Genome-wide association study identifies multiple susceptibility loci for diffuse large B-cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL

Promoting empowerment and self-care in older women through participatory action research: Analysis of the process of change

Aim: To generate and understand the process of change in the empowerment of women from 60 to 80 years old through a Participatory Action Research. Specific aim: To analyse the women participants' experiences concerning empowerment and self-care. Design: We use the Participatory Action Research approach (in its critical option) in the Socio-critical Paradigm and applying the Kemmis and McTaggart Model. Methods: A group of 10 women participants from 60 to 80 years old was created and developed the Participatory Action Research from June 2019 to May 2020. This group was involved in 22 group sessions, individual interviews, reflective diaries and triangulation with quantitative data. Results: Findings were interpreted based on the Gestalt Self Theory. Women generated changes in their empowerment based on three characteristics (self-determination, self-esteem and self-confidence) and, consequently, in their self-care. They did so according to two distinct patterns of behaviour: Leader women and follower women. The former took the lead in transforming their realities and the latter observed them and evolved in a slower and more reflective manner. These changes had an impact on the most individual level (inner world) and went beyond that barrier, modifying in turn their immediate surroundings and the social level (outer world). Conclusions: The group of older women began to consider their needs and consider themselves as important once they worked on their self-determination, self-esteem and self-confidence; we show these are key aspects to work on their empowerment and promote their self-care. Impact: The patterns of behaviour and dimensions of empowerment detected may help in future research designs and emancipatory community interventions in this population group.S

Vadose zone air as a biogenic source of methane in Nerja Cave system (South of Spain)

Subterranean air in karst cavities has often low methane contents in comparison to atmosphere and so karst systems have been considered a sink of atmospheric methane. Methane-oxidizing bacteria have been hypothesized as responsible for CH4 depletion in many caves around the world, although ionization radiation was also proposed as possible mechanism for this process. We measured CO2 and CH4 concentration and their C isotopic composition (d13C-CO2 and d13C-CH4) over 2 years within the Nerja cave system (South Spain) and in 9 boreholes drilled into the vadose zone (Triassic carbonate aquifer) surrounding the cave. According to d13C-CO2 and d13C-CH4 vadose zone of this karst system is a source of biogenic methane, produced both by acetate fermentation and CO2 reduction. Biogenic and atmospheric methane flows (along fractures from the vadose zone, and through ventilation, respectively) into the cave, where it is oxidized by methanotrophic bacteria that we detected on soil samples into the cave.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis

Background The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes. Methods We did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I (2) statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546). Findings We identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0.83, 95% CI 0.70-0.99; I-2= 51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0.65, 0 .40-1.06; I-2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0 .59, 0.40-0.87; I-2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0. 64, 95% CI 0.54-0.75; I-2= 18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1.54, 1.30-1.82; I-2= 0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0.40, 95% CI 0.18-0.87, I-2= 33%). Interpretation Early ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect. Copyright (c) The Author(s). Published by Elsevier Ltd

Family history of first degree as a risk factor for colorectal cancer

Objetivo: El objetivo de este estudio es evaluar la asociación entre antecedentes familiares (AF) de primer grado y cáncer colorrectal (CCR).Método: Se incluyeron 2857 controles y 1360 casos de CCR, del estudio MCC-Spain. La odds ratio (OR)y el intervalo de confianza del 95% (IC95%) de los AF de primer grado y el CCR se estimaron mediante regresión logística no condicional según la localización tumoral en los casos. Resultados: Los AF de primer grado duplicaron el riesgo de CCR (OR: 2,19; IC95%: 1,80-2,66), incrementándose en aquellos que presentaban dos o más (OR: 4,22; IC95%: 2,29-7,78) y en aquellos cuyos familiares fueron diagnosticados antes de los 50 años (OR: 3,24; IC95%: 1,52-6,91). Presentar AF se relacionó con estilos de vida como un menor consumo de vegetales. En cuanto a la asociación de los AF con la localización no se observaron diferencias significativas entre colon y recto, pero sí en la relación de estas con la edad de diagnóstico, presentando más AF los diagnosticados antes de los 50 años (OR: 4,79; IC95%:2,65-8,65).Conclusiones: Presentar AF de primer grado de CCR aumenta las probabilidades de desarrollar este cáncer, y también se elevan cuando el familiar es diagnosticado a edad temprana. Por ello, debe ser una población diana sobre la que incrementar las medidas de prevención.Objective To evaluate the association between first-degree family history and colorectal cancer (CRC). Method We analyzed data from 2857 controls and 1360 CRC cases, collected in the MCC-Spain project. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of association with the family history of CRC was estimated by non-conditional logistic regression. Results First-degree relatives doubled the risk of CRC (OR: 2.19; 95% CI: 1.80–2.66), increasing in those with two or more (OR: 4.22; 95% CI: 2.29–7.78) and in those whose relatives were diagnosed before 50 years (OR: 3.24; 95% CI: 1.52–6.91). Regarding the association of the family history with the location, no significant differences were observed between colon and rectum, but there were in the relation of these with the age of diagnosis, having more relatives those diagnosed before 50 years (OR: 4.79; 95% CI: 2.65–8.65). Conclusions First-degree relatives of CRC increase the chances of developing this tumor, they also increase when the relative is diagnosed at an early age. Therefore, it must be a target population on which to carry out prevention measures

Parental competences in fathers and mothers of very-low-birth-weight preterm infants

Objective: The goal was to analyze parental competences in Spanish families with very-low-birth-weight infants (≤32 weeks and/or less 1500 g) over 18 months of corrected age. Background: Parenting in families of very preterm infants is an interesting focus of research as we advance in the knowledge of how parental competences can have an important impact on child development. Method: Sixty-eight mothers and 56 fathers completed measures of parental competences, sociofamily risk, parental stress, social support, and emotional symptoms. Clinical characteristics and neonatal medical risk data were collected after birth. Statistical analyses were performed to compare parental competences with those of mothers and fathers of non-preterm infants. Generalized estimating equations were used for analysis, adjusted by family unit. Results: Mothers and fathers of preterm infants score higher in most dimensions of parental competences compared to a control group. Focusing on the preterm population, mothers score higher than fathers in daily involvement and mentalization and lower in parental self-care. When studied separately, we found different scores for fathers and mothers in parental competences (sociofamily risk, parental stress, social support, and emotional symptoms). Conclusion: Parents of preterm infants present better parental competences than parents of non-preterm infants when their children reach 18 months of age. It is important to consider the differences in parental competences between the mothers and fathers of these children. Implications: Our findings suggest the need to address parental competences to develop preventive and adaptive strategies in parents of preterm infants to promote positive parenting.This paper is part of the project PID2019‐110484RB‐I00 funded by MCIN/AEI/ 0.13039/501100011033. It was also funded by the 2017 (PI0052/2017) and 2019 (ITI‐0019‐2019) Cadiz‐integrated territorial initiative for biomedical research and the European Regional Development Fund (ERDF) 2014–2020, Andalusian Ministry of Health and Families, Spain. Funding informatio

Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis.

BACKGROUND: The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes. METHODS: We did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546). FINDINGS: We identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70-0·99; I2=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40-1·06; I2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40-0·87; I2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54-0·75; I2=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30-1·82; I2=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18-0·87, I2=33%). INTERPRETATION: Early ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect. FUNDING: UK Medical Research Council

Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis

BACKGROUND: To conduct a meta-analysis of performance of DNA methylation in women with high-grade cervical intraepithelial neoplasia (CIN2+). METHODS: Medline and Embase databases were searched for studies of methylation markers versus histological endpoints. Pooled sensitivity, specificity and positive predictive value (PPV) for CIN2+ were derived from bivariate models. Relative sensitivity and specificity for CIN2+ compared to cytology and HPV16/18 genotyping were pooled using random-effects models. RESULTS: Sixteen thousand three hundred thirty-six women in 43 studies provided data on human genes (CADM1, MAL, MIR-124-2, FAM19A4, POU4F3, EPB41L3, PAX1, SOX1) and HPV16 (L1/L2). Most (81%) studies evaluated methylation assays following a high-risk (HR)-HPV-positive or abnormal cytology result. Pooled CIN2+ and CIN3+ prevalence was 36.7% and 21.5%. For a set specificity of 70%, methylation sensitivity for CIN2+ and CIN3+ were 68.6% (95% CI: 62.9-73.8) and 71.1% (95% CI: 65.7-76.0) and PPV were 53.4% (95% CI: 44.4-62.1) and 35.0% (95% CI: 28.9-41.6). Among HR-HPV+ women, the relative sensitivity of methylation for CIN2+ was 0.81 (95% CI: 0.63-1.04) and 1.22 (95% CI: 1.05-1.42) compared to cytology of atypical squamous cells of undetermined significance, or greater (ASCUS+) and HPV16/18 genotyping, respectively, while relative specificity was 1.25 (95% CI: 0.99-1.59) and 1.03 (95% CI: 0.94-1.13), respectively. CONCLUSION: DNA methylation is significantly higher in CIN2+ and CIN3+ compared to <= CIN1. As triage test, DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping

Condensation water in heritage touristic caves: Isotopic and hydrochemical data and a new approach for its quantification through image analysis

Condensation water is a major factor in the conservation of heritage caves. It can cause dissolution of the rock substrate (and the pigments of rock art drawn on it) or covering thereof with mineral components, depending on the chemical saturation degree of the condensation water. In show caves, visitors act as a source of CO2 and thus modify the microclimate, favouring negative processes that affect the conservation of the caves. In spite of their interest, studies of the chemical composition of this type of water are scarce and not very detailed. In this work we present research on the condensation water in the Nerja Cave, one of the main heritage and tourist caves in Europe. The joint analysis of isotopic, hydrochemical, mineralogical and microbiological data and the use of image analysis have allowed us to advance in the knowledge of this risk factor for the conservation of heritage caves, and to demonstrate the usefulness of image analysis to quantify the scope of the possible corrosion condensation process that the condensation water could be producing on the bedrock, speleothem and rock art. To our knowledge, this application of image analysis (relative to the condensation water in caves) is the first one of this type that has been documentedNerja Cave Foundation Funding for open access charge: Universidad de Málaga / CBU

A mild neurofibromatosis type 1 phenotype produced by the combination of the benign nature of a leaky NF1-splice mutation and the presence of a complex mosaicism

Here we analyze the genetic and molecular basis responsible for a very benign phenotype observed in an NF1 patient. Quantification of cells carrying the NF1 mutation in different samples derived from the three embryonic layers revealed mosaicism. Furthermore, the construction of a minigene with patient's mutation (c.3198 − 314G>A) confirmed its benign nature due to the leakiness of the splicing mechanism that generated a proportion of correctly spliced transcripts. Hence, we concluded that the mild phenotype observed in this patient is the result of the presence of mosaicism together with the benign nature of a leaky NF1-splice mutation. Finally, with the aim of developing a personalized therapeutic approach for this patient, we demonstrated correction of the splicing defect by using specific antisense morpholino oligomers. Our results provide an example of the molecular complexity behind disease phenotypes and highlight the importance of using comprehensive genetic approaches to better assess phenotype-genotype correlation