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BACKGROUND. Spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein. New SMN-enhancing therapeutics are associated with variable clinical benefits. Limited knowledge of baseline and drug-induced SMN levels in disease-relevant tissues hinders efforts to optimize these treatments. METHODS. SMN mRNA and protein levels were quantified in human tissues isolated during expedited autopsies. RESULTS. SMN protein expression varied broadly among prenatal control spinal cord samples, but was restricted at relatively low levels in controls and SMA patients after 3 months of life. A 2.3-fold perinatal decrease in median SMN protein levels was not paralleled by comparable changes in SMN mRNA. In tissues isolated from nusinersen-treated SMA patients, antisense oligonucleotide (ASO) concentration and full-length (exon 7 including) SMN2 (SMN2-FL) mRNA level increases were highest in lumbar and thoracic spinal cord. An increased number of cells showed SMN immunolabeling in spinal cord of treated patients, but was not associated with an increase in whole-tissue SMN protein levels. CONCLUSIONS. A normally occurring perinatal decrease in whole-tissue SMN protein levels supports efforts to initiate SMN-inducing therapies as soon after birth as possible. Limited ASO distribution to rostral spinal and brain regions in some patients likely limits clinical response of motor units in these regions for those patients. These results have important implications for optimizing treatment of SMA patients and warrant further investigations to enhance bioavailability of intrathecally administered ASOs. FUNDING. SMA Foundation, SMART, NIH (R01-NS096770, R01-NS062869), Ionis Pharmaceuticals, and PTC Therapeutics. Biogen provided support for absolute real-time RT-PCR., Introduction The neuromuscular disease spinal muscular atrophy (SMA), affecting approximately 1 in 10,000 individuals, is the most common inherited cause of infant death (1). The most frequent and severe type [...]

Background: Chronic health conditions are highly prevalent among truck drivers due to many unique occupational and environmental stressors. Health promotion programs are shown to be effective in improving truck driver health outcomes; however, there is no research on whether such programs can increase the length of a driver's Department of Transportation (DOT) medical certificate. The purpose of this quality improvement project was to evaluate Fit to Pass (FTP), a remotely accessible health promotion program available for truck drivers on improved health outcomes and increased DOT medical certificate length. Method: Program evaluation included an evaluation of the FTP coaching guide against evidence-based practice guidelines. An analysis of a limited dataset of 22 truck driver records examined the effectiveness of the program in achieving improved health outcomes and increased medical certification length. Findings: A review of the literature revealed three major themes: (a) motivational interviewing to increase driver intention and self-efficacy; (b) mobile health care technology to connect hard-to-reach truck drivers; and (c) effectiveness of structured multicomponent health promotion programs. After participation in FTP, truck drivers experienced a mean decrease in weight and body mass index (BMI) of 4.6 lbs and 1.3 kg/m2, respectively. The lengths of initial DOT medical certificates were compared with DOT medical certificates received at the time of recertification (post—FTP). Only eight participants had the potential for improvement in certificate length. Of those, three truck drivers achieved an increased DOT medical certificate length at the time of recertification. Conclusion/Applications to Practice: FTP offers tailored and comprehensive health coaching for truck drivers using current evidence-based practice guidelines to educate and reinforce healthy lifestyle habits. Analysis of a limited dataset revealed a mean decrease in BMI and a trend of increased DOT medical certification lengths after participation in FTP; however, further research with larger sample sizes is recommended. [ABSTRACT FROM AUTHOR]

Purpose. Therapeutic advances in the treatment of spinal muscular atrophy (SMA) prompt the need for robust and efficient molecular diagnosis of this disease. Approximately five percent of SMA cases are attributable to one copy of SMN1 with a hypomorphic or inactivating variant in trans with a deleted or converted allele. These intragenic variants are challenging to definitively localize to SMN1 due to its sequence homology with the SMN2 gene. To enhance the clinical sensitivity of SMA diagnostic testing, we present an optimized gene-specific sequencing assay to localize variants to either SMN1 or SMN2. Methods. SMN1 and SMN2 genes are independently amplified by long-range allele-specific PCR. Long-range products are used in subsequent nested PCR reactions to amplify the coding exons of SMN1 and SMN2. The resulting products are sequenced using standard Sanger-based methodologies and analyzed for disease-associated alterations. Results. 83 probands suspicious for a clinical diagnosis of SMA with a nondiagnostic SMN dosage result were sequenced for intragenic variants in the SMN1 gene. Gene-specific sequencing revealed likely disease-associated variants in SMN1 in 42 cases (50.6%). Of the 42 variants, 27 are unique including 16 loss-of-function variants, 9 missense variants, 1 in-frame deletion variant, and 1 splice site variant. Conclusions. Herein, we describe an optimized assay for clinical sequencing of the full coding region of SMN1 and SMN2. This assay uses standard techniques and equipment readily available to most molecular diagnostic laboratories. [ABSTRACT FROM AUTHOR]

A study is conducted to analyze the role of SMN2 gene in decreasing the severity of the autosomal-recessive motor neuron disease called spinal muscular atrophy, caused by the homozygous loss of the SMN1 gene. Results reveal that a single-base substitution of guanine by cytosine at nucleotide 859 (c.859G>C) in the SMN2 gene is responsible for the increase in full-length transcripts, thus serving as a positive modifier of the SMA phenotype and decreasing the severity of the disease.

An examination of IPEDS data of graduation rates for racial/ethnic minority students at small, liberal arts colleges identified a distinctly large gap between racial/ethnic minority student graduation rates and their fellow white students. The authors then selected a subset of five colleges that appeared to have unusual success in minimizing this gap and investigated what those institutions are doing to decrease the gap in graduation rates between racial/ethnic minority students and their white peers. [ABSTRACT FROM AUTHOR]

With the Higher Education Act reauthorization resurfacing, it is necessary to recognize the undeniably permanent place online and distance education has taken in the landscape of higher education. The HEA must account for this new medium of learning and instruction in a way that has yet to be recorded. This paper offers a review of the historical context of distance education and the current policies for online education authorization, provides current examples to highlight the need for reform, and discusses the implications of changes to the HEA. Specifically, this paper demonstrates how the debates on distance education reflect the broader concerns of accessibility and affordability, accountability, and innovation faced by colleges and universities. Through analysis of policy and practice, the need to address the duplicative and discrepant nature of the system caused by the requirement for institutions and/or programs to adhere to the regulations of multiple states becomes evident. Addressing these concerns in a comprehensive way, as discussed in this paper, would further solidify online education as an enduring fixture within the contemporary concept of higher education, streamlining costs for institutions, and providing a pathway for a growing audience of individuals who desire the opportunity to pursue an advanced education. [ABSTRACT FROM AUTHOR]