关键词： Cost-effectiveness   economic analyses   physical therapy treatments   neurorehabilitation   QALY   DALY  

摘要： Purpose: To identify the existing evidence evaluating the cost-effectiveness of physiotherapy treatments for people with neurological disorders. Methods: Multiple databases were searched from database inception until July 2018. Studies estimating the cost-effectiveness as incremental cost-effectiveness ratios, cost per quality-adjusted life year, cost per disability-adjusted life year and cost per other measurable results were included. Physiotherapy Evidence Database scale, and Consensus on Health Economic Criteria list were used for rating the quality of the evidence. Results: Ten studies involving 1462 participants were included. Aerobic training, progressive strength training, and a pragmatic physiotherapy program (combination of stretching, strength, and balance training) were reported as potentially cost-effective for older adults with vascular cognitive impairment, falls prevention in Parkinson's disease and multiple sclerosis respectively. Physiotherapy as an adjuvant for pain control was also reported as cost-effective for reflex sympathetic dystrophy. One study testing extra physiotherapy-by-physiotherapy assistant in cerebral palsy and two studies testing extra therapy using a robotic arm and Wii therapy for hand rehabilitation in stroke were reported as not cost-effective. Conclusions: There are limited studies that have evaluated the cost-effectiveness of physiotherapy treatments in neurological disorders. Three studies that combined extra physiotherapy-by-physiotherapy assistant and novel interventions with conventional physiotherapy were found not cost-effective.

关键词： cardiopulmonary resuscitation   heart arrest  

摘要： Keywords: cardiopulmonary resuscitation; heart arrest EN cardiopulmonary resuscitation heart arrest 1031 1033 3 04/20/20 20200324 NES 200324 Extracorporeal cardiopulmonary resuscitation (ECPR) is expected to benefit the rescue of selected patients, particularly those who are refractory to conventional cardiopulmonary resuscitation (CPR).[1] Considering its invasive procedure and considerable resources, establishing a helpful criterion for initiating ECPR remains crucial. Low-flow duration (LFD) is one of the most common criteria to identify candidates for ECPR.[1] However, the association between LFD and favorable neurological outcome has not been sufficiently investigated in out-of-hospital cardiac arrests (OHCAs). LFD was defined as the time interval from initiation of any CPR (bystander CPR or CPR by emergency medical services personnel) to the initiation of ECPR. [Extracted from the article]

关键词： Editorials   cardiopulmonary arrest   cardiopulmonary resuscitation   quality and outcomes  

摘要： Keywords: Editorials; cardiopulmonary arrest; cardiopulmonary resuscitation; quality and outcomes EN Editorials cardiopulmonary arrest cardiopulmonary resuscitation quality and outcomes 887 890 4 04/20/20 20200317 NES 200317 B Article, see p 877 b Treatment of out-of-hospital cardiac arrest (OHCA) implies a multidisciplinary approach, including the immediate provision of high-quality cardiopulmonary resuscitation, targeted temperature management, consideration of immediate coronary angiography, and early neurological evaluation for prognostication. UMN-ECPR patients received a longer mean duration of professional CPR (60 minutes), as compared with conventional CPR patients from the ALPS cohort (35 minutes). When analyzing the effect of CPR duration on the outcome, a significant survival benefit was observed for UMN-ECPR patients compared with ALPS patients at each CPR duration interval. [Extracted from the article]

关键词： Malaria   Tafenoquine   Neuropsychiatric   Adverse events   Anti-malarial  

摘要： Background Tafenoquine is an 8-aminoquinoline anti-malarial drug recently approved as a single-dose (300 mg) therapy for Plasmodium vivax relapse prevention, when co-administered with 3-days of chloroquine or other blood schizonticide. Tafenoquine 200 mg weekly after a loading dose is also approved as travellers' prophylaxis. The development of tafenoquine has been conducted over many years, using various dosing regimens in diverse populations. Methods This review brings together all the preclinical and clinical data concerning tafenoquine central nervous system safety. Data were assembled from published sources. The risk of neuropsychiatric adverse events (NPAEs) with single-dose tafenoquine (300 mg) in combination with chloroquine to achieve P. vivax relapse prevention is particularly examined. Results There was no evidence of neurotoxicity with tafenoquine in preclinical animal models. In clinical studies in P. vivax relapse prevention, nervous system adverse events, mainly headache and dizziness, occurred in 11.4% (36/317) of patients with tafenoquine (300 mg)/chloroquine versus 10.2% (19/187) with placebo/chloroquine;and in 15.5% (75/483) of patients with tafenoquine/chloroquine versus 13.3% (35/264) with primaquine (15 mg/day for 14 days)/chloroquine. Psychiatric adverse events, mainly insomnia, occurred in 3.8% (12/317) of patients with tafenoquine/chloroquine versus 2.7% (5/187) with placebo/chloroquine;and in 2.9% (14/483) of patients with tafenoquine/chloroquine versus 3.4% (9/264) for primaquine/chloroquine. There were no serious or severe NPAEs observed with tafenoquine (300 mg)/chloroquine in these studies. Conclusions The risk:benefit of single-dose tafenoquine/chloroquine in P. vivax relapse prevention is favourable in the presence of malaria, with a low risk of NPAEs, similar to that seen with chloroquine alone or primaquine/chloroquine.

关键词： Inhibitors   Inhibition   Cancer   Peptides and proteins   Probes  

摘要： The immunoproteasome (iCP) is an isoform of the 20S proteasome that is expressed when cells are stressed or receive an inflammatory signal. The primary role of the iCP is to hydrolyze proteins into peptides that are compatible with being loaded into a MHC-I complex. When the activity of the iCP is dysregulated or highly expressed, it can lead to unwanted cell death. Some cancer types express the iCP rather than the standard proteasome, and selective inhibitors have been developed to exploit this difference. Here, we describe diseases known to be influenced by iCP activity and the current status for targeting the iCP to elicit a therapeutic response. We also describe a variety of chemical tools that have been developed to monitor the activity of the iCP in cells. Finally, we present the future outlook for targeting the iCP in a variety of disease types and with mechanisms besides inhibition.

关键词： Sulforaphane   Nrf2 signaling   Antioxidant   Neuroprotection   Neurological disorders  

摘要： Neurological disorders represent a great challenge and are the leading cause of death and disability globally. Although numerous complicated mechanisms are involved in the progressions of chronic and acute neurodegenerative disorders, most of the diseases share mutual pathogenic features such as oxidative stress, mitochondrial dysfunction, neuroinflammation, protein misfolding, excitotoxicity, and neuronal damage, all of these are the common targets of nuclear factor erythroid 2 related factor 2 (Nrf2) signaling cascade. No cure has yet been discovered to tackle these disorders, so, intervention approaches targeting phytochemicals have been recommended as an alternative form of treatment. Sulforaphane is a sulfur-rich dietary phytochemical which has several activities such as antioxidant, anti-inflammatory, and anti-tumor via multiple targets and various mechanisms. Given its numerous actions, sulforaphane has drawn considerable attention for neurological disorders in recent years. Nrf2 is one of the most crucial targets of sulforaphane which has potential in regulating the series of cytoprotective enzyme expressions that have neuroprotective, antioxidative, and detoxification actions. Neurological disorders are auspicious candidates for Nrf2-targeted treatment strategy. Sulforaphane protects various neurological disorders by regulating the Nrf2 pathway. In this article, we recapitulate current studies of sulforaphane-mediated Nrf2 activation in the treatment of various neurological disorders. (C) 2019 Elsevier B.V. All rights reserved.

关键词： Multiple sclerosis   EAE   Microbiota   Antibiotics   CNS autoimmunity   microbiome  

摘要： The gut microbiota regulates the host immune and nervous systems and plays an important role in the pathogenesis of autoimmune neurological disease multiple sclerosis (MS). There are considerable efforts currently being undertaken to develop therapies for MS based on the modulation of microbiota. Evidence from experimental models suggests that the manipulation of microbiota through diet or antibiotics prior to the disease development limits disease susceptibility. However, it is currently unclear if microbiota manipulation therapies would also have an impact on ongoing neurological disease. Here, we examined the effect of antibiotic-based microbiota modulation in spontaneous experimental autoimmune encephalomyelitis (EAE) mouse models of MS before and after the onset of autoimmune disease. Prophylactic antibiotic treatment led to a significant reduction of susceptibility to spontaneous EAE. In contrast, antibiotic treatment after the onset of spontaneous EAE did not show a significant amelioration. These results reveal that the perturbation of gut bacteria alters disease susceptibility but has minimal impact on the ongoing neurological disease.

关键词： Traumatic brain injury (TBI)   miR-193a   Neuroinflammation   microglial activation   NLRP3  

摘要： Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the world, and is tightly associated with microglia-regulated neuroinflammation. However, the activation profile of microglia during the pathophysiological responses is still not fully understood. Micro-RNAs (miRs), as noncoding RNAs, are involved in the progression of TBI. In this study, we attempted to explore the effects of miR-193a on TBI using the in vivo and in vitro studies. Following experimental TBI in mice, we found that miR-193a expression was significantly up-regulated in ipsilateral cortical tissues and in the microglia/ macrophages isolated from the ipsilateral cortical tissues, which was accompanied with markedly enhanced expression of pro-inflammatory factors. We then found that miR-193a hairpin inhibitor (antagomir) markedly reduced lesion volume, brain water contents and neuron death in TBI mice induced by the controlled cortical impact (CCI). In addition, cognitive dysfunction in TBI mice was markedly improved after miR-193a antagomir injection. Of note, CCI-induced activation of microglia was repressed by miR-193a inhibition, along with significantly reduced expression of neuroinflammatory markers, which were associated with the blockage of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The anti-neuroinflammation effects of miR-193a suppression were verified in lipopolysaccharide (LPS)-incubated microglial cells transfected with miR-193a inhibitor. In contrast, LPS-induced activation of microglial cells and the expression of pro-inflammatory factors was markedly further accelerated by the transfection of miR-193a mimic. Taken together, TBI resulted in a robust neuroinflammatory response that was closely associated with the up-regulated miR-193a expression mainly in microglia/macrophages;however, miR-193a suppression significantly alleviated post-traumatic neuroinflammation and cognitive dysfunction. Therefo