Vertical Macular Asymmetry Measures Derived From SD-OCT for Detection of Early Glaucoma.

PurposeTo test the hypothesis that vertical asymmetry in macular ganglion cell/inner plexiform layer (GCIPL) thickness can improve detection of early glaucoma.MethodsSixty-nine normal eyes and 101 glaucoma eyes had macular imaging with spectral-domain optical coherence tomography (OCT; 200 × 200 cube). The resulting GCIPL thickness matrix was grouped into a 20 × 20 superpixel array and superior superpixels were compared to their inferior counterparts. A global asymmetry index (AI) was defined as the grand mean of the asymmetry ratios. To measure local asymmetry, the corresponding thickness measurements of three rows above and below the horizontal raphe were compared individually and in combinations. Global and local AIs were compared to the best-performing GCIPL thickness parameters with area under the receiver operating curves (AUC) and sensitivity/specificities.ResultsAge or axial length did not influence AIs in normal subjects (P ≥ 0.08). Global and local AIs were significantly higher in the glaucoma group compared to normal eyes. Minimum (AUC = 0.962, 95% confidence interval [CI]: 0.936-0.989) and inferotemporal thickness (AUC = 0.944, 95% CI: 0.910-0.977; P = 0.122) performed best for detection of early glaucoma. The AUC for global AI was 0.851 (95% CI: 0.792-0.909) compared to 0.916 (95% CI: 0.874-0.958) for the best local AI. Combining minimum or inferotemporal GCIPL thickness and the best local AI led to higher partial AUCs (0.088 and 0.085, 90% specificity, P = 0.120 and 0.130, respectively) than GCIPL thickness measures.ConclusionsMacular vertical thickness asymmetry measures did not perform better than sectoral or minimum GCIPL thickness for detection of early glaucoma. Combining local asymmetry parameters with the best sectoral GCIPL thickness measures enhanced this task

Extinction of Hepatitis C Virus by Ribavirin in Hepatoma Cells Involves Lethal Mutagenesis

Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is under investigation as an antiviral strategy that aims at counteracting the adaptive capacity of viral quasispecies, and avoiding selection of antiviral-escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is important to establish whether ribavirin, the purine nucleoside analogue used in anti-HCV therapy, acts as a mutagenic agent during virus replication in cell culture. Here we report the effect of ribavirin during serial passages of HCV in human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity and of the transition types associated with ribavirin mutagenesis, resulting in HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the major contributory factor to mutagenesis since mycophenolic acid evoked a similar decrease in GTP without an increase in mutant spectrum complexity. The intracellular concentration of the other nucleoside-triphosphates was elevated as a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid-mediated, extinction of HCV occurred via a decrease of specific infectivity, a feature typical of lethal mutagenesis. We discuss some possibilities to explain disparate results on ribavirin mutagenesis of HCV

Cardiopulmonary Rehabilitation Improves Respiratory Muscle Function and Functional Capacity in Children with Congenital Heart Disease : A Prospective Cohort Study

Critical surgical and medical advances have shifted the focus of congenital heart disease (CHD) patients from survival to achievement of a greater health-related quality of life (HRQoL). HRQoL is influenced, amongst other factors, by aerobic capacity and respiratory muscle strength, both of which are reduced in CHD patients. This study evaluates the influence of a cardiopulmonary rehabilitation program (CPRP) on respiratory muscle strength and functional capacity. Fifteen CHD patients, ages 12 to 16, with reduced aerobic capacity in cardiopulmonary exercise testing (CPET) were enrolled in a CPRP involving strength and aerobic training for three months. Measurements for comparison were obtained at the start, end, and six months after the CPRP. A significant improvement of inspiratory muscle strength was evidenced (maximum inspiratory pressure 21 cm H2O, 23%, p < 0.01). The six-minute walking test showed a statistically and clinically significant rise in walked distance (48 m, p < 0.01) and a reduction in muscle fatigue (1.7 out of 10 points, p = 0.017). These results suggest CPRP could potentially improve respiratory muscle function and functional capacity, with lasting results, in children with congenital heart disease, but additional clinical trials must be conducted to confirm this finding

Direct-acting antivirals are effective and safe in HCV/HIV-coinfected liver transplant recipients who experience recurrence of hepatitis C: A prospective nationwide cohort study.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/µL. HIV-RNA was <50 copies/mL in 96% of patients. The DAA regimens administered were SOF + LDV ± RBV (34%), SOF + SMV ± RBV (31%), SOF + DCV ± RBV (27%), SMV + DCV ± RBV (5%), and 3D (3%), with no differences between the groups. Treatment was well tolerated in both groups. Rates of SVR (negative serum HCV-RNA at 12 weeks after the end of treatment) were high and similar for coinfected and monoinfected patients (95% and 94%, respectively; P = .239). Albeit not significant, a trend toward lower SVR rates among patients with advanced fibrosis (P = .093) and genotype 4 (P = .088) was observed. In conclusion, interferon-free regimens with DAAs for post-LT recurrence of HCV infection in HIV-infected individuals were highly effective and well tolerated, with results comparable to those of HCV-monoinfected patients

Illness perceptions and explanatory models of viral hepatitis B & C among immigrants and refugees: a narrative systematic review.

© 2015 Owiti et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants' knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. METHODS: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman's explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. RESULTS: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. CONCLUSION: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia

Twenty Years of Hepatitis C in the Treviso District (Local Health Unit 2): Treatments, Clinical Management and Cost Analysis

Chronic hepatitis C virus (HCV) infection is a global health problem, and about 10-30% of patients develop cirrhosis or hepatocellular carcinoma several years after being infected. In past decades, treatment of HCV infection was based on peginterferon and ribavirin, which lead to a sustained virologic response (SVR) in only 50-60% of patients. Since 2014, direct acting antiviral (DAA) agents have been available. Patients administered DAA agents usually reach SVR in 12 weeks. The aim of this study was to estimate the cost analysis of these innovative drugs while also taking into account the total health expenditure for managing HCV infection. The pharmaceutical and hospitalisation databases of the Local Health Unit (ULSS2) of Treviso were retrospectively analysed between 1997 and 2016 for each HCV patient. During this twenty-year period, people affected by HCV totalled 2,949; 277 of these patients were treated with DAA and, of these, only 2% did not reach SVR. The HCV genotype 1b was the most common, accounting for 58% of the total patients. The treatment for HCV genotype 3 was associated with higher costs. The expenses for the new treatments were found to be significantly higher compared to those for the old ones (i.e., peginterferon and ribavirin). The average costs for a cycle of therapy were €8,000 and €24,000 for interferon and DAA therapy, respectively. Total health care costs associated with HCV (excluding DAA treatments) for an individual HCV infection patient were estimated to be €32,000. Our results confirm the high efficacy of DAA therapy. Furthermore, these agents improve the clinical conditions and reduce both the treatment cost and health care in patients with HCV infection

Flavor violating leptonic decays of τ and μ leptons in the Standard Model with massive neutrinos

We have revisited the computations of the flavor violating leptonic decays of the τ and μ leptons into three lighter charged leptons in the Standard Model with massive neutrinos. We were driven by a claimed unnaturally large branching ratio predicted for the τ − → μ − l + l − (l = μ, e) decays (Pham, Eur Phys J C 8:513 1999), which was at odds with the corresponding predictions for the μ − → e−e−e+ processes (Petcov, Sov J Nucl Phys 25:340 1977). In contrast with the prediction in [17], our results are strongly suppressed and in good agreement with the approximationmade in Ref. [15], where masses and momenta of the external particles were neglected in order to deal with the loop integrals. However -as a result of keeping external momenta and masses in the computation of the dominant penguin and box diagrams- we even find slightly smaller branching fractions. Therefore, we confirm that any future observation of such processes would be an unambiguous manifestation of new physics beyond the Standard Model.Finally, we also acknowledge support from Conacyt through projects FOINS-296-2016 (Fronteras de la Ciencia), and 236394 and 250628 (Ciencia Básica)

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region