Blocking of interleukin-10 receptor--a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus

Chronic hepatitis C virus (HCV) infection is associated with weak CD4+ T-helper type 1 reactivity and enhanced interleukin-10 production to HCV antigens. Here we demonstrate in vitro that monoclonal antibody-induced blockade of IL-10 receptor (IL-10R) generates a favorable balance of CD4+ T-cell responses to HCV. The addition of anti-IL-10R to mononuclear cells leads to a dose-dependent increase of T-cell proliferative response to HCV core, non-structural proteins 3 and 4. In competition experiments, anti-IL-10R reversed the inhibitory effect of IL-10 on HCV-specific T-cell proliferation. Furthermore, the blockade of IL-10R altered the balance towards type 1 antiviral T-cell reactivity with an increased frequency of HCV-specific IFN-gamma producing T-cells and IFN-gamma secretion. The impact of IL-10R blockade on T-cell reactivity to HCV demonstrates the major role of IL-10 in suppressing antiviral T-cell responses. Blocking IL-10 activity may be a useful immunotherapy approach to enhance the efficacy of antiviral treatment in chronic hepatitis C.     

Public engagement in setting healthcare priorities: a ranking exercise in Cyprus

Background

In countries such as Cyprus the financial crisis and the recession have severely affected the funding and priority setting of the health care system. There is evidence highlighting the importance of population’ preferences in designing priorities for health care settings. Although public preferences have been thorough analysed in many countries, there is a research gap in terms of simultaneously investigating the relative importance and the weight of differing and competing criteria for determining healthcare priority settings. The main objective of the study was tο investigate public preferences for the relative utility and weight of differing and competing criteria for health care priority setting in Cyprus.

Methods

The ‘conjoint analysis’ technique was applied to develop a ranking exercise. The aim of the study was to identify the preferences of the participants for alternative options. Participants were asked to grade in a priority order 16 hypothetical case scenarios of patients with different disease and of diverse socio-economic characteristics awaiting treatment. The sample was purposive and consisted of 100 Cypriots, selected from public locations all over the country.

Results

It was revealed that the “severity of the disease” and the “age of the patient” were the key prioritization criteria. Participants assigned the smallest relative value to the criterion “healthy lifestyle”. More precisely, participants older than 35 years old assigned higher relative importance to “age”, while younger participants to the “severity of the disease”. The “healthy lifestyle” criterion was assigned to the lowest relative importance to by all participants.

Conclusion

In Cyprus, public participation in health care priority setting is almost inexistent. Nonetheless, it seems that the public’s participation in this process could lead to a wider acceptance of the healthcare system especially as a result of the financial crisis and the upcoming reforms implemented such as the establishment of the General System of Health Insurance.

     

Intraductal papilloma of the breast in an 11-year-old male patient: a case report

Intraductal papilloma (IP) constitutes a rare benign neoplasm among male population with only few reports on childhood patients. Herein, we describe an 11-year-old IP male patient who presented with spontaneous nipple discharge of his right breast.     

A Proposed Instrument for the Assessment of Job Satisfaction in Greek Mental NHS Hospitals

Since its introduction in 1983, the Greek NHS is under an almost constant reform, aiming improvement on the efficiency and the quality of provided services. The national program of psychiatric reform “Psychargos” introduced new models of therapeutic approach to the care of the mentally ill, that required expansion of the existing roles and development of new roles of the healthcare staff. Consequently, the efficient management of the healthcare workforce in Greek mental facilities was identified as a primary determinant of the successful implementation of the program. Primary objective of this study was the development of a research framework for the assessment of job satisfaction in Greek Mental Health Hospitals. Among the objectives was the evaluation of the capacity of the underlying motivators and hygiene factors and the identification of potential correlations of the global job satisfaction and the motivation and retention factors with the demographic, social and occupational characteristics of the employees. A custom questionnaire was developed, based on Herzberg two-factor theory, after a systematic review of the relevant literature. The instrument was constructed by two parts and 37 items. Ten items addressed the sociodemographic characteristics of the subjects, while the remaining 27 items were distributed in 11 subscales which addressed the global satisfaction index and the “retention” and the “motivation” variables. The instrument was validated by means of the Cronbach alpha for each subscale and by confirmatory factor analysis. The study was conducted at the Public Mental Hospital of Chania (PMHC). From the 300 employees of the PMHC, 133 subjects successfully responded to the questionnaire (response rate, 44.3%). In accordance to former surveys, subjects presented average scores in the global satisfaction index (GSI). The professional category of the employee was identified as the primary determinant of the GSI. Nurses presented statistically significant lower scores in comparison to the rest of the employees. Strong Pearson correlations were detected between GSI and “working conditions”, “interpersonal relations”, “organization”, “salary” and “supervision” factors. The retention factors presented stronger impact on GSI in comparison to the motivation ones. The results of the study indicate that the proposed instrument presents satisfactory validity and reliability for the assessment of job satisfaction in Greek mental NHS hospitals.     

Pharmacological Development of Target-Specific Delocalized Lipophilic Cation-Functionalized Carboranes for Cancer Therapy

Purpose

Tumor cell heterogeneity and microenvironment represent major hindering factors in the clinical setting toward achieving the desired selectivity and specificity to malignant tissues for molecularly targeted cancer therapeutics. In this study, the cellular and molecular evaluation of several delocalized lipophilic cation (DLC)-functionalized carborane compounds as innovative anticancer agents is presented.

Methods

The anticancer potential assessment of the DLC-carboranes was performed in established normal (MRC-5, Vero), cancer (U-87 MG, HSC-3) and primary glioblastoma cancer stem (EGFR^pos, EGFR^neg) cultures. Moreover, the molecular mechanism of action underlying their pharmacological response is also analyzed.

Results

The pharmacological anticancer profile of DLC-functionalized carboranes is characterized by: a) a marked in vitro selectivity, due to lower concentration range needed (ca. 10 fold) to exert their cell growth-arrest effect on U-87 MG and HSC-3, as compared with that on MRC-5 and Vero; b) a similar selective growth inhibition behavior towards EGFR^pos and EGFR^neg cultures (>10 fold difference in potency) without, however, the activation of apoptosis in cultures; c) notably, in marked contrast to cancer cells, normal cells are capable of recapitulating their full proliferation potential following exposure to DLC-carboranes; and, d) such pharmacological effects of DLC-carboranes has been unveiled to be elicited at the molecular level through activation of the p53/p21 axis.

Conclusions

Overall, the data presented in this work indicates the potential of the DLC-functionalized carboranes to act as new selective anticancer therapeutics that may be used autonomously or in therapies involving radiation with thermal neutrons. Importantly, such bifunctional capacity may be beneficial in cancer therapy.

     

Attitudes towards Olive Oil Usage,Domestic Storage,and Knowledge of Quality: A Consumers’ Survey in Greece

Consumption of unbranded olive oil obtained in bulk has previously been reported to be very high in Greece, underlining the need to investigate knowledge regarding its health attributes and storage practices, two areas that can affect oil quality. This study aimed to investigate Greek consumers’ use and choice of olive oil, their knowledge about its quality, as well as domestic storage practices of olive oil. A cross-sectional survey was conducted in a representative sample of 857 Greek households that consume olive oil, using a previously validated questionnaire. Most participating households use olive oil produced by themselves or by their extended family or friends (60.3%), and only 27.4% purchase branded olive oil, while 57% reported using extra virgin olive oil (EVOO). Only 38.4% of the respondents reported optimal domestic storage practices to maintain olive oil quality, with a significant greater percentage of non-producers group compared to olive oil producers. In all areas of Greece, the higher the knowledge of olive oil quality, the higher the probability of consumers selecting EVOO and perceiving olive oil price as low. The present survey highlights the need to heighten consumers’ knowledge of olive oil attributes and correct storage practices and awareness about branded EVOO and its superior quality.