Altered lysosomal positioning affects lysosomal functions in a cellular model of Huntington's disease.

Huntington's disease (HD) is a hereditary and devastating neurodegenerative disorder caused by a mutation in the huntingtin protein. Understanding the functions of normal and mutant huntingtin protein is the key to revealing the pathogenesis of HD and developing therapeutic targets. Huntingtin plays an important role in vesicular and organelle trafficking. Lysosomes are dynamic organelles that integrate several degradative pathways and regulate the activity of mammalian target of rapamycin complex 1 (mTORC1). In the present study, we found that the perinuclear accumulation of lysosomes was increased in a cellular model of HD derived from HD knock-in mice and primary fibroblasts from an HD patient. This perinuclear lysosomal accumulation could be reversed when normal huntingtin was overexpressed in HD cells. When we further investigated the functional significance of the increased perinuclear lysosomal accumulation in HD cells, we demonstrated that basal mTORC1 activity was increased in HD cells. In addition, autophagic influx was also increased in HD cells in response to serum deprivation, which leads to premature fusion of lysosomes with autophagosomes. Taken together, our data suggest that the increased perinuclear accumulation of lysosomes may play an important role in HD pathogenesis by altering lysosomal-dependent functions.

Short-Term Outcomes of the Boston Brace 3D Program Based on SRS and SOSORT Criteria: A Retrospective Study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is characterized by a lateral curvature of the spine with a Cobb angle greater than 10 degrees, accompanied by rotation of the vertebral body. Bracing has been shown to be effective in halting the progression of at-risk curves, and, in some cases, even improving the Cobb angle by 6° or more. The Boston Brace 3D is part of the Boston Orthotics and Prosthetics standardized scoliosis program. The orthosis is custom-fabricated from scans, computer-aided design (CAD), and computer-aided manufactured (CAM) thoracolumbosacral orthosis used in the non-operative management of AIS. AIM: To evaluate the outcomes of a scoliosis program utilizing the Boston Brace 3D orthosis for patients with AIS, based on SRS and SOSORT criteria. DESIGN: Retrospective study. METHODS: An electronic medical records search was conducted to identify first-time brace wearers fitted between 1 January 2018, and 30 June 2019, at Boston Orthotics and Prosthetics Boston area clinics that met the SRS/SOSORT research guidelines. The initial out-of-brace, in-brace, and last follow-up X-rays (taken at least 12 months after fitting) were compared. RESULTS: 84% of patients presenting with a single curve and 69% of patients with a double curve saw their curves improve (reduced 6° or more) or remain unchanged (±5°). Thirty-one patients started with a single curve between 25° and 30°, and thirty-two presented at 30° or below. Fifty-nine patients started with a double curve between 25° and 30°, and 59 patients presented at 30° or below. In general, the patients who wore their brace for more hours per day saw improved results. CONCLUSION: The Boston Brace 3D program is effective in controlling (and in some cases improving) curve progression in the non-operative management of adolescent idiopathic scoliosis. The approach is a repeatable system, as shown in this cohort of thirteen clinicians across six area clinics following the Boston Brace 3D clinical guidelines.

Environmental and Social Change Drive the Explosive Emergence of Zika Virus in the Americas.

Since Zika virus (ZIKV) was detected in Brazil in 2015, it has spread explosively across the Americas and has been linked to increased incidence of microcephaly and Guillain-Barré syndrome (GBS). In one year, it has infected over 500,000 people (suspected and confirmed cases) in 40 countries and territories in the Americas. Along with recent epidemics of dengue (DENV) and chikungunya virus (CHIKV), which are also transmitted by Aedes aegypti and Ae. albopictus mosquitoes, the emergence of ZIKV suggests an ongoing intensification of environmental and social factors that have given rise to a new regime of arbovirus transmission. Here, we review hypotheses and preliminary evidence for the environmental and social changes that have fueled the ZIKV epidemic. Potential drivers include climate variation, land use change, poverty, and human movement. Beyond the direct impact of microcephaly and GBS, the ZIKV epidemic will likely have social ramifications for women's health and economic consequences for tourism and beyond.