Premature aging and immune senescence in HIV-infected children

Objective: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. Design: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0\u20135 years, were studied for biological aging and immune senescence. Methods: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4+ and CD8+ cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. Results: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8+ recent thymic emigrant cells (CD45RA+CD31+) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28-CD57+), activated (CD38+HLA-DR+), and exhausted (PD1+) CD8+ cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4+ cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. Conclusions: HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8+ cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatmen

Negative immunodiffusion test results obtained with sera of paracoccidioidomycosis patients may be related to low-avidity immunoglobulin G2 antibodies directed against carbohydrate epitopes

Immunodiffusion (ID) is the serologic test most frequently used for the diagnosis and posttherapy follow-up of patients with paracoccidioidomycosis (PCM). The ID test is highly specific (100%), but its sensitivity is relatively low (90%), leading to false-negative results. The aim of this study was to determine the profiles of antibodies in sera from patients with proven PCM and with negative results in the ID test (IDneg) versus positive results in the ID test (IDpos). We analyzed 46 sera from patients with active PCM for total immunoglobulin G (IgG) and IgG subclass responses to Paracoccidioides brasiliensis gp43 antigen (treated or not treated with sodium metaperiodate) by enzyme-linked immunosorbent assay and immunoblotting. Immunoblotting showed that both IDneg and IDpos sera recognized predominantly the gp43 fraction of the P. brasiliensis antigen used in the ID test. IDneg sera contain low-avidity antibodies, low levels of specific IgG (total) and IgGI, and high levels of IgG2 compared with IDpos sera. The antibodies present in IDpos sera were predominantly directed against carbohydrate epitopes, since treatment with sodium metaperiodate resulted in a significant decrease in antibody reactivity. These data suggest that the lack of reactivity of sera from PCM patients in the ID test may be related to the production of low-avidity IgG2 antibodies directed against carbohydrate epitopes.10580280

The biogas chain and local sustainability: an environmental socioeconomic analysis of energy obtained from urban solid-waste from the Caximba land-fill in Curitiba, Parana, Brazil

Urban solid waste-derived renewable energy sources are currently being discussed as strategic choices; however, they have not yet been significantly included in world and/or Brazilian energetic matrixes. Feasibility studies must be carded out on the use of renewable sources and on related socioeconomic and environmental impacts. The research method was exploratory and was aimed at assessing the feasibility of generating energy from the Caximba (Parana, Brazil) sanitary landfill biogas chain, taking its socioeconomic and environmental sustainability into consideration; this landfill contains around 8 million tons of solid waste. The results showed that generating renewable energy was not economically feasible in the technological conditions defined by this case-study due to the plant's low-scale production. However, biogas production could become economically, environmentally and socially feasible if combined with carbon credit trading.1934839

A pilot field evaluation on heat stress in sugarcane workers in Costa Rica: What to do next?

BACKGROUND: Climate change is producing major impacts including increasing temperatures in tropical countries, like Costa Rica, where the sugarcane industry employs thousands of workers who are exposed to extreme heat. OBJECTIVES: This article outlines a pilot qualitative evaluation of working conditions and heat in the sugarcane industry. DESIGN: A literature review, direct observations and exploratory interviews with workers were conducted to reach a preliminary understanding of the dimensions of heat-related health issues in the sugarcane industry, as a basis for the design of future studies. RESULTS: The industry employs temporary workers from Nicaragua and Costa Rica as well as year-round employees. Temporary employees work 12-hour shifts during the harvest and processing ('zafra') season. In many cases, sugarcane field workers are required to carry their own water and often have no access to shade. Sugar mill workers are exposed to different levels of heat stress depending upon their job tasks, with the most intense heat and workload experienced by the oven ('caldera') cleaners. CONCLUSIONS: Research is needed to achieve better understanding of the multiple factors driving and interacting with heat exposures in the sugarcane industry in order to improve the health and safety of workers while maintaining worker productivity

Global Networks of Trade and Bits

Considerable efforts have been made in recent years to produce detailed topologies of the Internet. Although Internet topology data have been brought to the attention of a wide and somewhat diverse audience of scholars, so far they have been overlooked by economists. In this paper, we suggest that such data could be effectively treated as a proxy to characterize the size of the "digital economy" at country level and outsourcing: thus, we analyse the topological structure of the network of trade in digital services (trade in bits) and compare it with that of the more traditional flow of manufactured goods across countries. To perform meaningful comparisons across networks with different characteristics, we define a stochastic benchmark for the number of connections among each country-pair, based on hypergeometric distribution. Original data are thus filtered by means of different thresholds, so that we only focus on the strongest links, i.e., statistically significant links. We find that trade in bits displays a sparser and less hierarchical network structure, which is more similar to trade in high-skill manufactured goods than total trade. Lastly, distance plays a more prominent role in shaping the network of international trade in physical goods than trade in digital services.Comment: 25 pages, 6 figure

Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece

Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967–1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sons’ individuated dissent and activism who were now able to question the Patriarch’s authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A ‘different’ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Circulating Hepatitis B Surface Antigen Particles Carry Hepatocellular microRNAs

Hepatitis B virus (HBV) produces high quantities of subviral surface antigen particles (HBsAg) which circulate in the blood outnumbering virions of about 1\103–6 times. In individuals coinfected with the defective hepatitis Delta virus (HDV) the small HDV-RNA-genome and Delta antigen circulate as ribonucleoprotein complexes within HBsAg subviral particles. We addressed the question whether subviral HBsAg particles may carry in the same way cellular microRNAs (miRNAs) which are released into the bloodstream within different subcellular forms such as exosomes and microvescicles. Circulating HBsAg particles were isolated from sera of 11 HBsAg carriers by selective immunoprecipitation with monoclonal anti-HBs-IgG, total RNA was extracted and human miRNAs were screened by TaqMan real-time quantitative PCR Arrays. Thirty-nine human miRNAs were found to be significantly associated with the immunoprecipitated HBsAg, as determined by both comparative DDCT analysis and non-parametric tests (Mann-Whitney, p<0.05) with respect to controls. Moreover immunoprecipitated HBsAg particles contained Ago2 protein that could be revealed in ELISA only after 0.5% NP40. HBsAg associated miRNAs were liver-specific (most frequent = miR-27a, miR-30b, miR-122, miR-126 and miR-145) as well as immune regulatory (most frequent = miR-106b and miR-223). Computationally predicted target genes of HBsAg-associated miRNAs highlighted molecular pathways dealing with host-pathoge