Approach to Dyslipidemia, Lipodystrophy, and Cardiovascular Risk in Patients with HIV Infection

There is a significant prevalence (20%–80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment–associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Bacterial Biodiversity-Ecosystem Functioning Relations Are Modified by Environmental Complexity

Peer reviewedPublisher PD

Does HAART Efficacy Translate to Effectiveness? Evidence for a Trial Effect

Background: Patients who participate in clinical trials may experience better clinical outcomes than patients who initiate similar therapy within clinical care (trial effect), but no published studies have evaluated a trial effect in HIV clinical trials. Methods: To examine a trial effect we compared virologic suppression (VS) among patients who initiated HAART in a clinical trial versus in routine clinical care. VS was defined as a plasma HIV RNA #400 copies/ml at six months after HAART initiation and was assessed within strata of early (1996–99) or current (2000–06) HAART periods. Risk ratios (RR) were estimated using binomial models. Results: Of 738 persons initiating HAART, 30.6 % were women, 61.7 % were black, 30 % initiated therapy in a clinical trial and 67 % (n = 496) had an evaluable six month HIV RNA result. HAART regimens differed between the early and current periods (p,0.001); unboosted PI regimens (55.6%) were more common in the early and NNRTI regimens (46.4%) were more common in the current period. Overall, 78 % (95%CI 74, 82%) of patients achieved VS and trial participants were 16 % more likely to achieve VS (unadjusted RR 1.16, 95%CI 1.06, 1.27). Comparing trial to non-trial participants, VS differed by study period. In the early period, trial participants initiating HAART were significantly more likely to achieve VS than non-trial participants (adjusted RR 1.33; 95%CI 1.15, 1.54), but not in the current period (adjusted RR 0.98; 95%CI 0.87, 1.11). Conclusions: A clear clinical trial effect on suppression of HIV replication was observed in the early HAART period but not i

ADHD and Disruptive behavior scores – associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents

<p>Abstract</p> <p>Background</p> <p>Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorder (DBD). We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B) activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR) and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR).</p> <p>Methods</p> <p>A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes.</p> <p>Results</p> <p>We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD). In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD). In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior.</p> <p>Conclusion</p> <p>Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.</p

Using Phylogenetic, Functional and Trait Diversity to Understand Patterns of Plant Community Productivity

BACKGROUND:Two decades of research showing that increasing plant diversity results in greater community productivity has been predicated on greater functional diversity allowing access to more of the total available resources. Thus, understanding phenotypic attributes that allow species to partition resources is fundamentally important to explaining diversity-productivity relationships. METHODOLOGY/PRINCIPAL FINDINGS:Here we use data from a long-term experiment (Cedar Creek, MN) and compare the extent to which productivity is explained by seven types of community metrics of functional variation: 1) species richness, 2) variation in 10 individual traits, 3) functional group richness, 4) a distance-based measure of functional diversity, 5) a hierarchical multivariate clustering method, 6) a nonmetric multidimensional scaling approach, and 7) a phylogenetic diversity measure, summing phylogenetic branch lengths connecting community members together and may be a surrogate for ecological differences. Although most of these diversity measures provided significant explanations of variation in productivity, the presence of a nitrogen fixer and phylogenetic diversity were the two best explanatory variables. Further, a statistical model that included the presence of a nitrogen fixer, seed weight and phylogenetic diversity was a better explanation of community productivity than other models. CONCLUSIONS:Evolutionary relationships among species appear to explain patterns of grassland productivity. Further, these results reveal that functional differences among species involve a complex suite of traits and that perhaps phylogenetic relationships provide a better measure of the diversity among species that contributes to productivity than individual or small groups of traits

Simultaneous Recruitment of Drug Users and Men Who Have Sex with Men in the United States and Russia Using Respondent-Driven Sampling: Sampling Methods and Implications

The Sexual Acquisition and Transmission of HIV Cooperative Agreement Program (SATHCAP) examined the role of drug use in the sexual transmission of the human immunodeficiency virus (HIV) from traditional high-risk groups, such as men who have sex with men (MSM) and drug users (DU), to lower risk groups in three US cities and in St. Petersburg, Russia. SATHCAP employed respondent-driven sampling (RDS) and a dual high-risk group sampling approach that relied on peer recruitment for a combined, overlapping sample of MSM and DU. The goal of the sampling approach was to recruit an RDS sample of MSM, DU, and individuals who were both MSM and DU (MSM/DU), as well as a sample of sex partners of MSM, DU, and MSM/DU and sex partners of sex partners. The approach efficiently yielded a sample of 8,355 participants, including sex partners, across all four sites. At the US sites—Los Angeles, Chicago, and Raleigh–Durham—the sample consisted of older (mean age = 41 years), primarily black MSM and DU (both injecting and non-injecting); in St. Petersburg, the sample consisted of primarily younger (mean age = 28 years) MSM and DU (injecting). The US sites recruited a large proportion of men who have sex with men and with women, an important group with high potential for establishing a generalized HIV epidemic involving women. The advantage of using the dual high-risk group approach and RDS was, for the most part, the large, efficiently recruited samples of MSM, DU, and MSM/DU. The disadvantages were a recruitment bias by race/ethnicity and income status (at the US sites) and under-enrollment of MSM samples because of short recruitment chains (at the Russian site)

Seven decades of hydrogeomorphological changes in a near‐natural (Sense River) and a hydropower‐regulated (Sarine River) pre‐Alpine river floodplain in Western Switzerland

This is the peer reviewed version which has been published in final form at https://doi.org/10.1002/esp.5017 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Hydropower alteration of the natural flow and sediment regime can severely degrade hydromorphology, thereby threatening biodiversity and overall ecosystem processes of rivers and their floodplains. Using sequences of aerial images, we quantified seven decades (1938/1942–2013) of spatiotemporal changes in channel and floodplain morphology, as well as changes in the physical habitats, of three floodplain river reaches of the Swiss pre‐Alps, two hydropower‐regulated and one near‐natural. In the Sarine River floodplain, within the first decades of hydropower impairment, the magnitude and frequency of flood events (Q2, Q10, Q30) decreased substantially. As a result, the area of pioneer floodplain habitats that depend on flood activity and sediment dynamic, such as bare sediments, decreased dramatically by approximately 95%. However, by 2013 vegetated areas had generally increased in comparison to the pre‐regulation period in 1943, indicating general vegetative colonization. Between 1943 and 2013, the active channel underwent essential narrowing (up to 62% width reduction in the residual flow reach) and habitat turnover rates were very low (5% of the total floodplain area changed habitat type five to six times). In contrast, from the 1950s onwards, the near‐natural floodplain of the Sense River experienced recurrent narrowing and widening, and frequent changes between bare and vegetated areas, reflecting the shifting habitat mosaic concept typical for natural floodplains. In the three reaches investigated, we found that the active floodplain width and erosion of vegetated areas were primarily controlled by medium to large floods (Q10, Q30), which combined with reduced time intervals between ordinary floods ≥ Q2 most likely mobilized streambed sediments and limited the ability of vegetation to establish itself on bare gravel bars within the parafluvial zone. These findings can contribute to restoration action plans such as controlled flooding and sediment replenishments in the Sarine and other floodplain rivers of the Alps