No abstract

Given the rising incidence of stroke, several technology-driven methods for rehabilitation have recently been developed. Virtual reality (VR) is a promising therapeutic technology among them. We recently developed a neuroscientifically grounded VR system to aid recovery of motor function poststroke. The developed system provides unilateral and bilateral upper extremity (UE) training in a fully immersive virtual environment that may stimulate and activate mirror neurons (MNs) in the brain necessary for UE rehabilitation. Twenty-three participants were randomized to a VR group (n = 12) to receive VR intervention (8 h within 2 weeks) plus 8-h occupational therapy (OT) or a control group (n = 11) to receive time-matched OT alone. Treatment effects on motor recovery and cortical reorganization were investigated using the Barthel Index (BI), Fugl-Meyer Upper Extremity (FM-UE), and resting-state fMRI. Both groups significantly improved BI (P < 0.05), reflecting the recovery of UE motor function. The VR group revealed significant improvements on FM-UE scores (P < 0.05) than the control group. Neural activity increased after the intervention, particularly in the brain areas implicating MNs, such as in the primary motor cortex. Overall, results suggested that using a neuroscientifically grounded VR system might offer additional benefits for UE rehabilitation in patients receiving OT.

One major class of disease-causing RNAs is expanded repeating transcripts. These RNAs cause diseases via multiple mechanisms, including: (i) gain-of-function, in which repeating RNAs bind and sequester proteins involved in RNA biogenesis and (ii) repeat associated non-ATG (RAN) translation, in which repeating transcripts are translated into toxic proteins without use of a canonical, AUG, start codon. Herein, we develop and study chemical probes that bind and react with an expanded r(CGG) repeat (r(CGG)exp) present in a 5′ untranslated region that causes fragile X-associated tremor/ataxia syndrome (FXTAS). Reactive compounds bind to r(CGG)exp in cellulo as shown with Chem-CLIP-Map, an approach to map small molecule binding sites within RNAs in cells. Compounds also potently improve FXTAS-associated pre-mRNA splicing and RAN translational defects, while not affecting translation of the downstream open reading frame. In contrast, oligonucleotides affect both RAN and canonical translation when they bind to r(CGG)exp, which is mechanistically traced to a decrease in polysome loading. Thus, designer small molecules that react with RNA targets can be used to profile the RNAs to which they bind in cells, including identification of binding sites, and can modulate several aspects of RNA-mediated disease pathology in a manner that may be more beneficial than oligonucleotides.

A rapid ageing population coupled with changes in family structure has brought about profound implications to social policy in China. Although the past decade has seen a steady increase in public funding to long-term care (LTC), the narrow financing base and vast population have created significant unmet demand, calling for reforms in financing. This paper focuses on the financing of institutional LTC care by examining new models that have emerged from local policy experiments against two policy goals: equity and efficiency. Three emerging models are explored: Social Health Insurance (SHI) in Shanghai, LTC Nursing Insurance (LTCNI) in Qingdao a n dam e a n s -t e s t e dm o d e li nN a n j i n g .Af o c u s e ds ystematic narrative review of academic and grey literature is conducted to identify and assess these models, supplemented with qualitative interviews with government officials from relevant departments, care home staff and service users. This paper argues that, although SHI appears to be a convenient solution to fund LTC, this model has led to systematic bias in affordable access among participants of different insurance schemes, and has created a powerful incentive for the over-provision of unnecessary services. The means-tested method has been remarkably constrained by narrow eligibility and insufficiency of funding resources. The LTCNI model is by far the most desirable policy option among the three studied here, but the narrow definition of eligibility has substantively excluded a large proportion of elders in need from access to care, which needs to be addressed in future reforms. This paper proposes three lines of LTC financing reforms for policy-makers: (1) the establishment of a prepaid financing mechanism pooled specifically for LTC costs; (2) the incorporation of more stringent eligibility rules and needs assessment; and (3) reforming the dominant fee-for-service methods in paying LTC service providers.