Detrimental Impact of Interferon-Based Regimens for Chronic Hepatitis C on Vitamin D/Parathyroid Hormone Homeostasis

Background: Both the anti-infective and anti-inflammatory properties of vitamin D, an essential hormone of calcium homeostasis, have ample support in the literature. The high rates of vitamin D deficiency among patients with chronic hepatitis C are also well known. That supplementation with vitamin D may boost sustained viral response rates in vitamin D deficient, hepatitis C virus (HCV) infected patients undergoing Interferon-alpha (IFN) treatment, on the other hand, is controversial. Surprisingly, studies considering in this latter setting what are the effects of IFN treatment (with or without vitamin D supplementation) on the other major regulator of mineral metabolism, i.e. the Parathyroid hormone (PTH), are lacking. Aim: Evaluate the impact of interferon-based treatment against HCV (±cholecalciferol supplementation) on vitamin D and PTH homeostasis. Methods: A series of 40 consecutive patients received pegylated IFN plus ribavirin to treat chronic hepatitis C. At the discretion of their physician, some of them (N. = 27) received vitamin D supplementation while others did not (N. = 13). All had measured plasma 25-hydroxycholecalciferol and PTH concentrations at baseline, at completion of the 4th (TW4) and 12th treatment week (TW12) and at 24 weeks after the end of therapy (SVR24). Results: Plasma PTH concentration increased significantly from baseline during treatment, raising to 44.8 [30.7-57.2] pg/mL at TW4 (p=0.01), 47.0 [37.1-63.2] pg/mL at TW12 (p=0.006) to return to baseline levels in the follow-up (34.5 [27.6-43.0]; p=0.16). The proportion of patients who satisfied criteria for hyperparathyroidism was higher at TW12 (N=10, 25%) than at TW4 (N=6, 15%). There was no statistical correlation between vitamin D and PTH blood levels (ρ=-0.07; p=0.65). Conclusion: An increase in plasma PTH occurs systematically during IFN treatment of HCV patients and cannot be prevented by vitamin D supplementation

Study of Neutron From a Dense Plasma Focus Paco Instrument by Means of Nuclear Tracks Detectors

A most interesting feature of dense plasma foci is the acceleration of charge particle at energy in the range of MeV per nucleon. Using deuterium gas, this devices produce fusion D-D reactions, generation fast neutron pulses (~ 2.5 MeV). The device used in the present work is a Mather-type dense plasma focus, called PACO. It is a 2kJ device at 31 kV, with an oxygen-free copper anode, 50 mm long with 40 mm diameter. The coaxial cathode is formed by ten copper rods arranged in a squirrel cage configuration at a radius of 50 mm. The insulator in an annular Pyrex® tube located at the base of the anode. The energy store is provided by four 1 μF (40 kV, 40 nH) capacitors in parallel. The plasma focus was operated at 1.5 mb deuterium gas pressure. Neutron and accelerated particles are analyzed with material detectors (CR-39 Lantrack®) for different conditions. A detailed study is made of track diameters when the plastic is chemically etched with, 6N KOH at 60°C (±1) for 12

HSD17B13 and other liver fat-modulating genes predict development of hepatocellular carcinoma among HCV-positive cirrhotics with and without viral clearance after DAA treatment

Background: Genetic predisposition to accumulate liver fat (expressed by a polygenic risk score, GRS, based on the number of at-risk alleles of PNPLA3, TM6SF2, MBOAT7 and GCKR) may influence the probability of developing hepatocellular carcinoma (HCC) after hepatitis C treatment. Whether this holds true taking into account carriage of the HSD17B13:TA splice variant, also affecting lipogenesis, and achievement of viral clearance (SVR), is unknown. Methods: PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 variants were determined in a cohort of 328 cirrhotic patients free of HCC before starting treatment with direct acting antivirals (DAA). Results: SVR in the study cohort was 96%. At the end of follow-up, N = 21 patients had been diagnosed an HCC; none of the genes included in the GRS was individually associated with HCC development. However, in a Cox proportional hazards model, a GRS > 0.457 predicted HCC independently of sex, diabetes, albumin, INR and FIB4. The fit of the model improved adding treatment outcome and carriage of the HSD17B13:TA splice variant, with sex, GRS > 0.457, HSD17B13:TA splice variant and failure to achieve an SVR (hazard ratio = 6.75, 4.24, 0.24 and 7.7, respectively) being independent predictors of HCC. Conclusion: Our findings confirm that genes modulating liver fat and lipogenesis are important risk factors for HCC development among cirrhotics C treated with DAA

Avaluació de l’atenció integrada en Salut Mental i Addiccions: resultats qualitatius; grups focals i entrevistes

Atenció integrada; Salut mental; AddiccionsAtención integrada; Salud mental; AdiccionesIntegrated care; Mental health; AddictionsEl present document integra i presenta els resultats de l’anàlisi temàtica dels tres grups de participants escoltats i analitzats en el marc de la recerca per generar un model d’avaluació de l’atenció integrada en salut mental i addiccions (SMiA).El presente documento integra y presenta los resultados del análisis temático de los tres grupos de participantes escuchados y analizados en el marco de la investigación para generar un modelo de evaluación de la atención integrada en salud mental y adicciones (SMiA).This document incorporates and presents the results of the thematic analysis of the three groups of participants listened to and analysed as part of research to generate an evaluation model for integrated care in the field of mental health and addictions (MHA)

Nutritional status in post SARS-Cov2 rehabilitation patients

After prolonged hospitalization, the assessment of nutritional status and the identification of adequate nutritional support is of paramount importance. In this observational study, we aimed at assessing the presence of a malnutrition condition in SARS-Cov2 patients after the acute phase and the effects of a multidisciplinary rehabilitation program on nutritional and functional status

Una oportunitat per intercanviar bones pràctiques en l’atenció a la cronicitat a nivell europeu: el projecte JA-CHRODIS

Good practices; Chronic patient; JA-CHRODISBuenas prácticas; Paciente crónico; JA-CHRODISBones pràctiques; Pacient crònic; JA-CHRODISEl nombre de persones que pateixen malalties cròniques ha augmentat considerablement durant les últimes dècades. Aquesta situación ha provocat que el sistema sanitari hagi hagut de reorientar-se i desenvolupar diverses pràctiques que pretenen optimitzar l’atenció als pacients crònics. La Comissió Europea va posar en marxa el 2014 una acció conjunta en la qual han participat 60 institucions que pertanyen a 26 països de la Unió Europea; el projecte JA-CHRODIS. L’objectiu de l’acció ha consistit en identificar les millors experiències que s’estan duent a terme actualment a Europa en atenció a la cronicitat, a partir d’uns criteris d’avaluació unificats i consensuats, per tal de posar-les a disposició tant dels professionals com dels gestors i responsables polítics de serveis d’atenció a la salut a través d’un repositori; es permet així l’intercanvi d’informació sobre aquelles experiències més exitoses i es promou la transferència i la implementació de les millors pràctiques.El número de personas que sufren enfermedades crónicas ha aumentado considerablemente durante las últimas décadas. Esta situación ha provocado que el sistema sanitario haya tenido que reorientarse y desarrollar varias prácticas que pretenden optimizar la atención a los pacientes crónicos. La Comisión Europea puso en marcha el 2014 una acción conjunta en la cual han participado 60 instituciones que pertenecen en 26 países de la Unión Europea; el proyecto JA-CHRODIS. El objetivo de la acción ha consistido en identificar las mejores experiencias que se están llevando a cabo actualmente en Europa en atención a la cronicidad, a partir de unos criterios de evaluación unificados y consensuados, para ponerlas a disposición tanto de los profesionales cómo de los gestores y responsables políticos de servicios de atención a la salud a través de un repositorio; se permite así el intercambio de información sobre aquellas experiencias más exitosas y se promueve la transferencia y la implementación de las mejores prácticas.The number of people are living with a chronic disease has increased considerably during the last decades. This situation has caused a change in the health system. It has to reorient itself and develop several practices that aim to optimize the care of chronic patients. The European Commission launched in 2014 a joint action in which 60 institutions that belong in 26 countries of the European Union have participated; the JA-CHRODIS project. The objective of the action has been to identify the best experiences that is being currently carried out in Europe about attention to chronicity, based on unified and agreed evaluation criteria, to make them available to both professionals and managers and policy makers of health care services through a repository; In this way allows the exchange of information on those most successful experiences and promotes the transfer and implementation of best practices

Ancient horizontal gene transfer and the last common ancestors

Background The genomic history of prokaryotic organismal lineages is marked by extensive horizontal gene transfer (HGT) between groups of organisms at all taxonomic levels. These HGT events have played an essential role in the origin and distribution of biological innovations. Analyses of ancient gene families show that HGT existed in the distant past, even at the time of the organismal last universal common ancestor (LUCA). Most gene transfers originated in lineages that have since gone extinct. Therefore, one cannot assume that the last common ancestors of each gene were all present in the same cell representing the cellular ancestor of all extant life. Results Organisms existing as part of a diverse ecosystem at the time of LUCA likely shared genetic material between lineages. If these other lineages persisted for some time, HGT with the descendants of LUCA could have continued into the bacterial and archaeal lineages. Phylogenetic analyses of aminoacyl-tRNA synthetase protein families support the hypothesis that the molecular common ancestors of the most ancient gene families did not all coincide in space and time. This is most apparent in the evolutionary histories of seryl-tRNA synthetase and threonyl-tRNA synthetase protein families, each containing highly divergent “rare” forms, as well as the sparse phylogenetic distributions of pyrrolysyl-tRNA synthetase, and the bacterial heterodimeric form of glycyl-tRNA synthetase. These topologies and phyletic distributions are consistent with horizontal transfers from ancient, likely extinct branches of the tree of life. Conclusions Of all the organisms that may have existed at the time of LUCA, by definition only one lineage is survived by known progeny; however, this lineage retains a genomic record of heterogeneous genetic origins. The evolutionary histories of aminoacyl-tRNA synthetases (aaRS) are especially informative in detecting this signal, as they perform primordial biological functions, have undergone several ancient HGT events, and contain many sites with low substitution rates allowing deep phylogenetic reconstruction. We conclude that some aaRS families contain groups that diverge before LUCA. We propose that these ancient gene variants be described by the term “hypnologs”, reflecting their ancient, reticulate origin from a time in life history that has been all but erased”.National Science Foundation (U.S.) (Grant DEB 0830024)Exobiology Program (U.S.) (Grant NNX10AR85G)United States. National Aeronautics and Space Administration (Postdoctoral Program

Breast cancer incidence and overdiagnosis in Catalonia (Spain)

Introduction: Early detection of breast cancer (BC) with mammography may cause overdiagnosis and overtreatment, detecting tumors which would remain undiagnosed during a lifetime. The aims of this study were: first, to model invasive BC incidence trends in Catalonia (Spain) taking into account reproductive and screening data; and second, to quantify the extent of BC overdiagnosis. Methods: We modeled the incidence of invasive BC using a Poisson regression model. Explanatory variables were: age at diagnosis and cohort characteristics (completed fertility rate, percentage of women that use mammography at age 50, and year of birth). This model also was used to estimate the background incidence in the absence of screening. We used a probabilistic model to estimate the expected BC incidence if women in the population used mammography as reported in health surveys. The difference between the observed and expected cumulative incidences provided an estimate of overdiagnosis. Results: Incidence of invasive BC increased, especially in cohorts born from 1940 to 1955. The biggest increase was observed in these cohorts between the ages of 50 to 65 years, where the final BC incidence rates more than doubled the initial ones. Dissemination of mammography was significantly associated with BC incidence and overdiagnosis. Our estimates of overdiagnosis ranged from 0.4% to 46.6%, for women born around 1935 and 1950, respectively. Conclusions: Our results support the existence of overdiagnosis in Catalonia attributed to mammography usage, and the limited malignant potential of some tumors may play an important role. Women should be better informed about this risk. Research should be oriented towards personalized screening and risk assessment tools

Maize RNA PolIV affects the expression of genes with nearby TE insertions and has a genome-wide repressive impact on transcription

Abstract Background RNA-directed DNA methylation (RdDM) is a plant-specific epigenetic process that relies on the RNA polymerase IV (Pol IV) for the production of 24 nucleotide small interfering RNAs (siRNA) that guide the cytosine methylation and silencing of genes and transposons. Zea mays RPD1/RMR6 gene encodes the largest subunit of Pol IV and is required for normal plant development, paramutation, transcriptional repression of certain transposable elements (TEs) and transcriptional regulation of specific alleles. Results In this study we applied a total RNA-Seq approach to compare the B73 and rpd1/rmr6 leaf transcriptomes. Although previous studies indicated that loss of siRNAs production in RdDM mutants provokes a strong loss of CHH DNA methylation but not massive gene or TEs transcriptional activation in both Arabidopsis and maize, our total RNA-Seq analysis of rpd1/rmr6 transcriptome reveals that loss of Pol IV activity causes a global increase in the transcribed fraction of the maize genome. Our results point to the genes with nearby TE insertions as being the most strongly affected by Pol IV-mediated gene silencing. TEs modulation of nearby gene expression is linked to alternative methylation profiles on gene flanking regions, and these profiles are strictly dependent on specific characteristics of the TE member inserted. Although Pol IV is essential for the biogenesis of siRNAs, the genes with associated siRNA loci are less affected by the pol IV mutation. Conclusions This deep and integrated analysis of gene expression, TEs distribution, smallRNA targeting and DNA methylation levels, reveals that loss of Pol IV activity globally affects genome regulation, pointing at TEs as modulator of nearby gene expression and indicating the existence of multiple level epigenetic silencing mechanisms. Our results also suggest a predominant role of the Pol IV-mediated RdDM pathway in genome dominance regulation, and subgenome stability and evolution in maize