Development of a transmission-blocking malaria vaccine: Progress,challenges, and the path forward

New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives.     

The Roadmap concept: using early on-treatment virologic responses to optimize long-term outcomes for patients with chronic hepatitis B

Several large observational, longitudinal studies of the natural history of chronic hepatitis B (CHB) have demonstrated that high levels of hepatitis B virus (HBV) replication are associated with long-term risk of cirrhosis, decompensation, hepatocellular carcinoma, and liver-related mortality. The corollary is also true—profound and sustained suppression either spontaneously or during antiviral therapy will prevent disease progression and complications. Multiple analyses of various baseline factors and on-treatment responses have identified the absolute HBV DNA level after 24 weeks of therapy as the best predictor of long-term efficacy. Lower 24-week serum HBV DNA levels after lamivudine, telbivudine, or entecavir are associated with higher rates of maintained HBV DNA nondetectability, ALT normalization, HBeAg seroconversion, and lack of resistance. Patients with undetectable serum HBV DNA levels after 24 weeks have the best long-term outcomes while those with levels remaining above 10,000 copies per ml are unlikely to benefit from long-term therapy with that particular agent and either the addition or switch to another antiviral agent with increased potency but without cross resistance could be considered at this time point. In the future, improved on-treatment monitoring should facilitate treatment strategies to optimize long-term outcomes among patients receiving oral antiviral therapy for CHB.     

三维路径图技术在支架辅助栓塞颅内宽颈动脉瘤中的应用

目的探讨三维路径图技术在支架辅助栓塞颅内宽颈动脉瘤治疗中的应用。方法回顾性分析利用三维路径图技术对10例颅内宽颈动脉瘤患者进行介入栓塞治疗的过程和效果。结果10例动脉瘤均成功栓塞,术后即刻栓塞结果按改良的Raymond分级：动脉瘤完全栓塞7例（Ⅰ级）,瘤颈残留2例（Ⅱ级）,瘤体显影1例（Ⅲ级）。术后随访1～6个月,临床无再出血,急性缺血1例表现为下肢单瘫。结论三维路径图技术具有实时跟踪、高清晰度和精确度等优势,对栓塞治疗起着重要的指导作用。     

3D roadmap in neuroangiography: technique and clinical interest

We present the first clinical results obtained with a novel technique: the three-dimensional [3D] roadmap. The major difference from the standard 2D digital roadmap technique is that the newly developed 3D roadmap is based on a rotational angiography acquisition technique with the two-dimensional [2D] fluoroscopic image as an overlay. Data required for an accurate superimposition of the previously acquired 3D reconstructed image on the interactively made 2D fluoroscopy image, in real time, are stored in the 3D workstation and constitute the calibration dataset. Both datasets are spatially aligned in real time; thus, the 3D image is accurately superimposed on the 2D fluoroscopic image regardless of any change in C-arm position or magnification. The principal advantage of the described roadmap method is that one contrast injection allows the C-arm to be positioned anywhere in the space and allows alterations in the distance between the x-ray tube and the image intensifier as well as changes in image magnification. In the clinical setting, the 3D roadmap facilitated intravascular neuronavigation with concurrent reduction of procedure time and use of contrast medium.     

重视慢性乙型肝炎规范治疗基础上的个体化优化治疗

慢性乙型肝炎需要长期抗病毒治疗的概念,已经形成共识.但迄今为止,任何药物或治疗方案都难以使所有患者经长期抗病毒治疗达到并保持理想的治疗效果.研究和开发新的药物,提出并优化新的治疗方案无疑是提高治疗慢性乙型肝炎疗效的重要手段,近年在这方面已经取得许多重要进展.同样,对患者疗效的影响因素分析表明,在治疗前选择合适的患者、合适的时机、合适的药物、合适的方案,也是提高疗效的重要措施.     

The global roadmap for advancing development of vaccines against sexually transmitted infections: Update and next steps

In 2014, the World Health Organization, the US National Institutes of Health, and global technical partners published a comprehensive roadmap for development of new vaccines against sexually transmitted infections (STIs). Since its publication, progress has been made in several roadmap activities: obtaining better epidemiologic data to establish the public health rationale for STI vaccines, modeling the theoretical impact of future vaccines, advancing basic science research, defining preferred product characteristics for first-generation vaccines, and encouraging investment in STI vaccine development. This article reviews these overarching roadmap activities, provides updates on research and development of individual vaccines against herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, and discusses important next steps to advance the global roadmap for STI vaccine development.     

Nutrition and cancer: essential elements for a roadmap

Personalizing nutrition for cancer prevention and therapy will require a comprehensive understanding of "genotypes/phenotypes" in order to identify, evaluate, and prioritize appropriate points for dietary intervention. This nutritional preemption roadmap must begin with accurately assessing intakes/exposures of which bioactive food component(s) is needed to bring about a desired response in critical cellular processes (carcinogen metabolism, DNA repair, cell proliferation, apoptosis, inflammation, immunity, differentiation, angiogenesis, hormonal regulation and cellular energetic) within an individual. Understanding this "individuality" through a better understanding of the "omics" is fundamental to arriving at the correct destination and thus interpreting biological variables which establish the magnitude or direction of a response to bioactive food components.     

核苷(酸)类似物抗病毒治疗慢性乙型肝炎的优化策略

目前,我国有4种核苷(酸)类似物可用于慢性乙型肝炎(CHB)患者的抗病毒治疗,即拉米夫定、阿德福韦酯、恩替卡韦和替比夫定.但由于患者的性别、年龄、遗传背景、HBV感染途径、病毒基因型、病程长短、肝脏病变程度和对治疗药物敏感性等不同,即使有同样治疗适应证的患者按同样的规范方案治疗后,仍有相当一部分患者早期应答欠佳,从而影响了抗病毒治疗的长期疗效.如何进一步优化现有的治疗方案以提高远期疗效已成为国内外专家关注的热点问题.     

提高公立医院公益性的策略探讨

通过阐述我国公立医院公益性发展演变阶段,分析公益性弱化的原因,提出了以政府主导为原则,以实施政府购买卫生服务为实现路径,以建立完善购买服务制度、绩效考核制度、支付审核制度和监督管理制度等为依托,通过科学化的制度设计、强有力的制度保障和有效的执行策略来提高公立医院的公益性.