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.     

基于"心肺交互"的无创循环监测指标评估容量反应性研究进展

基于"心肺交互"的动态血流动力学指标是目前指导液体复苏的金标准,但这些指标的监测往往通过有创方法且操作较复杂。近年来,随着每搏连续无创血压监测系统(continuous non-invasive arterial pressure,CNAP)、血流动力学监测系统和超声测量血流动力学指标等无创手段在临床的出现,这些指标在容量治疗中的应用开辟了新的前景。文章描述了CNAP和超声测量的基于"心肺交互"的动态血流动力学指标及其评估患者容量反应性的临床应用。两种手段在临床上的应用存在一定的争议。CNAP评估患者容量反应性是临床液体治疗的新趋势,但其应用条件有限,故目前不提倡完全采用无创的方法来指导液体治疗。但是,其可以作为有创监测的补充,帮助临床医师进行正确的液体管理,减少不良事件的发生。     

Physiologically based pharmacokinetic modelling of oxycodone drug–drug interactions

Oxycodone is an opioid analgesic with several pharmacologically active metabolites and relatively narrow therapeutic index. Cytochrome P450 (CYP) 3A4 and CYP2D6 play major roles in the metabolism of oxycodone and its metabolites. Thus, inhibition and induction of these enzymes may result in substantial changes in the exposure of both oxycodone and its metabolites. In this study, a physiologically based pharmacokinetic (PBPK) model was built using GastroPlus™ software for oxycodone, two primary metabolites (noroxycodone, oxymorphone) and one secondary metabolite (noroxymorphone). The model was built based on literature and in house in vitro and in silico data. The model was refined and verified against literature clinical data after oxycodone administration in the absence of drug–drug interactions (DDI). The model was further challenged with simulations of oxycodone DDI with CYP3A4 inhibitors ketoconazole and itraconazole, CYP3A4 inducer rifampicin and CYP2D6 inhibitor quinidine. The magnitude of DDI (AUC ratio) was predicted within 1.5-fold error for oxycodone, within 1.8-fold and 1.3–4.5-fold error for the primary metabolites noroxycodone and oxymorphone, respectively, and within 1.4–4.5-fold error for the secondary metabolite noroxymorphone, when compared to the mean observed AUC ratios. This work demonstrated the capability of PBPK model to simulate DDI of the administered compounds and the formed metabolites of both DDI victim and perpetrator. However, the predictions for the formed metabolites tend to be associated with higher uncertainty than the predictions for the administered compound. The oxycodone model provides a tool for forecasting oxycodone DDI with other CYP3A4 and CYP2D6 DDI perpetrators that may be co-administered with oxycodone.     

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.