Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Comparing Homeless Persons’ Care Experiences in Tailored Versus Nontailored Primary Care Programs

Objectives. We compared homeless patients’ experiences of care in health care organizations that differed in their degree of primary care design service tailoring. Methods. We surveyed homeless-experienced patients (either recently or currently homeless) at 3 Veterans Affairs (VA) mainstream primary care settings in Pennsylvania and Alabama, a homeless-tailored VA clinic in California, and a highly tailored non-VA Health Care for the Homeless Program in Massachusetts (January 2011-March 2012). We developed a survey, the “Primary Care Quality-Homeless Survey," to reflect the concerns and aspirations of homeless patients. Results. Mean scores at the tailored non-VA site were superior to those from the 3 mainstream VA sites (P < .001). Adjusting for patient characteristics, these differences remained significant for subscales assessing the patient–clinician relationship (P < .001) and perceptions of cooperation among providers (P = .004). There were 1.5- to 3-fold increased odds of an unfavorable experience in the domains of the patient–clinician relationship, cooperation, and access or coordination for the mainstream VA sites compared with the tailored non-VA site; the tailored VA site attained intermediate results. Conclusions. Tailored primary care service design was associated with a superior service experience for patients who experienced homelessness