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.     

A note on implementation of decaying product correlation structures for quasi‐least squares

This note implements an unstructured decaying product matrix via the quasi‐least squares approach for estimation of the correlation parameters in the framework of generalized estimating equations. The structure we consider is fairly general without requiring the large number of parameters that are involved in a fully unstructured matrix. It is straightforward to show that the quasi‐least squares estimators of the correlation parameters yield feasible values for the unstructured decaying product structure. Furthermore, subject to conditions that are easily checked, the quasi‐least squares estimators are valid for longitudinal Bernoulli data. We demonstrate implementation of the structure in a longitudinal clinical trial with both a continuous and binary outcome variable. Copyright © 2014 John Wiley & Sons, Ltd.     

Chemically Accessible Hsp90 Inhibitor That Does Not Induce a Heat Shock Response

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Increased fracture risk in patients with type 2 diabetes mellitus: An overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools

Type 2 diabetes mellitus has recently been linked to an increased fracture risk. Since bone mass seems to be normal to elevated in patient with type 2 diabetes, the increased fracture risk is thought to be due to both an increased falling frequency and decreased bone quality. The increased falling frequency is mainly a result of complications of the disease such as a retinopathy and polyneuropathy. Bone quality is affected through changes in bone shape, bone micro-architecture, and in material properties such as bone mineralization and the quality of collagen. Commonly used methods for predicting fracture risk such as dual energy X-ray absorptiometry and fracture risk assessment tools are helpful in patients with type 2 diabetes mellitus, but underestimate the absolute fracture risk for a given score. New imaging modalities such as high resolution peripheral quantitative computed tomography are promising for giving insight in the complex etiology underlying the fragility of the diabetic bone, as they can give more insight into the microarchitecture and geometry of the bone. We present an overview of the contributing mechanisms to the increased fracture risk and the usefulness of imaging modalities and risk assessment tools in predicting fracture risk in patients with type 2 diabetes.     

Possible ways of reducing dental erosive potential of acidic beverages

Frequent consumption of acidic beverages is related to excessive tooth wear, namely dental erosion. Preventive measures may involve reduction or elimination of acidic drink consumption. However, the success of this approach is difficult to achieve as it is highly dependent on patient compliance. Therefore, a practical way of minimizing the erosive potential of popular acidic drinks may be their chemical modification. The aim of this article was to review the different methods of modification and their shortcomings. The available literature demonstrates that the erosive potential of most acidic beverages could be reduced. To date, the effectiveness of soluble calcium salts supplementation is the best established. However, modification can reduce the sensorial quality of the drink and shorten its shelf‐life. There is also a need to evaluate the lowest effective and safe dose of the additive.     

Advanced glycation end-products and receptor for advanced glycation end-products expression in patients with idiopathic pulmonary fibrosis and NSIP

Advanced glycation end products (AGEs) are associated with the pathogenesis of various diseases. AGEs induce excess accumulation of extracellular matrix and expression of profibrotic cytokines. In addition, studies on receptor for advanced glycation end products (RAGE) have shown that the ligand-RAGE interaction activates several intracellular signaling cascades associated with several fibrotic diseases. We investigated the expression of AGEs and RAGE in samples from patients with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP). Lung tissues and plasma samples from patients with IPF (n=10), NSIP (n=10), and control subjects (n=10) were obtained. Expression of AGEs and RAGE was determined by immunofluorescence assay of lung tissue. Circulating AGEs were measured by Western blot and enzyme-linked immunosorbent assay. Lungs with IPF showed strong expression for both AGEs and RAGE compared to that in NSIP and controls. However, no difference in AGE or RAGE expression was observed in lungs with NSIP compared to that in the controls. Levels of circulating AGEs also increased significantly in lungs of patients with IPF compared to those with NSIP and normal control. Increased AGE-RAGE interaction may play an important role in the pathogenesis of IPF.     

Lipid Accumulation Product Index to Predict Metabolic Syndrome in People Living with HIV

Background:Dyslipidemia and central obesity are the main components of metabolic syndrome, which represent important risk factors for cardiovascular diseases in people living with human immunodeficiency virus (HIV). The lipid accumulation product (LAP) index has been shown in studies as an efficient marker of metabolic syndrome in general adult population and its applicability in HIV-infected population is not discussed. We aimed to assess the accuracy of the LAP index to identify metabolic syndrome in people living with HIV.Methods:It is a cross-sectional study with 141 HIV-infected patients on antiretroviral therapy, conducted in a reference centre of infectious diseases in southeast Brazil. Evaluations included LAP index, anthropometric measurements and clinical and laboratorial variables. Metabolic syndrome was defined by International Diabetes Federation (IDF) criteria.Results:The prevalence of metabolic syndrome in our sample was 10.6%. A positive and significant correlation was found between the metabolic syndrome and LAP (r=0.401; P<0.01), metabolic syndrome and body mass index (r=0.361; P<0.01) and metabolic syndrome and waist circumference (r=0.427; P<0.01) in our sample. The analysis of the receiver-operating characteristic (ROC) curve revealed that the best cut-off value for LAP index to define metabolic syndrome was 59.4 (sensitivity 80%, specificity 79% and area under the curve (AUC) of 0.875. In female and male, analysis of the ROC curve revealed that the best cut-off value for LAP index to define metabolic syndrome was 56.3 (sensitivity 100%, specificity 82% and AUC of 0.929) and 52.0 (sensitivity 78%, specificity 74% and AUC of 0.838), respectively.Conclusion:Despite the low prevalence of metabolic syndrome in our sample, the ROC curves analyzes demonstrated a good diagnostic accuracy as an additional screening tool of metabolic syndrome according to the IDF.     

淡水产品中副溶血性弧菌带染状况的调查研究

目的探查副溶血性弧菌在淡水产品中的带染、药敏和毒力情况,为建立副溶血性弧菌食物中毒预警系统提供数据基础。方法依据GB/T 4789.7-2003食品卫生微生物检验标准中有关副溶血性弧菌的检验进行,分离培养选用科玛嘉弧菌显色培养基和TCBS两种培养基,用API20E试剂条进行生化鉴定。结果在140份淡水产品中,副溶血性弧菌的检出率为41.4%;不同地理区域副溶血性弧菌的检出率不同,在15%~75%之间,差异有统计学意义(P<0.05);分离菌株对环丙沙星、四环素、氯霉素和庆大霉素100%敏感,对链霉素的耐药率达到88.8%(71/80)。有19株菌株出现了多重耐药。结论建议政府加大对鱼饲料添加剂的管理,以防止耐药菌株的传播和扩散。分离菌株大多具有较强的毒力,存在引起食物中毒的可能性,提示在细菌性食物中毒的流行病学调查处理和实验室检验过程中,如食用了淡水产品,应考虑副溶血性弧菌的可能性。     

Interlaboratory Comparison as a Source of Information for the Product Evaluation Process. Case Study of Ceramic Tiles Adhesives

In this study, the results obtained by 19 laboratories participating in 2 editions of the interlaboratory comparison (ILC) determining 2 properties of ceramic tiles adhesives (CTAs), i.e., initial tensile adhesion strength and tensile adhesion strength after water immersion following EN 12004, were analyzed. The results show that participating laboratories maintain a constant quality of their work. The use of z-score analysis, under ISO 13528, allows for classifying 89.5% to 100% of laboratories as satisfactory, depending on the measurement’s kind and edition. The remaining laboratories are classified as questionable. The investigation of the predominant mode of failure of the CTA’s samples tested in the two editions shows significant differences. From the perspective of laboratories, the goal of the ILC has been achieved. From the standpoint of a manufacturer who evaluates a product’s properties when placing it on the market, the results indicate the necessity of a particular treatment of the product evaluation process because the variability of the obtained results is significant. It increases the possibility of the product failing to meet the assessment criteria verified by the construction market supervision authorities. The manufacturer must consider all possible variations in the risk analysis, including the ILC results, to improve the assessment process of CTAs.     

车前子酒炙工艺优选及其不同炮制品对比研究

[目的] 优选酒炙车前子的最佳炮制工艺,并对车前子生品、酒炙品、盐炙品进行对比研究。[方法] 以车前子中京尼平苷酸和毛蕊花糖苷的含量为考察指标,选择加酒量、闷润时间、炒制温度、炒制时间为考察因素,通过单因素实验优选车前子的最佳酒炙工艺。采用高效液相色谱-二极管阵列检测器（HPLC-DAD）建立车前子水提液指纹图谱测定方法,通过指标成分含量、不同炮制品水提液的出膏率及指纹图谱相似度分析不同炮制品间的差异。[结果] 酒炙车前子的最佳炮制工艺为每100 g车前子加黄酒10 g,闷润60 min,150℃下炒制9 min。经盐炙和酒炙后,车前子中的京尼平苷酸和毛蕊花糖苷的含量均较生品显著增加,而两种炮制品并无统计学差异;在出膏率方面,盐炙和酒炙车前子的出膏率无明显差异,但均高于生车前子。高效液相色谱（HPLC）指纹图谱显示车前子生品、盐炙品和酒炙品具有很好的相似度。[结论] 优选出的车前子酒炙工艺稳定可行,并与盐车前子在成分上具有一致性,鉴于酒车前子已不再流通,在经典名方的开发研究中,可考虑用现行通用的盐车前子取代。