Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation

Traumatic brain injury (TBI) induces secondary biochemical changes that contribute to delayed neuroinflammation, neuronal cell death, and neurological dysfunction. Attenuating such secondary injury has provided the conceptual basis for neuroprotective treatments. Despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed. In part, these failures likely reflect methodological differences between the clinical and animal studies, as well as inadequate pre-clinical evaluation and/or trial design problems. However, recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation. Here we critically analyze the current limitations and translational opportunities for developing successful neuroprotective therapies for TBI.     

Aged Skeletal Muscle Retains the Ability to Remodel Extracellular Matrix for Degradation of Collagen Deposition after Muscle Injury

Aging causes a decline in skeletal muscle function, resulting in a progressive loss of muscle mass, quality, and strength. A weak regenerative capacity is one of the critical causes of dysfunctional skeletal muscle in elderly individuals. The extracellular matrix (ECM) maintains the tissue framework structure in skeletal muscle. As shown by previous reports and our data, the gene expression of ECM components decreases with age, but the accumulation of collagen substantially increases in skeletal muscle. We examined the structural changes in ECM in aged skeletal muscle and found restricted ECM degradation. In aged skeletal muscles, several genes that maintain ECM structure, such as transforming growth factor β (TGF-β), tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and cathepsins, were downregulated. Muscle injury can induce muscle repair and regeneration in young and adult skeletal muscles. Surprisingly, muscle injury could not only efficiently induce regeneration in aged skeletal muscle, but it could also activate ECM remodeling and the clearance of ECM deposition. These results will help elucidate the mechanisms of muscle fibrosis with age and develop innovative antifibrotic therapies to decrease excessive collagen deposition in aged muscle.     

Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ET_B) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ET_B receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ET_B receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ET_B-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ET_B receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ET_B receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.     

The impact of compulsory cycle helmet legislation on cyclist head injuries in New South Wales,Australia: A rejoinder

This paper challenges the conclusion of a recent paper by Walter et al. (Accident Analysis and Prevention 2011, doi:10.1016/j.aap.2011.05.029) reporting that despite numerous data limitations repealing the helmet legislation in Australia could not be justified. This conclusion is not warranted because of the limited time period used in their analysis and the lack of data beyond a few years before the introduction of legislation, the failure to adequately account for the effect of the phasing in of the legislation, the effect of the marked reduction in child cyclists, and the non-comparability of the pedestrian and cycling injuries and related lack of consideration of the severity of head injuries. The extent to which helmet legislation deters people from cycling is discussed.     

Dummy humanoid robot simulating several trunk postures and abdominal shapes – Report of element technologies

Development of clothing in consideration of the shape and body function of a person with spinal cord injury is an important task. Then, a dummy robot with a deformation mechanism was developed in this study for evaluating the comfortable level of clothings. Specifically, a trunk joint mechanism and an abdominal mechanism that can realize various deformations of the abdominal area and various trunk poses were developed. The trunk joint mechanism was implemented in order to simulate the seated posture of persons with spinal cord injury. The abdominal deformation mechanism was implemented using linear actuators and rotating servomotors in order to simulate abdominal obesity of persons with spinal cord injury. Further, a tactile sensor system was developed for measuring the clothing pressure on the abdominal area and evaluating the comfort or discomfort of clothing.     

城市树木致伤风险可视化评估：以武汉市 中山公园为例

城市中的树木能提供多种生态系统服务，但树木倒 伏、树枝坠落也可能致人伤害，评估城市树木风险能有效地预 防伤害发生、保障人身安全。但当前研究的评估维度多聚焦于 树木自身，对城市人群致伤可能性的考量较少。建构了风险严 重性、风险可能性和致伤潜力3个维度的城市树木致伤风险指 数(I UTIR)评估方法，以武汉市中山公园为例展开树木致伤风险 评估，并分析了树木自身风险、致伤潜力与致伤风险之间的空 间关系。研究发现：68.7%的区域中，树木自身风险与致伤潜 力之间的空间关系呈现正相关性，25.1%的区域呈现负相关 性。在此基础上，提出了预防树木致伤风险的管理建议。为公 园规划设计和树木风险管理策略提供参考，从而减弱树木致伤 风险对人体健康的影响。     

Work-related chronic injuries of the forearm and hand: their specific diagnosis and management

Work-related chronic injuries occur in muscles, tendons, and nerves. Epidemiological, histological, and physiological data confirm their often disputed physical basis. Terms such as repetitive strain injury and cumulative trauma disorder, when used as a diagnosis, have obscured the issue for they are really statements of causation. Definitive diagnosis is required both to treat and prevent such injuries. Precise terminology that identifies the tissue and its pathology is required. A detailed assessment methodology is described that allows a precise diagnosis. A clear relationship to work stress is necessary both to establish the cause and formulate prevention strategies. Treatment must begin early and be appropriate to the tissue and the nature of the injury. Examples are presented and discussed. Early treatment begins before too much damage has been done and yields better results.     

How would increasing seat belt use affect the number of killed or seriously injured light vehicle occupants?

The expected effects of increasing seat belt use on the number of killed or seriously injured (KSI) light vehicle occupants have been estimated for three scenarios of increased seat belt use in Norway, taking into account current seat belt use, the effects of seat belts and differences in crash risk between belted and unbelted drivers. The effects of seat belts on fatality and injury risk were investigated in a meta-analysis that is based on 24 studies from 2000 or later. The results indicate that seat belts reduce both fatal and non-fatal injuries by 60% among front seat occupants and by 44% among rear seat occupants. Both results are statistically significant. Seat belt use among rear seat occupants was additionally found to about halve fatality risk among belted front seat occupants in a meta-analysis that is based on six studies. Based on an analysis of seat belt wearing rates among crash involved and non-crash involved drivers in Norway it is estimated that unbelted drivers have 8.3 times the fatal crash risk and 5.2 times the serious injury crash risk of belted drivers. The large differences in crash risk are likely to be due to other risk factors that are common among unbelted drivers such as drunk driving and speeding. Without taking into account differences in crash risk between belted and unbelted drivers, the estimated effects of increasing seat belt use are likely to be biased. When differences in crash risk are taken into account, it is estimated that the annual numbers of KSI front seat occupants in light vehicles in Norway could be reduced by 11.3% if all vehicles had seat belt reminders (assumed seat belt wearing rate 98.9%), by 17.5% if all light vehicles had seat belt interlocks (assumed seat belt wearing rate 99.7%) and by 19.9% if all front seat occupants of light vehicles were belted. Currently 96.6% of all (non-crash involved) front seat occupants are belted. The effect on KSI per percentage increase of seat belt use increases with increasing initial levels of seat belt use. Had all rear seat occupants been belted, the number of KSI front seat occupants could additionally be reduced by about 0.6%. The reduction of the number of KSI rear seat occupants would be about the same in terms of numbers of prevented KSI.     

Pressure Combined with Ischemia/Reperfusion Injury Induces Deep Tissue Injury via Endoplasmic Reticulum Stress in a Rat Pressure Ulcer Model

Pressure ulcer is a complex and significant health problem in long-term bedridden patients, and there is currently no effective treatment or efficient prevention method. Furthermore, the molecular mechanisms and pathogenesis contributing to the deep injury of pressure ulcers are unclear. The aim of the study was to explore the role of endoplasmic reticulum (ER) stress and Akt/GSK3β signaling in pressure ulcers. A model of pressure-induced deep tissue injury in adult Sprague-Dawley rats was established. Rats were treated with 2-h compression and subsequent 0.5-h release for various cycles. After recovery, the tissue in the compressed regions was collected for further analysis. The compressed muscle tissues showed clear cellular degenerative features. First, the expression levels of ER stress proteins GRP78, CHOP, and caspase-12 were generally increased compared to those in the control. Phosphorylated Akt and phosphorylated GSK3β were upregulated in the beginning of muscle compression, and immediately significantly decreased at the initiation of ischemia-reperfusion injury in compressed muscles tissue. These data show that ER stress may be involved in the underlying mechanisms of cell degeneration after pressure ulcers and that the Akt/GSK3β signal pathway may play an important role in deep tissue injury induced by pressure and ischemia/reperfusion.