Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder.

BCAS3 microtubule-associated cell migration factor (BCAS3) is a large, highly conserved cytoskeletal protein previously proposed to be critical in angiogenesis and implicated in human embryogenesis and tumorigenesis. Here, we established BCAS3 loss-of-function variants as causative for a neurodevelopmental disorder. We report 15 individuals from eight unrelated families with germline bi-allelic loss-of-function variants in BCAS3. All probands share a global developmental delay accompanied by pyramidal tract involvement, microcephaly, short stature, strabismus, dysmorphic facial features, and seizures. The human phenotype is less severe compared with the Bcas3 knockout mouse model and cannot be explained by angiogenic defects alone. Consistent with being loss-of-function alleles, we observed absence of BCAS3 in probands' primary fibroblasts. By comparing the transcriptomic and proteomic data based on probands' fibroblasts with those of the knockout mouse model, we identified similar dysregulated pathways resulting from over-representation analysis, while the dysregulation of some proposed key interactors could not be confirmed. Together with the results from a tissue-specific Drosophila loss-of-function model, we demonstrate a vital role for BCAS3 in neural tissue development.

Teaching Ultrasound-Guided Venous Cannulation to Newly Qualified Doctors.

Background Venous cannulation is an essential task that allows the intravenous administration of fluids and medications. In the United Kingdom, this task is often performed by newly qualified Foundation Year 1 (FY1) doctors; however, difficulties are commonly encountered. The usage of ultrasound increases the chance of successful cannulation, provided the operator has been trained. Some medical schools now include ultrasound in their undergraduate curricula, though this is far from universal. Methods Forty-eight FY1s received a one-hour teaching session on ultrasound-guided venous cannulation, delivered by near-peer Education Fellows. FY1s completed questionnaires immediately after the teaching session, and a follow-up questionnaire three months later. Findings 44.44% of FY1s felt "fairly" or "very" confident in ultrasound-guided venous cannulation at follow-up, compared to 6.66% before the session. Sixty-three attempts were made in the month before the follow-up survey, compared to six in the month prior to the teaching session. The success rate at follow-up was 60% (38/63), up from 50% (3/6) prior to the session. One third fewer cannulas were escalated to senior doctors (72 vs 48), although there was little change in escalations to anesthetists, from 15 vs 18. FY1s identified the lack of ultrasound machines on the wards as a barrier to using ultrasound-guided venous cannulation more often. Conclusion A short, near-peer teaching session can improve FY1s' confidence, usage, and success rates in ultrasound-guided venous cannulation.

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum.

Spontaneous Posterior Subdural Pyogenic Escherichia coli Abscess Secondary to Lumbar Spondylodiscitis.

Pyogenic subdural spinal collections are rare but an important pathology to recognise and manage appropriately. We report the case of a 56-year-old female who developed a posterior subdural spinal collection associated with local discitis. There was no direct communication between the infected disc and subdural space, and the collection was located posteriorly within the subdural space which makes this case all the more unusual. We discuss the need for spinal subdural collections to be considered as a differential in patients with back pain and lower limb neurology (especially when there is a known spinal infective focus), the importance of careful interpretation of imaging, and the pathophysiological mechanisms and organisms known to cause spinal subdural collections.