Evaluation of the efficacy and safety of text messages targeting adherence to cardiovascular medications in secondary prevention: the txt2heart Colombia randomised controlled trial (Preprint)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in the world. Prevalence is estimated at around 100 million patients worldwide. There is evidence that antiplatelet agents and antihypertensive medication reduce the risk of new vascular events in this population, but treatment adherence is very low. Objective: We developed an intervention based on behavioral modification techniques delivered via mobile short message services (SMS) to increase the adherence to pharmacologic treatment on patients with prior history of ASCVD. Methods: We conducted a randomized controlled clinical trial for patients with a prior diagnosis of cardiovascular event such as acute myocardial infarction, unstable angina, cerebrovascular disease or peripheral artery disease in one centre in Colombia. Patients randomized to the intervention arm were assigned to receive SMS daily for the first 4 weeks, five SMS on week 5: three SMS per week from week 6, and one SMS from 8th week until 52nd week. Patients in the control arm received a monthly SMS reminding them of the next study appointment, requesting information about changes in phone number, thanking them for participating in the study and reminding them of the importance of the study. Primary endpoint was change in Low Density Lipoprotein-Cholesterol (LDL-C) and the secondary endpoints were change in thromboxane B2 levels, heart rate, systolic and diastolic blood pressure. Medication adherence was measured with the Medication Adherence Report Scale (MARS 5), mortality and new cardiac hospitalization were assessed at one year end point. A logistic regression analysis and bivariate testing was performed. Results: Nine hundred and thirty patients were randomized, 805 (87%) completed follow up, and were analyzed for the primary endpoint. There was no difference between arms in change of LDL-C at 12 months (P=.41). or for any of the secondary outcomes. No adverse events were reported. Conclusions: In our study we did not find evidence that a behavior modification intervention delivered by SMS improved LDL-C, blood pressure levels or adherence at 12 months. More research is needed to evaluate whether different SMS strategies including personalized messages and with different timing are effective; future studies should include mixed methods to understand better why, for whom and in which context (e.g. health system, social environment) SMS interventions work (or not) to improve adherence in patients with ASCVD. Clinical Trial: Clinicaltrial.gov NCT03098186. Date of registration: March 31st 201

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

MYO9B polymorphisms in multiple sclerosis

"Single-nucleotide polymorphisms (SNPs) in the 30 region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS. European Journal of Human Genetics (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009""Single-nucleotide polymorphisms (SNPs) in the 30 region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS. European Journal of Human Genetics (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009""Single-nucleotide polymorphisms (SNPs) in the 30 region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First, 18 SNPs including 6 SNPs with previous evidence for association to immune disorders, were tested in 730 Finnish MS families, but no linkage or family-based association was observed. To ensure the power to detect variants with a modest effect size, we further analyzed 10 variants in 899 Finnish cases and 1325 controls, and in a total of 1521 cases and 1476 controls from Denmark, Norway and Sweden, but found no association. Our results thereby do not support a major function of the tested MYO9B variants in MS. European Journal of Human Genetics (2009) 17, 840-843; doi: 10.1038/ejhg.2008.251; published online 14 January 2009"Peer reviewe

Exacerbated fires in Mediterranean Europe due to anthropogenic warming projected with non-stationary climate-fire models

The observed trend towards warmer and drier conditions in southern Europe is projected to continue in the next decades, possibly leading to increased risk of large fires. However, an assessment of climate change impacts on fires at and above the 1.5 °C Paris target is still missing. Here, we estimate future summer burned area in Mediterranean Europe under 1.5, 2, and 3 °C global warming scenarios, accounting for possible modifications of climate-fire relationships under changed climatic conditions owing to productivity alterations. We found that such modifications could be beneficial, roughly halving the fire-intensifying signals. In any case, the burned area is robustly projected to increase. The higher the warming level is, the larger is the increase of burned area, ranging from ~40% to ~100% across the scenarios. Our results indicate that significant benefits would be obtained if warming were limited to well below 2 °C

Alveolar hypoxia, alveolar macrophages, and systemic inflammation

Diseases featuring abnormally low alveolar PO2 are frequently accompanied by systemic effects. The common presence of an underlying inflammatory component suggests that inflammation may contribute to the pathogenesis of the systemic effects of alveolar hypoxia. While the role of alveolar macrophages in the immune and defense functions of the lung has been long known, recent evidence indicates that activation of alveolar macrophages causes inflammatory disturbances in the systemic microcirculation. The purpose of this review is to describe observations in experimental animals showing that alveolar macrophages initiate a systemic inflammatory response to alveolar hypoxia. Evidence obtained in intact animals and in primary cell cultures indicate that alveolar macrophages activated by hypoxia release a mediator(s) into the circulation. This mediator activates perivascular mast cells and initiates a widespread systemic inflammation. The inflammatory cascade includes activation of the local renin-angiotensin system and results in increased leukocyte-endothelial interactions in post-capillary venules, increased microvascular levels of reactive O2 species; and extravasation of albumin. Given the known extrapulmonary responses elicited by activation of alveolar macrophages, this novel phenomenon could contribute to some of the systemic effects of conditions featuring low alveolar PO2

Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and development of pre-eclampsia: a case-control study and a meta-analysis

BACKGROUND: Pre-eclampsia is thought to have an important genetic component. Recently, pre-eclampsia has been associated in some studies with carriage of a common eNOS gene Glu298Asp polymorphism, a variant that leads to the replacement of glutamic acid by aspartic acid at codon 298. METHOD: Healthy women with singleton pregnancies were recruited from 7 district general hospitals in London, UK. Women at high risk of pre-eclampsia were screened by uterine artery Doppler velocimetry at 22–24 weeks of gestation and maternal blood was obtained to genotype the eNOS Glu298Asp polymorphism. Odds ratios (OR) and 95%CI, using logistic regression methods, were obtained to evaluate the association between the Glu298Asp polymorphism and pre-eclampsia. A meta-analysis was then undertaken of all published studies up to November 2005 examining the association of eNOS Glu298Asp genotype and pre-eclampsia. RESULTS: 89 women with pre-eclampsia and 349 controls were included in the new study. The Glu298Asp polymorphism in a recessive model was not significantly associated with pre-eclampsia (adjusted-OR: 0.83 [95%CI: 0.30–2.25]; p = 0.7). In the meta-analysis, under a recessive genetic model (1129 cases & 2384 controls) women homozygous for the Asp298 allele were not at significantly increased risk of pre-eclampsia (OR: 1.28 [95%CI: 0.76–2.16]; p = 0.34). A dominant model (1334 cases & 2894 controls) was associated with no increase of risk of pre-eclampsia for women carriers of the Asp298 allele (OR: 1.12 [95%CI: 0.84–1.49]; p = 0.42). CONCLUSION: From the data currently available, the eNOS Glu298Asp polymorphism is not associated with a significant increased risk of pre-eclampsia. However, published studies have been underpowered, much larger studies are needed to confirm or refute a realistic genotypic risk of disease, but which might contribute to many cases of pre-eclampsia in the population

Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study

<p>Abstract</p> <p>Background</p> <p>The endothelial nitric oxide synthase gene (<it>NOS3</it>) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the <it>NOS3 </it>gene in a population of Caucasian origin.</p> <p>Methods</p> <p>We examined the association of three common variants of the <it>NOS3 </it>gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the <it>NOS3 </it>variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between <it>NOS3 </it>polymorphisms and preeclampsia.</p> <p>Results</p> <p>The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association.</p> <p>Conclusions</p> <p>Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common <it>NOS3 </it>variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.</p