Prevalence and Risk Factors of MASLD and Liver Fibrosis amongst the Penitentiary Population in Catalonia: The PRISONAFLD Study.

BACKGROUND AND AIMS: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. METHOD: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. RESULTS: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. CONCLUSIONS: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population.

Assessing the oncolytic potential of rotavirus on mouse myeloma cell line Sp2/0-Ag14. / Evaluación del potencial oncolítico del rotavirus en la línea celular Sp2/0-Ag14 de mieloma de ratón

INTRODUCTION: Cancer is the second leading cause of death in the United States, surpassed only by cardiovascular disease. However, cancer has now overtaken cardiovascular disease as the main cause of death in 12 countries in Western Europe. The burden of cancer is posing a major challenge to health care systems worldwide and demanding improvements in methods for cancer prevention, diagnosis, and treatment. Alternative and complementary strategies for orthodox surgery, radiotherapy, and chemotherapy need to be developed. OBJECTIVE: To determine the oncolytic potential of tumor cell-adapted rotavirus in terms of their ability to infect and lysate murine myeloma Sp2/0-Ag14 cells. MATERIALS AND METHODS: We inoculated rotaviruses Wt1-5, WWM, TRUYO, ECwt-O, and WTEW in Sp2/0-Ag14 cells and we examined their infectious effects by immunocytochemistry, immunofluorescence, flow cytometry, and DNA fragmentation assays. RESULTS: Rotavirus infection involved the participation of some heat shock proteins, of protein disulfide isomerase (PDI), and integrin ß3. We detected the accumulation of viral antigens within the virus-inoculated cells and in the culture medium in all the rotavirus isolates examined. The rotavirus-induced cell death mechanism in Sp2/0-Ag14 cells involved changes in cell membrane permeability, chromatin condensation, and DNA fragmentation, which were compatible with cytotoxicity and apoptosis. CONCLUSIONS: The ability of the rotavirus isolates Wt1-5, WWM, TRUYO, ECwt-O, and WTEW to infect and cause cell death of Sp2/0-Ag14 cells through mechanisms that are compatible with virus-induced apoptosis makes them potential candidates as oncolytic agents.

Introducción. El cáncer es la segunda causa de muerte en los Estados Unidos, solamente superado por la enfermedad cardiovascular. Sin embargo, el cáncer aventaja a la enfermedad cardiovascular como primera causa de muerte en doce países de Europa occidental. Se requieren mejores métodos de prevención, diagnóstico y tratamiento para afrontar el gran desafío que el cáncer representa mundialmente para los sistemas de salud, y se necesita desarrollar estrategias alternativas y complementarias a la cirugía, la radioterapia y la quimioterapia convencionales. Objetivo. Evaluar el potencial oncolítico de rotavirus adaptados a células tumorales por su capacidad para infectar y lisar células Sp2/0-Ag14 de mieloma de ratón. Materiales and métodos. Los aislamientos de rotavirus Wt1-5, WWM, TRUYO, ECwt-O y WTEW se inocularon en células Sp2/0-Ag14 y se examinaron sus efectos infecciosos mediante inmunocitoquímica, inmunofluorescencia, citometría de flujo y ensayos de fragmentación del ADN. Resultados. La infección con los rotavirus Wt1-5, WWM, TRUYO, ECwt-O y WTEW implicó la participación de algunas proteínas de choque térmico, la proteína disulfuro isomerasa y la integrina ß3. La acumulación de antígenos virales intracelulares y extracelulares se detectó en todos los virus utilizados. Los mecanismos de muerte inducidos por los rotavirus en células Sp2/0-Ag14 indujeron cambios en la permeabilidad de la membrana celular, la condensación de cromatina y la fragmentación de ADN, los cuales fueron compatibles con citotoxicidad y apoptosis. Conclusiones. La capacidad de los rotavirus estudiados para infectar y causar la muerte de células Sp2/0-Ag14 mediante mecanismos compatibles con la apoptosis inducida viralmente los convierte en candidatos potenciales para ser utilizados como agentes oncolíticos.

Reinfection in a large cohort of prison inmates with sustained virological response after treatment of chronic hepatitis C in Catalonia (Spain), 2002-2016.

BACKGROUND: Prisoners and other high-risk patients who show a sustained virological response (SVR) after treatment for hepatitis C virus (HCV) can become reinfected. We aimed to calculate the rate of HCV reinfection in a large cohort of inmates with SVR and to determine factors that predict reinfection. METHODS: We included all inmates treated for hepatitis C in Catalonia (Spain) from January 2002 to December 2016 who achieved SVR and in whom viral load was subsequently determined. The incidence rate was calculated per 100 person-years (100 py) of follow up. Risk factors associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression. Hazard ratio (HR) and their 95% confidence intervals (CI) were calculated. RESULTS: 602 patients were included, with a mean age of 37.9 years: 95% were men, 74.1% had a history of intravenous drug use (IDU) and 28.7% were HIV-infected. Patients were followed for a total of 2154.9 years (average 3.58 ± 3.1 years). 63 (10.5%) had HCV reinfection. 41 (65.1%) presented different genotype/subgenotype, 8 the initial genotype/subgenotype, and in 14 (22.2%) the genotype could not be determined. Of the 21 reinfected patients who were interviewed, 20 (95.2%) reported IDU after antiviral treatment, and 7 (33.3%) during treatment. The overall incidence of reinfection was 2.9 cases per 100 py. All reinfections occurred in patients with IDU history. At multivariate level, HIV infection was associated with reinfection (HR = 3.03; CI:1.82-5.04). CONCLUSION: In HIV-infected inmates with IDU history, the rate of reinfection of HCV post-SVR is very high. Prisons play a key role in the detection and treatment of infection and reinfection by HCV and in the post-treatment monitoring in these patients, which should be combined with counseling and the optimization of the harm reduction programs. Effective control of these vulnerable groups favours the elimination of the HCV infection.

Experimental Adaptation of Rotaviruses to Tumor Cell Lines.

A number of viruses show a naturally extended tropism for tumor cells whereas other viruses have been genetically modified or adapted to infect tumor cells. Oncolytic viruses have become a promising tool for treating some cancers by inducing cell lysis or immune response to tumor cells. In the present work, rotavirus strains TRF-41 (G5) (porcine), RRV (G3) (simian), UK (G6-P5) (bovine), Ym (G11-P9) (porcine), ECwt (murine), Wa (G1-P8), Wi61 (G9) and M69 (G8) (human), and five wild-type human rotavirus isolates were passaged multiple times in different human tumor cell lines and then combined in five different ways before additional multiple passages in tumor cell lines. Cell death caused by the tumor cell-adapted isolates was characterized using Hoechst, propidium iodide, 7-AAD, Annexin V, TUNEL, and anti-poly-(ADP ribose) polymerase (PARP) and -phospho-histone H2A.X antibodies. Multiple passages of the combined rotaviruses in tumor cell lines led to a successful infection of these cells, suggesting a gain-of-function by the acquisition of greater infectious capacity as compared with that of the parental rotaviruses. The electropherotype profiles suggest that unique tumor cell-adapted isolates were derived from reassortment of parental rotaviruses. Infection produced by such rotavirus isolates induced chromatin modifications compatible with apoptotic cell death.

N-Acetylcysteine treatment of rotavirus-associated diarrhea in children.

Rotaviruses are the leading cause of severe, acute, and dehydrating diarrhea affecting children under 5 years of age worldwide. Despite an important reduction in rotavirus-caused deaths as a consequence of the rotavirus vaccine, alternative or complementary strategies for preventing or treating rotavirus-associated diarrhea are needed mainly in the poorest countries. We describe the cases of four rotavirus-unvaccinated 12-13-month-old girls and a 5-year-old boy who developed rotavirus-associated diarrhea confirmed by enzyme-linked immunosorbent assay, Western blotting, and immunochemistry analyses. After the first day of diarrheal episodes, three of the five patients were immediately administered oral N-acetylcysteine (NAC) 60 mg/kg daily, divided into three equal doses every 8 hours. The other two patients did not receive NAC and served as controls. Administration of NAC resulted in a decreased number of diarrheal episodes, excretion of fecal rotavirus antigen, and resolution of symptoms after 2 days of treatment. Our results suggest that NAC treatment after the first diarrheal episode could be an efficient strategy for treating rotavirus-affected children and preventing the associated severe life-threatening accompanying dehydration.