Estudio zoométrico realizado con ovinos de raza ripollesa

Peer Reviewe

Oral Contraceptive Use and Clinical Outcomes in Patients with Multiple Sclerosis

Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002, respectively). These patients were also more likely to have a benign disease course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p<0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for MSSS β: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course

Fingolimod Treatment Modulates PPARγ and CD36 Gene Expression in Women with Multiple Sclerosis

Fingolimod is an oral immunomodulatory drug used in the treatment of multiple sclerosis (MS) that may change lipid metabolism. Peroxisome proliferator-activated receptors (PPAR) are transcription factors that regulate lipoprotein metabolism and immune functions and have been implicated in the pathophysiology of MS. CD36 is a scavenger receptor whose transcription is PPAR regulated. The objective of this study was to evaluate whether fingolimod treatment modifies PPAR and CD36 gene expression as part of its action mechanisms. Serum lipoprotein profiles and PPAR and CD36 gene expression levels in peripheral leukocytes were analysed in 17 female MS patients before and at 6 and 12 months after fingolimod treatment initiation. Clinical data during the follow-up period of treatment were obtained. We found that fingolimod treatment increased HDL-Cholesterol and Apolipoprotein E levels and leukocyte PPARγ and CD36 gene expression. No correlations were found between lipid levels and variations in PPARγ and CD36 gene expression. PPARγ and CD36 variations were significantly correlated during therapy and in patients free of relapse and stable disease. Our results suggest that PPARγ and CD36-mediated processes may contribute to the mechanisms of action of fingolimod in MS. Further studies are required to explore the relation of the PPARγ/CD36 pathway to the clinical efficacy of the drug and its involvement in the pathogenesis of the disease.info:eu-repo/semantics/publishedVersio

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

Genome-wide association; Survival; COVID-19Asociación de todo el genoma; Supervivencia; COVID-19Associació de tot el genoma; Supervivència; COVID-19The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10−8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10−8). A total of 113 variants were associated with survival at P-value < 1.0 × 10−5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.Istituto Buddista Italiano Soka Gakkai funded A.R.’s and F.C.’s project “PAT-COVID: Host genetics and pathogenetic mechanisms of COVID-19” with the 8 × 1000 funds (ID n. 2020-226 2016_RIC_3), that, in part, included the present study. We also thank the generous contribution of Banca Intesa San Paolo to R.A. The funding organisations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript

Direct and label-free monitoring of albumin in 2D fatty liver disease model using plasmonic nanogratings

Reproducció del document publicat a: https://doi.org/10.3390/nano10122520Non-alcoholic fatty liver (NAFLD) is a metabolic disorder related to a chronic lipid accumulation within the hepatocytes. This disease is the most common liver disorder worldwide, and it is estimated that it is present in up to 25% of the world’s population. However, the real prevalence of this disease and the associated disorders is unknown mainly because reliable and applicable diagnostic tools are lacking. It is known that the level of albumin, a pleiotropic protein synthesized by hepatocytes, is correlated with the correct function of the liver. The development of a complementary tool that allows direct, sensitive, and label-free monitoring of albumin secretion in hepatocyte cell culture can provide insight into NAFLD’s mechanism and drug action. With this aim, we have developed a simple integrated plasmonic biosensor based on gold nanogratings from periodic nanostructures present in commercial Blu-ray optical discs. This sensor allows the direct and label-free monitoring of albumin in a 2D fatty liver disease model under flow conditions using a highly-specific polyclonal antibody. This technology avoids both the amplification and blocking steps showing a limit of detection within pM range (≈0.26 ng/mL). Thanks to this technology, we identified the optimal fetal bovine serum (FBS) concentration to maximize the cells’ lipid accumulation. Moreover, we discovered that the hepatocytes increased the amount of albumin secreted on the third day from the lipids challenge. These data demonstrate the ability of hepatocytes to respond to the lipid stimulation releasing more albumin. Further investigation is needed to unveil the biological significance of that cell behavior

Apolipoprotein E Polymorphism Interacts with Cigarette Smoking in Progression of Multiple Sclerosis

BACKGROUND AND PURPOSE: The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients. METHODS: Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated. RESULTS: There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS (P = 0.033) and MSSS (P = 0.023) in comparison with non-smokers. CONCLUSION: Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.info:eu-repo/semantics/publishedVersio

Impact of the COVID-19 pandemic on hepatitis B and C elimination: An EASL survey

Hepatitis B virus; Hepatitis C virus; COVID-19 pandemicVirus de la hepatitis B; Virus de la hepatitis C; Pandemia de COVID-19Virus de l'hepatitis B; Virus de l'hepatitis C; Pandèmia del COVID-19Background & Aims The World Health Organization (WHO) HBV and HCV elimination targets, set in 2016 and based on projections to 2030, were unable to consider the impact of intervening factors. To evaluate the impact of the COVID-19 pandemic on viral hepatitis elimination programs, the European Association for the Study of the Liver (EASL) conducted a survey in liver centers worldwide in 2021. Methods A web-based questionnaire was distributed (May-July 2021) to all EASL members representing clinical units providing HBV and HCV hepatitis care. Results are expressed as absolute numbers and reduction rates for each care activity. Results Data were collected from 32 European and 12 non-European clinical centers. Between January 2019 (pre-pandemic) and December 2020 (during the pandemic), chronic HBV consultations decreased by 32% and 26%, new referrals by 38% and 39%, HBV testing rates by 39% and 21% (for HBsAg detection) and 30% and 22% (for HBV DNA detection), and new HBV treatments by 20% and 44% (p = 0.328) in European and non-European centers, respectively. With regard to HCV during the same time frame, the overall reductions were 39% and 50% for consultations, 49% and 49% for new referrals, 11% and 38% for HCV RNA detection, and 51% and 54% for new HCV antiviral treatments for European and non-European Centers, respectively (p = 0.071). Conclusions All steps in the viral hepatitis care cascade have been hampered by the COVID-19 pandemic, with a comparable impact across different centers. These data reaffirm the pandemic’s major effect on global viral hepatitis elimination programs and suggest that actions to achieve the WHO 2030 targets should be reconsidered and revised to account for each country's progress relative to pre-pandemic values

Randomised phase 2 study (JADE) of the HBV capsid assembly modulator JNJ-56136379 with or without a nucleos(t)ide analogue in patients with chronic hepatitis B infection

Chronic hepatitis; Hepatitis BHepatitis crònica; Hepatitis BHepatitis crónica; Hepatitis BObjective We present the final analysis results of the phase 2 JADE study (ClinicalTrials.gov Identifier: NCT03361956). Design 232 patients with chronic hepatitis B (CHB) not currently treated at study start (NCT) at study start or virologically suppressed were randomised to receive 75 mg (part 1) or 250 mg (part 2) JNJ-56136379, a hepatitis B virus (HBV)–capsid assembly modulator, one time per day or placebo with nucleos(t)ide analogue (NA) (tenofovir disoproxil fumarate/entecavir) or JNJ-56136379 alone (NCT-only) for ≥24 and ≤48 weeks. Results In patients who are NCT hepatitis B e-antigen (HBeAg) positive, JNJ-56136379 75 mg+NA and 250 mg+NA showed limited mean (SE) hepatitis B surface antigen (HBsAg) declines (0.14 (0.10) and 0.41 (0.15), respectively) from baseline at Week 24 (primary endpoint; placebo+NA: 0.25 (0.11) log10 international unit (IU)/mL). In patients who are NCT HBeAg positive, mean (SE) HBV DNA declines at Week 24 were 5.53 (0.23) and 5.88 (0.34) for JNJ-56136379 75 mg+NA and 250 mg+NA, respectively, versus 5.21 (0.42) log10 IU/mL for placebo+NA. In NCT patients, mean (SE) HBV RNA declines were 2.96 (0.23) and 3.15 (0.33) versus 1.33 (0.32) log10 copies/mL, respectively. Patients with HBsAg declines had HBeAg and hepatitis B core-related antigen (HBcrAg) declines and some early on-treatment isolated alanine aminotransferase flares. Viral breakthrough occurred with JNJ-56136379 monotherapy with the emerging resistant-variant T33N, but not with JNJ-56136379+NA. JNJ-56136379 treatment beyond Week 24 had a generally small additional effect on viral markers. No study treatment-related serious adverse events or clinically significant changes in laboratory parameters occurred. Conclusions In patients with non-cirrhotic CHB, JNJ-56136379+NA showed pronounced reductions in HBV DNA and HBV RNA, limited HBsAg or HBeAg declines in patients who are NCT HBeAg positive, and was well tolerated, but no clear benefit with regards to efficacy of JNJ-56136379 over NA was observed.This study was sponsored by Janssen (award/grant number: not applicable)

Association between congenital toxoplasmosis and parent-reported developmental outcomes, concerns, and impairments in 3 year old children

Background: Information is lacking on the effects of congenital toxoplasmosis on development, behavior, and impairment in later childhood, as well as on parental concerns and anxiety. This information is important for counselling parents about the prognosis for an infected child and for policy decisions on screening. Methods: We prospectively studied a cohort of children identified by screening for toxoplasmosis in pregnant women or neonates between 1996 and 2000 in ten European centers. At 3 years of age, parents of children with and without congenital toxoplasmosis were surveyed about their child's development, behavior, and impairment, and about parental concerns and anxiety, using a postal questionnaire. Results: Parents of 178/223 (80%) infected, and 527/821 (64%) uninfected children responded. We found no evidence that impaired development or behavior were more common in infected children, or that any potential effect of congenital toxoplasmosis was masked by prenatal treatment. Parents of infected children were significantly more anxious and reported more visual problems in their children. Conclusion: On average, children aged three to four years with congenital toxoplasmosis identified by screening and treated during infancy in this European setting had risks of abnormal development and behavior similar to uninfected children. Parental anxiety about infected children needs to be addressed by clinicians. Future studies with longer follow up and clinician-administered assessments may be better able to detect any subtle differences in child outcomes

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.

Background: We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres. Methods: Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks. Results: The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres. Conclusion: Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies