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ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare, progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise functional role(s) leading to PHARC disease had not previously been characterized. Cell and zebrafish models were designed to demonstrate the causal link between an identified new missense mutation p.T253R, characterized in ABHD12 from a young patient, the previously characterized p.T202I and p.R352* mutations, and the associated PHARC. Measuring ABHD12 monoacylglycerol lipase activity in transfected HEK293 cells demonstrated inhibition with mutated isoforms. Both the expression pattern of zebrafish abhd12 and the phenotype of specific antisense morpholino oligonucleotide gene knockdown morphants were consistent with human PHARC hallmarks. High abhd12 transcript levels were found in the optic tectum and tract, colocalized with myelin basic protein, and in the spinal cord. Morphants have myelination defects and concomitant functional deficits, characterized by progressive ataxia and motor skill impairment. A disruption of retina architecture and retinotectal projections was observed, together with an inhibition of lens clarification and a low number of mechanosensory hair cells in the inner ear and lateral line system. The severe phenotypes in abhd12 knockdown morphants were rescued by introducing wild-type human ABHD12 mRNA, but not by mutation-harboring mRNAs. Zebrafish may provide a suitable vertebrate model for ABHD12 insufficiency and the study of functional impairment and potential therapeutic rescue of this rare, neurodegenerative disease.

Abstract As efforts to replace nonsustainable plastics increase, biocomposites from cellulose fibers and biodegradable polymers like poly(ε‐caprolactone) (PCL) are promising candidates. The necessary adhesion between fibers and matrix can be achieved by grafting polymeric chains onto the fibers. Herein, we report grafting of PCL onto Abaca fibers (AFs), a one‐pot method to obtain a composite containing grafted fiber and free PCL, and the characterization of prepared composite films. Three parameters for pretreatment (disintegration, drying, and solvent exchange) of AF were compared. Short and long PCL chains with molecular weights below and close to the chain entanglement weight of PCL were grafted from AFs. Using benzyl alcohol as an additional initiator, free PCL was simultaneously prepared. The unreacted monomer was removed by precipitation in water, resulting in ready‐made one‐pot composites. The biocomposites containing the free PCL and PCL‐grafted AFs were further processed by a combination of compounding and hot‐pressing. The analyzed mechanical (tensile) and rheological properties show a large dependence on the lengths of the PCL grafts. The herein‐reported composites pave the way for interesting bio‐based alternatives to plastic, especially looking at the tailoring of material properties.

Abstract Background The development of routines regarding medication is important to avoid medication-related harm. Medication review and medication reports have earlier been found to be effective, but their implementation is not always successful. The aim of this study was to evaluate the introduction of medication review/medication report in hospital and primary care, in terms of perceptions of the implementation strategy, adoption and sustainability, in one Swedish county. Methods The study included 105 clinics. Data was collected from interviews with managers immediately after implementation, survey data and registry data collected five years later. Quantitative data was analysed using non-parametric statistical tests. Open-ended questions were analysed with qualitative methods. Results The implementation activities were found satisfying, and managers were satisfied with their own influence over the process. After five years medication review and medication reports were reported mainly implemented by the managers. Facilitating factors reported were routines, staff influence, dedication, reminders, and a stable workforce, while hindering factors reported were organizational factors, less commitment and flaws in reporting. Registry data showed that performance of medication review was very limited in primary care. In hospital care medication review was registered in about one fifth of the patients, while medication reports, only relevant for hospital care, was registered in half of the patients. Conclusions The managers’ perceptions of the implementation process were mainly positive, and they found the new practices of medication review/medication report implemented. Implementation success, however, was not supported by registry data, showing the need for reliable outcome measures for implementation.