Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

A test of the resource security and the body mass index reference point hypotheses of body dissatisfaction amongst adolescents in eight countries

Objective. This study aimed to identify cultural-level variables that may influence the extent to which adolescents from different cultural groups are dissatisfied with their bodies.

Design. A sample of 1730 male and 2000 female adolescents from Australia, Fiji, Malaysia, Tonga, Tongans in New Zealand, China, Chile, and Greece completed measures of body satisfaction, and the sociocultural influences on body image and body change questionnaire, and self-reported height and weight. Country gross domestic product and national obesity were recorded using global databases.

Results. Prevalence of obesity/overweight and cultural endorsement of appearance standards explained variance in individual-level body dissatisfaction (BD) scores, even after controlling for the influence of individual differences in body mass index and internalization of appearance standards.

Conclusions. Cultural-level variables may account for the development of adolescent BD.     

缺氧缺血I生脑损伤新生大鼠脑神经细胞凋亡及脑组织中Rho GDP解离抑制因子和Bcl-2表达的变化

目的研究RhoGDP解离抑制因子（Rho GDP dissociation inhibitor 2,RhoGDI2）mRNA及Bcl-2mRNA的表达在缺氧缺血性脑损伤（hypoxic-ischemic brain damage,HIBD）中的作用和机制。方法30只新生7日龄SD大鼠按照完全随机化方法分为假手术组及HIBD6h和48h组,每组10只。采用流式细胞仪检测脑细胞凋亡情况,并用Real—timeRT—PCR方法测定脑组织中RhoGDI2和Bcl-2mRNA表达水平。结果（1）新生大鼠HIBD后48h结扎侧大脑半球脑水肿明显。（2）HIBD6h出现典型的凋亡细胞峰,细胞凋亡率为（1．40±0．12）％。HIBD48h凋亡峰更为明显,细胞凋亡率达到（15．86±0．98）％。缺氧缺血后与假手术组相比,差异有统计学意义（P〈0．01）。（3）假手术组大鼠RhoGDI2和Bcl-2mRNA表达水平较高（4．12±0．74、2．55±0．65）,在HIBD6h后二者表达开始下降（3．19±0．77、1．96±0．36）,48h降低更加明显（1．04±0．18、1．06±0．17）,与假手术组比较,HIBD各时间点RhoGDI2和Bcl-2mRNA的表达均明显降低,差异有统计学意义（P〈0．01）。（4）缺氧缺血后各时间点RhoGDI2mRNA的表达和Bcl-2mRNA的表达呈正相关（r=0．831,P〈0．05）。结论脑缺氧缺血后,随着凋亡的出现,RhoGDI2和Bcl-2mRNA表达水平降低,提示RhoGDI2表达失衡可能通过Bcl-2参与新生大鼠HIBD中凋亡的发生。     

我国居民医疗保健支出与国民经济发展的多维尺度分析

文章分析了我国从1998年开始建立社会医疗保险制度以来,卫生总费用与国民经济的发展变化趋势,城乡居民可支配收入与医疗保健支出的相关性及地区差异性.结果显示,卫生总费用的增长与国民经济发展总体相适应,城乡居民可支配收入与医疗保健支出呈高度相关(r城市=0.989,r农村=0.993);但各省(区、市)家庭可支配收入与医疗保健支出之间相关性不强(r=-0.554),存在明显的地区差异.建议通过加强中央统筹,提高政府对卫生总费用、社会医疗保险支付的能力,建立与当地经济发展相适应的医疗服务价格体系,缩小地区差距.     

Lysophosphatidylcholine enhances I(Ks) currents in cardiac myocytes through activation of G protein, PKC and Rho signaling pathways

Lysophosphatidylcholine (LPC) is a bioactive phospholipid that accumulates rapidly in the ischemic myocardium. In recent years, it has been shown that some of the actions of LPC are mediated through the activation of the membrane G proteins. However, the precise mechanism(s) responsible for the LPC-related intracellular signaling in the regulation of cardiac ion channels are still poorly understood. The present study was undertaken to examine whether LPC regulates the slow component of the delayed rectifier K⁺ current (I_Ks) and, if so, what intracellular signals are important for this process. Isolated guinea pig cardiac myocytes were voltage-clamped using the whole-cell configuration of the patch-clamp method. The bath application of 1-palmitoyl-lysophosphatidylcholine (LPC-16) concentration-dependently (EC₅₀ = 0.7 μM) and reversibly increased I_Ks in atrial cells, but failed to potentiate I_Ks in ventricular myocytes. In contrast, 1-oleoyl-lysophosphatidylcholine (LPC-18:1) only produced a slight I_Ks increase, and 1-caproyl-lysophosphatidylcholine (LPC-6) or the LPC-16 precursor (phosphatidylcholine) had no effect on I_Ks. Pretreatment of atrial cells with an antibody against the N-terminus of the G2A receptor significantly reduced the LPC-16-induced potentiation of I_Ks. The inhibition of heterotrimeric G protein, phospholipase C (PLC) and protein kinase C (PKC) significantly reduced LPC-16-induced enhancement of I_Ks. Moreover, the blockade of Rho and Rho-kinase by specific inhibitors also inhibited the activity of LPC-16. Immunohistochemical studies demonstrated that G2A was densely distributed in the plasma membrane of atrial myocytes. Therefore, the present study suggests that the activation of a G protein (probably Gα_q) by LPC-16 potentiates I_Ks currents through the PLC-PKC and Rho-kinase pathways.     

From the Cover: Global mapping of Al,Cu, Fe,and Zn in-use stocks and in-ground resources

Human activity has become a significant geomorphic force in modern times, resulting in unprecedented movements of material around Earth. An essential constituent of this material movement, the major industrial metals aluminium, copper, iron, and zinc in the human-built environment are mapped globally at 1-km nominal resolution for the year 2000 and compared with the locations of present-day in-ground resources. While the maps of in-ground resources generated essentially combine available databases, the mapping methodology of in-use stocks relies on the linear regression between gross domestic product and both in-use stock estimates and the Nighttime Lights of the World dataset. As the first global maps of in-use metal stocks, they reveal that a full 25% of the world''s Fe, Al, Cu, and Zn in-use deposits are concentrated in three bands: (i) the Eastern seaboard from Washington, D.C. to Boston in the United States, (ii) England, Benelux into Germany and Northern Italy, and (iii) South Korea and Japan. This pattern is consistent across all metals investigated. In contrast, the global maps of primary metal resources reveal these deposits are more evenly distributed between the developed and developing worlds, with the distribution pattern differing depending on the metal. This analysis highlights the magnitude at which in-ground metal resources have been translocated to in-use stocks, largely from highly concentrated but globally dispersed in-ground deposits to more diffuse in-use stocks located primarily in developed urban regions.     

Out of sight but not out of mind: Home countries' macroeconomic volatilities and immigrants' mental health

We provide the first empirical evidence that better economic performances by immigrants' countries of origin, as measured by lower consumer price index (CPI) or higher gross domestic product, improve immigrants' mental health. We use an econometrically‐robust approach that exploits exogenous changes in macroeconomic conditions across immigrants' home countries over time and controls for immigrants' observable and unobservable characteristics. The CPI effect is statistically significant and sizeable. Furthermore, the CPI effect diminishes as the time since emigrating increases. By contrast, home countries' unemployment rates and exchange rate fluctuations have no impact on immigrants' mental health.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.