We have identified a mutation in KIAA0196 as the cause of the form of RSS characterised in our cohort. The ubiquitous expression and highly conserved nature of strumpellin, the product of KIAA0196, is consistent with the complex and multisystem nature of this disorder.
Autosomal recessive PRUNE1 mutations are reported to cause a severe neurodevelopmental disorder with microcephaly, hypotonia, and brain malformations. We describe clinical and neuropathological features in a cohort of nine individuals of Cree descent who, because of a founder effect, are homozygous for the same PRUNE1 mutation. They follow the course of a combined neuromuscular and neurodegenerative disease, rather than a pure failure of normal development. This cohort presented in infancy with features of lower motor neuron disease, such as hypotonia, contractures, tongue fasciculations, and feeding difficulties in the absence of congenital brain anomalies and microcephaly. A neurodegenerative course followed with onset of seizures, spasticity, and respiratory insufficiency. Muscle biopsies showed denervation/reinnervation features, nonspecific atrophy and end‐stage atrophy. Autopsy findings in two patients are also described, suggesting length dependent central motor axon degeneration, peripheral motor axon degeneration, possible spinal motor neuron degeneration, and accumulation of beta amyloid precursor protein inclusions in select brainstem nuclei. Exome sequencing and homozygosity mapping identified a homozygous PRUNE1 mutation in a canonical splice site, which produces two abnormal PRUNE1 mRNA products. Based on our studies and the histopathology and phenotypic data, we provide further evidence that this disorder leads to a neurodegenerative disease affecting both the peripheral and central nervous systems and suggest that the pathogenic c.521‐2A>G mutation could lead to an altered effect on tubulin dynamics.
Physician wellness is critical for patient safety and quality of care. Coaching has been successfully and widely applied across many industries to enhance well-being but has only recently been considered for physicians. This review aimed to summarize the existing evidence on the effect of coaching by trained coaches on physician well-being, distress and burnout. MEDLINE, Embase, ERIC, PsycINFO and Web of Science were searched without language restrictions to December 21, 2022. Studies of any design were included if they involved physicians of any specialty undergoing coaching by trained coaches and assessed at least one measure along the wellness continuum. Pairs of independent reviewers determined reference eligibility. Risk of bias was assessed using the Cochrane Risk of Bias Tools for Randomized Controlled Trials (RCTs) and for Non-randomized Studies of Interventions (ROBINS-I). Meta-analysis was not possible due to heterogeneity in study design and outcome measures as well as inconsistent reporting. The search retrieved 2531 references, of which 14 were included (5 RCTs, 2 non-randomized controlled studies, 4 before-and-after studies, 2 mixed-methods studies, 1 qualitative study). There were 1099 participants across all included studies. Risk of bias was moderate or serious for non-RCTs, while the 5 RCTs were of lower risk. All quantitative studies reported effectiveness of coaching for at least one outcome assessed. The included qualitative study reported a perceived positive impact of coaching by participants. Evidence from available RCTs suggests coaching for physicians can improve well-being and reduce distress/burnout. Non-randomized interventional studies have similar findings but face many limitations. Consistent reporting and standardized outcome measures are needed.
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