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Spinal muscular atrophy (SMA) is associated with developmental disruption of motor axons in ventral roots of the spinal cord alongside motor axon degeneration. The pathogenesis of peripheral axonal change during development is pertinent to understand treatment response. Nerve excitability techniques, stimulating the median motor nerve at the wrist, were utilised to investigate axonal change during neurodevelopment in 24 children with SMA, compared with 71 age‐matched controls. Longitudinal axonal response to nusinersen treatment in 18 children was also investigated. Significant differences in axonal development were noted in the youngest children with SMA, signified by reduced compound muscle action potential (CMAP) (P = 0.030), higher axonal threshold (P = 0.016), rheobase (minimal current amplitude of infinite duration, required to generate an action potential) (P = 0.012) and greater changes in depolarising and hyperpolarising threshold electrotonus. Subexcitability increased in all children with SMA, compared to controls. With treatment, nerve excitability changes were observed prominently in young children, with increases in CMAP, reduction in axonal threshold, fanning‐in of threshold electrotonus, increase in resting current–threshold slope and reduction in subexcitability. Whilst motor axons continue to mature in SMA, developmental delays in passive and active membrane properties occur especially in early childhood. Concurrently, motor axons actively undergo degeneration. Nusinersen restores the developmental trajectory of motor axons reducing degeneration, especially in children with early treatment initiation. Our findings move the field forward in understanding the developmental aspect of childhood‐onset motor neurone diseases and changes in axonal function associated with disease modification. Key points: Pathomechanisms in spinal muscular atrophy involve concurrent neurodevelopmental and neurodegenerative processes.The greatest delays in maturation of the passive and active properties of the peripheral motor axon are seen in early childhood.Nusinersen facilitates developmental recovery of the motor axon whilst also reducing neurodegeneration.Axonal dysfunction is reversed with SMN repletion particularly when intervention occurs early in development. [ABSTRACT FROM AUTHOR]

Objectives: To elucidate the motor unit response to intrathecal nusinersen in children with symptomatic spinal muscular atrophy (SMA) using a novel motor unit number estimation technique.Methods: MScanFit MUNE studies were sequentially undertaken from the abductor pollicis brevis muscle after stimulation of the median nerve in a prospective cohort of symptomatic children with SMA, undergoing intrathecal treatment with nusinersen at a single neuromuscular centre from June 2017 to August 2019. Electrophysiological measures included compound muscle action potential (CMAP), motor unit number estimation (MUNE), motor unit number contributing to 50%-100% of CMAP (N50) and measures of collateral reinnervation including largest single motor unit potential (LSMUP) and amplitude of the smallest unit contributing to N50 (A50).Results: Twenty children (median age 99 months, range 4-193) were followed for a median of 13.8 (4-33.5) months. Therapeutic intervention was an independent and significant contributor to an increase in CMAP (p = 0.005), MUNE (p = 0.001) and N50 (p = 0.04). The magnitude of this electrophysiological response was increased in children with shorter disease durations (p<0.05). Electrophysiological changes delineated children who were functionally stable from those who attained clinically significant gains in motor function.Interpretation: Nusinersen therapy facilitated functional innervation in SMA through recovery of smaller motor units. Delineation of biomechanisms of therapeutic response may be the first step in identifying potential novel targets for disease modification in this and other motor neuropathies. MScanFit MUNE techniques may have a broader role in establishing biomarkers of therapeutic response in similar adult-onset diseases. [ABSTRACT FROM AUTHOR]

During the past few years many of you will have noticed that the number of male medical students has been steadily diminishing. Although most medical schools try to widen participation [...]

Grape phylloxera, Daktulosphaira uitifoliae (Fitch) (Hemiptera Phylloxeridae) is a damaging pest of grapevines ( Vitis spp.) around the world, and the management of this pest requires early detection of infestations. Here, we describe the development and validation of a sensitive DNA test for grape phylloxera that can be applied to soil. Species-specific primers were developed for grape phylloxera in the internal transcribed space region 2, and their specificity was confirmed after thorough screening by using a wide range of vineyard organisms and aphid genera. Preliminary testing of the detection limits of the grape phylloxera-specific primers was conducted using field-sourced soil types spiked with a known number of grape phylloxera. The assay was converted to a real-time polymerase chain reaction format (TaqMan MGB). This assay, in combination with DNA extraction from soil, can detect phylloxera crawlers added to soil. The assay was evaluated in the field at a recently detected grape phylloxera infestation site from the Yarra Valley in Victoria, Australia. The DNA assay proved to be substantially more sensitive than a standard ground survey for detecting grape phylloxera presence on vine roots in the infested vineyard. Moreover, unlike the ground survey, the assay provided quantitative information on grape phylloxera infestations, because grape phylloxera DNA concentrations in samples from vines closely matched the numbers of grape phylloxera crawlers collected with emergence traps placed at the base of vines. Unlike other detection techniques, the method can be applied at any time of the year, and it can be potentially modified to provide specific information on the virulence levels of the particular grape phylloxera genotypes responsible for any new infestations. [ABSTRACT FROM AUTHOR]

Abstract: Grape phylloxera (Daktulosphaira vitifoliae, Fitch) is an encroaching problem for the Australian wine industry with four new outbreaks recorded in the past 5 years. Whilst quarantine- and phylloxera-resistant rootstocks are the recommended long-term management strategies, there are at present no short-term options for recently infested vineyards. In this study, an assay for assessing the impact of the systemic insecticides thiamethoxam (Actara®; two applications at a concentration of 2000ppm active ingredient) and imidacloprid (Confidor®; one and two applications at a concentration of 2000ppm active ingredient) on suppression of phylloxera populations on grapevine roots was developed. Results from in vitro and in planta trials showed that both insecticides resulted in reduced phylloxera numbers and improved vine vigour. Imidacloprid was found to have a greater effect on phylloxera suppression and vine vigour improvement. Therefore imidacloprid has the potential to be successfully used for phylloxera suppression in the field, but will require further validation under field conditions before recommendations can be made. The assay developed provides a screening procedure for future chemical testing against phylloxera. [Copyright &y& Elsevier]

Focuses on the expected U.S. Supreme Court ruling that can stop racial discrimination in medical school admissions in the U.S. as of July 2003. Reason provided by students of University of Michigan for suing their university; Explanation provided by the university regarding use of racial preference; Opinion of Jordan Cohen, president of the Association of American Medical Colleges (AAMC), regarding support of AAMC for the University of Michigan.