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Background: Type 2 diabetes mellitus, cardiovascular disease and chronic obstructive pulmonary disease contribute significantly to societal and individual impact globally. High-quality management of these long-term health conditions is important to prevent deterioration of health, although potentially more complex for patients with intellectual disabilities in residential care. Disease management in this context particularly benefits from complete and accurate recording of disease management. Without complete records, long-term health conditions are more difficult to track due to the level of uncertainty regarding which clinical examinations have and have not been performed. This study therefore aims to examine the recording routines of quality indicators for disease monitoring for chronically ill patients with intellectual disabilities in Dutch residential care. Methods: This retrospective study utilised medical record data from a large Dutch long-term care provider. We assessed the occurrence of cardiovascular disease (ICPC-2 codes K74, K75, K76, K89 and K90), type 2 diabetes mellitus (T90, T90.02) and/or COPD (R91, R95). For adults with intellectual disabilities and long-term condition, we analysed data entries in an 18-month period (between July 2020 and December 2021). Observed consultation rates were calculated and presented in median with interquartile range and contrasted against the baseline number of consultations in primary care. Information on recorded quality indicators was presented in frequencies and percentages. Findings: Of the three long-term conditions investigated, the most common was type 2 diabetes mellitus (8.6%; n = 287), followed by cardiovascular disease (5.8%; n = 195) and COPD (3.0%; n = 101). Of those who received management for their long-term condition from their contracted GP, patients with type 2 diabetes mellitus, cardiovascular disease, or COPD had fewer consultations in 2021 than the Dutch baseline. Discussion of lifestyle was often not recorded. Disease monitoring quality indicators were recorded more often but at a lower frequency than expected. Conclusions: Because of the infrequent recording of quality indicators, recording of management of long-term conditions for patients with intellectual disabilities in long-term care appears suboptimal. Although this may not directly harm individual patients, it may jeopardise the quality of management of long-term conditions, as suboptimal recording limits opportunities for evaluation and improvement. Within a broader trend towards data-driven work methods in healthcare, recording of quality indicators requires attention from practice, research and policy.

Abstract People with intellectual disabilities experience overall poorer health and healthcare access than the general population. It is largely unknown how this applies to asthma and chronic obstructive pulmonary disease (COPD) management by general practitioners (GPs). In a 10-year retrospective matched cohort study, n = 34,429, we examined year prevalence of asthma and COPD in adult patients with and without intellectual disabilities and potential differences in the delivery of asthma and COPD disease management activities in Dutch general practices (2010–2019). We collected information on patient characteristics, comorbidity, consultation patterns, use and outcomes of asthma/COPD control questionnaires, spirometry measurement, pulmonology referrals, and prescribed medication. Asthma patients with intellectual disabilities suffered more frequently from obesity (53.2% vs. 39.5% without intellectual disabilities), and both asthma and COPD patients with intellectual disabilities were more frequently current smokers (45.2% vs. 22.1% without intellectual disabilities, and 76.6% vs. 51.4% without intellectual disabilities, respectively). Also, a statistically significant larger number of asthma patients with intellectual disabilities were prescribed antibiotics (69.9% vs. 54.5%). COPD patients with intellectual disabilities, compared with matched controls without intellectual disabilities, received significantly more often either no COPD-related practice consultation at all (respectively 20.8% vs. 8.5%, p = 0.004) or a large number of practice consultations (>31 consultations, respectively 16.7% vs. 5.3%, p = 0.004). For asthma, there was no statistical difference between patients with or without intellectual disabilities regarding the number and type of consultations. The asthma year point prevalence in patients with intellectual disabilities was, from 2014 onward, significantly higher, and in 2019 was 8.7% vs. 6.0% for people without intellectual disabilities. For COPD, it was comparable in both groups. Both asthma and COPD patients with intellectual disabilities appeared considerably younger in age than patients without intellectual disabilities. Our findings warrant further research into the causes of the differences found for asthma and COPD and whether they also infer differences in the quality or the effectiveness of GP disease management, especially for young adults with intellectual disabilities.

Abstract Co-pyrolysis of chicken manure with tree bark was investigated to mitigate salinity and potentially toxic element (PTE) concentrations of chicken manure-derived biochar. The effect of tree bark addition (0, 25, 50, 75 and 100 wt%) on the biochar composition, surface functional groups, PTEs and polycyclic aromatic hydrocarbons (PAH) concentration in the biochar was evaluated. Biochar-induced toxicity was assessed using an in-house plant growth assay with Arabidopsis thaliana. This study shows that PTE concentrations can be controlled through co-pyrolysis. More than 50 wt% of tree bark must be added to chicken manure to reduce the concentrations below the European Biochar Certificate-AGRO (EBC-AGRO) threshold. However, the amount of PAH does not show a trend with tree bark addition. Furthermore, co-pyrolysis biochar promotes plant growth at different application concentrations, whereas pure application of 100 wt% tree bark or chicken manure biochar results in decreased growth compared to the reference. In addition, increased plant stress was observed for 100 wt% chicken manure biochar. These data indicate that co-pyrolysis of chicken manure and tree bark produces EBC-AGRO-compliant biochar with the potential to stimulate plant growth. Further studies need to assess the effect of these biochars in long-term growth experiments.

Abstract Background To reduce the impact of chronic diseases (cardiovascular disease, diabetes mellitus type 2, and chronic lung disease (asthma or chronic obstructive pulmonary disease (COPD)), it is imperative that care is of high quality and suitable to patients’ needs. Patients with intellectual disabilities (ID) differ from the average patient population in general practice because of their limitations in adaptive behaviour and intellectual functioning, and concomitant difficulties recognising and reacting to disease symptoms, proactively searching health information, and independently managing diseases effectively. Because of these differences, information on their care needs is essential for suitable chronic disease management (CDM). Inadequate recognition of the care needs of this vulnerable population may hamper the harmonisation of evidence-based and person-centred care, compounded by issues such as stigma, misconceptions, and diagnostic overshadowing. This study therefore aimed to explore the needs of patients with ID from perspectives of both patients and of healthcare providers (HCPs) in the context of CDM in general practice. Methods This qualitative study recruited patients with ID for face-to-face individual interviews and HCPs for focus groups. With the Chronic Care Model as the underlying framework, semi-structured interviews and focus-group guides were defined to explore patients’ care needs and HCPs’ perspectives. All interviews and focus groups were audio-recorded and transcribed verbatim. Using Atlas.ti software, data were analysed using reflexive thematic analysis. Results Between June and September 2022, 14 patients with ID and cardiovascular disease, diabetes mellitus type 2, and/or asthma/COPD were interviewed; and 32 general practitioners and practice nurses participated in seven focus groups. We identified six care needs underpinning suitable CDM: trusting relationship between patient and HCP; clear expectations about the CDM process; support in disease management; directive decision-making; support in healthy lifestyle; accessible medical information. Conclusions This vulnerable patient population has complex care needs that must be acknowledged for suitable CDM. Although HCPs largely recognise these needs, organisational factors and lack of training or experience with patients with ID hamper HCPs’ ability to fully adjust care provision to these needs. Access to, and knowledge of, easy-language information on chronic diseases and communication guidelines could aid HCPs to facilitate patients in managing their diseases more adequately.

Abstract A large proportion of HIV-coinfected visceral leishmaniasis (VL-HIV) patients exhibit chronic disease with frequent VL recurrence. However, knowledge on immunological determinants underlying the disease course is scarce. We longitudinally profiled the circulatory cellular immunity of an Ethiopian HIV cohort that included VL developers. We show that chronic VL-HIV patients exhibit high and persistent levels of TIGIT and PD-1 on CD8+/CD8- T cells, in addition to a lower frequency of IFN-γ+ TIGIT- CD8+/CD8- T cells, suggestive of impaired T cell functionality. At single T cell transcriptome and clonal resolution, the patients show CD4+ T cell anergy, characterised by a lack of T cell activation and lymphoproliferative response. These findings suggest that PD-1 and TIGIT play a pivotal role in VL-HIV chronicity, and may be further explored for patient risk stratification. Our findings provide a strong rationale for adjunctive immunotherapy for the treatment of chronic VL-HIV patients to break the recurrent disease cycle.

IntroductionFollowing harmonization efforts by the Belgian National Reference Center for SARS-CoV-2, semi-quantitative PCR test (SQ-PCR) results, used as a proxy for viral load, were routinely collected after performing RT-qPCR tests.MethodsWe investigated both the personal characteristics associated with SQ-PCR results and the transmission dynamics involving these results. We used person-level laboratory test data and contact tracing data collected in Belgium from March 2021 to February 2022. Personal characteristics (age, sex, vaccination, and laboratory-confirmed prior infection) and disease stage by date of symptom onset were analyzed in relation to SQ-PCR results using logistic regression. Vaccine effectiveness (VE) against a high viral load (≥107 copies/mL) was estimated from the adjusted probabilities. Contact tracing involves the mandatory testing of high-risk exposure contacts (HREC) after contact with an index case. Odds ratios for test positivity and high viral load in HREC were calculated based on the SQ-PCR result of the index case using logistic regression models adjusted for age, sex, immunity status (vaccination, laboratory-confirmed prior infection), variant (Alpha, Delta, Omicron), calendar time, and contact tracing covariates.ResultsWe included 909,157 SQ-PCR results of COVID-19 cases, 379,640 PCR results from index cases, and 72,052 SQ-PCR results of HREC. High viral load was observed more frequently among recent cases, symptomatic cases, cases over 25 years of age, and those not recently vaccinated (>90 days). The vaccine effectiveness (VE) of the primary schedule in the first 30 days after vaccination was estimated at 47.3% (95%CI 40.8–53.2) during the Delta variant period. A high viral load in index cases was associated with an increased test positivity in HREC (OR 2.7, 95%CI 2.62–2.79) and, among those testing positive, an increased likelihood of a high viral load (OR 2.84, 95%CI 2.53–3.19).

To reach the estimated food demands for 2050 in decreasingly suiting climates, current agricultural techniques have to be complemented by sustainably intensified practices. The current study repurposed wheat crop residues into biochar, and investigated its potential in different plant cultivation systems, including a hydroponic cultivation of wheat. Biochars resulting from varying pyrolysis parameters including feedstock composition (straw and chaff) and temperature (450°C and 600°C), were tested using a fast plant screening method. Biochar WBC450, produced from a combination of chaff and straw at 450°C, was selected for further plant experiments, and used in a static leaching experiment in the Arabidopsis thaliana cultivation medium. Increased pH and EC were observed, together with an increase of most macronutrient (K, Mg, P, S) and a decrease of most micronutrient (Fe, Mn, Zn) concentrations. Considering plant growth, application of biochar resulted in concentration-dependent effects in both tested plant species (A. thaliana and wheat). It improved the vegetative yield across all tested cultivation systems. Increases in K and S, and concentration-dependent decreases in Fe and Na content in wheatgrass were observed. Biochar influenced the reproduction of hydroponically cultivated wheat by increasing the number of spikes and the number of seeds per spike. The antioxidative capacity of wheat grass, and the seed sugar and starch contents remained unaffected by biochar application. This study contributes to innovation in soilless cultivation approaches of staple crops, within the framework of closing waste loops for a circular bioeconomy.

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse. Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD. Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported. Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP

Background: Sports are associated with numerous physiological and psychological benefits. However, it is unclear to what extent adults with congenital heart disease(CHD) participate in sports and whether this is safe. Furthermore, little is known about lifestyle habits in this group. Methods: Consecutive patients diagnosed with atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot and transposition of the great arteries who underwent open-heart surgery during childhood between 1968 and 1980 were included in a longitudinal follow-up study. Patients underwent cardiological investigations every 10 years and completed a questionnaire regarding sports participation in 2011 and in 2021. Results: Of the 2021 cohort(n = 204, mean age:50 years, 46%female), 49% participated in sports. Compared to the general Dutch population they invested less time in sport(female: p = 0.03, male: p = 0.03). Patients participating in sports had better exercise capacity (p

Species lists play an important role in biology and practical domains like conservation, legislation, biosecurity and trade regulation. However, their effective use by non-specialist scientific and societal users is sometimes hindered by disagreements between competing lists. While it is well-known that such disagreements exist, it remains unclear how prevalent they are, what their nature is, and what causes them. In this study, we argue that these questions should be investigated using methods based on taxon concept rather than methods based on Linnaean names, and use such a concept-based method to quantify disagreement about bird classification and investigate its relation to research effort. We found that there was disagreement about 38% of all groups of birds recognized as a species, more than three times as much as indicated by previous measures. Disagreement about the delimitation of bird groups was the most common kind of conflict, outnumbering disagreement about nomenclature and disagreement about rank. While high levels of conflict about rank were associated with lower levels of research effort, this was not the case for conflict about the delimitation of bird groups. This suggests that taxonomic disagreement cannot be resolved simply by increasing research effort.

Influenza is one of the leading causes of disease-related mortalities worldwide. Several strategies have been implemented during the past decades to hinder the replication cycle of influenza viruses, all of which have resulted in the emergence of resistant virus strains. The most recent example is baloxavir marboxil, where a single mutation in the active site of the target endonuclease domain of the RNA-dependent-RNA polymerase renders the recent FDA approved compound ∼1000-fold less effective. Raltegravir is a first-in-class HIV inhibitor that shows modest activity to the endonuclease. Here, we have used structure-guided approaches to create rationally designed derivative molecules that efficiently engage the endonuclease active site. The design strategy was driven by our previously published structures of endonuclease-substrate complexes, which allowed us to target functionally conserved residues and reduce the likelihood of resistance mutations. We succeeded in developing low nanomolar equipotent inhibitors of both wild-type and baloxavir-resistant endonuclease. We also developed macrocyclic versions of these inhibitors that engage the active site in the same manner as their 'open' counterparts but with reduced affinity. Structural analyses provide clear avenues for how to increase the affinity of these cyclic compounds.

Abstract Since the onset of the coronavirus disease (COVID-19) pandemic in Belgium, UZ/KU Leuven has played a crucial role as the National Reference Centre (NRC) for respiratory pathogens, to be the first Belgian laboratory to develop and implement laboratory developed diagnostic assays for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and later to assess the quality of commercial kits. To meet the growing demand for decentralised testing, both clinical laboratories and government-supported high-throughput platforms were gradually deployed across Belgium. Consequently, the role of the NRC transitioned from a specialised testing laboratory to strengthening capacity and coordinating quality assurance. Here, we outline the measures taken by the NRC, the national public health institute Sciensano and the executing clinical laboratories to ensure effective quality management of molecular testing throughout the initial two years of the pandemic (March 2020 to March 2022).

Abstract Background Biochar is a relatively new development in sustainable agricultural management that can be applied to ameliorate degraded and less fertile soils, especially sandy-textured ones, to improve their productivity with respect to crop production through improved nutrient availability. However, as the literature has shown, the response of sandy-textured soils to biochar varies in terms of effect size and direction. Therefore, the present study systematically reviewed the available evidence to synthesize the impact of biochar amendments on aspects of the nutrient cycle of sandy-textured soils. Methods Both peer-reviewed and gray literature were searched in English in bibliographic databases, organizational web pages, and Internet search engines. Articles underwent a two-stage screening (title and abstract, and full-text) based on predefined criteria, with consistency checks. Validity assessments were conducted, utilizing specifically designed tools for study validity. Data extraction involved categorizing the various properties of the nutrient cycle into nine main Soil and Plant Properties (SPPs), each of which was studied independently. Nine meta-analyses were performed using a total of 1609 observations derived from 92 articles. Comparing meta-averages with and without correction for publication bias suggests that publication bias plays a minor role in the literature, while some indication for publication bias is found when accounting for heterogeneity by means of meta-regressions. Review findings According to the results, soil total and available nitrogen [N], phosphorous [P] and potassium [K], plant nutrient level, and potential cation exchange capacity (CEC) increased by 36% (CI [23%, 50%]), 34% (CI [15%, 57%]), 15% (CI [1%, 31%]), and 18% (CI [3%, 36%), respectively, and N2O emission and mineral nutrient leaching decreased by 29% (CI [− 48%, − 3%]) and 38% (CI [− 56%, − 13%). On average, however, biochar had no effect on soil mineral nitrogen and nutrient use efficiency. Publication bias was identified in the response of effective CEC. After corrections for publication bias, the response shifted from 36% to a negative value of − 34% (CI [− 50%, − 14%]). Meta-regression found that the effect modifiers experimental continent, biochar application rate, and soil pH, explain result heterogeneity. Stronger responses came from the continent of South America, higher application rates, and higher pH soils. Overall, biochar is found useful for many SPPs of nutrient cycling of sandy-textured soils, thereby contributing to increased crop yields in such soils.

Background: Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as valve stenosis and regurgitation. This study aimed to investigate sex differences in blood and imaging biomarkers and to describe the long-term prognostic value of blood and echocardiographic biomarkers. Methods: Patients were included from 2 prospective observational cohort studies; they underwent venous blood sampling and transthoracic echocardiography including speckle tracking. Analyzed blood biomarkers were red-cell distribution width (RDW), creatinine, C-reactive protein (CRP), troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP), and transforming growth factor-beta (TGF-β). Sex differences were analyzed at baseline. Associations between biomarkers and arrhythmia-free and intervention-free survival were determined by Cox regression, adjusted for age and sex. Results: A total of 182 patients with BAV were included: median age 34; interquartile range [IQR]: 23-46 years; 55.5% male. CRP, NT-proBNP, and RDW were higher in women, whereas creatinine, troponin T and TGF-β were higher among men. After a median follow-up time of 6.9 (IQR: 6.5-9.9) years, arrhythmia-free and intervention-free survival was, 81.0% and 73.1%, respectively. NT-proBNP was associated with both arrhythmia-free and intervention-free survival (hazard ratio [HR], 1.94, P = 0.005 and HR, 2.06, P = 0.002, respectively). On echocardiography higher left atrial (LA) size, left ventricular end-diastolic diameter (LVEDD), left ventricular (LV) mass index and E/e’ ratio were associated with lower arrhythmia-free survival, whereas higher LA size, LV mass index, aortic valve peak velocity, and aortic regurgitation were associated with lower intervention-free survival. Conclusions: Differences were observed in blood biomarkers between men and women with BAV. Besides LV systolic parameters, diastolic LV function and NT-proBNP should have a more prominent role as prognostic markers in clinical care. Résumé: Contexte: La bicuspide valvulaire aortique (BVA) est une anomalie cardiaque congénitale fréquente. Les patients atteints d’une BVA présentent des risques de complications à long terme, comme la sténose valvulaire ou la régurgitation valvulaire. Cette étude visait 1) à évaluer les différences entre les sexes en ce qui concerne les biomarqueurs sanguins et les biomarqueurs à l’imagerie; et 2) à décrire la valeur pronostique à long terme des biomarqueurs sanguins et échocardiographiques. Méthodologie: Des patients de 2 études de cohortes observationnelles prospectives ont été inclus dans l’analyse. Des échantillons de sang veineux ont été prélevés, et des échocardiographies transthoraciques, y compris le suivi des marqueurs acoustiques, ont été effectuées. Les biomarqueurs sanguins analysés étaient les suivants : indice de distribution des globules rouges (IDR), créatinine, protéine C-réactive (CRP), troponine T, propeptide natriurétique de type B N-terminal (NT-proBNP) et facteur de croissance transformant β (TGF-β). Les différences entre les sexes ont été analysées au départ. Les liens entre les biomarqueurs et la survie sans arythmie et sans intervention ont été déterminés par la régression de Cox, avec correction en fonction de l’âge et du sexe. Résultats: Cent quatre-vingt-deux patients présentant une BVA étaient inclus (âge médian de 34 [écart interquartile : 23-46] ans, 55,5 % hommes). La CRP, la NT-proBNP et l’IDR étaient plus élevées chez les femmes, alors que la créatinine, la troponine T et le TGF-β étaient plus élevés chez les hommes. Après une période de suivi médiane de 6,9 (écart interquartile : 6,5-9,9) ans, les taux de survie sans arythmie et sans intervention étaient respectivement de 81,0 % et de 73,1 %. La NT-proBNP a été associée à la survie sans arythmie (rapport des risques instantanés [RRI] : 1,94, p = 0,005) et à la survie sans intervention (RRI : 2,06, p = 0,002). À l’échocardiographie, des valeurs élevées pour la taille de l’oreillette gauche, le diamètre télédiastolique du ventricule gauche (VG), l’indice de masse du VG et le rapport E/e’ étaient associées à un faible taux de survie sans arythmie, alors que des valeurs élevées pour la taille de l’oreillette gauche, l’indice de masse du VG, la vitesse maximale aortique et la régurgitation aortique étaient associées à un faible taux de survie sans intervention. Conclusions: Les biomarqueurs sanguins variaient en fonction du sexe des personnes présentant une BVA. Outre les paramètres systoliques du VG, la fonction VG diastolique et la NT-proBNP devraient être davantage utilisées comme marqueurs pronostiques en soins cliniques.

Abstract Background People with intellectual disabilities (ID) face barriers in cancer care contributing to poorer oncological outcomes. Yet, understanding cancer risks in the ID population remains incomplete. Aim To provide an overview of cancer incidence and cancer risk assessments in the entire ID population as well as within ID‐related disorders. Methods This systematic review examined cancer risk in the entire ID population and ID‐related disorders. We systematically searched PubMed (MEDLINE) and EMBASE for literature from January 1, 2000 to July 15, 2022 using a search strategy combining terms related to cancer, incidence, and ID. Results We found 55 articles assessing cancer risks in the ID population at large groups or in subgroups with ID‐related syndromes, indicating that overall cancer risk in the ID population is lower or comparable with that of the general population, while specific disorders (e.g., Down's syndrome) and certain genetic mutations may elevate the risk for particular cancers. Discussion The heterogeneity within the ID population challenges precise cancer risk assessment at the population level. Nonetheless, within certain subgroups, such as individuals with specific ID‐related disorders or certain genetic mutations, a more distinct pattern of varying cancer risks compared to the general population becomes apparent. Conclusion More awareness, and personalized approach in cancer screening within the ID population is necessary.