Notes

The hot combination bun logon corticobasal deterioration.
001). The time to follow-up decreased from 67 to 34 days (P < .001). Follow up visits by telemedicine were more also more likely to be within 30 days (62% vs. 32%, P < .001).

A QI intervention for ADHD care increased rates of follow-up within 30 days, particularly when telemedicine was used, and decreased the number of days to follow-up. This intervention could serve as a model to improve follow-up for ADHD in other settings.
A QI intervention for ADHD care increased rates of follow-up within 30 days, particularly when telemedicine was used, and decreased the number of days to follow-up. This intervention could serve as a model to improve follow-up for ADHD in other settings.Several advances in nanomedicine have been accompanied by rising concerns about the bioaccumulation and toxicity of gold nanoparticles (AuNPs). Here, we assessed the in vivo fate of diversely sized AuNPs that were injected into mice as a computed tomography contrast agent and examined with multi-scale analyses across the organ, tissue, cell, and subcellular levels. After focusing on the strong detected accumulation in livers, our data revealed a set of three clear, exposure-time-dependent patterns based on i) AuNPs deposit morphology and ii) readily identifiable phenotypes for AuNP-impacted subcellular vesicles. Importantly, we detected no obvious differences in liver function, liver cell apoptosis, or autophagy upon exposure to AuNPs. Thus, our study illustrates an accessible experimental and high-resolution data interpretation framework for quickly obtaining and contextualizing informative trends about any AuNP-triggered patterns of subcellular damage in nanomedicine studies; these can help guide cytotoxity and safety testing of diagnostic nanomedical technologies.As molecularly targeted agents (MTAs) and immunotherapies have widely demonstrated delayed toxicity profile after multiple treatment cycles, the traditional phase I dose-finding designs may not be appropriate anymore because they just account for the acute toxicities occurring in the early period of treatment. When the dose-limiting toxicity (DLT) assessment window is prolonged to account for late-onset DLTs, it will cause logistic issues if the enrollment is suspended until all the DLT information is collected. We propose a novel framework to estimate the toxicity probability in the scenarios where some patients' DLT information are not complete and then implement the Bayesian optimal interval (BOIN) design to make decisions on dose escalation/de-escalation. Our proposed approach maintains BOIN's transparency by simply comparing the estimated toxicity probability with the escalation/de-escalation boundaries to decide the next dose level. The numerical studies show that our proposed framework can achieve comparable operating characteristics as other dose-finding designs considering late-onset DLTs, thus providing an attractive option of phase I dose-finding clinical trials for MTAs and immunotherapies.
Game-based rehabilitation is an emerging therapeutic intervention that allows intensive, repetitive, task-based training to improve upper limb (UL) function following stroke, based on the principles of neuro-plasticity and motor (re)learning. Rehabilitation using commercial gaming system will be motivating, enjoyable, challenging and affordable. Therefore, the present study aims at assessing the effectiveness of an intensive, functional, gamified rehabilitation program using the ArmAble™ device in improving UL motor function in people with stroke.

In this single-blinded, multi-centric, randomized clinical trial, 120 adults with acute/sub-acute unilateral stroke will be randomized to receive an intensive, functional, gamified training program using the ArmAble™ or task-based training along with a conventional therapy for 2h/day, 6days/week for 2weeks, followed by a home-based, functional rehabilitation program for another 4weeks (~30min/day, 6days/week). Primary outcomes evaluated by a blinded assessor at the baseline, 2weeks and 6weeks' post-intervention will include the Fugl-Meyer assessment - upper extremity and the action research arm test. A linear mixed effect regression model or relevant non-parametric tests will be used to analyze the data for all outcomes. see more An intention-to-treat analysis will be used with missing data handled by multiple imputation.

Rehabilitation provided with the ArmAble™ device, if found effective, can be used from the early stages post-stroke to provide intensive, repetitive, gamified training to improve UL motor function.

CTRI/2020/09/027651.
CTRI/2020/09/027651.Many microorganisms can accumulate biomass in the form of lipids and polysaccharides, which can be used for biofuels, bioplastics, food and feed. Some innovative bioprocesses exploit the competitive advantage provided by such accumulation ability, mainly under N-starvation, to select high-accumulating strains against biological contaminants, by using uncoupled nutrient feeding. However, there is no general and easily comparable parameter available to compare biomass accumulation ability among different microbial strains, which could measure the competitive advantage. Here, a parameter termed "fattening factor" (ηx) is described to quantify such strain-specific biomass accumulation ability in bacteria, yeasts and microalgae. This parameter measures how many fold a microbial population can increase its biomass just as the result of accumulation. It is derived from considerations about the main metabolic aspects of cells' response to N-starvation, which induces variations in cell cycle, biomass production and biochemical composition. The fattening factor described here should be easily estimatable in N-starvation for every culturable microbial strain, by measuring the amount of accumulated biomass.Multi-modal combination therapy has attracted great attention, owing to the unsatisfactory therapeutic efficacy of conventional chemotherapy. Mesoporous silica-coated gold nanorods possess great potential in photothermal therapy and drug delivery. In this work, we fabricate a dual-responsive nanohybrid for combination treatment of the malignant tumor. In this system, gold nanorods are coated with the degradable mesoporous silica, and the chemotherapy drug doxorubicin (DOX) and photosensitizer (IR820) are co-loaded inside the pores of the silica. The encapsulation of hyaluronic acid (HA) endow the nanohybrids with mammary carcinoma targeting ability and better biocompatibility, owning to CD44+ receptor overexpressed in some cancer cells. As-prepared nanohybrids exhibit high responsiveness to a high glutathione (GSH) level and degrade rapidly in the presence of hyaluronidase (HAase) and GSH after endocytosis by 4T1 cells, allowing the efficient release of loaded DOX and IR 820 in tumor sites. Interestingly, near-infrared (NIR) laser not only triggers the generation of reactive oxygen species, but also remarkable photothermal efficacy originating from GNRs. Therefore, upon the irradiation of 808 nm NIR light, the combinatorial photodynamic, photothermal and chemotherapy is achieved, accordingly leading to a highly efficient antitumor outcome in vitro and in vivo. This strategy provides an ideal approach to constructing multimodal cancer therapy system. STATEMENT OF SIGNIFICANCE • Dual-responsive nanohybrids for combinatorial therapy of breast cancer. • The nanohybrids exhibit both HAase and GSH stimuli-responsive behavior. • The nanohybrids exhibit light-activated PDT/PTT/chemotherapy. • The nanohybrids show good biosafety for potential clinical application.Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) show great therapeutic potential for osteoarthritis (OA). However, their low bioavailability through intraarticular injection inhibits the process of clinical application. In the present study, an injectable Diels-Alder crosslinked hyaluronic acid/PEG (DAHP) hydrogel was developed as an intraarticular delivery platform for MSC-sEVs. Our results showed that the DAHP hydrogel could be prepared easily and that its gelation properties were suitable for intraarticular administration. In vitro studies demonstrated that the DAHP hydrogel could achieve sustained release of MSC-sEVs mainly by degradation control and preserve the therapeutic functions of sEVs. An in vivo experiment revealed that the DAHP hydrogel could enhance the efficacy of MSC-sEVs for OA improvement. This study provides a suitable delivery platform for MSC-sEVs-based OA therapy. STATEMENT OF SIGNIFICANCE Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) have shown a high potential as a cell-free therapeutic factor for treating osteoarthritis (OA). The sustained release of these MSC-sEVs in the joint space is essential for their clinical application. Herein, an injectable Diels-Alder crosslinked hyaluronic acid/PEG (DAHP) hydrogel was developed for intraarticular release of MSC-sEVs. The properties of the DAHP hydrogel, namely gelation features, cytocompatibility, sustained release, and functional maintenance of MSC-sEVs, make it suitable for intraarticular injection and delivery of sEVs. The efficacy of MSC-sEVs was enhanced by the intraarticularly injected DAHP hydrogel. Our present study provides a promising sustained delivery platform for MSC-sEVs for treating OA.Silk fiber is renowned for its superb mechanical properties, such as over 7 times the toughness of Kevlar 49 Fibre. As the spider silk is tougher than any man-made fiber, there is a lot to be learned from spider silk. Recently, it has been reported that a large portion of the properties of silk is from naturally formed nano-fishnet structures of silk, but neither its formation mechanism nor its formation condition has been explained. Here, we show how the formation and disappearance of nano-fishnet of silk is determined by humidity, and how the humidity-dependency of nano-fishnet formation can be overcome by changing density of Arginine through sequence mutation. We demonstrate that the nano-fishnet-structured silk exhibits higher strength and toughness than its counterparts. This information on controllable nano-fishnet formation of silk is expected to pave the way for development of protein and synthetic fiber design. STATEMENT OF SIGNIFICANCE Silk fibers are a very interesting material in that it exhibits superb mechanical properties such as 7 times the toughness of Kevlar 49 Fibre, despite being only composed of proteins. Therefore, it is important that we understand the principle of its high mechanical properties so that it may be applied in designing synthetic fibers. Recently, it has been reported that a large portion of its mechanical property comes from its nano-fishnet structures, but no detailed explanation on the condition or mechanism of formation. Through molecular dynamic simulations, we simulated the nano-fishnet formation of silk and analyzed the condition and mechanism behind it, and showed how the formation of nano-fishnet structures could be controlled by changing the density of Arginine residues. Our study provides information on fiber enhancement mechanism that could be applied to synthetic and protein fiber design.Nepenthes pitcher plants grow in nutrient-poor soils and produce large pitfall traps to obtain additional nutrients from animal prey. Previous research has shown that the digestive secretion in N. rafflesiana is a sticky viscoelastic fluid that retains insects much more effectively than water, even after significant dilution. Although the retention of prey is known to depend on the fluid's physical properties, the details of how the fluid interacts with insect cuticle and how its sticky nature affects struggling insects are unclear. In this study, we investigated the mechanisms behind the efficient prey retention in N. rafflesiana pitcher fluid. By measuring the attractive forces on insect body parts moved in and out of test fluids, we show that it costs insects more energy to free themselves from pitcher fluid than from water. Moreover, both the maximum force and the energy required for retraction increased after the first contact with the pitcher fluid. We found that insects sink more easily into pitcher fluid than water and, accordingly, the surface tension of N.
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