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.     

Investigating driver injury severity patterns in rollover crashes using support vector machine models

Rollover crash is one of the major types of traffic crashes that induce fatal injuries. It is important to investigate the factors that affect rollover crashes and their influence on driver injury severity outcomes. This study employs support vector machine (SVM) models to investigate driver injury severity patterns in rollover crashes based on two-year crash data gathered in New Mexico. The impacts of various explanatory variables are examined in terms of crash and environmental information, vehicle features, and driver demographics and behavior characteristics. A classification and regression tree (CART) model is utilized to identify significant variables and SVM models with polynomial and Gaussian radius basis function (RBF) kernels are used for model performance evaluation. It is shown that the SVM models produce reasonable prediction performance and the polynomial kernel outperforms the Gaussian RBF kernel. Variable impact analysis reveals that factors including comfortable driving environment conditions, driver alcohol or drug involvement, seatbelt use, number of travel lanes, driver demographic features, maximum vehicle damages in crashes, crash time, and crash location are significantly associated with driver incapacitating injuries and fatalities. These findings provide insights for better understanding rollover crash causes and the impacts of various explanatory factors on driver injury severity patterns.     

Domestic demand-side response with heat pumps: controls and tariffs

ABSTRACT

Electric heat pumps feature prominently in projected energy transitions in the UK and elsewhere. Owing to their high electricity consumption, heat pumps are viewed as important targets for demand-side response (DSR). Findings are presented from a field trial of a new control system that aims to optimize heat pump performance, including under time-varying tariff conditions. The trial involved monitoring 76 properties with heat pumps, but without dedicated heat storage; 31 of these received the control system. Interviews were conducted with a subsample of 12 participants. The controller successfully evened out electricity demand over the day (reducing the evening peak), but this was associated with increased late night and daytime temperatures. Interview participants reported some disturbance owing to overnight heating and noise, as well as usability issues with the controller interface and hardware. These issues present risks to the future acceptability of such systems. While the system delivered short-term demand reductions successfully, longer-term demand shifting risked causing unacceptable disturbance to occupants. Future control systems could overcome some of the issues identified in this pioneering trial through more effective zoning, using temperature caps or installing dedicated heat storage, but these may either limit the available flexibility or be challenging to achieve.     

Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.     

Fluoro-Photoacoustic Polymeric Renal Reporter for Real-Time Dual Imaging of Acute Kidney Injury

Photoacoustic (PA) imaging agents detect disease tissues and biomarkers with increased penetration depth and enhanced spatial resolution relative to traditional optical imaging, and thus hold great promise for clinical applications. However, existing PA imaging agents often encounter the issues of slow body excretion and low-signal specificity, which compromise their capability for in vivo detection. Herein, a fluoro-photoacoustic polymeric renal reporter (FPRR) is synthesized for real-time imaging of drug-induced acute kidney injury (AKI). FPRR simultaneously turns on both near-infrared fluorescence (NIRF) and PA signals in response to an AKI biomarker (γ-glutamyl transferase) with high sensitivity and specificity. In association with its high renal clearance efficiency (78% at 24 h post-injection), FPRR can detect cisplatin-induced AKI at 24 h post-drug treatment through both real-time imaging and optical urinalysis, which is 48 h earlier than serum biomarker elevation and histological changes. More importantly, the deep-tissue penetration capability of PA imaging results in a signal-to-background ratio that is 2.3-fold higher than NIRF imaging. Thus, the study not only demonstrates the first activatable PA probe for real-time sensitive imaging of kidney function at molecular level, but also highlights the polymeric probe structure with high renal clearance.     

Assessment of the static fit of automobile lap-belt systems on front-seat passengers

While automobile seat belts are recognized as reducing injury in frontal collisions, the lap belt can cause injury to the abdominal contents during impact. A lap belt which is malpositioned, i.e., above the anterior superior iliac spines (ASIS) of the pelvis before impact, is suggested as a causative factor in many of these injuries. A questionnaire was completed by 198 adult passengers on lap-belt fit as well as vehicle, anthropometric and behavioural factors. All measures were self-reported. The fit of automobile seat belts was also investigated in the laboratory to determine some of the factors thought important in the pre-impact position of the lap belt. Seven factors, subject size, subject sitting posture, clothing thickness, vehicle configuration, vehicle seat position, seat back angle and the handling of the belt by the occupant, were assessed on 51 subjects sitting in six simulated vehicles. The sample purposely included a disproportionate number of tall, short, heavy and thin subjects.

The questionnaire responses indicated that a high proportion (49%) of lap belts were found to be malpositioned in a normal sitting posture. Moving around in the seat, especially slouching, greatly increased the proportion of malpositions. It was noteworthy that wearing a heavy winter coat did not cause belt malposition. A high incidence of malpositioned lap belts was also found in the laboratory study with 42% of the belts having their centre-lines above the ASIS and 89% having part of the belt overlying the ASIS in a normal upright seated position with the seat in the middle of its fore/aft movement. Slouching in the seat significantly increased this proportion. The malposition rate was adversely affected by a forward seat position in a significant manner. There was a large increase in the malposition rate when the occupant attached the belt compared to when the experimenter attached it, with malposition rates of 43% and 19% respectively in the rearmost seat position. There was no statistically significant effect of clothing thickness on belt fit. Although statistically significant correlations between belt inclination and malposition were found, no clear-cut belt-angle existed above which satisfactory fit existed.     

Transfer of the horizontal patient: The effect of a friction reducing assistive device on low back mechanics

Recognizing that the transfer of bedridden patients is associated with a high rate of low back injuries, various devices have been developed to assist with sparing the patient handlers. The purpose of this study was to quantify the friction-reducing ability of three different ‘sliding’ patient transfer devices together with the subsequent consequences on the low back loads of people performing the transfers. Coefficients of friction of the devices were determined by ‘transferring’ a standard object and a ‘patient’ over several surfaces common to a hospital setting. Then three participants performed controlled transfers with the various devices. Electromyography to measure muscle activation levels together with external forces and kinematic positional data were collected during push, pull and twist transfers. Spine loads were estimated with a three-dimensional biomechanical static link-segment model of the human body. Simply sliding a patient on a cotton sheet (control condition) produced a coefficient of friction of 0.45. The assistive devices substantially reduced friction by well over one-half (coefficients of 0.18?–?0.21). However, when using the devices the subjects adopted a variety of postures and techniques, such that there were no consistent influences on trunk inclination, low back compression or muscle activation profiles. Direct measurement of reduced friction between the bed and the patient with a friction-reducing device together with measurement of the back loads when actually transferring a patient formed a proof of principle. Specifically, while the device lowers friction, the transfer technique adopted by the lifter must be proper to reduce low back loading and any subsequent risks of back troubles associated with patient transfers. The direction of hand forces and torso position remains important.     

The determinants of fishing vessel accident severity

The study examines the determinants of fishing vessel accident severity in the Northeastern United States using vessel accident data from the U.S. Coast Guard for 2001–2008. Vessel damage and crew injury severity equations were estimated separately utilizing the ordered probit model. The results suggest that fishing vessel accident severity is significantly affected by several types of accidents. Vessel damage severity is positively associated with loss of stability, sinking, daytime wind speed, vessel age, and distance to shore. Vessel damage severity is negatively associated with vessel size and daytime sea level pressure. Crew injury severity is also positively related to the loss of vessel stability and sinking.     

The response of the adult and ATD heads to impacts onto a rigid surface

Given the high incidence of TBI, head injury has been studied extensively using both cadavers and anthropomorphic test devices (ATDs). However, few studies have benchmarked the response of ATD heads against human data. Hence, the objective of this study is to investigate the response of adult and ATD heads in impact, and to compare adult Hybrid III head responses to the adult head responses.     

建筑室内人员污染源散发特性与有效散发模型

基于典型人员污染物指标的散发机制与特点并结合中国人员体型特征数据分析了年龄、性别、活动水平对人员污染源散发的影响关系,同时通过借助不稳定性系数给出了由人体气味污染不稳定性因素作用引起的CO2减少量的确定方法,并根据其与人体CO2产生量之间的叠加关系建立了人员污染源有效散发量的计算模型。研究结果表明,中国男性与女性的CO2散发水平存在差异,并且人体CO2散发水平随活动强度的变化率与年龄、性别有关;此外,人体气味污染不稳定性因素对CO2减少率的影响程度随通风换气次数、人员污染源作用时间的变化关系存在显著变化阶段和相对稳定阶段。