A Decline in New HIV Infections in South Africa: Estimating HIV Incidence from Three National HIV Surveys in 2002, 2005 and 2008

Three national HIV household surveys were conducted in South Africa, in 2002, 2005 and 2008. A novelty of the 2008 survey was the addition of serological testing to ascertain antiretroviral treatment (ART) use.We used a validated mathematical method to estimate the rate of new HIV infections (HIV incidence) in South Africa using nationally representative HIV prevalence data collected in 2002, 2005 and 2008. The observed HIV prevalence levels in 2008 were adjusted for the effect of antiretroviral treatment on survival. The estimated "excess" HIV prevalence due to ART in 2008 was highest among women 25 years and older and among men 30 years and older. In the period 2002-2005, the HIV incidence rate among men and women aged 15-49 years was estimated to be 2.0 new infections each year per 100 susceptible individuals (/100pyar) (uncertainty range: 1.2-3.0/100pyar). The highest incidence rate was among 15-24 year-old women, at 5.5/100pyar (4.5-6.5). In the period 2005-2008, incidence among men and women aged 15-49 was estimated to be 1.3/100 (0.6-2.5/100pyar), although the change from 2002-2005 was not statistically significant. However, the incidence rate among young women aged 15-24 declined by 60% in the same period, to 2.2/100pyar, and this change was statistically significant. There is evidence from the surveys of significant increases in condom use and awareness of HIV status, especially among youth.Our analysis demonstrates how serial measures of HIV prevalence obtained in population-based surveys can be used to estimate national HIV incidence rates. We also show the need to determine the impact of ART on observed HIV prevalence levels. The estimation of HIV incidence and ART exposure is crucial to disentangle the concurrent impact of prevention and treatment programs on HIV prevalence

Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots

Kaletra® (Abott Laboratories) is a co-formulated medication used in the treatment of HIV-1-infected children, and it contains the two antiretroviral protease inhibitor drugs lopinavir and ritonavir. We validated two new ultrafast and high-throughput mass spectrometric assays to be used for therapeutic drug monitoring of lopinavir and ritonavir concentrations in whole blood and in plasma from HIV-1-infected children. Whole blood was blotted onto dried blood spot (DBS) collecting cards, and plasma was collected simultaneously. DBS collecting cards were extracted by an acetonitrile/water mixture while plasma samples were deproteinized with acetone. Drug concentrations were determined by matrix-assisted laser desorption/ionization-triple quadrupole tandem mass spectrometry (MALDI-QqQ-MS/MS). The application of DBS made it possible to measure lopinavir and ritonavir in whole blood in therapeutically relevant concentrations. The MALDI-QqQ-MS/MS plasma assay was successfully cross-validated with a commonly used high-performance liquid chromatography (HPLC)–ultraviolet (UV) assay for the therapeutic drug monitoring (TDM) of HIV-1-infected patients, and it showed comparable performance characteristics. Observed DBS concentrations showed as well, a good correlation between plasma concentrations obtained by MALDI-QqQ-MS/MS and those obtained by the HPLC-UV assay. Application of DBS for TDM proved to be a good alternative to the normally used plasma screening. Moreover, collection of DBS requires small amounts of whole blood which can be easily performed especially in (very) young children where collection of large whole blood amounts is often not possible. DBS is perfectly suited for TDM of HIV-1-infected children; but nevertheless, DBS can also easily be applied for TDM of patients in areas with limited or no laboratory facilities

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.</p> <p>Methods/design</p> <p>Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.</p> <p>The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.</p> <p>Discussion</p> <p>In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.</p> <p>Trial registration</p> <p>ISRCTN33941607</p

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Metabolic network failures in Alzheimer's disease: A biochemical road map

IntroductionThe Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance.MethodsFasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted.Results Multivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ1–42, tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease.DiscussionMetabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.Analytical BioScience

Water-extractable organic matter and its fluorescence fractions in response to minimum tillage and organic farming in a Cambisol.

Background: Minimum tillage (MT) and organic farming (OF) are increasingly conducted in agricultural managements from the interest of optimizing soil conditions and developing sustainable agriculture. Our understanding of their effects on water-extractable organic matter (WEOM) is still insufficient. Methods: To study the effects of MT and OF on WEOM, we analyzed soil materials sampled at two depths (0&ndash;8-cm-upper soil and 12&ndash;25-cm-deeper soil) from long-term field experiments using different farming and tillage methods. The content, composition, and quality of WEOM were examined. Results: The results showed organic farming significantly decreased water-extractable organic carbon and nitrogen, but had positive effect on WEOM humic-like components revealed by parallel factor analysis with excitation&ndash;emission matrix, soil organic carbon (SOC), total nitrogen (TN), as well as SOC/TN. In addition, organic farming increased the aromaticity and condensation of WEOM as indicated by specific UV absorption and humification index. MT had no effect on WEOM both quantitatively and qualitatively but significantly decreased SOC and TN of the whole investigated soil profile. The depth effect was significant with strong stratification of WEOM, WEOM components as well as SOC and total N in upper soil. Moreover, the WEOM spectroscopic quality showed sharp differences between the upper and deeper soils. Conclusions: The results indicated that in the combined presence both tillage management and farming management, farming management imposed more influence on WEOM than tillage, and organic farming may facilitate the transformation of WEOM and lead to formation of WEOM with high stability. MT significantly changed the distribution of SOC and WEOM in soil, profile but did not increase the contents of SOC and WEOM in the site of the present study. However, the presence of larger pool of WEOM in MT&nbsp;+&nbsp;OF treatment at upper soil is likely to fuel possibly greater microbial activity and more rapid nutrient cycling in soil which can be favorable practice with potential in improving soil conditions in view of developing a sustainable ecosystem in the studied site[Figure not available: see fulltext.]

Response of water extractable organic matter and its fluorescence fractions to organic farming and tree species in poplar and robinia-based alley cropping agroforestry systems.

Organic farming and agroforestry both have the potential to develop sustainable and environmental-friendly agroecosystems and to sequester more soil organic C (SOC). In a long-term field trial, we evaluated the effect of 21-year organic farming and 4-year agroforestry (Robinia and Poplar-based alley cropping system) on water extractable organic matter (WEOM). The technique combining excitation emission matrix (EEM) spectra with parallel factor analysis (PARAFAC) was used to reveal the components of WEOM. In addition, WEOM was characterized by UV absorbance and fluorescence spectra. Organic farming generally increased SOC and total N contents but decreased the WEOM content as well as the WEOM components indicated by the maximum fluorescence intensity (Fmax). Specific UV absorbance (SUVA) and humification index (HIX) of WEOM in organic farming implied WEOM in the organic farming had more components with aromatic structure but less humified. Higher fluorescence (FI) and freshness indices (BIX) of WEOM in organic farming system indicated that a higher percentage of WEOM was microbial-derived in the organic than in the integrated farming system. Robinia showed positive effect on SOC and total N contents in comparison with poplar and had stronger effects on the WEOM components, although the WEOM content did not differ between the two tree species. The significant farming&nbsp;&times;&nbsp;trees interactions on SOC and water extractable organic carbon (WEOC) indicated that the robinia effects were more pronounced in the organic farming system. Thus, the change of SOC was the result of interactive effect of farming and hedgerow trees in an agroforestry system. The low-input organic farming and robinia tended to result in change of quality of WEOM and led to enrichment of substances of high stability in WEOM. From above, the combination of organic farming and robinia trees is an important means for developing sustainable agricultural systems and soil carbon sequestration

Microbial communities and residues in robinia- and poplar-based alley-cropping systems under organic and integrated management.

Organic farming and agroforestry are considered as sustainable alternative agricultural practices for intensive agriculture. In a long-term field trial in Scheyern Germany, we evaluated the effects of 21-year organic farming and 4-year agroforestry (robinia and poplar) on microbial community and microbial residues. Microbial biomass and microbial community were determined by fumigation-extraction method and the analysis of phospholipid fatty acid (PLFA), respectively. Microbial residues were evaluated by the measurement of amino sugars. The results showed that organic farming had significantly positive effect on soil organic carbon (SOC) but that it tended to decrease microbial biomass C (MBC), PLFA functional guilds, muramic acid (MurN), and glucosamine (GlcN). Robinia system, however, significantly increased SOC and had the potential to enhance MBC, PLFA functional guilds especially Gram (+), but it tended to decrease MurN and GlcN, in comparison with poplar system. The hedgerow tree did not show significantly positive effect on SOC and microbial properties except the abundance of fungi and Gram (+) bacterial, after 4-year establishment period. The principal component analysis of the PLFA profile showed that in comparison with other investigated treatments, robinia system under organic farming had significantly a different microbial community structure. It also indicated tree species-specific effect on microbial community in the organic farming was stronger than that in the integrated farming. In summary, the short-term introduction of trees into an existing agricultural system will not substantially change the microbial biomass, but it has certain influence on the abundance of specific microbial groups in the hedgerow. Although organic farming did not show positive effect on overall microbial indices, we still see positive effect on SOC after 21-year organic farming and its additive effect with robinia on SOC in current study. We expect that alley-cropping agroforestry system that combines organic farming and robinia hedgerow has a great potential for sequestering SOC and developing sustainable agroecosystems with time