Codon 215 Mutations in Human Immunodeficiency Virus—Infected Pregnant Women

In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated a two-thirds reduction of perinatal human immunodeficiency virus (HIV) type 1 transmission with zidovudine chemoprophylaxis. However, zidovudine alone does not fully suppress HIV replication, and chemoprophylaxis with zidovudine alone might select for zidovudine-resistant viral variants, decreasing the efficacy of zidovudine prophylaxis and affecting future responses to combined antiretroviral regimens. Sixty-two HIV-infected pregnant women consecutively enrolled in the ongoing Swiss HIV and Pregnancy Study were prospectively evaluated for the presence or development of zidovudine resistance by analysis of codon 215 of the reverse transcriptase gene. Six women (9.6%) harbored a codon T215Y/F mutation, which is associated with high-level resistance to zidovudine. Postnatal evaluation was completed in all children of mothers harboring the mutation. None was HIV-infected. The observed prevalence of codon 215 mutations of 9.6% raises important concerns regarding the future use of the PACTG 076 regime

Adverse events of raltegravir and dolutegravir.

To compare the frequency and risk factors of toxicity-related treatment discontinuations between raltegravir and dolutegravir. Prospective cohort study. All antiretroviral therapy (ART)-naïve and ART-experienced HIV-infected individuals from the Swiss HIV Cohort Study who initiated raltegravir or dolutegravir between 2006 and 2015 were investigated concerning treatment modification within the first year. Of 4041 patients initiating ART containing raltegravir (n = 2091) or dolutegravir (n = 1950), 568 patients discontinued ART during the first year, corresponding to a rate of 15.5 [95% confidence interval (CI) 14.5-16.9] discontinuations per 100 patient-years. Only 10 patients on raltegravir (0.5%) and two patients on dolutegravir (0.1%) demonstrated virologic failure. The main reason for ART discontinuation was convenience expressed as patient's wish, physician's decision, or treatment simplification (n = 302). Toxicity occurred in 4.3% of patients treated with raltegravir and 3.6% with dolutegravir, respectively. In multivariable analysis, the only independent risk factor for discontinuing ART because of toxicity was female sex (hazard ratio 1.98, 95% CI 1.45-2.71, P < 0.001).Neuropsychiatric complaints were the most commonly reported toxic adverse events and more frequent in the dolutegravir (n = 33, 1.7%) compared with the raltegravir group (n = 13, 0.6%). Risk of discontinuation for neurotoxicity was lower for raltegravir than for dolutegravir in multivariable analysis (hazard ratio 0.46, 95% CI 0.22-0.96, P = 0.037). In this, large cohort raltegravir and dolutegravir-containing regimen demonstrated a high virologic efficacy. Drug toxicity was infrequent and discontinuation because of neuropsychiatric events within the first year of treatment was only marginal higher with dolutegravir compared with raltegravir. However, monitoring of neurotoxic side-effects of dolutegravir is important

Increasing impacts of land use on biodiversity and carbon sequestration driven by population and economic growth

Biodiversity and ecosystem service losses driven by land-use change are expected to intensify as a growing and more affluent global population requires more agricultural and forestry products, and teleconnections in the global economy lead to increasing remote environmental responsibility. By combining global biophysical and economic models, we show that, between the years 2000 and 2011, overall population and economic growth resulted in increasing total impacts on bird diversity and carbon sequestration globally, despite a reduction of land-use impacts per unit of gross domestic product (GDP). The exceptions were North America and Western Europe, where there was a reduction of forestry and agriculture impacts on nature accentuated by the 2007-2008 financial crisis. Biodiversity losses occurred predominantly in Central and Southern America, Africa and Asia with international trade an important and growing driver. In 2011, 33% of Central and Southern America and 26% of Africa's biodiversity impacts were driven by consumption in other world regions. Overall, cattle farming is the major driver of biodiversity loss, but oil seed production showed the largest increases in biodiversity impacts. Forestry activities exerted the highest impact on carbon sequestration, and also showed the largest increase in the 2000-2011 period. Our results suggest that to address the biodiversity crisis, governments should take an equitable approach recognizing remote responsibility, and promote a shift of economic development towards activities with low biodiversity impacts

Miners and mining in the Late Bronze Age: a multidisciplinary study from Austria

The extraction and processing of metal ores, particularly those of copper and tin, are regarded as among the principal motors of Bronze Age society. The skills and risks of mining lie behind the weapons, tools and symbols that drove political and ideological change. But we hear much less about the miners themselves and their position in society. Who were these people? Were they rich and special, or expendable members of a hard-pressed workforce? In this study the spotlight moves from the adits, slags and furnaces to the bones and seeds, providing a sketch of dedicated prehistoric labourers in their habitat. The Mauken miners were largely dependent on imported meat and cereals, and scarcely hunted or foraged the resources of the local forest. They seem to be the servants of a command economy, encouraged to keep their minds on the jo

Reply to: Soils need to be considered when assessing the impacts of land-use change on carbon sequestration

Industrial Ecolog

The Role of Transient Receptor Potential Channel 6 Channels in the Pulmonary vasculature

Canonical or classical transient receptor potential channel 6 (TRPC6) is a Ca2+-permeable non-selective cation channel that is widely expressed in the heart, lung, and vascular tissues. The use of TRPC6-deficient ("knockout") mice has provided important insights into the role of TRPC6 in normal physiology and disease states of the pulmonary vasculature. Evidence indicates that TRPC6 is a key regulator of acute hypoxic pulmonary vasoconstriction. Moreover, several studies implicated TRPC6 in the pathogenesis of pulmonary hypertension. Furthermore, a unique genetic variation in the TRPC6 gene promoter has been identified, which might link the inflammatory response to the upregulation of TRPC6 expression and ultimate development of pulmonary vascular abnormalities in idiopathic pulmonary arterial hypertension. Additionally, TRPC6 is critically involved in the regulation of pulmonary vascular permeability and lung edema formation during endotoxin or ischemia/reperfusion-induced acute lung injury. In this review, we will summarize latest findings on the role of TRPC6 in the pulmonary vasculature