New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitant

DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study

BACKGROUND: Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients. METHODS: We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience's MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). RESULTS: All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). CONCLUSIONS: DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection.This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013–2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigación Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid B2017/BMD-3703. Programa de Investigación de la Consejería de Sanidad de la Comunidad de Madrid to JLJ. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by “Instituto de Salud Carlos III” [grant number CP14/0010 and CP17CIII/00007, respectivelly]

New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitants

Brief Report: CYP27B1 rs10877012 T Allele Was Linked to Non-AIDS Progression in ART-Naïve HIV-Infected Patients: A Retrospective Study.

HIV/AIDS progression is linked to vitamin D, which is regulated by several key cytochromes P450 (CYP). Single nucleotide polymorphisms (SNPs) in CYP genes influence vitamin D metabolism and serum levels. The objective of this study was to evaluate the association between CYP SNPs and the clinical AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. We performed a retrospective study in 661 ART-naïve HIV-infected patients who were stratified by their AIDS progression pattern [181 long-term nonprogressors (LTNPs), 332 moderate progressors, and 148 rapid progressors (RPs)]. Four CYP SNPs (CYP2R1 rs10500804, CYP2R1 rs1993116, CYP27B1 rs10877012, and CYP24A1 rs6013897) were genotyped using Agena Bioscience's MassARRAY platform. Correction for multiple testing was performed using the false discovery rate (Benjamini-Hochberg procedure). The adjusted regression showed a significant association only for CYP27B1 rs10877012 SNP. When analyzing all HIV patients, the rs10877012 T allele was protective against AIDS progression (ordinal outcome) under the dominant [adjusted odds ratio (aOR) = 0.69; P = 0.021) and additive (aOR) = 0.75; P = 0.025] inheritance models. When analyzing LTNPs versus RPs, the rs10877012 T allele also showed a significant protective association under the dominant (aOR = 0.45; P = 0.004) and additive (aOR = 0.54; P = 0.008) inheritance models. P values remained significant after correcting by multiple comparisons only for the comparison of LTNPs versus RPs (extreme phenotypes). The CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients. The rs10877012 SNP seems to have an impact on the clinical AIDS progression, possibly modifying vitamin D levels, which could be relevant for the pathogenesis of HIV infection.This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigación Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid (B2017/BMD-3703). CIBER-BBN is an initiative funded by the VINational R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 "Cancer Nanomedicine from the Bench to the Bedside" supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by “Instituto de Salud Carlos III” [grant number CP14/0010and CP17CIII/00007, respectivelly].Programa de Investigación de la Consejería de Sanidad de la Comunidad de Madrid to JLJ.S

HCV eradication with DAAs differently affects HIV males and females: A whole miRNA sequencing characterization

Gender-specific consequences after HCV eradication are unexplored. MicroRNAs (miRNAs) play a crucial role in the immune response against viral infections. However, few have highlighted miRNA role in sex-biased disease or therapy response. We aim to assess gender differences reflected in the miRNA expression of HIV/HCV-coinfected patients who achieve sustained virological response (SVR) with direct acting antivirals (DAAs). We conducted a prospective study of miRNA expression in PBMCs from 28 chronic HIV/HCV-coinfected patients (HIV/HCV) at baseline and after achieving SVR with DAAs. Sixteen HIV-monoinfected patients (HIV) and 36 healthy controls (HC) were used as controls. Identification of significant differentially expressed (SDE) miRNAs was performed with generalized linear model and mixed GLMs. We also explored putative dysregulated biological pathways. At baseline, the HIV/HCV patients showed differences in the miRNA profile concerning the HIV group (165 and 102 SDE miRNAs for males and females, respectively). Gender-stratified analysis of HIV/HCV group at baseline versus at SVR achievement showed higher differences in males (80 SDE miRNAs) than in females (55 SDE miRNAs). After SVR, HIV/HCV group showed similar values to HIV individuals, especially in females (1 SDE miRNA). However, ten miRNAs in males remained dysregulated, which were mainly involved in cancer, fatty acid, and inflammatory pathways. Taken together, our results show gender-biased dysregulation in the miRNA expression profile of PBMCs after HCV eradication with DAAs. These differences were normalized in females, while miRNA profile and their target-related pathways in males lack of normalization, which may be related to a high-risk of developing liver-related complications.This work has been supported by grants from Institute of Health Carlos III, Spain [PI15CIII/00031 and PI18CIII/00020/ to AFR and VB] and the Foundation Universidad Alfonso X el Sabio-Santander, Spain [Grant no. 1.010.932 to AFR]. AFR is supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII), Spain [CP14/CIII/00010 and CPII20CIII/0001]. This study has been conducted within the Spanish AIDS Research Network (RIS), The SPANISH AIDS Research Network – funded by the Institute of Health Carlos III (ISCIII) [RD16CIII/0002/0002].S

Post-mortem neuropathologic examination of a 5-case series of CAR T-cell treated patients

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most important. However, the physiopathology is unknown and neuropathologic information is scarce.Materials and methods: Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed.Results: Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them.Conclusions: In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings

Drinking patterns and effects of alcohol on instagram intimes of covid-19

Introducción: Compartir “eventos de la bebida” se ha convertido en una práctica habitual entre las personas jóvenes en redes como Instagram. La pandemia por el Covid-19 ha reestructurado tanto sus pautas de consumo de alcohol, como los usos que hacen de las redes sociales. Objetivos y Métodos: Describir en profundidad las pautas de consu- mo de alcohol y los efectos de este consumo que se muestran en Instagram en una muestra de 118 jóvenes y ado- lescentes en España a través de la etnografía digital. Resultados y Conclusiones: Instagram es parte de la fiesta, parte imbricada en la vida cotidiana de las personas jóvenes, en la que se comparten regularmente imágenes deseables de las pautas de consumo de alcohol y sus efectos. Adolescentes y jóvenes construyen un modelo online idealizado de pautas de consumo de alcohol en el que sólo son visibles los efectos de la fase de desinhibición tras el consumo y se obvian el resto de las fases de los efectos del alcohol en el organismo. Es fundamental incluir estas nuevas formas de transmisión de las pautas de consumo de alcohol en la normativa española que regula la venta y uso de alcoholIntroduction: Sharing “drinking events” has become a common practice among young people on Instagram. The Covid-19 pandemic has restructured both their alcohol consumption patterns and their use of social networks. Ob- jective and Methods: To describe in depth the patterns of alcohol consumption and the effects of this consumption shown on Instagram in a sample of 118 young people and adolescents in Spain through digital ethnography. Results and Conclusions: Instagram is part of the party, part embedded in the daily lives of young people, in which desirable images of drinking patterns and their effects are regularly shared. Adolescents and young people build an idealized online model of alcohol consumption patterns in which only the effects of the disinhibition phase after consumption are visible and the rest of the phases of the effects of alcohol on the body are ignored. It is essential to include these new forms of transmission of alcohol consumption patterns in the Spanish regulations that regulate the sale and use of alcoho

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Relationship between self-reported dietary intake and physical activity levels among adolescents: The HELENA study

Background Evidence suggests possible synergetic effects of multiple lifestyle behaviors on health risks like obesity and other health outcomes. Therefore it is important to investigate associations between dietary and physical activity behavior, the two most important lifestyle behaviors influencing our energy balance and body composition. The objective of the present study is to describe the relationship between energy, nutrient and food intake and the physical activity level among a large group of European adolescents. Methods The study comprised a total of 2176 adolescents (46.2% male) from ten European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. Dietary intake and physical activity were assessed using validated 24-h dietary recalls and self-reported questionnaires respectively. Analyses of covariance (ANCOVA) were used to compare the energy and nutrient intake and the food consumption between groups of adolescents with different physical activity levels (1st to 3rd tertile). Results In both sexes no differences were found in energy intake between the levels of physical activity. The most active males showed a higher intake of polysaccharides, protein, water and vitamin C and a lower intake of saccharides compared to less active males. Females with the highest physical activity level consumed more polysaccharides compared to their least active peers. Male and female adolescents with the highest physical activity levels, consumed more fruit and milk products and less cheese compared to the least active adolescents. The most active males showed higher intakes of vegetables and meat, fish, eggs, meat substitutes and vegetarian products compared to the least active ones. The least active males reported the highest consumption of grain products and potatoes. Within the female group, significantly lower intakes of bread and cereal products and spreads were found for those reporting to spend most time in moderate to vigorous physical activity. The consumption of foods from the remaining food groups, did not differ between the physical activity levels in both sexes. Conclusion It can be concluded that dietary habits diverge between adolescents with different self-reported physical activity levels. For some food groups a difference in intake could be found, which were reflected in differences in some nutrient intakes. It can also be concluded that physically active adolescents are not always inclined to eat healthier diets than their less active peers.The HELENA study took place with the financial support of the European Community Sixth RTD Framework Programme (Contract FOOD-CT: 2005-007034). This work was also partially supported by the European Union, in the framework of the Public Health Programme (ALPHA project, Ref: 2006120), the Swedish Council for Working Life and Social Research (FAS), the Spanish Ministry of Education (EX-2007-1124, and EX-2008-0641), and the Spanish Ministry of Health, Maternal, Child Health and Development Network (number RD08/0072) (JPRL, LAM)