Institutional one health and animal-human health connections in Nthongoni,Eastern Kenya

In recent years, there has been increased global advocacy for the use of a collaborative, multisectoral, and transdisciplinary approach: a One Health approach, with the goal to achieve optimal health outcomes for people, animals and their shared environment. This study explored One Health implementation and practice in Kenya. Further, I used a case study of Nthongoni, a remote rural area in Eastern Kenya, to help us to understand and think about implementation of One Health in an area where mainstream biomedical system runs parallel to or is in conflict with, a deeply entrenched indigenous health system. I used a qualitative research approach including participant observation, and key informant and general respondents' in-depth interviews. Data was transcribed verbatim, translated, checked for consistency and coded for content and thematic analysis. The findings indicate that although Kenya's One Health approach was hailed as a key strategy and a model for other countries in the region, the approach faced significant challenges including insufficient funding, competing priorities and concerns over its sustainability. But while the formal One Health is embroiled in structural and politico-economic influences that curtail its operationalization and success, this study illuminates a lay one health that is part of lived realities in Nthongoni, inviting us to reflect on the place for and status of traditional healers, and meaning of health for people and animals. The study further provokes our thoughts over whether One Health should integrate or do away with traditional health systems, or be abandoned altogether. I argue that incorporating traditional health knowledge and practitioners in One Health might help to make health care more robust and culturally responsive. The work contributes to debates on anthropology of health in general and to anthropological understanding of both the lay one health and the institutional One Health agenda.     

Development and validation of standardized severity rating scale to assess the consistency of drug-drug interaction severity among various drug information resources

BackgroundThe consistency in reporting the severity of drug interactions across the drug information resources is important in guiding the appropriate clinical use of drug-pairs, to minimize the associated adverse events. This necessitates the need of a standardized severity rating scale, that can accommodate the different severity ratings of the same interacting drug-pair into a reasonable severity category, that can ease the consistency assessment among different drug information resources.ObjectiveTo develop and validate a standardized severity rating scale that can ease the consistency assessment among the various drug information resources.MethodsThe definitions of various severity rating categories as documented in the eight drug information resources was consolidated to develop a standardized severity rating scale. Thus developed rating scale was validated using twenty commonly used drug-pairs. Fleiss' kappa score was used as an indicator for assessing overall consistency among various drug information resources, whereas, Cohen's kappa was used as an indicator of level of consistency between two drug information resources and between individual drug information resource and newly developed standardized severity rating scale.ResultsThe newly developed standardized severity rating scale classifies the severity of drug-drug interactions into three categories namely mild, moderate and major. The Fleiss' kappa score was improved from 0.047 to 0.176, indicating improved strength of agreement [Average pairwise agreement: 16% Vs 36.7%] among various drug information resources. The average pairwise Cohen's kappa was 0.082 [Strength of agreement: poor] in original severity ratings whereas it was improved to 0.198 [Strength of agreement: almost equal to fair] in standardized severity rating scale.ConclusionThe newly developed standardized severity rating scale can be used as a tool to assess the consistency of severity rating categories among the various drug information resources.     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Interactions between immune response to fungal infection and microRNAs: The pioneer tuners

Due to their physiological and biological characteristics, numerous fungi are potentially emerging pathogens. Active dynamicity of fungal pathogens causes life-threatening infections annually impose high costs to the health systems. Although immune responses play crucial roles in controlling the fate of fungal infections, immunocompromised patients are at high risk with high mortality. Tuning the immune response against fungal infections might be an effective strategy for controlling and reducing the pathological damages. MicroRNAs (miRNAs) are known as the master regulators of immune response. These single-stranded tuners (18-23 bp non-coding RNAs) are endogenously expressed by all metazoan eukaryotes and have emerged as the master gene expression controllers of at least 30% human genes. In this review article, following the review of biology and physiology (biogenesis and mechanism of actions) of miRNAs and immune response against fungal infections, the interactions between them were scrutinised. In conclusion, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. Undoubtedly, advanced studies in this field, further identifying of miRNA roles in governing the immune response, pave the way for inclusion of miRNA-related immunotherapeutic in the treatment of life-threatening fungal infections.     

新型冠状病毒肺炎（COVID-19）患者抗病毒用药监护的研究进展

为提高抗病毒药物在新型冠状病毒肺炎(COVID-19)患者尤其是需要多药联合患者中的合理性和安全性,结合《新型冠状病毒肺炎诊疗方案(试行第七版)》提到的抗病毒药物,通过查阅文献、搜集各抗病毒药物说明书和MCDEX合理用药信息支持系统的相关信息,总结这些抗病毒药物的临床药动学特征、药物相互作用及不良反应信息,提出合理的用药监护建议。从药动学和药物相互作用角度加强抗病毒药物在COVID-19患者中的用药监护,可提高药物使用安全性,保障患者的合理用药。     

Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease

Abstract

To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins.