A pharmacokinetic -- viral kinetic model describes the effect of alisporivir monotherapy or in combination with peg-IFN on 2 hepatitis C virologic response

Alisporivir is a cyclophilin inhibitor with demonstrated in vitro and in vivo activity against hepatitis C 11 virus (HCV). We estimated antiviral effectiveness of alisporivir alone or in combination with 12 pegylated-Inteferon (peg-IFN) in 88 patients infected with different HCV genotypes treated for four 13 weeks. The pharmacokinetics of both drugs were modeled and used as driving functions for the viral 14 kinetic model. Genotype was found to significantly affect pegylated-Inteferon effectiveness ($\epsilon$= 86.3% 15 and 99.1% in genotype-1/4 and genotype-2/3, respectively, p\textless{}10 -7) and infected cells loss rate ($\delta$= 16 0.22 vs 0.39 day -1 in genotype-1/4 and genotype-2/3, respectively, p\textless{}10 -6). Alisporivir effectiveness 17 was not significantly different across genotype and was high for doses $\ge$600 mg QD. We simulated 18 virologic responses with other alisporivir dosing regimens in HCV genotype-2/3 patients using the 19 model. Our predictions consistently matched the observed responses, demonstrating that this model 20 could be a useful tool for anticipating virologic response and optimize alisporivir-based therapies

Optimization of culture conditions of Streptomyces antibioticus strain 1083 to improve the antimicrobial activity against Aeromonas hydrophila

Fish is a healthy, high protein and low fat food that encourages the health and growth of people, especially children. However, in fact fish is very sensitive to many diseases which affects the productivity and quality of fish. Therefore, identifying the cause of the diseases and finding preventive measures become an urgent task today. In the previous study, we isolated Streptomyces antibioticus strain 1083 that has the ability to antagonize Aeromonas hydrophila - a pathogenic bacterium in fish. Based on the obtained results, we continue to perform this study to determine optimal conditions for the culture of S. antibioticus strain 1083 in order to produce antimicrobial compounds against A. hydrophila. The production of antagonists by the strain 1083 was optimized by controlling the condition of different inoculations such as media, pH, temperature and incubation period. The results indicated that International Streptomyces Project 2 (ISP2) was the best medium for S. antibioticus strain 1083 to produce the highest antimicrobial activity against A. hydrophila with 32 mm in diameter of inhibited zone. The actinomycete strain 1083 could express the maximum antimicrobial activity when they were incubated in shaker incubator (200rpm) at 40oC with pH8 in 8 days. The ability of the actinomycete strain in antagonism against A. hydrophila was evaluated by adding different culture medium volume of S. antibioticus strain 1083. With adding 10% cultured solution volume of S. antibioticus strain 1083 into the culture medium of A. hydrophila, after 1 day of inoculation the number of pathogenic bacteria cells were completely eliminated

ANNOUNCEMENT OF THE SUSTAINABLE DEVELOPMENT REPORT OF VIETNAMESE HOTEL ENTERPRISES

The purpose of this study is to examine the factors affecting the publication of sustainability reports from the perspective of managers at 4-5 star hotels in Vietnam. Issues of corporate size, profitability, legal regulation, corporate governance and technology of the company were mentioned as factors that may affect the publication of the report on sustainable development. The author has synthesized the relevant background theory as well as previous outstanding studies on the issue of publishing sustainable development reports. SPSS 20 software was used to test the relationship between the factors affecting the publication of the Sustainable Development Report based on the manager's point of view. The results of the study show that the factors of business size, profitability, and legal regulations all affect the publication of sustainable development reports at 4-5 star hotels in Vietnam. A new finding of this study is that the two factors of corporate governance and the company's technology combine into a public governance factor based on technology and it is the technology that has the strongest influence on the publication of the Sustainable Development Report. The study once again confirms the relationship between the factors affecting the publication of the Sustainable Development Report and is a document to help researchers understand better in the research context in Vietnam, one of the leading countries in the world developing countries and have limited access to and use of secondary data

Investigation of anti-inflammatory lignans from the leaves of Symplocos sumuntia Buch-Ham ex D Don (Symplocaceae)

Purpose: To investigate the anti-inflammatory activity of Symplocos sumuntia Buch.-Ham. ex D. Don and identify the main secondary metabolites responsible for this effect.Methods: The in vitro anti-inflammatory activity of the plant extract and isolated compounds was determined in terms of the ability to inhibit the production of nitric oxide (NO), and expressions of iNOS and COX-2 proteins in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Compounds were isolated and identified by spectroscopic methods.Results: The methanol extract of S. sumuntia leaves showed strong inhibitory effects on nitric oxide (NO) production and expression of iNOS and COX-2 in LPS-induced RAW264.7 cells. A phytochemical assay-guided fractionation of the methanol extract of S. sumuntia leaves led to the isolation of four lignans which are arctigenin (1), matairesinol (2), monomethylpinoresinol (3) and pinoresinol (4). These compounds were identified for the first time from S. sumuntia. All four compounds inhibited the production of nitric oxide (NO), with arctigenin showing the most potent activity with half-maximal inhibitory concentration (IC50) value of 4.08 μM.Conclusion: S. sumuntia is a promising source of anti-inflammatory agents, which may clarify to the therapeutic use of this plant in Vietamese traditional medicine.Keywords: Symplocos sumuntia, Symplocos caudata, Lignan, Arctigenin, Anti-inflammator

Ebola Virus Infection: a review on the pharmacokinetic and pharmacodynamic properties of drugs considered for testing in human efficacy trials

International audienceThe 2014-2015 outbreak of Ebola virus disease (EVD) is the largest epidemic to date in terms of number of cases, of death and affected areas. In October 2015, no antiviral agents had proven an antiviral efficacy in patients. However in September 2014 WHO inventoried and regularly updated since then a list of potential drug candidates with demonstrated antiviral efficacy in vitro or in animal models. This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537) and anticoagulant drug (rNAPc2).Here, we review the pharmacokinetic and pharmacodynamic information that are presently available on these drugs, using data obtained in healthy volunteers for pharmacokinetics and data obtained in human clinical trials or animal models for pharmacodynamics. Future studies evaluating these drugs in clinical trials will be critical to confirm their efficacy in humans, propose appropriate doses and evaluate the possibility of treatment combinations

The effect of emotional intelligence on the performance of auditors

This study aims to evaluate the impact of effective emotional intelligence on the work of auditors in Ho Chi Minh City, Ho Chi Minh. The authors conducted a survey for 355 auditors at companies and organizations operating in the field of auditing. The results show that there were 4 factors of emotional intelligence that affect job performance, arranged in the following sequence: (1) Perception of emotions, (2) Positive thinking with emotions, (3) Understand emotions, (4) Control emotions. This is the basis for the authors to give some implications to improve the emotional intelligence characteristics of auditors towards work efficiency

Risk assessment, implementation of occupational health, safety and hygiene in small and medium manufacturing enterprises: A case study in central Vietnam

This study aims to identify and evaluate the influence of the factors affecting the implementation of occupational health and safety of employees and employers and its impact on occupational health and safety and legalize risk assessment in small and medium-sized manufacturing enterprises in central Vietnam through the survey among 246 business representatives and data processing through the software SPSS 20 and AMOS 20. The results show that there are 3 factors affecting the implementation of occupational health, safety and hygiene. In order: (1) Safety regulations and instructions; (2) Occupational health, safety policy and (3) Occupational health and safety training. There is no relationship between the impacts on the implementation of occupational health and safety of the employer. In addition, a very interesting finding about the relationship of factors implementing occupational health and safety of employers was a positive influence on the legalization of risk assessment activities. On the basis of these results, employees, business owners and state management agencies will have grounds to offer useful solutions in risk assessment in order to better perform safety work and occupational health

Bringing social and cultural considerations into environmental management for vulnerable coastal communities: Responses to environmental change in Xuan Thuy National Park, Nam Dinh Province, Vietnam

This paper elaborates the importance of considering social and cultural factors within management responses to environmental change in coastal areas. The case study taken is Xuan Thuy National Park in Nam Dinh Province, Vietnam. This is a marginalised coastal area where rising sea levels, increasing storm surges and saltwater intrusion place pressure on coastal ecosystems, yet where communities continue to rely on these same ecosystems for agriculture- and aquaculture-related livelihoods. We interview stakeholders in Xuan Thuy National Park, connecting these with a narrative review of existing research into social and environmental change in the park to understand research gaps and challenges for vulnerable coastal areas like the Nam Dinh coast. Based on our findings, we suggest that whilst the effects of a changing environment on physical health and economic activity are increasingly well understood, effects on wellbeing and social relations can be even more immediate and profound in daily living. In turn, we argue environmental management has a crucial role to play not only for ecosystem-based adaptation, but also in sustaining wellbeing and allowing culturally meaningful practices to continue – especially in coastal regions where changes can be even more intense and immediate. However, we caution that whilst techno-scientific solutions grounded in environmental management do have significant potential in reducing impacts of extreme events and slower-onset environmental changes, they must not divert attention away from structural issues that can make some people or areas more vulnerable in the first instance

Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study

Background By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fl uid, including clearance parameters. Methods In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fl uid at follow-up every 3–6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodefi cient mice to test for infectivity. We used a linear mixed-eff ect model to analyse the dynamics of virus persistence in seminal fl uid over time. Findings We enrolled 26 participants and tested 130 seminal fl uid specimens; median follow up was 197 days (IQR 187–209 days) after enrolment, which corresponded to 255 days (228–287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73–181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fl uid of –0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fl uid at 115 days (90% prediction interval 72–160) and 294 days (212–399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in aff ected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. Interpretation Time to clearance of Ebola virus RNA from seminal fl uid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted \u3b4 and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted \u3bb, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis