Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi-Ethnic Study of Atherosclerosis).

BACKGROUND:APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS AND RESULTS:Cross-sectional associations of APOL1 genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The APOL1 high-risk genotypes were not significantly associated with other clinical CVD outcomes. CONCLUSIONS:Among blacks without baseline CVD, the APOL1 high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD

Geochemistry of fluid discharges from Peteroa volcano (Argentina-Chile) in 2010-2015: Insights into compositional changes related to the fluid source region(s).

This study presents the first geochemical data of fluid discharges collected from February 2010 to March 2015 from the Planchon-Peteroa-Azufre Volcanic Complex (PPAVC), located in the Transitional Southern Volcanic Zone (TSVZ) at the border between Argentina and Chile. During the study period, from January 2010 to July 2011, Peteroa volcano experienced phreatic to phreatomagmatic eruption possibly related to the devastating Maule earthquake occurred on February 27, 2010. The compositional dataset includes low temperature (from 43.2 to 102 degrees C) gas discharges from (i) the summit of Peteroa volcano and (ii) the SE flank of Azufre volcano, both marked by a significant magmatic fluid contribution, as well as bubbling gases located at the foothill of the Peteroa volcanic edifice, which showed a chemical signature typical of hydrothermal fluids. In 2012, strong compositional changes affected the Peteroa gases from the summit area: the acidic gas species, especially SO2, increased, suggesting an input of fluids from magma degassing. Nevertheless, the R/Ra and delta C-13-CO2 values decreased, which would imply an enhanced contribution from a meteoric-hydrothermal source. In 2014-2015, the chemical and isotopic compositions of the 2010-2011 gases were partially restored. The anomalous decoupling between the chemical and the isotopic parameters was tentatively interpreted as produced by degassing activity from a small batch of dacitic magma that in 2012 masked the compositional signature of the magmatic fluids released from a basaltic magma that dominated the gas chemistry in 2010-2011. This explanation reliably justifies the observed geochemical data, although the mechanisms leading to the change in time of the dominating magmatic fluid source are not clear. At this regard, a geophysical survey able to provide information on the location of the two magma batches could be useful to clarify the possible relationships between the compositional changes that affected the Peteroa fluid discharges and the 2010-2011 eruptive activity.FONDECYT Iniciacion Project 11100372 FONDAP "Centro de Excelencia en Geotermia de los Andes" 15090013 Universidad de Buenos Aires UBACyT 20020120300077BA IDEAN institute (UBA-CONICET) Laboratory of Fluid and Rock Geochemistry of the Department of Earth Sciences (Florence, Italy

Influence of depression and interpersonal support on adherence to antiretroviral therapy among people living with HIV

BackgroundPoor adherence and under-utilization of antiretroviral therapy (ART) services have been major setbacks to achieving 95-95-95 policy goals in Sub-Saharan Africa. Social support and mental health challenges may serve as barriers to accessing and adhering to ART but are under-studied in low-income countries. The purpose of this study was to examine the association of interpersonal support and depression scores with adherence to ART among persons living with HIV (PLWH) in the Volta region of Ghana.MethodsWe conducted a cross-sectional survey among 181 PLWH 18 years or older who receive care at an ART clinic between November 2021 and March 2022. The questionnaire included a 6-item simplified ART adherence scale, the 20-item Center for Epidemiologic Studies Depression Scale (CES-D), and the 12-item Interpersonal Support Evaluation List-12 (ISEL-12). We first used a chi-squared or Fisher’s exact test to assess the association between these and additional demographic variables with ART adherence status. We then built a stepwise multivariable logistic regression model to explain ART adherence.ResultsART adherence was 34%. The threshold for depression was met by 23% of participants, but it was not significantly associated with adherence in multivariate analysis(p = 0.25). High social support was reported by 48.1%, and associated with adherence (p = 0.033, aOR = 3.45, 95% CI = 1.09–5.88). Other factors associated with adherence included in the multivariable model included not disclosing HIV status (p = 0.044, aOR = 2.17, 95% CI = 1.03–4.54) and not living in an urban area (p = 0.00037, aOR = 0.24, 95% CI = 0.11–0.52).ConclusionInterpersonal support, rural residence, and not disclosing HIV status were independent predictors of adherence to ART in the study area

Association between IL-18 gene polymorphisms and biopsy-proven giant cell arteritis

7 pages, 1 figure, 1 table.-- Research article.[Introduction] The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis (GCA).[Methods] In total, 212 patients diagnosed with biopsy-proven GCA were included in this study. DNA from patients and matched controls was obtained from peripheral blood. Samples were genotyped for the IL18-137 G>C (rs187238), the IL18-607 C>A (rs1946518), and the IL18-1297 T>C (rs360719) gene polymorphisms with polymerase chain reaction, by using a predesigned TaqMan allele discrimination assay.[Results] No significant association between the IL18-137 G>C polymorphism and GCA was found. However, the IL18 -607 allele A was significantly increased in GCA patients compared with controls (47.8% versus 40.9% in patients and controls respectively; P = 0.02; OR, 1.32; 95% CI, 1.04 to 1.69). It was due to an increased frequency of homozygosity for the IL18 -607 A/A genotype in patients with GCA (20.4%) compared with controls (13.4%) (IL18 -607 A/A versus IL18 -607 A/C plus IL18 -607 C/C genotypes: P = 0.04; OR, 1.59; 95% CI, 1.02 to 2.46). Also, the IL18-1297 allele C was significantly increased in GCA patients (30.7%) compared with controls (23.0%) (P = 0.003; OR, 1.48; 95% CI, 1.13 to 1.95). In this regard, an increased susceptibility to GCA was observed in individuals carrying the IL18-1297 C/C or the IL18-1297 C/T genotypes compared with those carrying the IL18-1297 T/T genotype (IL18-1297 C/C plus IL18-1297 T/C versus IL18-1297 T/T genotype in GCA patients compared with controls: P = 0.005; OR, 1.61; 95% CI, 1.15 to 2.25). We also found an additive effect of the IL18 -1297 and -607 polymorphisms with TLR4 Asp299Gly polymorphism. The OR for GCA was 1.95 for combinations of genotypes with one or two risk alleles, whereas carriers of three or more risk alleles have an OR of 3.7.[Conclusions] Our results show for the first time an implication of IL18 gene-promoter polymorphisms in the susceptibility to biopsy-proven GCA. In addition, an additive effect between the associated IL18 and TLR4 genetic variants was observed.This study was supported by a grant from Fondo de Investigaciones Sanitarias PI06-0024 (Spain) and in part by Junta de Andalucía, grupo CTS-180 (Spain). This work was partially supported by the RETICS Program, RD08/0075 (RIER), from Instituto de Salud Carlos III (ISCIII).Peer reviewe

microRNA-34a and Long Non-Coding RNA MALAT1 Is Associated With HPV Status and Viral Load In Premalignant Cervical Lesions

Background: Cervical cancer (CC) is one of the most common gynecological malignancies in the world, and human papillomavirus (HPV) infection is the most important risk factor for their development. Although there are methods for the early detection of CC and HPV infection, but there are not highly sensitive and specific, for it´s necessary to investigate alternatives such as miR-34a and MALAT1, implicated in the pathogenesis of CC. The objective was to evaluate the association of HPV status, viral load, the presence of coinfections, and the grade of CC precursor lesions with miR-34a and MALAT1 expression in patients with high and low-grade cervical lesions (CL) and patients without CL but HPV+. Methods: Liquid-based cervical cytology (LBCC) specimens were obtained from 67 women diagnosed with low and high-grade CL, as well as LBCC HPV+, from which DNA and RNA were extracted. From DNA we genotyped and quantified the viral load for HPV 16, 18, and 51. From RNA, we performed a retrotranscription and evaluated the expression of MALAT1 (n=67) and miR-34a (n=29), all using a droplet-digital PCR assay. Statistical analysis was performed with SPSS 27.0 software using U Mann-Whitney and Kruskal-Wallis tests. Results: We identified a statistically significant association between the under-expression of miR-34a, HPV+ status (p=0.010), coinfections (p=0.030), low (p =0.042), and high viral load (p=0.014), but not with the lesion grade. Also, MALAT1 overexpression was associated with HPV+ status (p=0.008) and high viral load (p =0.027), but not with co-infections or the grade of CC precursor lesions. Conclusions: The expression of MALAT1 and miR-34a are associated with HPV status and viral load, but not with the grade of CC precursor lesions

Sickle Cell Trait and the Risk of ESRD in Blacks

Blacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to APOL1 high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown. In a large population-based cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated 9909 self-reported blacks (739 with SCT and 243 with hemoglobin C trait). Incident ESRD occurred in 40 of 739 (5.4%) individuals with SCT, six of 243 (2.5%) individuals with hemoglobin C trait, and 234 of 8927 (2.6%) noncarriers. The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT and 4.0 per 1000 person-years for noncarriers. Compared with individuals without SCT, individuals with SCT had a hazard ratio for ESRD of 2.03 (95% confidence interval, 1.44 to 2.84). Hemoglobin C trait did not associate with prevalent CKD or ESRD. The incidence rate for ESRD among participants with APOL1 high-risk genotypes was 6.6 per 1000 person-years, with a hazard ratio for ESRD of 1.77 (95% confidence interval, 1.31 to 2.38) for participants with, compared with those without, APOL1 high-risk genotypes. In this cohort, SCT strongly associated with risk of progression to ESRD in blacks, and this degree of risk for ESRD was similar to that conferred by APOL1 high-risk genotypes. These results may have important public policy implications for genetic counseling of SCT carriers

Spatiotemporal analysis identifies ABF2 and ABF3 as key hubs of endodermal response to nitrate

Nitrate is a nutrient and a potent signal that impacts global gene expression in plants. However, the regulatory factors controlling temporal and cell type–specific nitrate responses remain largely unknown. We assayed nitrate-responsive transcriptome changes in five major root cell types of the Arabidopsis thaliana root as a function of time. We found that gene-expression response to nitrate is dynamic and highly localized and predicted cell type–specific transcription factor (TF)–target interactions. Among cell types, the endodermis stands out as having the largest and most connected nitrate-regulatory gene network. ABF2 and ABF3 are major hubs for transcriptional responses in the endodermis cell layer. We experimentally validated TF–target interactions for ABF2 and ABF3 by chromatin immunoprecipitation followed by sequencing and a cell-based system to detect TF regulation genome-wide. Validated targets of ABF2 and ABF3 account for more than 50% of the nitrate-responsive transcriptome in the endodermis. Moreover, ABF2 and ABF3 are involved in nitrate-induced lateral root growth. Our approach offers an unprecedented spatiotemporal resolution of the root response to nitrate and identifies important components of cell-specific gene regulatory networks

Transforming healthcare through regenerative medicine

Regenerative medicine therapies, underpinned by the core principles of rejuvenation, regeneration and replacement, are shifting the paradigm in healthcare from symptomatic treatment in the 20th century to curative treatment in the 21st century. By addressing the reasons behind the rapid expansion of regenerative medicine research and presenting an overview of current clinical trials, we explore the potential of regenerative medicine to reshape modern healthcare

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30