Snake venom phospholipase A2s exhibit strong virucidal activity against SARS-CoV-2 and inhibit the viral spike glycoprotein interaction with ACE2.

The COVID-19 pandemic caused by SARS-CoV-2 requires new treatments both to alleviate the symptoms and to prevent the spread of this disease. Previous studies demonstrated good antiviral and virucidal activity of phospholipase A2s (PLA2s) from snake venoms against viruses from different families but there was no data for coronaviruses. Here we show that PLA2s from snake venoms protect Vero E6 cells against SARS-CoV-2 cytopathic effects. PLA2s showed low cytotoxicity to Vero E6 cells with some activity at micromolar concentrations, but strong antiviral activity at nanomolar concentrations. Dimeric PLA2 from the viper Vipera nikolskii and its subunits manifested especially potent virucidal effects, which were related to their phospholipolytic activity, and inhibited cell-cell fusion mediated by the SARS-CoV-2 spike glycoprotein. Moreover, PLA2s interfered with binding both of an antibody against ACE2 and of the receptor-binding domain of the glycoprotein S to 293T/ACE2 cells. This is the first demonstration of a detrimental effect of PLA2s on ß-coronaviruses. Thus, snake PLA2s are promising for the development of antiviral drugs that target the viral envelope, and could also prove to be useful tools to study the interaction of viruses with host cells.

Effect of music therapy on stress in chemically dependent people: a quasi-experimental study / Efeito da musicoterapia sobre o estresse de dependentes químicos: estudo quase-experimental / Efecto de la musicoterapia sobre el estrés de dependientes químicos: estudio cuasi-experimental

ABSTRACT Objective: to evaluate the effect of music therapy on the stress of chemically dependent people. Method: quasi-experimental study conducted at a philanthropic institution with 18 chemically dependent people undergoing treatment. Salivary cortisol (stress hormone) was collected in three moments: before, 60 minutes after, and 120 minutes after a music therapy group intervention. Statistical analysis adopted a significance level of p < 0.05 and used the Wilcoxon and Kruskal-Wallis non-parametric tests. Results: after 60 minutes of intervention, there was a statistically significant reduction in mean salivary cortisol levels (p < 0.001). A reduction was also noted after 120 minutes, but without statistical significance (p = 0.139). Conclusion: a single session of 60 minutes of group music therapy was able to reduce stress (salivary cortisol levels) of chemically dependent people.

RESUMO Objetivo: avaliar o efeito da musicoterapia sobre o estresse de dependentes químicos. Método: estudo quase-experimental realizado em instituição filantrópica com 18 dependentes químicos em tratamento. O cortisol salivar (hormônio do estresse) foi coletado antes, 60 e 120 minutos após única intervenção musicoterapêutica realizada em grupo. A análise estatística adotou nível de significância de p < 0,05 mediante aplicação dos testes não paramétricos de Wilcoxon e de Kruskal-Wallis. Resultados: após 60 minutos da intervenção musicoterapêutica, houve redução estatisticamente significante nas médias dos níveis de cortisol salivar (p < 0,001). Após 120 minutos, também houve redução, mas sem significância estatística (p = 0,139). Conclusão: sessão única de 60 minutos de musicoterapia em grupo mostrou-se capaz de reduzir o estresse (níveis de cortisol salivar) de dependentes químicos.

RESUMEN Objetivo: evaluar el efecto de la musicoterapia sobre el estrés de dependientes químicos. Método: estudio cuasi-experimental realizado en institución filantrópica con 18 dependientes químicos en tratamiento. El cortisol salivar (hormona del estrés) fue recogido antes, 60 y 120 minutos después de una única intervención musicoterapéutica realizada en grupo. El análisis estadístico adoptó un nivel de significancia de p <0,05 mediante la aplicación de las pruebas no paramétricas de Wilcoxon y de Kruskal-Wallis. Resultados: después de 60 minutos de la intervención musicoterapéutica, hubo reducción estadísticamente significativa en las medias de los niveles de cortisol salivar (p <0,001). Después de 120 minutos, también hubo reducción, pero sin significancia estadística (p = 0,139). Conclusión: uma única sesión de 60 minutos de musicoterapia en grupo se mostró capaz de reducir el estrés (niveles de cortisol salivar) de dependientes químicos.

Effect Analysis of Hospital Expenses after Calling off Drug - addition and Price Adjustment of Medical Service in Public Hospitals / 现代医院

Objective To provide advice and basis for further reform of the medical service price by analyzing the effect on hospital expenses after calling off drug-addition and price adjustment of medical service in public hospitals at the end of 2016. Methods Comparing the changes of hospital expenses based on the data of hospital expenses before and after the implementation of the price reform policy in a provincial public hospital in Sichuan. Results After canceling the drug-addition and adjustment of medical service price, whether in the whole hospital, in the surgical department or in the non-operative department, the average cost of drugs for discharged patients has been reduced, the average costs of surgical operation and anesthesia has been increased, the ratio of change remains consistent with the policy adjustment range, the composition of drug charges and bed fee has been decreased and the proportion of drugs still ranks first in the composition ratio. Conclusion Canceling the drug-addition and price adjustment of medical service have a significant effect on hospital expenses. The adjustment of medical service price reflects the technical value of medical staff.

Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population-based study.

The authors compared the effectiveness of thiazide diuretic (TD), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic hypertension using MarketScan Databases 2010-2014. Multivariable Cox regression models assessed whether the addition of a new antihypertensive drug, treatment discontinuation, or switch and major cardiovascular or cerebrovascular events varied across groups. A total of 565 009 patients started monotherapy with ACEIs (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a higher risk for either drug addition or discontinuation than patients who took ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68-0.70] vs HR, 0.81 [95% CI, 0.80-0.81]), ARBs (HR, 0.67 [95% CI, 0.66-0.68] vs HR, 0.66 [95% CI, 0.65-0.67]), and CCBs (HR, 0.85 [95% CI, 0.84-0.87] vs HR, 0.94 [95% CI, 0.93-0.95]). Conversely, patients who took TDs experienced a lower risk of clinical events compared with patients who took ACEIs (HR, 1.24 [95% CI, 1.15-1.33]), ARBs (HR, 1.28 [95% CI, 1.18-1.39]), and CCBs (HR, 1.35 [95% CI, 1.25-1.46]). Our results provide a strong rationale for choosing TDs as first-line monotherapy for the control of hypertension.

Impact Analysis of the Drug Zero Plus Policies for Patients' Burden in a Tertiary Hospital / 中国医院管理

In order to effectively assess the impact of the drug zero plus policies on the burden of patients in the process of the separation of clinic from pharmacy in Shanghai,the cost data of a drug zero plus hospital and the maternal hospital from 2013 to 2014 was collected,and then the average cost,average pharmacy cost,average person cost,return rate and the ratio of pharmacy were analyzed.The results show the indicators of the burden of patients decreased significantly,while it was suggested that the government needs to increase compensation,continue to adjust the medical price and strengthen medical insurance to persistently promote the separation of clinic from pharmacy.

Novel antiviral activity of bromocriptine against dengue virus replication.

Dengue virus (DENV) infectious disease is a major public health problem worldwide; however, licensed vaccines or specific antiviral drugs against this infection are not available. To identify novel anti-DENV compounds, we screened 1280 pharmacologically active compounds using focus reduction assay. Bromocriptine (BRC) was found to have potent anti-DENV activity and low cytotoxicity (half maximal effective concentration [EC50], 0.8-1.6 µM; and half maximal cytotoxicity concentration [CC50], 53.6 µM). Time-of-drug-addition and time-of-drug-elimination assays suggested that BRC inhibits translation and/or replication steps in the DENV life cycle. A subgenomic replicon system was used to verify that BRC restricts RNA replication step. Furthermore, a single amino acid substitution (N374H) was detected in the NS3 protein that conferred resistance to BRC. In summary, BRC was found to be a novel DENV inhibitor and a potential candidate for the treatment of DENV infectious disease.

Identification and Analysis of Antiviral Compounds Against Poliovirus.

The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

Effects of National Medicine Policy on the Use of Essential Medicines in A Public Hospital at County-level / 中国药房

OBJECTIVE:To provide reference for promoting the further implementation of national essential medicine system and related policies. METHODS:Hospital information system(HIS),Excel 2007 and SPSS 13.0 software were adopted to statisti-cally compare the changes in equipping the specific varieties of national essential medicines and the differences in the overall use of national essential medicines before and after implementing the National Essential Medicine System (2012 edition)(referred to NEMS,2012 edition) and cancelling drug addition policy in a public hospital in Chengdu. RESULTS:After implementing the NEMS(2012 edition),60 kinds of equipping national essential medicines increased in the hospital,including 38 kinds of chemical medicines and biological products,22 kinds of Chinese patent medicines;compared with before,the percentage of essential medi-cines to prescription drugs,prescription rate of essential medicines,average essential medicine in a single prescription and prescrip-tion rate of all essential medicines were significantly improved(P0.05). CONCLUSIONS:After implementing the NEMS(2012 edition)and cancelling drug addition policy,the equipping na-tional essential medicines are still insufficient,some indexes do not meet the requirements of Sichuan Province. It is suggested that the public medical and health institution at county-level should to choose suitable national essential medicines based on its specific situation;strengthen publicity and education,improve the popularity of physicians to national essential medicine system;strengthen the assessment and management of the use of essential medicines for physicians. Meanwhile,the government and the relevant de-partments are suggested to explore more effective and reasonable compensation mechanism to improve the enthusiasm of physicians to use the national essential medicines.

Reward-system effect (BAS rating), left hemispheric "unbalance" (alpha band oscillations) and decisional impairments in drug addiction.

The current research explored the impact of cortical frontal asymmetry (left-lateralization effect) and Behavioral Activation System (BAS) on Substance Use Disorder (SUD) in decisional processes using the Iowa Gambling Task (IGT). Forty SUD participants and forty-two controls (CG) were tested using the IGT. Behavioral responses (gain/loss options), BIS/BAS scores and lateralized alpha band modulation (LTA) were considered. The SUD group increased the tendency to opt in favor of the immediate reward (loss strategy) more than the long-term option (win strategy) compared to the CG. Secondly, higher reward-subscale scores were observed in SUD. Thirdly, SUD showed an increase in left-hemisphere activation in response to losing (with immediate reward) choices in comparison with the CG. An imbalanced left hemispheric effect related to higher BAS trait could explain this "reward bias," because these components were found to explain (through the regression analysis) the main behavioral deficits.

Empirical study of the compensation mechanism with the drug addition policy canceled at municipal public hospitals of Anshan city / 中华医院管理杂志

Objective To explore the feasibility of various compensation approaches and their combination after canceling the drug addition at municipal public hospitals in Anshan city.Methods 2008~201 1 medical services,balance of payments of Anshan municipal public hospitals during 2008~201 1 were analyzed,to calculate the balance of profit and loss of the hospitals with the drug addition canceled,as well as the effects of various compensation models and their combinations on hospitals’balance,government financial burden,costs of health insurance and patients’out-of-packet costs.Results Without drug addition,hospitals are found with surplus drop,and doubled number of years in deficit.Losses incurred by the canceling can be covered partly by pricing adjustment of medical services or collection of pharmaceutical service surcharge,with complete compensation by collection of medical service surcharge;government financial subsidies for large equipment depreciation or medical services offer part of the compensation,which is affordable by government finance.Such deficits cannot be covered completely by any single approach,yet they can be greatly eased by a combination of the approaches mentioned above.With impacts on all stakeholders in consideration,the optimal solution is the combination of the scheme with adjusted services price plus collection of pharmaceutical service surcharge and medical services compensation.Conclusion With the drug addition policy canceled,the establishment and perfection of the compensation mechanism calls for a synergy of pricing,health insurance and government finance.

A computational hypothesis for allostasis: delineation of substance dependence, conventional therapies, and alternative treatments.

The allostatic theory of drug abuse describes the brain's reward system alterations as substance misuse progresses. Neural adaptations arising from the reward system itself and from the antireward system provide the subject with functional stability, while affecting the person's mood. We propose a computational hypothesis describing how a virtual subject's drug consumption, cognitive substrate, and mood interface with reward and antireward systems. Reward system adaptations are assumed interrelated with the ongoing neural activity defining behavior toward drug intake, including activity in the nucleus accumbens, ventral tegmental area, and prefrontal cortex (PFC). Antireward system adaptations are assumed to mutually connect with higher-order cognitive processes occurring within PFC, orbitofrontal cortex, and anterior cingulate cortex. The subject's mood estimation is a provisional function of reward components. The presented knowledge repository model incorporates pharmacokinetic, pharmacodynamic, neuropsychological, cognitive, and behavioral components. Patterns of tobacco smoking exemplify the framework's predictive properties: escalation of cigarette consumption, conventional treatments similar to nicotine patches, and alternative medical practices comparable to meditation. The primary outcomes include an estimate of the virtual subject's mood and the daily account of drug intakes. The main limitation of this study resides in the 21 time-dependent processes which partially describe the complex phenomena of drug addiction and involve a large number of parameters which may underconstrain the framework. Our model predicts that reward system adaptations account for mood stabilization, whereas antireward system adaptations delineate mood improvement and reduction in drug consumption. This investigation provides formal arguments encouraging current rehabilitation therapies to include meditation-like practices along with pharmaceutical drugs and behavioral counseling.

Rational Consideration on Canceling Drug Addition / 中国卫生经济

Objective: Through deeply analyzing “Canceling Drug Addition” policy in the pilot public hospitals, it manages to confront the challenges of “drug maintaining medicine, pharmaceuticals government tenders, pharmaceutical services and essential drug system”, provides advices and suggestions for deepening medical reform. Methods: From systemically learning and understanding the current medical reform policies, closely connected with practice, sketch out a good policy of “addressing both the symptoms and root causes”. Results: Canceling Drug Addition is an operation in the “deep water area” of health care reform, affecting the situation as a whole, which must be supported by relevant reform policies and implementation measures. Conclusion: It is necessary to discuss Canceling Medicine Markup, to innovate the current drug pricing policy and to improve the current price of medical services system, to build hospital quality mechanisms.

Progress of dopamine D3 receptors / 国际儿科学杂志

The role of dopamine D3 receptors playing in drug dependence has attracted a lot of attention.Pharmacological experiments suggest that dopamine D3 receptors be involved in mechanism of drug addiction and affect the movement and behavior of rodents. Dopamine D3 receptor gene is considered as a candidate gene related to dopaminergic system dysfunction including schizophrenic disorders and essential tremor.