 30 min at a moderate intensity on two separate occasions. Following exercise, participants recovered for 30 min while breathing either sea level air or low oxygen air simulating high altitude (equivalent to 4500 m elevation). Blood samples and hunger ratings were collected pre-exercise and post-recovery. Heart rate was recorded throughout exercise and recovery and used to calculate caloric expenditure. Post-exercise energy expenditure was significantly higher (p = 0.03) following high altitude recovery (139 ± 15 kcal) compared to sea-level recovery (98 ± 11 kcal). Participants reported a lower desire to eat when they recovered in the high altitude environment (p = 0.01), though post-recovery leptin concentrations were similar between the two conditions. Post-exercise exposure to a simulated high altitude environment represents a promising method for increasing daily caloric expenditure and lowering appetite. Given the pilot nature of this study, future research is needed to address the question of high altitude recovery on a larger sample over a longer time period and with robust measures of caloric expenditure.

BackgroundSalvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. ObjectiveThis study aims to evaluate prostate-specific membrane antigen–positron emission tomography (PSMA-PET)–based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model’s performance, aiming to improve clinical management of recurrent prostate cancer. MethodsThis multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET–based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. ResultsBaseline characteristics of 1029 patients undergoing sRT PSMA-PET–based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (

Abstract Twenty percent of children with T‐cell lymphoblastic lymphoma (T‐LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low‐risk subgroup in pediatric T‐LBL, yet these high‐risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high‐risk T‐LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T‐LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018 and 2023, we discovered a previously unknown high‐risk biological subgroup of children with T‐LBL. This subgroup is characterized by NOTCH1 gene fusions, found in 21% of our T‐LBL cohort (6/29). All patients presented with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Blood CCL17 (C‐C Motif Chemokine Ligand 17, TARC) levels were measured at diagnosis in 26/29 patients, and all six patients with NOTCH1 gene fusions patients exclusively expressed highly elevated blood CCL17 levels, defining a novel and previously not known clinically relevant biomarker for T‐cell lymphoblastic lymphoma. Four out of these six patients relapsed during therapy, a fifth developed a therapy‐related acute myeloid leukemia during maintenance therapy. These data indicate that T‐LBL patients with a NOTCH1 fusion have a high risk of relapse which can be easily identified using a blood CCL17 screening at diagnosis. Further molecular characterization through NOTCH1 gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies.

Abstract Coastal flood managers seek to anticipate future flood risk and as a result consider the adaptation of flood defences. Instead of crest heightening, dikes can be adapted to include hydrodynamic reducing vegetated foreshores to form a nature‐based hybrid flood defence, for instance; at managed realignments. In this study we investigated the potential of vegetated revetments as a natural continuous connection between the realigned dike and restored foreshore. We applied the historic grass sod transplantation technique with the aim to improve our understanding of the strength of a transplanted sod revetment. In Living Lab Hedwige‐Prosperpolder, dikes were available for in‐situ experiments during managed realignment preparations. We transplanted grass sods and studied erosion resistance after one growth season. Our results show transplanted sod vegetation continued to grow and started to attach to the clay layer. While erosion occurred under extreme wave impact and overflow, the sod pulling method revealed individual sod strength. In conclusion, sod transplantation is a good technique to source local material for green realigned dike revetments. A vegetated dike revetment can hereby create a natural continuous connection between the realigned dike and foreshore, which benefits flood protection as well as flora and fauna.

● Four highlights are identified for agriculture and water from the multi-pollutant perspective.● Large variations in time and space for multiple pollutants in waters and their sources.● Scientific agenda should account for multiple pollutants in agricultural strategies. Agriculture is an important cause of multiple pollutants in water. With population growth and increasing food demand, more nutrients, plastics, pesticides, pathogens and antibiotics are expected to enter water systems in the 21st century. As a result, water science has been shifting from single-pollutant to multi-pollutant perspectives for large-scale water quality assessments. This perspective paper summarizes and discusses four main highlights related to water pollution and agriculture from the multi-pollutant perspective. These highlights reveal the spatial and temporal distribution and main sources of multiple pollutants in waters. Based on the highlights, a scientific agenda is proposed to prioritize solutions for sustainable agriculture (UN Sustainable Development Goal 2) and clean water (UN Sustainable Development Goals 6 and 14). This agenda points out that when formulating solutions for water pollution, it is essential to take into account multiple pollutants and their interactions beyond biogeochemistry.

● A new MARINA-Nutrients model was developed to assess air and water pollution in Europe.● Agriculture is responsible for 55% of N and sewage for 67% of P in rivers.● Almost two-fifths of reactive N emissions to air are from animal housing and storage.● Nearly a third of the basin area produces over half of N emissions to air and nutrients in rivers.● Over 25% of river export of N ends up in the Atlantic Ocean and P in the Mediterranean Sea. Nutrient pollution of air and water is a persistent problem in Europe. However, the pollution sources are often analyzed separately, preventing the formulation of integrative solutions. This study aimed to quantify the contribution of agriculture to air, river and coastal water pollution by nutrients. A new MARINA-Nutrients model was developed for Europe to calculate inputs of nitrogen (N) and phosphorus (P) to land and rivers, N emissions to air, and nutrient export to seas by river basins. Under current practice, inputs of N and P to land were 34.4 and 1.8 Tg·yr–1, respectively. However, only 12% of N and 3% of P reached the rivers. Agriculture was responsible for 55% of N and sewage for 67% of P in rivers. Reactive N emissions to air from agriculture were calculated at 4.0 Tg·yr–1. Almost two-fifths of N emissions to air were from animal housing and storage. Nearly a third of the basin area was considered as pollution hotspots and generated over half of N emissions to air and nutrient pollution in rivers. Over 25% of river export of N ended up in the Atlantic Ocean and of P in the Mediterranean Sea. These results could support environmental policies to reduce both air and water pollution simultaneously, and avoid pollution swapping.

Abstract The oomycete Pythium flevoense was diagnosed as the cause of dermatitis in a young adult female harbour porpoise (Phocoena phocoena) that had been trapped in a pound net in a temperate saltwater environment. Disease from Pythium sp. infection—pythiosis—is infrequently diagnosed in humans, horses, dogs, cattle, and few other mammalian species. Pythiosis is typically associated with exposure to tropical or subtropical freshwater conditions, and typically caused by Pythium insidiosum. However, until now, pythiosis has been reported in neither marine mammals nor temperate saltwater conditions, and P. flevoense is not known as a cause of pythiosis in mammals. This porpoise developed generalised dermatitis despite treatment and euthanasia was necessary. Histopathological evaluation revealed a chronic active erosive dermatitis, with intralesional hyphae morphologically consistent with a Pythium sp. PCR analysis and sequencing of affected skin matched Pythium flevoense with a 100% similarity to the reference strain. Additional diagnostics excluded other pathogens. Based on this case report, P. flevoense needs to be considered as a mammalian pathogen. Furthermore, harbour porpoises and possibly other marine mammals may be at risk of infection with P. flevoense, and pythiosis should be included in the differential diagnosis of dermatitis in marine mammals.

The MRGPRX family of receptors (MRGPRX1-4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently1. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions2-5. MRGPRX2 couples to both Gi and Gq in mast cells6. Here we describe agonist-stabilized structures of MRGPRX2 coupled to Gi1 and Gq in ternary complexes with the endogenous peptide cortistatin-14 and with a synthetic agonist probe, respectively, and the development of potent antagonist probes for MRGPRX2. We also describe a specific MRGPRX4 agonist and the structure of this agonist in a complex with MRGPRX4 and Gq. Together, these findings should accelerate the structure-guided discovery of therapeutic agents for pain, itch and mast cell-mediated hypersensitivity.