Is oral food challenge test useful for avoiding complete elimination of cow's milk in Japanese patients with or suspected of having IgE-dependent cow's milk allergy?

BackgroundCow's milk, along with hen's egg, are common causes of food allergies in children worldwide. Accidental ingestion of milk is common and often induces severe allergic reactions. Oral food challenge test (OFC) is usually performed in patients with or suspected of having a food allergy. However, the evidence of whether cow's milk OFC is useful in IgE-dependent cow's milk allergy patients to avoid total elimination is not known.MethodsAfter setting the clinical question and outcomes, we performed a systematic review for relevant articles published from January 1, 2000 to August 31, 2019 using PubMed® and Ichushi-Web databases. Each article was then evaluated for the level of evidence. All positive results of the OFC were defined as adverse events.ResultsForty articles were selected in this study. Our review revealed that cow's milk OFC was able to avoid the complete elimination of cow's milk in 66% of the patients with cow's milk allergy. We also found that adverse events occurred frequently (50.5%).ConclusionsThis analysis supports the recommendation of conducting cow's milk OFC to avoid complete elimination of cow's milk, however the test should be conducted with careful consideration of the patient's safety. As the methods of OFC and subjects varied among the articles selected in this study, further studies are needed to obtain higher quality evidence.     

Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers

Background and aimsConsumption of foods that modulate inflammatory stress in genetically-prone individuals may influence development of cardiometabolic diseases. Isoflavones in soy-derived foods function as phytoestrogens, have antioxidant and anti-inflammatory activity, inhibit protein-tyrosine kinase activity, and may be atheroprotective. We examined the relationship between soy food consumption and inflammatory responses to endotoxemia, postprandial responses to oral lipid tolerance test (OLTT), and insulin sensitivity from frequently sampled intravenous tolerance tests (FSIGTT).Methods and resultsWe administered low-dose endotoxin (LPS 1 ng/kg) to induce transient endotoxemia in young, healthy volunteers (N = 215) of African (AA), and European (EA) ancestry as part of the GENE Study. We further supported these findings in two independent samples: the MECHE Study and NHANES. Soy food consumption was a significant predictor of peak cytokine response following LPS. Individuals with moderate-high (>1.48 mg/day, N = 65) vs. low-no (<1.48 mg/day, N = 150) isoflavone consumption had significantly higher tumor necrosis factor alpha (TNFα) post-LPS (AUC, P = 0.009). Further, high-isoflavone consumers were protected against inflammation-induced decline in insulin sensitivity (S_I) in GENE. We observed significant differences by soy consumption in the interferon gamma (IFNγ) response to OLTT, and the insulin response to OGTT in MECHE, as well as significantly lower fasting insulin, and 2-hour glucose post-OGTT in EA NHANES subjects.ConclusionWe demonstrate that soy consumption may influence inflammatory and metabolic responses. In research of nutritional exposures, measuring evoked phenotypes may be more informative than describing resting characteristics.The GENE Study was registered under NCT00953667 and the MECHE Study under NCT01172951, both at clinicaltrials.gov.     

新型冠状病毒肺炎疫情防控期间我国血吸虫病防治工作面临的影响和挑战调查

目的　了解新型冠状病毒肺炎疫情防控期间我国血吸虫病防治工作开展情况,评估新型冠状病毒肺炎疫情对我国血吸虫病防治工作的影响。方法　2020年4月,在我国12个血吸虫病流行省份各选择3个县（市、区）,采用问卷调查的方法了解2020年1–3月当地血吸虫病防治工作开展情况,应用比较分析的方法评价新型冠状病毒肺炎疫情对我国血吸虫病防治工作的影响。结果　在本次调查的12个省（直辖市、自治区）、36个县（市、区）中,新型冠状病毒肺炎疫情高、中风险地区占66.67%。各地血吸虫病防治工作部署、人群血吸虫病查治病、药物灭螺、健康教育开展情况较2019年同期减少44.26% ~ 91.56%,血吸虫病传播控制省受影响程度较大;血吸虫病防治总经费收入较预期下降23.39%,总经费支出增长41.22%。36个调查县（市、区）均认为新型冠状病毒肺炎疫情对血防工作产生了短期影响,并以工作部署、人力资源和疫情监测等3个方面受影响最为突出。结论　受新型冠状病毒肺炎疫情影响,我国各地常规血防工作均受到不同程度影响。应加强政策支持、保障经费落实,以保质保量完成各项血吸虫病防治工作任务。     

Stability versus reactivity of ”3+1” mixed-ligand technetium-99m complexes in vitro and in vivo

”3+1” technetium-99m mixed-ligand complexes as relevant to the development of a third generation of ^99mTc radiopharmaceuticals were investigated in vivo and in vitro in the blood of rats. Surprisingly, in whole blood the complexes, which proved to be stable in saline, PBS of pH 7.4 and in plasma, were converted into two radioactive, more hydrophilic metabolites. Small structural differences in the complex molecule have a profound influence on the rate of metabolism of the complexes. To obtain an understanding of this unexpected reactivity, transchelation reactions with glutathione (GSH) were hypothesized and this hypothesis substantiated by challenge experiments carried out with a series of ^99mTc and analogous rhenium complexes and GSH. In vitro studies in human plasma, whole blood and erythrocytes also revealed conversion of the complexes, though, at a much slower rate. Structural parameters influencing the stability of the complexes and consequences for the radiopharmaceutical design are discussed. Received 28 January and in revised form 14 April 1998     

Alcohol Sensitivity and Smoking History in Men and Women

Many studies have found genetic effects to contribute to alcoholism risk in both men and women. Based on preliminary evidence for shared genetic risk between smoking and drinking problems, a re-analysis of alcohol challenge data on 412 Australian twins was performed to explore the possibility that smoking may diminish or moderate the intoxicating effects of alcohol. We found history of smoking to be strongly associated with self-reported intoxication after alcohol challenge in women (women: r = -0.44 ± 0.08; men: r = -0.21 ±0.08), comparable with self-reported average weekly consumption of alcohol, which was more strongly associated in men (women: r = -0.37 ±0.07; men: r = -0.54 ±0.06). Structural equation model-fitting indicated a strong association between heavy drinking and smoking, but the association between smoking and postalcohol intoxication remained even when the effects of heavy drinking were controlled for. These results prompt the question of whether smoking cigarettes directly influences the transition from moderate to excessive use of alcohol by diminishing feelings of alcohol intoxication.     

中国参与艾滋病预防控制的草根非政府组织调研报告

通过对中国草根NGO的调查,发现它们在中国的艾滋病预防工作中起着不可替代的作用。主要表现在:为服务对象和大众提供广泛的交流平台;通过生产自救为感染者及其组织提供经济来源和项目经费;弥补政府工作上的不足;是政府工作的推动力;起到技术支持和政策倡导的作用;是申请和参与全球基金艾滋病防治项目的重要力量。调查还发现:草根NGO发展所面临的首要问题是资金匮乏问题,人力资源缺乏和治理结构不合理,也是制约其发展的重要因素。缺乏政府在法律上的支持极大地限制了草根NGO获取资金和开展活动的能力。据此,在三个层面提出了政策建议:⑴政府把草根NGO当做合作伙伴,提供有利的政策环境及技术和资金等支持;⑵草根NGO需要提升自己的能力,加强与政府和其他NGO的交流与合作;⑶国际组织应规范其对草根NGO的资助,增加透明度。为了帮助草根NGO发展,构想建立一个协调机构,代表草根NGO向政府和国际组织争取资金和项目,并协助进行资金的管理和分配工作,推动草根NGO之间的交流和联系,实现资源共享。     

我国艾滋病经性传播新特征与防治面临的挑战

我国艾滋病传播流行已演变为经性途径传播为主,2016年经性途径传播占当年新报告HIV感染者人数的95%,异性性行为占67%,男男性行为占28%。异性性行为作为主要流行方式以西南地区为主;男男性行为作为主要流行方式则以东北及全国大、中城市为主。老年人和青年学生两个特殊人群的疫情呈现上升,且分别以异性性行为和男男性行为感染为主。检测发现HIV感染者和治疗HIV感染者两个控制措施的落实力度加大,配偶间传播明显减少,但仍有约1/3的HIV感染者未诊断。艾滋病经性途径传播在我国还将持续一段时间,控制艾滋病经性传播仍然面临诸多挑战。     

Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study

Mild cognitive impairment (MCI) often represents an early form of Alzheimer disease (AD). In both MCI and AD, characteristic cholinergic changes may occur. Functional magnetic resonance imaging (fMRI) may help to examine neurochemical changes in early disease by studying signal reactivity to pharmacological challenge. In this study, MCI patients [n=28; mean age 73.6+/-7.5; mini mental state examination (MMSE) 27.0+/-1.2] were scanned during task performance in a randomized trial under three different medication regimes: at baseline [BL; no galantamine (GAL)], after a single oral dose of GAL (SD), and after prolonged exposure (steady state: SS). Memory tasks included an episodic face-encoding task and a parametric n-letter back working memory (WM) task. Alterations in brain activation patterns before and after treatment were analyzed for both tasks using multilevel statistical analysis. Significant increases in brain activation from BL were observed after prolonged exposure only. For face encoding (n=28), these involved left prefrontal areas, the anterior cingulate gyrus, left occipital areas, and left posterior hippocampus. For working memory (n=28), increased activation was found in right precuneus and right middle frontal gyrus, coinciding with increased accuracy scores after GAL treatment. In conclusion, cholinergic challenge produces alterations in brain activation patterns in elderly MCI patients that can be detected with fMRI. This should encourage further functional imaging studies to examine the status of neurotransmitter systems in disease.     

Evaluation of Dengue Virus strains for human challenge studies

Discordance between the measured levels of dengue virus neutralizing antibody and clinical outcomes in the first-ever efficacy study of a dengue tetravalent vaccine (Lancet, Nov 2012) suggests a need to re-evaluate the process of pre-screening dengue vaccine candidates to better predict clinical benefit prior to large-scale vaccine trials. In the absence of a reliable animal model and established correlates of protection for dengue, a human dengue virus challenge model may provide an approach to down-select vaccine candidates based on their ability to reduce risk of illness following dengue virus challenge. We report here the challenge of flavivirus-naïve adults with cell culture-passaged dengue viruses (DENV) in a controlled setting that resulted in uncomplicated dengue fever (DF). This sets the stage for proof-of-concept efficacy studies that allow the evaluation of dengue vaccine candidates in healthy adult volunteers using qualified DENV challenge strains well before they reach field efficacy trials involving children. Fifteen flavivirus-naïve adult volunteers received 1 of 7 DENV challenge strains (n = 12) or placebo (n = 3). Of the twelve volunteers who received challenge strains, five (two DENV-1 45AZ5 and three DENV-3 CH53489 cl24/28 recipients) developed DF, prospectively defined as ≥2 typical symptoms, ≥48 h of sustained fever (>100.4 °F) and concurrent viremia. Based on our study and historical data, we conclude that the DENV-1 and DENV-3 strains can be advanced as human challenge strains. Both of the DENV-2 strains and one DENV-4 strain failed to meet the protocol case definition of DF. The other two DENV-4 strains require additional testing as the illness approximated but did not satisfy the case definition of DF. Three volunteers exhibited effusions (1 pleural/ascites, 2 pericardial) and 1 volunteer exhibited features of dengue (rash, lymphadenopathy, neutropenia and thrombocytopenia), though in the absence of fever and symptoms. The occurrence of effusions in milder DENV infections counters the long-held belief that plasma leakage syndromes are restricted to dengue hemorrhagic fever/dengue shock syndromes (DHF/DSS). Hence, the human dengue challenge model may be useful not only for predicting the efficacy of vaccine and therapeutic candidates in small adult cohorts, but also for contributing to our further understanding of the mechanisms behind protection and virulence.