Gentechnologie bij landbouwhuisdieren

Een overzicht van de ontwikkelingen van het kloneren van landbouwhuisdieren, met het oog op mogelijke consequenties voor beleid en regelgeving. Er wordt ingegaan op de techniek van dna modificatie, de invloed op veehouderij, fokkerij, praktijk, dierenwelzijn en -gezondheid, nationale veiligheid en regelgeving en de toekomstige ontwikkelingen in de nabije toekoms

A nonequilibrium extension of the Clausius heat theorem

We generalize the Clausius (in)equality to overdamped mesoscopic and macroscopic diffusions in the presence of nonconservative forces. In contrast to previous frameworks, we use a decomposition scheme for heat which is based on an exact variant of the Minimum Entropy Production Principle as obtained from dynamical fluctuation theory. This new extended heat theorem holds true for arbitrary driving and does not require assumptions of local or close to equilibrium. The argument remains exactly intact for diffusing fields where the fields correspond to macroscopic profiles of interacting particles under hydrodynamic fluctuations. We also show that the change of Shannon entropy is related to the antisymmetric part under a modified time-reversal of the time-integrated entropy flux.Comment: 23 pages; v2: manuscript significantly extende

Treatment with liraglutide or naltrexone-bupropion in patients with genetic obesity:a real-world study

Background: Rare genetic obesity commonly features early-onset obesity, hyperphagia, and therapy-resistance to lifestyle interventions. Pharmacotherapy is often required to treat hyperphagia and induce weight loss. We describe clinical outcomes of glucagon-like peptide-1 analogue liraglutide or naltrexone-bupropion treatment in adults with molecularly confirmed genetic obesity (MCGO) or highly suspected for genetic obesity without definite diagnosis (HSGO). Methods: We conducted a real-world cohort study at the Obesity Center CGG at Erasmus University Center, Rotterdam, Netherlands, between March 19, 2019, and August 14, 2023. All patients with MCGO and HSGO who were treated with either liraglutide or naltrexone-bupropion were included. Liraglutide 3 mg and naltrexone-bupropion were administered according to the manufacturer's protocol. Treatment evaluation occurred short-term, after 12 weeks on maximum or highest-tolerated dose, preceded by the 4–5 week dose escalation phase. Differences in anthropometrics, body composition, metabolic markers, self-reported appetite, eating behaviour, and quality of life (QoL) were evaluated. Findings: Ninety-eight adults were included in the analysis: 23 patients with MCGO and 75 patients with HSGO, with median BMI of 42.0 kg/m2 (IQR 38.7–48.2) and 43.7 kg/m2 (IQR 38.0–48.7), respectively. After liraglutide treatment, median weight at evaluation significantly decreased compared to baseline in both groups: −4.7% (IQR −6.0 to −1.5) in patients with MCGO and −5.2% (IQR −8.1 to −3.5) in patients with HSGO. Additionally, improvements were observed in appetite, fat mass, fasting glucose, and HbA1c in both patients with MCGO and with HSGO. Patients with HSGO also reported significant improvements in several domains of QoL and eating behaviour. In patients with MCGO and HSGO treated with naltrexone-bupropion, mean weight at evaluation significantly differed from baseline: −5.2% ± 5.8 in patients with MCGO and −4.4% ± 4.7 in patients with HSGO. Appetite, fat mass, and waist circumference significantly decreased in both groups. Obesity-related comorbidities improved in significant proportions of patients treated with liraglutide or naltrexone-bupropion. Interpretation: In conclusion, our short-term findings show potential of liraglutide and naltrexone-bupropion as treatment options for adults with (a clinical phenotype of) genetic obesity. Funding: MB, EvdA, and EvR are supported by the, a non-profit foundation supporting academic obesity research.</p

Compliance to DMD care considerations in the Netherlands

Background and objective: To optimize care for patients with DMD, it is essential to know to what extent current care complies with the recommended monitoring frequencies suggested by the DMD care considerations. The objective of this study was to investigate the current care for patients with DMD in the Netherlands and to what extent the care complies with the international care considerations.Methods: A cross-sectional questionnaire was carried out among the Dutch DMD patients and caregivers about the patients' functional and health status, visits to healthcare professionals, clinical tests and assessments, therapy, medication use and access to medical aids and devices. Compliance to guidelines was defined by comparing the frequency of visits to health care providers and clinical tests with the recommended frequencies derived from the care considerations of 2010.Results: Eighty-four participants completed the questionnaire. The majority of participants met the recommended visit frequencies to a neuromuscular specialist and cardiologist. Compliance was suboptimal for respiratory assessments in the non-ambulatory phase, monitoring of side effects of corticosteroid use and neuromuscular assessments. Disease specific information supply was perceived as sufficient and participants were satisfied with the received care.Conclusions: This study identifies areas in which compliance is lacking. Countries, such as the Netherlands, working according to a shared care system require easy and low-threshold communication between health care centers and a clear division of roles and responsibilities to reach optimal compliance. In the Netherlands the Duchenne Center Netherlands has the coordinating role.Neurological Motor Disorder

Compact & droog : eindrapport

In dit project wordt kennis ontwikkeld die toegespitst is op het zo optimaal en compact mogelijk vervoeren van snijbloemen (in termen van vervoerskosten, CO2, en productkwaliteit): bij elke vervoersoptie wordt gekeken naar wat wel/niet kan inzake productkwaliteit; de economische voordelen; en hoe risico's te verkleinen. Verschillende testverpakkingen zullen gevuld worden met vullingsgraden, die de praktijk wenselijk, nog werkbaar en acceptabel acht. In door Wageningen UR begeleide pilots zal aangetoond worden, dat hierdoor de kwaliteit (waarschijnlijk) niet nadelig beïnvloed wordt en in sommige situaties zelfs voordeel oplevert

Baseline fat fraction is a strong predictor of disease progression in Becker muscular dystrophy

In Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate among patients. This complicates clinical trials, as clinically relevant changes are difficult to capture within the typical duration of a trial. Therefore, predictors for disease progression are needed. We assessed if temporal increase of fat fraction (FF) in BMD follows a sigmoidal trajectory and whether fat fraction at baseline (FFbase) could therefore predict FF increase after 2 years (Delta FF). Thereafter, for two different MR-based parameters, we tested the additional predictive value to FFbase. We used 3-T Dixon data from the upper and lower leg, and multiecho spinecho MRI and 7-T P-31 MRS datasets from the lower leg, acquired in 24 BMD patients (age: 41.4 [SD 12.8] years). We assessed the pattern of increase in FF using mixed-effects modelling. Subsequently, we tested if indicators of muscle damage like standard deviation in water T-2 (stdT(2)) and the phosphodiester (PDE) over ATP ratio at baseline had additional value to FFbase for predicting Delta FF. The association between FFbase and Delta FF was described by the derivative of a sigmoid function and resulted in a peak Delta FF around 0.45 FFbase (fourth-order polynomial term: t = 3.7, p < .001). StdT(2) and PDE/ATP were not significantly associated with Delta FF if FFbase was included in the model. The relationship between FFbase and Delta FF suggests a sigmoidal trajectory of the increase in FF over time in BMD, similar to that described for Duchenne muscular dystrophy. Our results can be used to identify muscles (or patients) that are in the fast progressing stage of the disease, thereby facilitating the conduct of clinical trials.Orthopaedics, Trauma Surgery and Rehabilitatio

Association of elbow flexor MRI fat fraction with loss of hand-to-mouth movement in patients with Duchenne muscular dystrophy

Background and Objectives To study the potential of quantitative MRI (qMRI) fat fraction (FF) as a biomarker in nonambulant patients with Duchenne muscular dystrophy (DMD), we assessed the additive predictive value of elbow flexor FF to age at loss of hand-to-mouth movement. Methods Nonambulant patients with DMD (age >= 8 years) were included. Four-point Dixon MRI scans of the right upper arm were performed at baseline and at the 12-, 18-, or 24-month follow-up. Elbow flexor FFs were determined from 5 central slices. Loss of hand-to-mouth movement was determined at study visits and by phone calls every 4 months. FFs were fitted to a sigmoidal curve by use of a mixed model with random slope to predict individual trajectories. The added predictive value of elbow flexor FF to age at loss of hand-to-mouth movement was calculated from a Cox model with the predicted FF as a time-varying covariate, yielding a hazard ratio. Results Forty-eight MRIs of 20 patients with DMD were included. The hazard ratio of a percent-point increase in elbow flexor FF for the time to loss of hand-to-mouth movement was 1.12 (95% confidence interval 1.04-1.21; p = 0.002). This corresponded to a 3.13-fold increase in the instantaneous risk of loss of hand-to-mouth movement in patients with a 10-percent points higher elbow flexor FF at any age. Discussion In this prospective study, elbow flexor FF predicted loss of hand-to-mouth movement independently of age. qMRI-measured elbow flexor FF can be used as a surrogate endpoint or stratification tool for clinical trials in nonambulant patients with DMD. Classification of Evidence This study provides Class II evidence that qMRI FF of elbow flexor muscles in patients with DMD predicts loss of hand-to-mouth movement independently of age.Neuro Imaging Researc