Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Electronic clinical records in primary care for estimating disease burden and management. An example of COPD

Chronic obstructive pulmonary disease (COPD) is a significant health problem in developed countries. We aimed to estimate the prevalence of COPD in a single Spanish healthcare area. We also aimed to assess if there are any differences in prevalence and spirometry use among primary care services by utilizing already registered information. We designed a cross-sectional study to determine the prevalence of COPD and the performance of spirometries in each primary care service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of 2.6% for individuals older than 39 years. The prevalence increased with age and was much higher in men. Significant heterogeneity was found in the prevalence of COPD and spirometry use among primary care services. COPD was underdiagnosed and there was wide variability in spirometry use in our area. Greater efforts are needed to diagnose COPD in order to improve its clinical outcomes and to refine registries so that they can be used as reliable sources of information     

Optimizing access and configuration of trauma centre care in New South Wales

IntroductionGetting the right patient, to the right place, at the right time is dependent on a multitude of modifiable and non-modifiable factors. One potentially modifiable factor is the number and location of trauma centres (TC). Overabundance of TC dilutes volumes and could be associated with worse outcomes. We describe a methodology that evaluates trauma system reconfiguration without reductions in potential access to care. We used the mature trauma system of New South Wales (NSW) as a model given the perceived overabundance of urban major trauma centres (MTC).MethodsWe first evaluated potential access to TC care via ground and air transport through the use of geographic information systems (GIS) network analysis. Potential access was defined as the proportion of the population living within 60-min transport time from a potential scene of injury to a TC by ground or rotary-wing aircraft. Sensitivity analyses were carried out in order to account for potential pre-hospital interventions and/or transport delays; travel times of 15-, 30-, 45-, 60-, and 90-min were also analyzed. We then evaluated if the current configuration of the system (number of urban MTS in the Sydney basin) could be optimized without reductions in potential access to care using two GIS methodologies: location-allocation and individual removal of MTC.Results86% of the NSW population has potential access to a TC within 60 min ground travel time; potential access improves to 99% with rotary-wing transport. The 1% of the population without potential TC access lives in 48% of the land area (>384,000km2). Utilizing two different methodologies we identified that there was no change in potential access by ground transport after removing 1 or 2 MTC in the Sydney basin at the 30-, 45-, and 60-min transport times. However, 0.02% and 0.5% of the population would not have potential access to MTC care at 15 min after removing one and two MTC respectively.DiscussionRedistribution of the number of MTC in the Sydney basin could be achieved without a significant impact on potential access to care. Our approach can be utilized as an initial tool to evaluate a trauma system where overabundance of coverage is present.     

电子线照射对小鼠胰岛素生长因子相关蛋白表达的影响

目的：探讨电子线对胰岛素生长因子-1家族蛋白表达的影响，为研究辐射对肝脏的早期损伤提供依据。方法：采用电子线照射小鼠，照射剂量为1、2、4 Gy，用Western blot法检测照射后12、48和72 h小鼠肝脏中胰岛素生长因子1受体（IGF-1R）、胰岛素生长因子结合蛋白1（IGFBP1）、胰岛素生长因子结合蛋白4（IGFBP4）和胰岛素生长因子1（IGF-1）蛋白表达水平的改变。结果：照射剂量为1 Gy时，与对照组相比，IGF-1蛋白在照射后48 h时表达增加，IGFBP1、IGFBP4和IGF1R蛋白的表达在照射后12、48和72 h均表达减少。照射剂量为2 Gy时，IGF-1和IGFBP4蛋白在照射后48 h时表达增加，其余时间点表达减少。IGFBP1蛋白在照射后12 h时表达增加，48和72 h时表达减少。IGF1R蛋白在照射后3个时间点均呈现为表达减少。照射剂量4 Gy时，肝脏中IGF-1、IGFBP1和IGFBP4蛋白均表达减少，IGF1R蛋白在照射后12 h时表达增加，48、72 h时均表达减少（均为P < 0.05）。结论：电子线照射后小鼠肝脏中胰岛素生长因子-1家族蛋白多以下调表达为主，与前期基因表达的结果相一致，有可能作为反映放射性工作人员早期肝脏损伤的生物标志物之一。     

Prevalence of and factors contributing to anxiety,depression and cognitive disorders among urban elderly in Odisha – A study through the health systems’ Lens

IntroductionGrowing geriatric mental health needs of urban population in India pose several programmatic challenges. This study aimed to assess anxiety, depression and cognitive disorders among urban elderly, and explore availability of social support mechanisms and of a responsive health system to implement the national mental health programme.Methods244 respondents were randomly selected from Berhampur city. We administered a semi-structured interview schedule to assess substance abuse, chronic morbidity, anxiety, depression and cognitive abilities. Further, in-depth interviews were conducted with 25 key informants including district officials, psychiatrists, and programme managers. We used R software and ‘thematic framework’ approach, respectively, for quantitative and qualitative data analysis. Ethical standards were complied with.ResultsAbout half of the respondents were economically dependent; 57.3% had moderate to severe anxiety; 46.7% had moderate to severe depression; while about 25% had severe cognitive impairments. We found association of chewing tobacco (1.34(0.28–2.40)) and depression (0.52(0.37–0.68)) with anxiety; negative perception about elderly-friendly society (1.64(0.75–2.53)) and physical inactivity (2.88(1.60–4.16)) with depression; and age (-0.11(-0.20 – -0.02)) and physical inactivity (-3.44(-5.13 – -1.74)) with cognitive disorders. Qualitative analysis revealed lack of awareness, social stigma, poor availability of trained human resources, and poor political commitment as important systemic barriers to early detection and treatment of mental ailments among the elderly.ConclusionEstablishing tobacco cessation centres, sensitizing community about mental health needs of elderly, incentivizing physical activity of elderly, integrating mental health with primary care, multi-skilling providers and developing a cadre of community counsellors need urgent attention of policy makers and programme implementers.     

外科重症病人脑电双频指数指导靶控输注咪达唑仑的镇静效果

目的评价外科重症监护病房(SICU)病人脑电双频指数(BIS)指导靶控输注(TCI)咪达唑仑的镇静效果。方法SICU病人30例,随机分为3组(n=10):A组采用恒速输注咪达唑仑0．06 mg·kg-1·h-1镇静;B组采用咪达唑仑TCI镇静,初始血浆靶浓度为60 ng/ml;C组在BIS指导下咪达唑仑TCI镇静,初始血浆靶浓度为60 ng／ml。每30 min采用Ramsay镇静评分评估镇静深度,若Ramsay镇静评分小于或大于4分,则A组输注速率增加或减少0．02 mg·kg-1·h-1,B组血浆靶浓度增加或减少20 ng／ml。C组若BIS大于或小于70,则血浆靶浓度增加或减少20 ng／ml。B、C组均随机抽取30份2 ml动脉血样,测定咪达唑仑血药浓度,用偏离性和精密度评价TCI系统的性能。结果咪达唑仑TCI系统的偏离性为12．5％,精密度为22．5％。咪达唑仑实测血药浓度与Ramsay镇静评分的相关系数为0．67(P<0．05)。镇静过程中C组Ramsay镇静评分4分所占比例(54％)高于A组(28％)和B组(40％)(P<0．01)。结论咪达唑仑TCI系统的性能可靠,用于SICU病人以BIS为70调控咪达唑仑TCI,可产生良好的镇静效果。