Endoplasmic Reticulum and Mitochondria Contacts Correlate with the Presence and Severity of NASH in Humans

The interaction between the mitochondria and the endoplasmic reticulum (ER) is essential for hepatocyte function. An increase in ER-mitochondria contacts (ERMCs) is associated with various metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes, and its progressive form non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. However, the role of ERMCs in the progression of NAFL to NASH is still unclear. We assessed whether ERMCs could correlate with NAFLD severity. We used a proximity ligation assay to measure the abundance of ERMCs in liver biopsies from patients with biopsy-proven NAFLD (n = 48) and correlated the results with histological and metabolic syndrome (MetS) features. NAFLD patients were included according to inclusion and exclusion criteria, and then assigned to NAFL (n = 9) and NASH (n = 39) groups. ERMCs density could discriminate NASH from NAFL (sensitivity 61.5%, specificity 100%). ERMCs abundance correlated with hepatocellular ballooning. Moreover, the density of ERMCs increased with an increase in the number of MetS features. In conclusion, ERMCs increased from NAFL to NASH, in parallel with the number of MetS features, supporting a role for this interaction in the pathophysiology of NASH

Fibrosis Evaluation by Transient Elastography in Patients With Long-Term Sustained HCV Clearance

BACKGROUND: Reversibility of advanced fibrosis after HCV-clearance is an important goal of therapy. OBJECTIVES: Measuring liver stiffness (LS) by transient elastography (TE) might be helpful in this setting. PATIENTS AND METHODS: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC) and sustained virological response (SVR) after Peg-Interferon (IFN) plus ribavirin since at least 18 months. HCV-eradication was confirmed searching for serum HCV-RNA (TMA® sensitivity > 5-10 IU/ml). Data from literature reported the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). RESULTS: TE was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in 28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed since achieving SVR was 36 months (range: 18-77, SD¬¬:18). Stratifying patients according to the histological stage assessed before treatment, a clear-cut gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P = 0.001). Overall, 86 patients had lower values of LS than the expected LS values according to Metavir-stage. At multivariate logistic analysis γ-GT and histological steatosis were independently associated with persistence of higher values of LS. CONCLUSION: Long term responders to IFN-based therapies have lower LS values than those who are untreated and still viraemic. High levels of γ-GT and liver steatosis, all markers of insulin resistance, may hamper reduction of liver stiffness after HCV-clearance

Acute Infections and Environmental Exposure to Organochlorines in Inuit Infants from Nunavik

The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p < 0.05). No association was found when postnatal exposure was considered. These results show a possible association between prenatal exposure to OCs and acute infections early in life in this Inuit population

'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

Self-similarity of contact line depinning from textured surfaces

The mobility of drops on surfaces is important in many biological and industrial processes, but the phenomena governing their adhesion, which is dictated by the morphology of the three-phase contact line, remain unclear. Here we describe a technique for measuring the dynamic behaviour of the three-phase contact line at micron length scales using environmental scanning electron microscopy. We examine a superhydrophobic surface on which a drop’s adhesion is governed by capillary bridges at the receding contact line. We measure the microscale receding contact angle of each bridge and show that the Gibbs criterion is satisfied at the microscale. We reveal a hitherto unknown self-similar depinning mechanism that shows how some hierarchical textures such as lotus leaves lead to reduced pinning, and counter-intuitively, how some lead to increased pinning. We develop a model to predict adhesion force and experimentally verify the model’s broad applicability on both synthetic and natural textured surfaces.National Science Foundation (U.S.) (CAREER Award 0952564)DuPont MIT AllianceNational Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Science Foundation (U.S.) (Award ECS-0335765

Selling lottery products to minors: factors affecting retailer compliance

Illegal gambling by adolescent minors has become a major issue in many societies and lottery gambling is often considered a "gateway" to gambling more generally among this age group. The purpose of this study was to identify the influencing factors that affect retailer compliance concerning the selling of lottery products to minors. The research team received the original data (i) directly from the sales agents of the Austrian Lotteries after their responsible gambling training of the retailer in 2014/2015 (Round 1: n = 5032), (ii) directly from a third-party agency carrying out test purchases (i.e., "mystery shopping") in 2014 (Round 2: n = 1421), and (iii) retailers’ responses to their attitudes to youth protection issues (through direct interface with the research team) in 2015 (Round 3: n = 4516). The data from a total of 1036 participants who had taken part in all three rounds was analyzed in the present study. Results showed that in 13.1% of mystery shopping checks (n = 1421), lottery products were sold to a test purchaser under the age of 16 years. The analysis also showed that the older the test purchaser, the greater the likelihood that a lottery product was sold. Under-age lottery sales to girls were over three times more prevalent than sales to boys. Finally, the analysis showed that the higher the number of responsible gambling training sessions completed in the past and the more positive the attitude towards mystery shopping, the higher the compliance rate not to sell a lottery product to young mystery shoppers. Recommendations to increase compliance and raise the awareness among retailers are presented

Can Monkeys Make Investments Based on Maximized Pay-off?

Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella) and thirteen macaques (Macaca fascicularis, Macaca tonkeana) in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible