Role of orexin-1 receptors in the dorsal hippocampus (CA1 region) in expression and extinction of the morphine-induced conditioned place preference in the rats

Abstract Orexinergic system is involved in reward processing and drug addiction. Objectives here, we investigated the effect of intra-hippocampal CA1 administration of orexin-1 receptor (OX1r) antagonist on the expression, and extinction of morphine-induced place preference in rats. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. Two experimental plots were designed; SB334867 as a selective OX1r antagonist was dissolved in 12% DMSO, prepared in solutions with different concentrations (3, 30, and 300 nM), and microinjected into the CA1 and some neighboring regions (0.5 μl/side), bilaterally. CPP score and locomotor activity were recorded during the CPP test. Results demonstrated that intra-CA1 administration of the OX1r antagonist attenuates the expression of morphine-induced CPP. Furthermore, higher concentrations of SB334867 facilitated the extinction period of morphine-induced CPP and reduced its latency. Nevertheless, solely administration of DMSO did not have any influence on the CPP scores and locomotion in both phases. Our findings suggest that OX1rs in the CA1 region of the hippocampus are involved in the expression of morphine CPP. Moreover, blockade of OX1rs could facilitate extinction and may extinguish the ability of drug-related cues. It seems that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behaviors. Keywords Reward Orexin-1 receptor Dorsal hippocampus (CA1) Extinction Morphine Conditioned place preference Ra

Orexin 1 receptors in the anterior cingulate and orbitofrontal cortex regulate cost and benefit decision-making

Abstract Orexin neurons are discretely localized within the lateral hypothalamus and have widespread projections into all areas of the brain. In addition, several lines of evidence specify that orexins may also participate in the regulation of a variety of affective and cognitive processes. The Orexin-1 receptor (OX1r) is distributed extensively throughout the prefrontal cortex (PFC). Delay-based decision- making is mediated largely by the orbitofrontal cortex (OFC) while effort- based decision-making is controlled by the anterior cingulated cortex (ACC). Hence, in the present study, a series of experiments were conducted to clarify the role of OX1r in the mPFC (ACC and/or OFC) in cost and benefit decision-making. The rats were trained in a delay and/or effort-based form of cost-benefit T-maze decision-making task. Two goal arms were different in the amount of accessible reward and cost. Before surgery, all animals were selecting the high reward arm and pay the cost on almost every trial. During the test days, the rats received local injections of either DMSO 20% /0.5 μl, as a vehicle, or SB334867 (3, 30 and 300 nM/0.5 μl), as a selective OX1r antagonist, within the ACC and/or OFC. The results of this study showed that the bilateral microinjection of SB334867 into ACC and/or OFC changed the preference to a low reward arm with no cost, indicating the role of OX1 receptors in cost and benefit decision- making. From these results, it can be implied that OX1 receptors in the mPFC play a crucial role for allowing the animal to evaluate and pay the cost to acquire greater rewards. Keywords Delay-based decision-making Effort-based decision-making Orexin Orbitofrontal cortex Anterior cingulate cortex Ra

The contributions of public health policies and healthcare quality to gender gap and country differences in life expectancy in the UK

Background: In many high-income countries, life expectancy (LE) has increased, with women outliving men. This gender gap in LE (GGLE) has been explained with biological factors, healthy behaviours, health status, and sociodemographic characteristics, but little attention has been paid to the role of public health policies that include/affect these factors. This study aimed to assess the contributions of avoidable causes of death, as a measure of public health policies and healthcare quality impacts, to the GGLE and its temporal changes in the UK. We also estimated the contributions of avoidable causes of death into the gap in LE between countries in the UK. // Methods: We obtained annual data on underlying causes of death by age and sex from the World Health Organization mortality database for the periods 2001–2003 and 2014–2016. We calculated LE at birth using abridged life tables. We applied Arriaga’s decomposition method to compute the age- and cause-specific contributions into the GGLE in each period and its changes between two periods as well as the cross-country gap in LE in the 2014–2016 period. // Results: Avoidable causes had greater contributions than non-avoidable causes to the GGLE in both periods (62% in 2001–2003 and 54% in 2014–2016) in the UK. Among avoidable causes, ischaemic heart disease (IHD) followed by injuries had the greatest contributions to the GGLE in both periods. On average, the GGLE across the UK narrowed by about 1.0 year between 2001–2003 and 2014–2016 and three avoidable causes of IHD, lung cancer, and injuries accounted for about 0.8 years of this reduction. England & Wales had the greatest LE for both sexes in 2014–2016. Among avoidable causes, injuries in men and lung cancer in women had the largest contributions to the LE advantage in England & Wales compared to Northern Ireland, while drug-related deaths compared to Scotland in both sexes. // Conclusion: With avoidable causes, particularly preventable deaths, substantially contributing to the gender and cross-country gaps in LE, our results suggest the need for behavioural changes by implementing targeted public health programmes, particularly targeting younger men from Scotland and Northern Ireland

The effects of different concentrations of probiotic Saccharomyces cerevisia on growth performance and survival rate of rainbow trout (Oncorhynchus mykiss), fry and resistance against salinity

In the present study, a yeast strain Saccharomyces cerevisia var. elipsoidous, acting as probiotic, was administered to rainbow trout (Oncorhynchus mykiss Walbaum, 1792) fry during a period of 21 days and the effects of the yeast on improvement of growth and resistance against environmental stress were evaluated with respect to fish fed on yeast free feed (control group). The control treatment consisted of a standard commercial diet, and the treatments consisted of the control diet supplemented with 0, 1, 5 and 10% yeast (w/w). The results demonstrate the beneficial effects of probiotics on the characteristics of rainbow trout, as the Specific Growth Ratio (SGR), body weight gain (%BWG) and protein conversion ratio (PER) in 5% yeast-fed fish were significantly (P<0.05) enhanced by probiotic administration. On the contrary, no effect on the fry growth performance, mortality, condition factor (CF), food conversion ratio (FCR) and histological assessment was shown. A significant (P<0.05) increase in lipid content of the carcass was detected in diets with probiotic compareD to 0% and the control treatments. Ash and protein contents of the carcass increased and decreased with an increase in yeast amount, respectively. Challenge with different levels of salinity (10 and 15 ppt) after 24 h revealed 100% survival in treatments containing yeast as probiotic, and difference with control group was significant (p<0.05) indicating that S. cerevisia could enhance the resistance against salinity stress. Addition of yeast in concentration of 5% to the diet is recommended during the early period of rainbow trout fry farming to achieve the best results on growth performance and feed efficiency.Keywords: Saccharomyces cerevisia var. elipsoidous, Oncorhynchus mykiss, probiotic, survival and growth rate, carcass qualityAfrican Journal of Biotechnology, Vol. 13(10), pp. 1160-1168, 5 March, 201

A Cost-Minimization Analysis of Day-Care Versus in-Patient Surgery for Five Most Common General Surgical Procedures

Objective: This study aimed to compare costs of Day-care versus in-patient surgery for five most common general surgical proce-dures in a general hospital in Iran. Methods: In this retrospective study the records of all patients who underwent five most common general surgical operations (in-cluding Hernia, Hemorrhoid, Fistula, Pilonidal Sinus and Varicocele) between March 2011 and March 2013 were reviewed. The data about costs of these procedures was collected by a checklist, designed by the authors, one year before and one year after establishing the Day-Care ward in the hospital. The checklist was designed on the basis of 14 financial items related to surgical patients. All costs were measured from the provider's perspective. Results: The results of this study showed that after implementing day-care surgery ward, inpatient care costs, such as medi-cine/drugs, physician visits, medical consumable, personnel and hotel, reduced significantly per each procedure. However, the costs directly associated with each surgery, such as drugs and consumable, surgeon's wage and anesthesia costs, between these two periods was not significantly different. The highest amount of savings was related to the personnel costs, with 997,000 IRR reductions. On average, total cost of each procedure was reduced by 2,031,358 IRR after implementation of day-care ward. Conclusion: The findings from this study demonstrate that day-care surgery is a cost saving method compared to in-patient surgery for five most common general surgical procedures. It is recommended that hospital managers consider establishing day-care ward and conducting surgical procedures, in particular elective general surgical procedures, in this regimen, to decrease hospital costs and to make hospital beds free, for other patients who are more in need of specialized medical and nursing skills

Economic evaluation of participatory learning and action with women's groups facilitated by Accredited Social Health Activists to improve birth outcomes in rural eastern India

BACKGROUND: Neonatal mortality remains unacceptably high in many low and middle-income countries, including India. A community mobilisation intervention using participatory learning and action with women’s groups facilitated by Accredited Social Health Activists (ASHAs) was conducted to improve maternal and newborn health. The intervention was evaluated through a cluster-randomised controlled trial conducted in Jharkhand and Odisha, eastern India. This aims to assess the cost-effectiveness this intervention. METHODS: Costs were estimated from the provider’s perspective and calculated separately for the women’s group intervention and for activities to strengthen Village Health Sanitation and Nutrition Committees (VHNSC) conducted in all trial areas. Costs were estimated at 2017 prices and converted to US dollar (USD). The incremental cost-effectiveness ratio (ICER) was calculated with respect to a do-nothing alternative and compared with the WHO thresholds for cost-effective interventions. ICERs were calculated for cases of neonatal mortality and disability-adjusted life years (DALYs) averted. RESULTS: The incremental cost of the intervention was USD 83 per averted DALY (USD 99 inclusive of VHSNC strengthening costs), and the incremental cost per newborn death averted was USD 2545 (USD 3046 inclusive of VHSNC strengthening costs). The intervention was highly cost-effective according to WHO threshold, as the cost per life year saved or DALY averted was less than India’s Gross Domestic Product (GDP) per capita. The robustness of the findings to assumptions was tested using a series of one-way sensitivity analyses. The sensitivity analysis does not change the conclusion that the intervention is highly cost-effective. CONCLUSION: Participatory learning and action with women’s groups facilitated by ASHAs was highly cost-effective to reduce neonatal mortality in rural settings with low literacy levels and high neonatal mortality rates. This approach could effectively complement facility-based care in India and can be scaled up in comparable high mortality settings

Participatory women’s groups and counseling through home visits to improve child growth in rural eastern India: protocol for a cluster randomised controlled trial

Background: Childhood stunting (low height-for-age) is a marker of chronic undernutrition and predicts children’s subsequent physical and cognitive development. An estimated 52 million children in India are stunted. There is a broad consensus on determinants of child undernutrition and interventions to address it, but a lack of operational research testing strategies to increase the coverage of these interventions in high burden areas. Our study aims to assess the impact, costeffectiveness, and scalability of a community intervention involving a government-proposed community-based worker to improve growth in children under two

Cost and cost-effectiveness of mHealth interventions for the prevention and control of type 2 diabetes mellitus: a protocol for a systematic review

INTRODUCTION: Type 2 diabetes mellitus (T2DM) remains one of the most common chronic diseases of adulthood which creates high degrees of morbidity and mortality worldwide. The incidence of T2DM continues to rise and recently, mHealth interventions have been increasingly used in the prevention, monitoring and management of T2DM. The aim of this study is to systematically review the published evidence on cost and cost-effectiveness of mHealth interventions for T2DM, as well as assess the quality of reporting of the evidence. METHODS AND ANALYSIS: A comprehensive review of PubMed, EMBASE, Science Direct and Web of Science of articles published until January 2019 will be conducted. Included studies will be partial or full economic evaluations which provide cost or cost-effectiveness results for mHealth interventions targeting individuals diagnosed with, or at risk of, T2DM. The quality of reporting evidence will be assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results will be presented using a flowchart following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Graphical and tabulated representations of the results will be created for both descriptive and numerical results. The cost and cost-effectiveness values will be presented as reported by the original studies as well as converted into international dollars to allow comparability. As we are predicting heterogenous results, we will conduct a narrative and interpretive analysis of the data. ETHICS AND DISSEMINATION: No formal approval or review of ethics is required for this systematic review as it will involve the collection and analysis of secondary data. This protocol follows the current PRISMA-P guidelines. The review will provide information on the cost and cost-effectiveness of mHealth interventions targeting T2DM. These results will be disseminated through publication and submission to conferences for presentations and posters. PROSPERO REGISTRATION NUMBER: CRD42019123476

Diagnostic and Therapeutic Costs of Patients With a Diagnosis of Or Suspected of Coronavirus Disease in Iran

Objectives: To understand the social and individual effects of the disease and make decisions on the allocation of health resources, it is necessary to understand the economic burden of coronavirus disease (COVID-19); however, there are limited data in this field. This study aimed to estimate diagnostic and therapeutic costs of patients with a diagnosis of or suspected of COVID-19 disease admitted to hospitals in northeast Iran. Methods: This descriptive and analytical research was conducted as a retrospective study using the data collected from 2980 patients admitted to 30 hospitals from February to April 2020 in Iran. For data collection, an appropriate data capture tool was designed to record detailed resource use. A multivariate regression analysis was performed to examine the association between the treatment costs and sociodemographic, disease severity, and underlying diseases. Data were analyzed using Excel 2017 (Microsoft, Redmond, WA) and SPSS version 21 software (SPSS Inc., Chicago, IL). Results: The inpatient costs per patient were Int$416, of which 74% were paid by social health insurance systems, 19% by the government, and 7% by the patients. The largest cost components were hoteling (37%) and medicine (36%). The 4 subscales of age, sex, underlying disease, and severity predicted 48.6% of the cost variance. Conclusion: Understanding the economic consequences of diseases can help policymakers to make plans to reduce out-of-pocket payments and make plans for funding. Since COVID-19 is a newly emerging disease and there is no definitive cure for the disease, the discovery of an effective medicine may alter medical costs and reduce the hospital length of stay, therefore significantly reducing treatment costs