Selective Hydrogenations and Dechlorinations in Water Mediated by Anionic Surfactant Stabilized Pd Nanoparticles

We report a facile, inexpensive and green method for the preparation of Pd nanoparticles in aqueous medium stabilized by anionic sulfonated surfactants sodium 1-dodecanesulfonate 1a, sodium dodecylbenzenesulfonate 1b, dioctyl sulfosuccinate sodium salt 1c and poly(ethylene glycol) 4-nonylphenyl-3-sulfopropyl ether potassium salt 1d simply obtained by stirring aqueous solutions of Pd(OAc)2 with the commercial anionic surfactants further treated under hydrogen atmosphere for variable times. The aqueous Pd nanoparticles solutions were tested in the selective hydrogenation reactions of aryl-alcohols, -aldehydes and -ketones leading to complete conversion to the deoxygenated products even in the absence of strong Brønsted acids in the reduction of aromatic aldehydes and ketones, in the controlled semi-hydrogenation of alkynes leading to alkenes and in the efficient hydro-dechlorination of aromatic substrates. In all cases the micellar media were crucial to stabilize the metal nanoparticles, to dissolve substrates, to steer product selectivity and to enable recycling. What is interesting is also that a benchmark catalyst like Pd/C can be often surpassed in activity and/or selectivity in the reactions tested by simply switching to the appropriate commercially available surfactant, thereby providing an easy to use, flexible and practical catalytic system capable of efficiently addressing a variety of synthetically significant hydrogenation reactions

V1a AVP receptor is required for neurohypophyseal hormonedependent differentiation in C2C12 cells

Vasopressin (AVP), oxytocin (OT) and related peptides induce differentiation and hypertrophy in myogenic cells expressing the V1a-vasopressin receptor (V1aR) or the oxytocin receptor (OTR). Either receptor can transduce both ligand signals. Binding of AVP and OT to the V1aR the target cells activates phosphatidylinositol hydrolysis, which in turn releases Ca2+ from internal stores. The AVP-dependent increase in cytosolic Ca2+ induces the activation of calcium/calmodulin-dependent kinase (CaMK) and calcineurin signaling, two pathways required for the full expression of the differentiated phenotype. Here we investigate the role of V1aR in myogenesis and hypertrophy by ectopically restoring V1aR expression and function using the C2C12 cell line, which is an experimental model of satellite cells that do not respond to AVP treatment. Our results show that AVP treatment enhances myogenic differentiation in V1aR-transfected C2C12 cultures alone. Moreover, calcium imaging analyses performed in individual control and V1aR-transfected C2C12 cells demonstrated that the presence of V1aR is sufficient to make C2C12 cells responsive to neurohypophyseal hormones stimulation, as demonstrated by the rapid and sustained release of calcium from internal stores observed in V1aR-transfected cells. These data demonstrate that, despite the high levels of OTR expressed by C2C12 cells, both AVP and OT failed to stimulate the differentiation program, thereby indicating that the presence of V1aR is essential to mediate the effects of neurohypophyseal hormones on myogenic differentiation in C2C12 cells

La rigenerazione del muscolo scheletrico nei topi è stimolata dalla iperespressione locale del recettore V1a della vasopressina

Skeletal muscle regeneration in mice is stimulated by local overexpression of V1a-vasopressin receptor Skeletal muscle has a remarkable capacity to regenerate after mechanical or pathological injury. We show that the V1a receptor (V1aR) for vasopressin, a potent myogenic-promoting factor that stimulates differentiation and hypertrophy in vitro, is expressed in mouse skeletal muscle and modulated during regeneration after experimental injury. We used gene delivery by electroporation to overexpress the myc-tagged vasopressin V1aR in specific muscles, thus sensitizing them to circulating vasopressin. The correct localization on the surface of the fibers of the recombinant product was demonstrated by confocal immunofluorescence directed against the myc tag. V1aR overexpression dramatically enhanced regeneration. When compared with mock-transfected controls, V1aR overexpressing muscles exhibited significantly accelerated activation of satellite cells and increased expression of differentiation markers. Downstream of V1aR activation, calcineurin was strongly up-regulated and stimulated the expression of IL-4, a potent mediator of myogenic cell fusion. The central role of calcineurin in mediating V1aR-dependent myogenesis was also demonstrated by using its specific inhibitor, cyclosporine A. This study identifies skeletal muscle as a physiological target of hormones of the vasopressin family and reveals a novel in vivo role for vasopressin-dependent pathways. These findings unveil several steps, along a complex signaling pathway, that may be exploited as potential targets for the therapy of diseases characterized by altered muscle homeostasis and regeneration

The influence of risk perceptions on close contact frequency during the SARS-CoV-2 pandemic.

Human behaviour is known to be crucial in the propagation of infectious diseases through respiratory or close-contact routes like the current SARS-CoV-2 virus. Intervention measures implemented to curb the spread of the virus mainly aim at limiting the number of close contacts, until vaccine roll-out is complete. Our main objective was to assess the relationships between SARS-CoV-2 perceptions and social contact behaviour in Belgium. Understanding these relationships is crucial to maximize interventions' effectiveness, e.g. by tailoring public health communication campaigns. In this study, we surveyed a representative sample of adults in Belgium in two longitudinal surveys (survey 1 in April 2020 to August 2020, and survey 2 in November 2020 to April 2021). Generalized linear mixed effects models were used to analyse the two surveys. Participants with low and neutral perceptions on perceived severity made a significantly higher number of social contacts as compared to participants with high levels of perceived severity after controlling for other variables. Our results highlight the key role of perceived severity on social contact behaviour during a pandemic. Nevertheless, additional research is required to investigate the impact of public health communication on severity of COVID-19 in terms of changes in social contact behaviour

Drug Treatment Experiences: Rural and Urban Comparisons

This study sought to investigate treatment-seeking behaviors among drug users in rural populations and how they compare to their urban counterparts. Data for this analysis were drawn from the Miami and Immokalee sites of the National Institute on Drug Abuse's Cooperative Agreement Program for AIDS outreachhtervention research study targeting high-risk out-of-treatment injection drug users and crack smokers. Findings indicate that Miami subjects were 2.57 times more likely to have been in drug treatment compared to their rural counterparts. This differential may be explained in terms of the availability, accessibility, and acceptability of health care services. [Translations are provided in the International Abstracts Section of this issue.

Large-scale mass wasting on the Miocene continental margin of western India

A giant mass-transport complex was recently discovered in the eastern Arabian Sea, exceeding in volume all but one other known complex on passive margins worldwide. The complex, named the Nataraja Slide, was drilled by International Ocean Discovery Program (IODP) Expedition 355 in two locations where it is ∼300 m (Site U1456) and ∼200 m thick (Site U1457). The top of this mass-transport complex is defined by the presence of both reworked microfossil assemblages and deformation structures, such as folding and faulting. The deposit consists of two main phases of mass wasting, each consisting of smaller pulses, with generally fining-upward cycles, all emplaced just prior to 10.8 Ma based on biostratigraphy. The base of the deposit at each site is composed largely of matrix-supported carbonate breccia that is interpreted as the product of debris-flows. In the first phase, these breccias alternate with well-sorted calcarenites deposited from a high-energy current, coherent limestone blocks that are derived directly from the Indian continental margin, and a few clastic mudstone beds. In the second phase, at the top of the deposit, muddy turbidites dominate and become increasingly more siliciclastic. At Site U1456, where both phases are seen, a 20-m section of hemipelagic mudstone is present, overlain by a ∼40-m-thick section of calcarenite and slumped interbedded mud and siltstone. Bulk sediment geochemistry, heavy-mineral analysis, clay mineralogy, isotope geochemistry, and detrital zircon U-Pb ages constrain the provenance of the clastic, muddy material to being reworked, Indus-derived sediment, with input from western Indian rivers (e.g., Narmada and Tapti rivers), and some material from the Deccan Traps. The carbonate blocks found within the breccias are shallow-water limestones from the outer western Indian continental shelf, which was oversteepened from enhanced clastic sediment delivery during the mid-Miocene. The final emplacement of the material was likely related to seismicity as there are modern intraplate earthquakes close to the source of the slide. Although we hypothesize that this area is at low risk for future mass wasting events, it should be noted that other oversteepened continental margins around the world could be at risk for mass failure as large as the Nataraja Slide

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial

BackgroundAntiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate.MethodsThis multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of <200 copies per mL), and the median CD4 count was 466 cells per μL (308-624). HIV-1 RNA concentrations at delivery were available for 605 (94%) participants. Of these, 395 (98%) of 405 participants in the combined dolutegravir-containing groups had viral suppression at delivery compared with 182 (91%) of 200 participants in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (estimated difference 6·5% [95% CI 2·0 to 10·7], p=0·0052; excluding the non-inferiority margin of -10%). Significantly fewer participants in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (52 [24%] of 216) had a composite adverse pregnancy outcome than those in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (70 [33%] of 213; estimated difference -8·8% [95% CI -17·3 to -0·3], p=0·043) or the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (69 [33%] of 211; -8·6% [-17·1 to -0·1], p=0·047). The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups. The proportion of participants who had a preterm delivery was significantly lower in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (12 [6%] of 208) than in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (25 [12%] of 207; -6·3% [-11·8 to -0·9], p=0·023). Neonatal mortality was significantly higher in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (ten [5%] of 207 infants) than in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (two [1%] of 208; p=0·019) or the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (three [2%] of 202; p=0·050).InterpretationWhen started in pregnancy, dolutegravir-containing regimens had superior virological efficacy at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. The dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest frequency of composite adverse pregnancy outcomes and of neonatal deaths.FundingNational Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health