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Abstract Background Undiagnosed cases of hepatitis C virus (HCV) infection result in significant morbidity and mortality, further transmission, and increased public health costs. Testing in emergency departments (EDs) is an opportunity to expand HCV screening. The goal of this project was to increase the proportion of eligible patients screened for HCV in urban areas. Methods An opportunistic automated HCV screening program was implemented in the EDs of 4 public hospitals in Spain and Portugal at different periods between 2018 and 2023. HCV prevalence was prospectively evaluated, and single-step or reflex testing was used for confirmation in the same sample. Results More than 90% of the population eligible for testing were screened in the participating centers. We found HCV antibody seroprevalence rates ranging from 0.6 to 3.9%, with between 19 and 53% of viremic individuals. Conclusions Opportunistic HCV screening in EDs is feasible, does not disrupt ED activities, is highly effective in increasing diagnosis, and contributes to WHO’s HCV elimination goals.

Background & Aims: Many people with HCV and HBV infection are unaware of their condition, particularly at-risk and vulnerable populations who face barriers for screening and linkage to care. Emergency departments are often their only point of contact with the health system. Methods: This is a prospective study investigating HBsAg and HCV antibody testing, with reflex testing for HDV antibodies and HCV RNA, in adults attending an emergency department and requiring a blood test. Positive cases were linked to care. A cost-effectiveness analysis was performed. Results: From February 2020 to February 2022, a total of 17,560 individuals were screened. HBsAg was detected in 91 (0.5%), HCV RNA in 128 (0.7%), and HDV antibodies in two (0.01%) individuals. Nearly 40% of positive cases were unaware of their condition. Linkage to care was achieved in 42 of 56 HBsAg-positive and 45 of 69 HCV RNA-positive participants who were candidates for referral. HCV and HBV screening vs. no screening yielded 1.06 and 0.42 additional quality-adjusted life-years, respectively, with incremental cost–utility ratios of €7,629 and -€147 per quality-adjusted life-year gained, respectively, and proved even more cost-effective in patients with hepatitis C aged 40–70 years. Conclusions: On emergency department screening for hepatitis B, C, and D in Barcelona, the prevalence of HBsAg was 0.5% and HCV RNA 0.7%, approximately threefold higher than that observed in the general population. This strategy diagnosed patients with active HCV infection and no risk factors, who would not have been screened according to the current recommendations. Screening and linkage to care of viral hepatitis is cost-effective in this setting. Impact and implications: We evaluated the performance and cost-effectiveness of a viral hepatitis screening programme implemented in an emergency department, which aimed to identify and link to care people living with hepatitis B and C. Our findings reveal a threefold higher prevalence of hepatitis B and C than in the general Spanish population, possibly attributable to the role of the emergency department as the main healthcare gateway for vulnerable populations, who have a higher prevalence of viral hepatitis. Risk factors for viral hepatitis could not be identified in most people living with hepatitis B and C attending the emergency department; hence, screening beyond risk factors should be considered in hepatitis detection strategies. Emergency department screening is cost-effective for hepatitis C and is a cost-saving strategy for hepatitis B in our setting. These data should inform future updates to clinical guidelines.

Background & Aims: HBsAg proteins are useful to identify HBV inactive carriers (ICs), but data on chronic hepatitis D (CHD) are scarce. This study aimed to describe HBsAg composition in CHD, its changes during the evolution, and the potential association with clinical outcomes. In addition, we assess the composition of HBsAg across different HBV genotypes and validate previous results on HBsAg proteins in an independent HBV cohort. Methods: Quantitative HBsAg, medium HBsAg proteins (MHBs), and large HBsAg proteins (LHBs) were measured in two cohorts. The first cohort consisted of patients with CHD. A cross-sectional study of samples from two European institutions (N = 46) was conducted. Outcomes were assessed in a retrospective–prospective study of those patients with a follow-up of >1 year (n = 36), and the longitudinal evolution of HBsAg proteins in those with samples >5 years apart (n = 12) was analysed. The second cohort consisted of patients with HBeAg-negative HBV, and a cross-sectional study was performed (N = 141). Results: Forty-one (89%) patients with CHD had detectable HDV-RNA, and the presence of HDV-RNA was associated with higher LHBs proportion (p = 0.010). Baseline MHBs (p = 0.051) and MHBs proportion (p = 0.086) tended to be higher in those developing clinical outcomes (9/36, 25%) after a median follow-up of 5.9 years. Patients in which HDV-RNA became spontaneously undetectable during follow-up (5/31, 16.1%) tended to present lower MHBs proportion (p = 0.085). In the longitudinal study, changes in LHBs proportion were observed (p = 0.041), whereas MHBs proportion remained stable (p = 0.209). Regarding HBV, ICs showed lower LHBs proportion (p = 0.027). LHBs and MHBs differed significantly according to HBV genotype, regardless of the HBV phase. Conclusions: Patients with CHD with detectable HDV-RNA presented higher LHBs proportion than those with undetectable HDV-RNA. A trend toward having higher baseline MHBs proportion was observed in patients who developed clinical outcomes or remained with detectable HDV-RNA. This study validates the different HBsAg composition in HBV ICs and reveals the HBV-genotype influence in HBsAg composition. Impact and implications: The composition of HBsAg in chronic hepatitis D differs in patients with detectable and undetectable HDV viral load and may help predict the likelihood of achieving undetectable HDV viraemia and the development of clinical events such as decompensation. The composition of the surface antigen is also useful to distinguish inactive carriers of HBV, and it varies according to HBV genotype.

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Este escrito sistematiza las reflexiones teórico-metodológicas para el abordaje de las personas adultas mayores en situación de vulnerabilidad y el proceso vivencial en la co-formación de una red de personas adultas mayores en la comunidad de Santa Rita de Alajuela, como parte del proyecto Pedagogía Social 2013-2018, de la Universidad Nacional (UNA), en el Centro de Investigación y Docencia en Educación (CIDE), en la División de Educación Básica (DEB). La metodología parte del paradigma naturalista, que considera que las personas adultas y adultas mayores participantes son constructoras de su pasado y actores sociales de su presente; ámbito que aborda la pedagogía social mediante la investigación-acción participativa. Una de las reflexiones a las que llega el equipo de investigación es que la población adulta mayor en dichas comunidades no solo requiere de atención física en salud, sino de espacios de recreación y de ocio, entendidos como herramientas para mejorar la salud integral, que contribuye en horas de alegría, de bienestar, de calidad de vida, lo que se verá reflejado en la salud emocional y física de las personas adultas mayores.

Introduction An estimated 290 million people are living with hepatitis B virus (HBV) worldwide; in Spain, the prevalence of hepatitis B virus surface antigen (HBsAg) is 0.4%. In our setting, many HBsAg-positive individuals are not linked to care, which implies a barrier to receiving treatment and controlling the infection. The main objective of this project is to evaluate the performance of a programme designed to achieve appropriate linkage to specialist care of HBsAg-positive individuals, newly tested or previously tested and lost to follow-up.Methods and analysis This is a retrospective and prospective study in which all HBsAg-positive cases recorded in the microbiology database will be identified. The retrospective phase will include cases detected between 2018 and 2020, and the prospective phase will run from January 2021 to June 2022. The project will be carried out in a tertiary university hospital covering the northern health area of Barcelona with a catchment population of 450 000 inhabitants and 16 affiliated primary care centres. The central laboratory detects approximately 1200 HBsAg-positive individuals every year; therefore, we expect to identify around 4000 patients over the duration of the project. The medical records of HBsAg-positive individuals will be consulted to identify and retrieve those who have not been appropriately linked to care. Candidates will be contacted to offer specialist disease assessment and follow-up. A website will be created to provide HBV-related information to primary care physicians, and a mobile phone application will be available to patients to improve the linkage circuits and ensure follow-up continuity.Ethics and dissemination The Vall d’Hebrón Hospital Ethics Committee (PR(AG)201/2021) and the Spanish Agency of Medicines and Medical Devices approved this study. The findings will be disseminated through peer-reviewed publications and conference presentations. This programme could increase the number of HBsAg-positive individuals properly linked to care and achieve better HBV monitoring, which will have a positive impact on WHO’s viral hepatitis elimination goals.

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women.

Background & Aims: Although EASL guidelines recommend anti-HDV testing in all HBsAg-positive individuals, HDV infection remains an underdiagnosed condition. We describe the impact of an HDV screening program by reflex anti-HDV testing in all HBsAg-positive samples and compare the results before and after its implementation. Methods: In total, 2,236 HBsAg-positive determinations were included from January 2018 to December 2021. Only the first sample from each participant was evaluated: 1,492 samples before reflex anti-HDV testing (2018–2020) and 744 samples after (2021). Demographic and clinical characteristics of anti-HDV-positive patients were collected. Results: Before reflex testing, anti-HDV had been tested in 7.6% (114/1492) of HBsAg-positive individuals: 23% (91/390) attended in an academic hospital and only 2% (23/1,102) in primary care centres. After reflex testing was established, 93% (691/744) of HBsAg-positive cases were evaluated for anti-HDV: 91% (533/586) in the academic hospital and 100% (158/158) in primary care. The anti-HDV-positive prevalence was similar before and after reflex testing: 9.6% (11/114) and 8.1% (56/691), respectively. However, the absolute number of anti-HDV-positive patients increased. Most anti-HDV-positive patients were young, HBeAg-negative, Caucasian males. HDV-RNA was detectable in 35 (65%) of 54 tested, HBV-DNA was undetectable in 64%, and alanine aminotransferase levels were normal in 48%. Conclusions: Anti-HDV reflex testing quintupled the absolute number of diagnoses of chronic hepatitis D infection. Before the reflex test, a large percentage of HBsAg-positive individuals had not undergone any anti-HDV determination. Implementation of reflex testing increases the diagnosis of patients with chronic hepatitis D. Lay summary: Chronic hepatitis delta (CHD) is a viral disease caused by HDV, which requires the presence of HBV to propagate. HDV infection can cause rapid progression to cirrhosis, among other severe complications. The prevalence of CHD worldwide is controversial, and the infection often goes unrecognised, mainly because of unawareness among physicians. Use of reflex testing in other viral hepatitis has proven to increase detection and linking-to-care of infected patients. Implementation of anti-HDV testing in all HBsAg-positive patients has led to a 5-fold increase in the number of HDV diagnoses in an academic hospital and primary care centres.

BackgroundTolvaptan (TV) is the first vasopressin-receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). No publications report TV experience in real clinical practice during the first year of treatment.MethodsA prospective study of an initial cohort of 220 rapidly progressing patients treated with TV for 12 months. The tolerability of TV, the evolution of the estimated glomerular filtration rate (eGFR), analytical parameters, and blood pressure were analyzed.ResultsA total of 163 patients (78.2%) received TV for 1 year. The main causes of treatment withdrawal were the aquaretic effects (11%), eGFR deterioration (5%), and hepatic toxicity (2.3%). eGFR decreased significantly after 1 month of treatment without further changes. The decrease in eGFR in the first month was higher in patients with an initially higher eGFR. The eGFR drop during the first year of treatment with TV was lower than that reported by patients in the 2 years prior to TV treatment (–1.7 ± 7.6 vs. –4.4 ± 4.8 mL/min, p = 0.003). Serum sodium and uric acid concentrations increased, and morning urinary osmolality decreased in the first month, with no further changes. Blood pressure decreased significantly without changes in antihypertensive medication.ConclusionTV treatment is well tolerated by most patients. Liver toxicity is very rare and self-limited. TV reduces eGFR in the first month without showing further changes during the first year of treatment. Patients with a higher starting eGFR will suffer a greater initial drop, with a longer recovery. We suggest using the eGFR observed after a month of treatment as the reference for future comparisons and calculating the rate of eGFR decline in patients undergoing TV treatment.

Abstract Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5′ end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p

ABSTRACT The measurement and interpretation of HBV DNA and RNA levels in HBV infected patients treated with antiviral therapy supports the objective of HBV disease management. Here, we quantified circulating HBV RNA through a standardized and sensitive assay in follow-up samples from both naive and treated patients as a marker of infection evolution. HBV DNA (HBV DNA for use in Cobas 6800/8800 Automated Roche Molecular Systems), RNA (Roche HBV RNA Investigational Assay for use in the Cobas 6800/8800; Roche), HBeAg and HBsAg (Elycsys HBsAg chemiluminescence immunoassay by Cobas 8000; Roche), and core-related antigen (Lumipulse G chemiluminescence assay; Fujirebio) levels were measured in cohorts of untreated or nucleos(t)ide treated, HBV-infected subjects in an outpatient hospital setting. HBV DNA levels in untreated people were 3.6 log10 higher than corresponding RNA levels and were stable over 5 years of observation. While only five of 52 treated patients had DNA levels below the lower limit of quantification (10 IU/mL) at the end of follow-up, 13 had HBV RNA levels persistently above this limit, including eight with undetectable DNA. In samples with undetectable core-related antigen we observed a median HBsAg titer 2.7-fold higher than in samples with undetectable RNA (adjusted P = 0.012). Detectable HBV RNA with undetectable HBV DNA was a negative predictor of HBsAg decrease to a level ≤100 IU/mL (P = 0.03). In naive patients the difference between HBV DNA and RNA was higher than previously reported. HBV RNA rapidly decreased during treatment. However, in some cases, it was detectable even after years of effective therapy, being a negative predictor of HBsAg decrease. The investigational RNA assay for use on the Cobas 6800/8800 instruments is a sensitive and standardized method that could be applied in general management of HBV infection. IMPORTANCE This study focused on the quantification of circulating HBV RNA by using a standardized and sensitive assay. Thanks to this system we observed a higher difference between circulating HBV DNA and RNA than previously reported. In treated patients, HBV RNA decreased together with DNA, although some patients presented detectable levels even after years of successful antiviral treatment, suggesting a persistent viral transcription. Of note, the detection of viral RNA when HBV DNA is undetectable was a negative predictor of HBsAg decrease to a level ≤100 IU/mL. This assay could be extremely helpful in HBV patients management to study viral transcription and to identify those treated patients that may achieve sustained viral suppression.

Resumen: Introducción: Para la estimación del filtrado glomerular renal (FG) en trasplantados renales se emplean las ecuaciones MDRD y CKD-EPI de 2009 que han mostrado diferencias importantes cuando se comparan con el FG medido con técnicas de referencia. Objetivo: Analizar el rendimiento de las ecuaciones MDRD, CKD-EPI de 2009 y de 2012 en 270 pacientes trasplantados renales de un año de evolución, comparando con el FG medido con aclaramiento plasmático de 51Cr-EDTA. Resultados: El FG medido fue 43,0 ± 11,4 (18,2-79,4) mL/min/1,73 m2, con niveles de creatinina de 1,42 ± 0,46 (0,60-4,33) mg/dL y de cistatina C de 1,45 ± 0,53 (0,42-3,48) mg/L. El FG medido se correlacionó moderadamente con creatinina (r = −0,61; p

Background: When estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques. Objective: To analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year. Results: The mean measured GFR was 43.0 ± 11.4 (18.2–79.4) ml/min/1.73 m2, with creatine levels of 1.42 ± 0.46 (0.60–4.33) mg/dl and cystatin C levels of 1.45 ± 0.53 (0.42–3.48) mg/l. This correlated moderately with creatinine (r=–0.61, p

BackgroundThe treatment of chronic hepatitis C virus (HCV) with direct-acting antivirals has undergone a spectacular revolution and added significant value to healthcare systems and patients. The aim of the study was to evaluate the efficiency and value of Sofosbuvir (SOF)-based regimens for a target population of 85,959 chronic HCV patients treated in Spain during 2015-2019, compared to previous therapeutic strategies (peginterferon/ and ribavirin in double/triple therapy with telaprevir or boceprevir).MethodsA previously developed lifetime Markov model was adapted to simulate the disease HCV evolution. In SOF-based regimens, all patients (100%) were treated regardless with sustained virological response (SVR) of 93-98%, obtained from real-world data. In previous therapeutic, only ≥F2 patients were treated according to clinical practice (38%) with an average SVR of 61% taken from published literature. The value was measured as clinical and economic impact in terms of avoided HCV-related mortality and liver complications; total costs and quality-adjusted life years (QALYs) applying an annual 3% discount rate.ResultsCompared to previous therapeutic, during lifetime, SOF-based regimens reduced decompensated cirrhosis by 89%, hepatocellular carcinoma by 77% and liver transplant by 84%, decreasing the cost associated to liver complications management in €770 million. SOF-based regimens also decreased liver-related mortality by 82%. Besides, SOF-based regimens gained 310,765/QALYs, saving €274 million (considering drugs, monitoring, and HCV management).ConclusionFor Spain, SOF-based regimens offer value for HCV patients in terms of lowering HCV-related liver disease burden and generating significant cost savings for the health system, contributing to the WHO goal.

Background: Hepatitis C virus (HCV) management is a challenge in patients with substance use disorder (SUD). This study aimed to describe an HCV screening and linkage to care program in SUD patients, and analyze the characteristics of this population in relation to HCV infection, particularly the impact of psychiatric comorbidities (dual diagnosis). Methods: This study was a prospective clinical cohort study using a collaborative, multidisciplinary model to offer HCV care (screening, diagnosis, and therapy) to individuals with SUD attending a dedicated hospital clinic. The characteristics of the participants, prevalence of HCV infection, percentage who started therapy, and adherence to treatment were compared according to the patients’ consumption characteristics and presence of dual diagnosis. HCV screening, diagnosis, treatment initiation, and sustained virologic response were analyzed. Results: 528 individuals attended the center (November 2018–June 2019) and 401 (76%) accepted screening. In total, 112 (28%) were anti-HCV-positive and 42 (10%) had detectable HCV RNA, but only 20 of the latter started HCV therapy. Among the 253 (63%) patients with a dual diagnosis, there were no differences in HCV infection prevalence versus patients with SUD alone ( p = 0.28). Dual diagnosis did not lead to a higher risk of HCV infection or interfere with linkage to care or treatment. Conclusion: This study found a high prevalence of dual diagnosis and HCV infection in SUD patients, but dual diagnosis was not associated with an increased risk of acquiring HCV or more complex access to care. Despite use of a multidisciplinary management approach, considerable barriers to HCV care remain in this population that would need more specific focus.

Background & Aims: Health-related quality of life (HRQoL) determined by patient-reported outcomes (PROs) is impaired in chronic hepatitis B (CHB) and C patients, but there are no data regarding patients with chronic hepatitis D (CHD). The aim of this study was to assess PRO scores in untreated patients with CHD and compare them with those obtained for patients with CHB. Methods: Patients with CHD completed 3 PRO instruments (Chronic Liver Disease Questionnaire [CLDQ], Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-F], and Work Productivity and Activity Impairment [WPAI]), and the results were compared with those of patients mono-infected with CHB. Results: In total, 125 patients were included: 43 with CHD and 82 with CHB. Overall, baseline PROs showed differences between both groups. Several assessments, such as the worry score from CLDQ (p = 0.0118), functional well-being from FACIT-F (p = 0.0281), and activity impairment from WPAI (p = 0.0029) showed a significant trend to worse scores in patients with CHD than with CHB. In addition, the linear regression model supports the finding that having CHD as opposed to having CHB was a predictor of a higher worry score (CLDQ) and a higher activity impairment (WPAI). Conclusions: In this first assessment in CHD, PROs recorded in patients with CHD showed a significant impairment in some domains of HRQoL questionnaires in comparison with those with CHB. Studies in larger cohorts with lengthier follow-up are needed to fully assess patient-reported quality of life over the course of CHD. Lay summary: Chronic hepatitis D (CHD) is a viral disease that causes rapid evolution to liver cirrhosis, amongst other severe complications, when compared to patients with chronic hepatitis B (CHB). Health-related quality of life in chronic hepatitis C and CHB has been reported widely, but no studies have been performed on patient-reported outcomes in patients with CHD. Results showed that CHD patients reported worse outcomes in psychological domains such as worry and emotional well-being, as well as in physical domains such as abdominal symptoms, physical well-being, and activity impairment in comparison with patients with CHB.

Background & Aims: Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC. Methods: We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively. Results: HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were always >99% (99.3–100%), whereas PPV ranged between 13% and 24%. Conclusions: In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease. Lay summary: Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis.

IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.

Nucleos(t)ide analogues with high barrier to resistance are regarded as the principal therapeutic option for chronic hepatitis B (CHB). Treatment with entecavir (ETV), tenofovir disoproxil (TDF) and the later released tenofovir alafenamide (TAF) is highly effective at controlling hepatitis B virus (HBV) infection and, in the vast majority of patients, is well tolerated. No significant differences in viral suppression have been described among the different regimens, although an earlier achievement in biochemical response has been suggested first under TDF and recently under TAF. High barrier to resistance NAs rarely achieve hepatitis B surface antigen sero-clearance, and therefore should be maintained life-long in most cases. This has increased concerns about treatment-related toxicity, especially in patients under TDF with additional risk factors for kidney and bone impairment. TAF has shown a better bone and kidney safety profile than TDF, although it is not yet available worldwide due to its higher cost. Emergence of adverse events should be monitored since treatment-switch to ETV/TAF seems to be effective and safe in HBV mono-infected subjects. Finally, although an effective antiviral treatment leads to a clear improvement in clinical outcome of CHB patients; the risk of developing hepatocellular carcinoma (HCC) is not completely avoided with viral suppression. Whether tenofovir-based regimens provide any additional benefit over ETV in HCC prevention remains unclear and requires further investigation.

Indicators of environmental policies in force in Mexico, fossil fuels will continue to be used in industrial sectors, especially marine fuels, such as marine diesel oil, in port systems for some time. Considering this, we have evaluated several methods corresponding to a top-down system for determining fuel consumption and sulfur dioxide atmospheric emissions for the port of Veracruz in 2020 by type of ship on a daily resolution, considering a sulfur content of 0.5% mass by mass in marine fuel. After analyzing seven methods for determining sulfur dioxide atmospheric emission levels, Goldsworthy’s method was found to be the best option to characterize this port. The port system has two maritime zones, one of which is in expansion, which represented 55.66% of fuel consumption and 23.05% of atmospheric emissions according to the typology of vessels. We found that higher fuel consumption corresponded to container vessels, and tanker vessels represented higher atmospheric emission levels in the berthing position. The main differences that we found in the analysis of the seven methods of the top-down system corresponded to the load factor parameter, main and auxiliary engine power, and estimation of fuel consumption by type of vessel.

Abstract Background Despite the high sustained virological response rates achieved with current directly-acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 5–10% of treated patients do not respond to current antiviral therapies, and basal resistance to DAAs is increasingly detected among treatment-naïve infected individuals. Identification of amino acid substitutions (including those in minority variants) associated with treatment failure requires analytical designs that take into account the high diversification of HCV in more than 86 subtypes according to the ICTV website (June 2017). Methods The methodology has involved five sequential steps: (i) to design 280 oligonucleotide primers (some including a maximum of three degenerate positions), and of which 120 were tested to amplify NS3, NS5A-, and NS5B-coding regions in a subtype-specific manner, (ii) to define a reference sequence for each subtype, (iii) to perform experimental controls to define a cut-off value for detection of minority amino acids, (iv) to establish bioinformatics’ tools to quantify amino acid replacements, and (v) to validate the procedure with patient samples. Results A robust ultra-deep sequencing procedure to analyze HCV circulating in serum samples from patients infected with virus that belongs to the ten most prevalent subtypes worldwide: 1a, 1b, 2a, 2b, 2c, 2j, 3a, 4d, 4e, 4f has been developed. Oligonucleotide primers are subtype-specific. A cut-off value of 1% mutant frequency has been established for individual mutations and haplotypes. Conclusion The methodological pipeline described here is adequate to characterize in-depth mutant spectra of HCV populations, and it provides a tool to understand HCV diversification and treatment failures. The pipeline can be periodically extended in the event of HCV diversification into new genotypes or subtypes, and provides a framework applicable to other RNA viral pathogens, with potential to couple detection of drug-resistant mutations with treatment planning.

Introducción: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente aunque los datos disponibles generalmente son tras el inicio del tratamiento renal sustitutivo. Objetivo: Conocer la situación global de la poliquistosis renal autosómica dominante en el ámbito sanitario de Granada. Material y métodos: Desde enero 2007 hasta diciembre 2016 hemos recogido información clínica, familiar y demográfica de todos los pacientes con poliquistosis renal autosómica dominante, estuvieran o no en tratamiento renal sustitutivo, atendidos en el área de Granada. Se han utilizado los programas informáticos SPSS 15.0 y GenoPro. Resultados: Mil ciento siete pacientes diagnosticados, el 50,6% son varones. Se han estudiado 4-6 generaciones/familia. El 99,1% de raza caucásica. Hay áreas geográficas con mayor concentración. No hay antecedentes familiares en el 2,43%. La edad media de diagnóstico es de 34 ± 17,8 años y en el 57,7% de los casos, el diagnóstico se produce después de tener descendencia. El principal motivo de diagnóstico son los antecedentes familiares (46,4%). La edad media de entrada en técnica es de 54,2 ± 11,05 años. El 96,3% de los fallecidos tenían algún grado de insuficiencia renal en el momento del exitus. La edad media del exitus es de 60,9 ± 14,10 años, siendo desconocida la principal causa de muerte (33,5%) seguida de la cardiovascular (27,8%). Conclusiones: Casos y familias se concentran en algunas áreas geográficas, un número importante de individuos están sin diagnosticar, fallecen antes por causa cardiovascular y se diagnostican tarde respecto al momento reproductivo. Dado que no hay tratamiento curativo, la estrategia de prevención primaria mediante el diagnóstico genético preimplantacional adquiere protagonismo.

Introduction: Although autosomal dominant polycystic kidney disease is the most common hereditary kidney disease, available data tend to be limited to after initiation of renal replacement therapy. Objective: To ascertain an overview of autosomal dominant polycystic kidney disease within the health area of Granada in southern Spain. Materials and methods: From January 2007 to December 2016, we collected clinical, family and demographic information about all patients with autosomal dominant polycystic kidney disease, irrespective of whether or not they were treated with RRT, in the Granada health area. The computer software SPSS 15.0 and GenoPro were used. Results: 50.6% of the 1107 diagnosed patients were men. 99.1% were Caucasian and 4â6 generations/family were studied. The geographical distribution was heterogeneous. There was no family history in 2.43%. The mean age of diagnosis was 34.0 ± 17.80 years and the diagnosis was made after having offspring in 57.7% of cases. The main reason for diagnosis was family history (46.4%). The mean age of initiation of renal replacement therapy was 54.2 ± 11.05 years. 96.3% of the deceased had some degree of renal failure at the time of death. The mean age of death was 60.9 ± 14.10 years, the main cause of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%). Conclusions: Cases and families were concentrated in certain geographical areas and a significant number of individuals were undiagnosed prior to cardiovascular death or diagnosed late after reproduction. Given that there is currently no curative treatment, the primary prevention strategy of preimplantation genetic diagnosis should play a leading role. Resumen: Introducción: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente aunque los datos disponibles generalmente son tras el inicio del tratamiento renal sustitutivo. Objetivo: Conocer la situación global de la poliquistosis renal autosómica dominante en el ámbito sanitario de Granada. Material y métodos: Desde enero 2007 hasta diciembre 2016 hemos recogido información clínica, familiar y demográfica de todos los pacientes con poliquistosis renal autosómica dominante, estuvieran o no en tratamiento renal sustitutivo, atendidos en el área de Granada. Se han utilizado los programas informáticos SPSS 15.0 y GenoPro. Resultados: Mil ciento siete pacientes diagnosticados, el 50,6% son varones. Se han estudiado 4-6 generaciones/familia. El 99,1% de raza caucásica. Hay áreas geográficas con mayor concentración. No hay antecedentes familiares en el 2,43%. La edad media de diagnóstico es de 34 ± 17,8 años y en el 57,7% de los casos, el diagnóstico se produce después de tener descendencia. El principal motivo de diagnóstico son los antecedentes familiares (46,4%). La edad media de entrada en técnica es de 54,2 ± 11,05 años. El 96,3% de los fallecidos tenían algún grado de insuficiencia renal en el momento del exitus. La edad media del exitus es de 60,9 ± 14,10 años, siendo desconocida la principal causa de muerte (33,5%) seguida de la cardiovascular (27,8%). Conclusiones: Casos y familias se concentran en algunas áreas geográficas, un número importante de individuos están sin diagnosticar, fallecen antes por causa cardiovascular y se diagnostican tarde respecto al momento reproductivo. Dado que no hay tratamiento curativo, la estrategia de prevención primaria mediante el diagnóstico genético preimplantacional adquiere protagonismo. Keywords: Autosomal dominant polycystic kidney disease, Polycystic, Epidemiology, Palabras clave: Poliquistosis renal autosómica dominante, Poliquistosis, Epidemiología

Atmospheric emissions from vessels at 38 Pacific and Gulf-Caribbean Mexican ports were determined for nitrogen oxides, sulfur dioxide, particulates, carbon monoxide, non-methane volatile organic compounds, and carbon dioxide. The emissions have been estimated using a bottom-up methodology in the maneuver and hoteling phases, by vessel type, from 2005 to 2020. Maritime traffic in Mexico’s Pacific zone contributes approximately with 60% of the country’s total ship emissions, with the remaining 40% in Gulf-Caribbean ports. The highest atmospheric emissions were found at the Manzanillo and Lázaro Cárdenas ports on the Pacific coast, as well as the Altamira and Veracruz ports on the Gulf-Caribbean coast. The contribution of the atmospheric emissions by vessel type at Pacific ports was Container 67%, Bulk Carrier 32%, Tanker 0.8%, and RoRo 0.4%. For Gulf-Caribbean ports it was Container 76%, Bulk Carrier 19%, Tanker 3%, and RoRo 2%. This study incorporates the International Maritime Organization implementations on reductions of sulfur content in marine fuel, from 4.5% mass by mass from 2005 to 2011, to 3.5% from 2012 to 2019, to 0.5% beginning in 2020. Overall, sulfur dioxide emissions were reduced by 89%.

Background and aims: Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and Methods: We retrospectively evaluated 22 consecutive adult LT recipients (16 mo-noinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results: Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion: The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied. Patients who carry Resistant Associated Substitutions (RASs) may not obtain benefits from treatment, and are at a risk of disease progression. Whether HCV RASs persist depends on their type: NS3-4A variants often disappear gradually after DAA therapy is stopped, whereas NS5A variants tend to persist for more than 2 years. The best way to prevent emergence of resistant variants is to eliminate the virus at the first treatment using highly potent DAAs with genetic barriers to resistance. For those who fail an NS5A inhibitor, deferral of treatment is recommended pending the availability of additional data if they do not have cirrhosis or reasons for urgent re-treatment. If re-treatment is needed, the most commonly used strategy is sofosbuvir as backbone therapy plus a drug from a class other than that previously used, for 24 weeks. Unless it is contraindicated, weight-based ribavirin should also be added. If available, nucleotide-based (eg, sofosbuvir) triple or quadruple DAA regimens may be considered. The optimal treatment for patients who fail an NS5A inhibitor and those with multidrug-resistant variants remains to be defined, and research efforts should continue to focus on treatment for these patients.

Este artículo científico se ocupa de examinar el tema de la idoneidad de la historia clínica como prueba en un proceso de responsabilidad civil médica, y para tal fin se escogieron como ejes temáticos el desarrollo de sus generalidades, se destaca la importancia y repercusiones de la historia clínica, se señalan sus características generales, se enuncia el acto médico con sus implicaciones éticas y legales, se hacen unas consideraciones finales y se concluye con el examen del valor jurídico de las historias clínicas, donde se espera despejar los interrogantes al respecto.

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics.

BackgroundElimination of hepatitis C virus (HCV) infection requires high diagnostic rates and universal access to treatment. Around 40% of infected individuals are unaware of their infection, which indicates that effective screening strategies are needed. We analyzed the efficiency (incremental cost-utility ratio, ICUR) of 3 HCV screening strategies: a) general population of adults, b) high-risk groups, and c) population with the highest anti-HCV prevalence plus high-risk groups.MethodsAn analytical decision model, projecting progression of the disease over a lifetime, was used to establish the candidate population for HCV screening. HCV data were obtained from the literature: anti-HCV prevalence (0.56%-1.54%), viremic patients (31.5%), and percentage of undiagnosed persons among those with viremia (35%). It was assumed that most patients would be treated and have HCV therapy response (98% SVR); transition probabilities, utilities, and disease management annual costs were obtained from the literature. Efficiency over the life of patients under the National Health System perspective was measured as quality-adjusted life years (QALY) and total cost (screening, diagnosis, pharmacological and disease management). A discount rate of 3% was applied to costs and outcomes.ResultsScreening of the adult population would identify a larger number of additional chronic hepatitis C cases (N = 52,694) than screening the highest anti-HCV prevalence population plus high-risk groups (N = 42,027) or screening high-risk groups (N = 26,128). ICUR for the general population vs. high-risk groups was €8914/QALY gained per patient (€18,157 incremental cost and 2.037 QALY). ICUR for the general population vs. population with highest anti-HCV prevalence plus high-risk groups was €7,448/QALY gained per patient (€7,733 incremental cost and 1.038 QALY). These ICUR values are below the accepted efficiency threshold (€22,000-€30,000).ConclusionHCV screening and treatment of the general adult population is cost-effective compared to screening of high-risk groups or the population with the highest anti-HCV prevalence plus high-risk groups.

[This corrects the article DOI: 10.1371/journal.pone.0184550.].

This paper established the different paradigms and trends in research practices that take place within the División de Educación Básica (Elementary Education Division-DEB, for its name in Spanish) of Centro de Investigacion y Docencia en Educación (CIDE, from its name in Spanish) at Universidad Nacional (UNA) in Costa Rica. As such, these research practices have established diverse trends towards conceiving and doing research within DEB. As a process, these practices have been created and developed throughout time while establishing a historical constant in the academic curricular dynamics of DEB -as it can be observed in the study career programs, course syllabus and final graduation projects as well. In the 1990s, research at DEB was mainly descriptive-exploratory and it was characterized by data analysis focused on descriptive statistics and linearity from a positivist approach. At the same time, educational practices linked to a social approach in communities at risk were developed, and a quality-oriented research line emerged. Currently, research work at DEB is developed from a qualitative paradigm approach, thus allowing research circularity and recursiveness. It is then concluded, that this research trend allows new possibilities regarding current socio-pedagogical demands as well as developing teaching abilities to respond to socio educational problems and social transformation.

Background We aimed to investigate the early changes in liver and spleen stiffness measurement (LSM, SSM) in hepatitis C virus (HCV) patients with compensated advanced chronic liver disease (cACLD) treated with new antivirals (DAA) to elucidate factors determining the initial change in stiffness and its implications for the long-term follow up of HCV-cured patients. Methods: A total of 41 patients with cACLD who started DAA therapy underwent LSM and SSM at baseline, week 4, end of treatment (EOT), 24 and 48 weeks of follow up using transient elastography. Results: LSM improved rapidly during the first 4 weeks of treatment (baseline: 20.8kPa; week 4: 17.5kPa, p = 0.002), with no significant changes between week 4 and EOT (18.3kPa, p = 0.444) and between EOT and 48-week follow up (14.3kPa, p = 0.148). Likewise, SSM improved rapidly (baseline: 45.7kPa; week 4: 33.8kPa, p = 0.047), with no significant changes between week 4 and EOT (30.8kPa, p = 0.153) and between EOT and 48-week follow up (31.2kPa, p = 0.317). A higher decrease in LSM was observed in patients with baseline ALT ⩾ twofold upper limit normal (2 × ULN) than in those with ALT < 2 × ULN (–5.7kPa versus –1.6kPa). Patients who presented a decrease in LSM ⩾ 10% during treatment compared with those with LSM < 10% decrease, showed lower SSM values, higher platelet counts and lower bilirubin levels at 24-week follow up. Those with decrease in SSM ⩾ 10%, presented a higher increase in platelets than those with SSM < 10% change ( p = 0.015). Conclusions: LSM and SSM decrease very rapidly during DAA treatment in cACLD patients suggesting that it most probably reflects a reduction in inflammation rather than in fibrosis. cACLD patients should be maintained under surveillance independently of stiffness changes, because advanced fibrosis can still be present.

Hepatitis B virus (HBV) reactivation in patients with resolved HBV infection (HBsAg negative, antiHBc positive) is uncommon, but potentially fatal. The role of HBV prophylaxis in this setting is uncertain. The aim of this study was to compare the efficacy of tenofovir disoproxil fumarate (TDF) prophylaxis versus close monitoring in antiHBc-positive, HBsAg-negative patients under treatment with rituximab (RTX)-based regimens for hematologic malignancy.PREBLIN is a phase IV, randomized, prospective, open-label, multicenter, parallel-group trial conducted in 17 hospitals throughout Spain. Anti-HBc-positive, HBsAg-negative patients with undetectable HBV DNA were randomized to receive TDF 300 mg once daily (Group I) or observation (Group II). The primary endpoint was the percentage of patients showing HBV reactivation during 18 months following initiation of RTX treatment. Patients with detectable HBV DNA (Group III) received the same dose of TDF and were analyzed together with Group I to investigate TDF safety.Sixty-one patients were enrolled in the study, 33 in the TDF treatment group and 28 in the observation group. By ITT analysis, HBV reactivation was 0% (0/33) in the study group and 10.7% (3/28) in the observation group (p = 0.091). None of the patients in either group showed significant differences in liver function parameters between baseline and the last follow-up sample. TDF was generally well tolerated and there were no severe treatment-related adverse events.In patients with hematological malignancy and resolved hepatitis B infection receiving RTX-based regimens, HBV reactivation did not occur in patients given TDF prophylaxis.

LEGO Mindstorms es un juego que se usa como herramienta para el aprendizaje de distintas áreas de conocimiento. Una persona puede aprender acerca de programación mediante distintos lenguajes y aplicaciones para compilar el código de la solución planteada y resolver una situación particular. Sin embargo, la enseñanza de programación es sólo un fundamento teórico y poco práctico. Por estas razones, se pretende enseñar a programar mediante un lenguaje sencillo y una plataforma que permita visualizar el código gráficamente y validarlo específicamente con las instrucciones programadas sobre un robot.

This Bristol Myers Squibb-sponsored symposium was chaired by Mark Thursz, who oversaw a novel news bulletin-themed symposium with sessions provided by a distinguished, international team of roving reporters; Charles Gore from the World Hepatitis Alliance, Jean-Michel Pawlotsky from France, Alessandra Mangia from Italy, Ashley Brown and Graham Foster from London, Heiner Wedemeyer from Germany, and Rafael Esteban from Spain.

The optimal timing to treat recurrent hepatitis-C virus (HCV) after liver transplantation (LT) remains uncertain. We compared the outcome of early (acute phase) and deferred (chronic phase) antiviral treatment for recurrent HCV infection in this population. Consecutive HCV genotype-1 infected LT patients receiving antiviral therapy between 2001-2010 were retrospectively classified according to histology at treatment start into the early or deferred treatment group. Measured endpoints included sustained virological response (SVR) rates and long-term survival. The study cohort comprised 105 patients: 60 (57%) received early treatment (ET) and 45 (43%) deferred treatment (DT). The median interval from LT to antiviral start was 3 (1-9) and 18 months (11-74) in ET and DT respectively. The SVR rate was similar in both treatment groups (23% ET and 36% DT; p = 0.27). After a median follow-up of 5.8 years, all-cause and liver-related mortality were similar in both groups. Variables independently associated with mortality included pre-treatment bilirubin > 2 mg/dL (HR 6.1, 95%CI: 2.8-13.7; p < 0.001), donor age > 60 (HR 3.1, 95%CI: 1.4-6.7; p = 0.01), and failure to achieve SVR (HR 10.3, 95%CI: 1.3-18.3; p = 0.03). In conclusion, early treatment of recurrent HCV is safe, but does not lead to higher SVR rates. In HCV-infected LT recipients, elevated bilirubin, older donor age, and failure to achieve SVR are independently associated with increased mortality.

The research, on which this paper is based, is focused on learning evaluation. The topic selected was: “Operationalization of the University’s Pedagogic Model: An analysis of learning evaluation in four study programs of the Basic Education Division (DEB ) of the Center for Research and Teaching in Education (CIDE), at Universidad Nacional (UNA), Costa Rica”. This research includes an analysis of principles, strategies, and instruments used in the DEB to evaluate learning, with the purpose of contributing to generate evaluation methods that are more coherent with the Pedagogic Model. The information was collected through focal studies and questionnaires responded by teachers and students; the results reported a need of coordination throughout the entire University to fulfill UNA’s Pedagogic Model in terms of learning evaluation.Recibido 14 de junio de 2013 • Corregido 30 de julio de 2013 • Aceptado 31 de julio de 2013Los resultados de la investigación que compartimos en el presente artículo centra su mirada en la evaluación de los aprendizajes. El tema seleccionado fue: Operacionalización del modelo pedagógico universitario: Una mirada desde la evaluación de los aprendizajes en cuatro carreras de la División de Educación Básica (DEB) del Centro de Investigación y Docencia en Educación (CIDE) de la Universidad Nacional de Costa Rica (UNA). En dicha investigación se analizaron los principios, estrategias e instrumentos que se aplican en la DEB para evaluar los aprendizajes, con el fin de contribuir a la reflexión y generación de espacios evaluativos más coherentes con lo planteado en el Modelo pedagógico. Producto de la recolección de información mediante el diseño de matrices y la aplicación de cuestionarios dirigidos a docentes y estudiantes, así como los estudios focales, se llega al análisis de los resultados que evidencian la necesidad de trabajar coordinadamente en toda la Universidad para visibilizar y concretizar el Modelo pedagógico de la UNA en lo concerniente a la evaluación de los aprendizajes.

Context: the increase in the processing capacity of machines and developments in combinatorial search algorithms reduces the time required to decipher the information fraudulently. Bear in mind this, there is a need to generate new ways of encoding information for secure transmission. Method: in this paper a symmetrical and extensible model for digital communications encryption is presented, taking advantage of the chaos generated by nonlinear dynamic systems. Results: the developed model proved to encrypt messages in time synchronization, encryption and decryption less than 1 ms with an entropy higher than 6 using the Rössler attractor for its implementation. Conclusions: the algorithm is presented as an alternative to traditional algorithms demonstrating greater efficiency in the management of computing resources and raises the groundwork for continuing their study on the interested academic community due to the variety of dynamical systems nonlinear.

Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p

Background and Aims. The risk of recurrent hepatitis B virus (HBV) infection and prognosis of liver transplantation in patients with HBV has dramatically changed with the use of prophylaxis including hepatitis B immune globulin (HBIg) and antiviral agents.Methods. This study analyzes the prognostic value of HBV DNA level before orthotopic liver transplantation (OLT) and the effect of HBV prophylaxis on rates of HBV recurrence and survival. Between 1988 and 2008, 859 patients underwent OLT in our center; 60 patients had HBV-related liver disease and in 49, HBV DNA was determined by real time-PCR before OLT. Survival and HBV recurrence were analyzed according to preoperative viral load (HBV DNA

Accumulation of mercury (Hg) by arrow cane (Gynerium sagittatum) (Aubl) Beauv. in vitro RESUMEN En este estudio se evaluó, in vitro, la capacidad de acumulación de mercurio (Hg) que pueda poseer la caña flecha (Gynerium sagittatum) (Aubl) Beauv. como una alternativa viable de ser implementada para la rehabilitación de suelos contaminados. Este estudio fue realizado en el laboratorio de Biotecnología Vegetal de la Universidad de Sucre (9º18’ N, 75º23’ O). Se usó un diseño experimental de bloques al azar, un análisis de varianza para comparación de medias, una prueba de Tukey (p≤0,05) para la establecer las diferencias significativas entre los tratamientos, pruebas de normalidad (Kolmogorov-Smirnov) y test de homogeneidad de varianza de Bartlett. Los análisis de mercurio se realizaron en un espectrofotómetro de absorción atómica Thermo Electron S4, provisto de una celda con ventanas de cuarzo, por el método de espectroscopia de absorción atómica con vapor frío. Los resultados muestran que la parte de la planta que presenta mayor acumulación es la raíz con 55,98 µg g-1 HgT, seguida de los tallos-hojas con 14,84 µg g-1 HgT, valores relacionados con el grado de concentración del metal en el medio de cultivo. Además, la acumulación de mercurio en raíces y tallos aumentó con el tiempo. En conclusión, in vitro esta planta acumula Hg debido a las altas concentraciones en sus tejidos sin afectar la viabilidad de las plantas.Palabras clave: fitorremediación, remoción, metales pesados.ABSTRACTIn this in vitro study was evaluated the potential for accumulation of mercury (Hg) that can hold the cane arrow (Gynerium sagittatum) (Aubl) Beauv. as a viable alternative to be implemented for the rehabilitation of contaminated soils. This study was conducted at the Plant Biotechnology Laboratory, University of Sucre (9º 18' N, 75° 23' W). An experimental design was randomized block, an analysis of variance to compare means, Tukey test (p ≤ 0.05) to establish significant differences between the treatments, tests of normality (Kolmogorov-Smirnov) and homogeneity test Bartlett variance. The mercury analyses were performed on atomic absorption spectrophotometer Thermo Electron S4, a cell equipped with quartz windows, by the method of atomic absorption spectrometry with cold steam. The results show that the plant part that presents the greatest accumulation is the root with 55.98 mg g-1 HgT, followed by the stems, leaves 14.84 g g-1 HgT and these values ​​are related to the degree of metal concentration in the culture medium. Furthermore, the accumulation of mercury in roots and stems increased with time. In conclusion, in vitro this plant accumulates due to the high Hg concentrations in their tissues without affecting the viability of plants.Key words: Phytoremediation, removal, heavy metals.

Recibido 26 de octubre de 2009 • Aceptado 02 de diciembre de 2009 • Corregido 17 de febrero de 2010 En el constante cambio que vivimos, la Pedagogía, en tanto ciencia de la educación, ciencia de la relacionalidad entre seres humanos, es el producto de acuerdos, de procesos comunicativos, procesos socioculturales entrelazados de forma compleja. La atención a la diversidad es una preocupación creciente en ambientes y sociedades plurales, y el lenguaje, como rasgo cultural permite describir nuestras circunstancias y reflexionar sobre ellas para comprenderlas, redimensionar el presente, valorar el pasado e imaginar el futuro. Si tenemos en cuenta que el habla es sólo una de las manifestaciones del lenguaje, si las diversas formas de expresión del cuerpo constituyen formas de lenguaje, se impone la necesidad de pensar cómo nos comunicamos en los procesos pedagógicos.

Recibido 15 de mayo 2007 • Aprobado 19 de junio 2007 Consideraciones en torno a la pertinencia de establecer un modelo pedagógico en una institución de educación superior universitaria, así como los aspectos que deben caracterizarlo, con el propósito de orientar los procesos educativos hacia nuevas perspectivas críticas. Lo anterior con fundamento en los resultados de una investigación llevada a cabo por un equipo académico de la Universidad Nacional.

El tratamiento de la hepatitis crónica B ha cambiado en los últimos años con la introducción de los antivirales orales (lamivudina, adefovir, entecavir, telbivudina y tenofovir) que junto con los interferones (estándar y pegilado) constituyen el arsenal terapéutico. Ello ha posibilitado incrementar las indicaciones terapéuticas ya que los antivirales orales permiten tratar a los pacientes con enfermedad hepática avanzada y descompensada. La mayor limitación de estos fármacos es la emergencia de cepas del VHB resistentes. El reto del futuro es evitar las resistencias y conseguir la supresión persistente de la replicación viral que evite la progresión de la enfermedad hepática y el desarrollo de complicaciones asociadas a la infección crónica por VHB.

El presente artículo trata de analizar la creación de las propuestas curriculares como producto de la convergencia de microprocesos institucionales y personales y macroprocesos sociales, lo cual se denomina en la teoría sociológica como desarrollos sintéticos. El escrito parte de la idea de que la creación de productos curriculares sólidos, transita por procesos históricos previos, los cuales son sistematizados e interpretados por los actores sociales en escenarios a veces antagónicos académicamente. Para ilustrar tales procesos, utiliza el ejemplo de la creación de la Maestría en Pedagogía con énfasis en Diversidad en los Procesos Educativos de la División de Educación Básica del Centro de Investigación y Docencia en Educación de la Universidad Nacional, Costa Rica, donde enfatiza en el impacto que los cambios sociales van generando en la discusión académica y cómo esta va convergiendo en la creación de un plan de estudios y en el desarrollo de una carrera.

This study assesses the presence and outcome of genotype mixtures in the polymerase/surface and X/preCore regions of the HBV genome in patients with chronic hepatitis B virus (HBV) infection. Thirty samples from ten chronic hepatitis B patients were included. The polymerase/surface and X/preCore regions were analyzed by deep sequencing (UDPS) in the first available sample at diagnosis, a pre-treatment sample, and a sample while under treatment. HBV genotype was determined by phylogenesis. Quasispecies complexity was evaluated by mutation frequency and nucleotide diversity. The polymerase/surface and X/preCore regions were validated for genotyping from 113 GenBank reference sequences. UDPS yielded a median of 10,960 sequences per sample (IQR 16,645) in the polymerase/surface region and 11,595 sequences per sample (IQR 14,682) in X/preCore. Genotype mixtures were more common in X/preCore (90%) than in polymerase/surface (30%) (p

AimTo evaluate HBV quasispecies (QA) complexity in the preCore/Core regions in relation to HBeAg status, and explore QA changes under natural evolution and nucleoside analogue (NUC) treatment.MethodsUltra-deep pyrosequencing of HBV preCore/Core regions in 30 sequential samples (baseline [diagnosis], treatment-free, and treatment-nonresponse) from 10 retrospectively selected patients grouped according to HBeAg status over time: HBeAg+ (N = 4), HBeAg- (N = 2), and fluctuating HBeAg (transient seroreversion/seroconversion pattern) (N = 4). QA complexity was defined by Shannon entropy, mutation frequency, nucleotide diversity, and mutation frequency of amino acids (MfAA) in preCore and Core.ResultsThe QA was less complex in HBeAg+ than in HBeAg- or fluctuating HBeAg. High complexity in preCore was associated with decreased viral replication (preCore MfAA negatively correlated with HBV-DNA, p = 0.005). QA complexity in the treatment-free period negatively correlated with values seen during treatment. Specific variants were mainly selected in the Core region in HBeAg- and fluctuating HBeAg patients, suggesting higher immune pressure than in HBeAg+.ConclusionsThe negative correlation between QA natural evolution and on-treatment evolution indicates the importance of pre-treatment QA study to predict QA changes in NUC nonresponders. Study of QA complexity could be useful for managing HBV infection.

Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited.Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients.Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls.IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p