Development of a new wheelchair for wheelchair basketball players in the Netherlands

AbstractThe aim of the development of a new basketball wheelchair was to reduce the weight of the frame, to develop a program to fit anthropometric measurements to design a custom made wheelchair and to develop high-end wheels to increase propulsion efficiency by reducing rolling resistance. The redesigning process resulted in a frame which is 30% lighter than current aluminium wheelchair frames, a program that links anthropometric data to a CAD model of wheelchairs and a new wheel. Several tests were performed to evaluate the new wheelchair. The tests showed promising results with respect to improving both technical performance combined with the athlete's performance

Modeling dominant height growth using permanent plot data for Pinus brutia stands in the Eastern Mediterranean region

Aim of the study: At current, forest management in the Eastern Mediterranean region is largely based on experience rather than on management plans. To support the development of such plans, this study develops and compares site index equations for pure even-aged Pinus brutia stands in Syria using base-age invariant techniques that realistically describe dominant height growth.Materials and methods: Data on top height and stand age were obtained in 2008 and 2016 from 80 permanent plots capturing the whole range of variation in site conditions, stand age and stand density. Both the Algebraic Difference Approach (ADA) and the Generalized Algebraic Difference Approach (GADA) were used to fit eight generalized algebraic difference equations in order to identify the one which describes the data best. For this, 61 permanent plots were used for model calibration and 19 plots for validation.Main results: According to both biological plausibility and model accuracy, the so-called Sloboda equation based on the GADA approach showed the best performance.Research highlights: The study provides a solid classification and comparison of Pinus brutia stands growing in the Eastern Mediterranean region and can thus be used to support sustainable forest management planning.Keywords: site index; Generalized Algebraic Difference Approach (GADA); Sloboda equation

The course of mental health problems in children presenting with abdominal pain in general practice

Objective. To investigate the course of mental health problems in children presenting to general practice with abdominal pain and to evaluate the extent to which abdominal pain characteristics during follow-up predict the presence of mental health problems at 12 months' follow-up. Design. A prospective cohort study with one-year follow-up. Setting. 53 general practices in the Netherlands, between May 2004 and March 2006. Subjects. 281 children aged 4-17 years. Main outcome measures. The presence of a depressive problem, an anxiety problem, and multiple non-specific somatic symptoms at follow-up and odds ratios of duration, frequency, and severity of abdominal pain with these mental health problems at follow-up. Results. A depressive problem persisted in 24/74 children (32.9%; 95% CI 22.3-44.9%), an anxiety problem in 13/43 (30.2%; 95% CI 17.2-46.1%) and the presence of multiple non-specific somatic symptoms in 75/170 children (44.1%; 95% CI 36.7-51.6%). None of the abdominal pain characteristics predicted a depressive or an anxiety problem at 12 months' follow-up. More moments of moderate to severe abdominal pain predicted the presence of multiple nonspecific somatic symptoms at follow-up. Conclusions. In one-third of the children presenting to general practice for abdominal pain, anxiety and depressive problems persist during one year of follow-up. Characteristics of the abdominal pain during the follow-up period do not predict anxiety or depressive problems after one-year follow-up. We recommend following over time children seen in primary care with abdominal pain

Ganciclovir therapeutic drug monitoring in transplant recipients

BACKGROUND: The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance. OBJECTIVES: To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in a transplant patient population. METHODS: An observational study was performed in transplant recipients from June 2018 to February 2020. Dose adjustments were advised by the TDM pharmacist as part of clinical care. For prophylaxis, a trough concentration (Cmin) of 1-2 mg/L and an AUC24h of >50 mg·h/L were aimed for. For treatment, a Cmin of 2-4 mg/L and an AUC24h of 80-120 mg·h/L were aimed for. RESULTS: Ninety-five solid organ and stem cell transplant patients were enrolled. Overall, 450 serum concentrations were measured; with a median of 3 (IQR = 2-6) per patient. The median Cmin and AUC24h in the treatment and prophylaxis groups were 2.0 mg/L and 90 mg·h/L and 0.9 mg/L and 67 mg·h/L, respectively. Significant intra- and inter-patient patient variability was observed. The majority of patients with an estimated glomerular filtration rate of more than 120 mL/min/1.73 m2 and patients on continuous veno-venous haemofiltration showed underexposure. The highest Cmin and AUC24h values were associated with the increase in liver function markers and decline in WBC count as compared with baseline. CONCLUSIONS: This study revealed that a standard weight and kidney function-based dosing regimen resulted in highly variable ganciclovir Cmin and under- and over-exposure were observed in patients on dialysis and in patients with increased renal function. Clearly there is a need to explore the impact of concentration-guided dose adjustments in a prospective study

Molecular dynamics simulations reveal that AEDANS is an inert fluorescent probe for the study of membrane proteins

Computer simulations were carried out of a number of AEDANS-labeled single cysteine mutants of a small reference membrane protein, M13 major coat protein, covering 60% of its primary sequence. M13 major coat protein is a single membrane-spanning, α-helical membrane protein with a relatively large water-exposed region in the N-terminus. In 10-ns molecular dynamics simulations, we analyze the behavior of the AEDANS label and the native tryptophan, which were used as acceptor and donor in previous FRET experiments. The results indicate that AEDANS is a relatively inert environmental probe that can move unhindered through the lipid membrane when attached to a membrane protein

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

Rationale &amp; Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting &amp; Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P &lt; 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P &lt; 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P &lt; 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P &lt; 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.</p

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes