WHO working group meeting to amend WHO Recommendations to assure the quality,safety and efficacy of live attenuated yellow fever vaccines

The current WHO Recommendations to assure the quality, safety and efficacy of live attenuated yellow fever vaccines were adopted in 2010. This document recommends that vaccine virus master and working seed lots should be tested for viscerotropism, immunogenicity and neurovirulence in monkeys. A vaccine manufacturer has reported, recently, discrepancies on the clinical scoring of monkeys during assessment of working seed lots and suggested aligning neurotropism assessment of yellow fever vaccines virus seed lots with that of neurovirulence testing of polio vaccines virus seed lots. In this approach, clinical signs are recorded but do not form part of the assessment or pass/fail criteria. At its 71^st meeting in August 2020, the ECBS agreed to establish a drafting group and to consult with manufacturers and other stakeholders on the proposed amendment. Then a survey had been conducted to seek opinions of stakeholders on the neurotropism testing and revision of current WHO Recommendations for yellow fever vaccines. It was recognized from the answers of the survey that the test for neurovirulence in monkeys presents several technical challenges which could be addressed in the amended version of the Recommendations.On 18–19 March 2021, a virtual WHO working group meeting was held to discuss a proposed draft of the amended text with participants of yellow fever vaccine manufacturers and relevant regulators. Overall, there was a consensus among manufacturers and regulators that clinical evaluation provides important information and should be retained as part of the neurotropism test. However, there was also agreement that the test is somewhat subjective, and that analysis can be difficult. It was recognized that there was potential for improvement in both test execution and analysis to increase harmonization between manufacturers. Alternative tests to the non-human primates neurovirulence test would be useful but it was agreed that none seem to be sufficiently developed at present. Based on these working group discussions, it was proposed that the appendix on neurotropism test to be further revised by the WHO drafting group and submitted to ECBS for review and adoption.Issues other than neurotropism test were discussed in the meeting as well. There were a number of points identified during the meeting, such as new platform of production, animal models, deep sequencing, international standards, that are outside the current recommendations that are worthy of further discussion. Therefore, it is recommended that there would be a future meeting with various stakeholders to discuss the potential revision of the whole Recommendations for yellow fever vaccines in order to meet the current needs.     

基于弥散张量成像的脑白质微结构分析方法在视路损伤中的应用进展

视觉通路包括视神经、视交叉、视束、视放射及视皮质。常规磁共振检查技术难以发现视路损伤后白质纤维微结构改变,眼科学检查也存在一定的局限性及主观性,且不能探测后视路的变化。弥散张量成像(diffusion tensor imaging,DTI)作为一种新兴的磁共振成像技术,通过各种后处理分析方法结合不同的参数进行分析,可提供组织的微结构信息,并能够直观显示活体白质纤维束,在无创地探索疾病的神经病理机制、评估预后方面起着重要的作用。近年来随着DTI后处理方法的不断创新,其在视路损伤中的研究越来越多。本文在介绍DTI的主要参数及常见脑白质微结构分析方法的同时,阐述了其在视路损伤研究中的应用,并进一步对各种分析方法的优缺点进行总结。     

Contemporary Epidemiology of and Risk Factors Associated with Removal of a Pathologically Normal Appendix in Children with Suspected Appendicitis

BackgroundThe goal of this study was to characterize contemporary performance benchmarks and risk factors associated with negative appendectomy (NA) in children with suspected appendicitis.MethodsA multicenter retrospective cohort analysis of children undergoing appendectomy for suspected appendicitis was performed using data from the 2016–2021 NSQIP-Pediatric Appendectomy Targeted Public Use Files. Multivariable regression was used to evaluate the influence of year, age, sex, and WBC count on NA rate, and to generate rate estimates for NA based on different combinations of demographic characteristics and WBC profiles.Results100,322 patients were included from 140 hospitals. The overall NA rate was 2.4%, and rates decreased significantly during the study period (2016: 3.1% vs. 2021: 2.3%, p < 0.001). In adjusted analyses, the highest risk for NA was associated with a normal WBC (<9000/mm³; OR 5.31 [95% CI: 4.87–5.80]), followed by female sex (OR 1.55 [95% CI: 1.42–1.68]) and age <5 years (OR 1.64 [95% CI 1.39, 1.94]). Model-estimated risk for NA varied significantly across demographic and WBC strata, with a 14.4-fold range in rates between subgroups with the lowest and highest predicted risk (males 13–17 years with elevated WBC [1.1%] vs. females 3–4 years with normal WBC [15.8%]).ConclusionsContemporary NA rates have decreased over time, however NA risk remains high in children without a leukocytosis, particularly for girls and children <5 years of age. These data provide contemporary performance benchmarks for NA in children with suspected appendicitis and identify high-risk populations where further efforts to mitigate NA risk should be targeted.Level of EvidenceIII.     

Development of white matter microstructure and executive functions during childhood and adolescence: a review of diffusion MRI studies

Diffusion magnetic resonance imaging (dMRI) provides indirect measures of white matter microstructure that can be used to make inferences about structural connectivity within the brain. Over the last decade, a growing literature of cross-sectional and longitudinal studies have documented relationships between dMRI indices and cognitive development. In this review, we provide a brief overview of dMRI methods and how they can be used to study white matter and connectivity and review the extant literature examining the links between dMRI indices and executive functions during development. We explore the links between white matter microstructure and specific executive functions: inhibition, working memory and cognitive shifting, as well as performance on complex executive function tasks. Concordance in findings across studies are highlighted, and potential explanations for discrepancies between results, together with challenges with using dMRI in child and adolescent populations, are discussed. Finally, we explore future directions that are necessary to better understand the links between child and adolescent development of structural connectivity of the brain and executive functions.     

Parenchymal calcification is associated with the neurological prognosis in patients with congenital rubella syndrome

Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor.     

Evolution of white matter tract microstructure across the life span

The human brain undergoes dramatic structural change over the life span. In a large imaging cohort of 801 individuals aged 7–84 years, we applied quantitative relaxometry and diffusion microstructure imaging in combination with diffusion tractography to investigate tissue property dynamics across the human life span. Significant nonlinear aging effects were consistently observed across tracts and tissue measures. The age at which white matter (WM) fascicles attain peak maturation varies substantially across tissue measurements and tracts. These observations of heterochronicity and spatial heterogeneity of tract maturation highlight the importance of using multiple tissue measurements to investigate each region of the WM. Our data further provide additional quantitative evidence in support of the last‐in‐first‐out retrogenesis hypothesis of aging, demonstrating a strong correlational relationship between peak maturational timing and the extent of quadratic measurement differences across the life span for the most myelin sensitive measures. These findings present an important baseline from which to assess divergence from normative aging trends in developmental and degenerative disorders, and to further investigate the mechanisms connecting WM microstructure to cognition.     

A new aspect of in vitro antimicrobial leukocyte- and platelet-rich plasma activity based on flow cytometry assessment

The current literature suggests that the antibacterial effect of leukocyte- and platelet-rich plasma (L-PRP) is directly related to platelet and leukocyte concentrations. The aim of this study was twofold: first, to evaluate the antimicrobial effect of L-PRP against selected bacterial strains in vitro, and second, to correlate this effect with leukocyte and platelet content in the final concentration. Blood was collected from 20 healthy males, and L-PRP, acellular plasma (AP), and autologous thrombin were consecutively prepared. Flow cytometry analysis of the blood, L-PRP, and AP was performed. The L-PRP gel, liquid L-PRP, and thrombin samples were tested in vitro for their antibacterial properties against seven selected bacterial strains using the Kirby–Bauer disk-diffusion method. There was notable antimicrobial activity against selected bacterial strains. No statistically significant correlations between antimicrobial activities and the platelet concentration in L-PRP were observed. Statistically significant positive correlations between selected leukocyte subtypes and antimicrobial activity were noted. A negative correlation was found between elevated monocyte count and antimicrobial activity of L-PRP against one bacterial strain studied. L-PRP possesses antimicrobial activity and can be potentially useful in the fight against certain postoperative infections. The bactericidal effect of L-PRP is caused by leukocytes, and there exists a relationship among selected leukocyte subtypes and L-PRP antimicrobial activity.     

Formulation and evaluation of carrot seed oil-based cosmetic emulsions

The present study deals with the evaluation of antiaging potential of carrot seed oil-based cosmetic emulsions. Briefly, cosmetic emulsions composed of carrot seed oil in varying proportions (2, 4, and 6% w/v) were prepared using the hydrophile–lipophile balance (HLB) technique. Coconut oil, nonionic surfactants (Tween 80 and Span 80), and xanthan gum were used as the oil phase, emulgent, and emulsion stabilizer, respectively. The formed emulsions were evaluated for various physical, chemical, and biochemical parameters such as the zeta potential, globule size measurement, antioxidant activity, sun protection factor (SPF), skin irritation, and biochemical studies. The zeta potential values ranged from ?43.2 to ?48.3, indicating good stability. The polydispersity index (PDI) of various emulsion formulations ranged from 0.353 to 0.816. 1,1-Diphenyl-2-picrylhydrazyl- (DPPH) and nitric oxide-free radical scavenging activity showed the antioxidant potential of the prepared carrot seed oil emulsions. The highest SPF value (6.92) was shown by F3 having 6%w/v carrot seed oil. Histopathological data and biochemical analysis (ascorbic acid (ASC) and total protein content) suggest that these cosmetic emulsions have sufficient potential to be used as potential skin rejuvenating preparations.     

Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra‐high risk for psychosis

In schizophrenia patients, cognitive functions appear linked to widespread alterations in cerebral white matter microstructure. Here we examine patterns of associations between regional white matter and cognitive functions in individuals at ultra‐high risk for psychosis. One hundred and sixteen individuals at ultra‐high risk for psychosis and 49 matched healthy controls underwent 3 T magnetic resonance diffusion‐weighted imaging and cognitive assessments. Group differences on fractional anisotropy were tested using tract‐based spatial statistics. Group differences in cognitive functions, voxel‐wise as well as regional fractional anisotropy were tested using univariate general linear modeling. Multivariate partial least squares correlation analyses tested for associations between patterns of regional fractional anisotropy and cognitive functions. Univariate analyses revealed significant impairments on cognitive functions and lower fractional anisotropy in superior longitudinal fasciculus and cingulate gyrus in individuals at ultra‐high risk for psychosis. Partial least squares correlation analysis revealed different associations between patterns of regional fractional anisotropy and cognitive functions in individuals at ultra‐high risk for psychosis compared to healthy controls. Widespread higher fractional anisotropy was associated with better cognitive functioning for individuals at ultra‐high risk for psychosis, but not for the healthy controls. Furthermore, patterns of cognitive functions were associated with an interaction‐effect on regional fractional anisotropy in fornix, medial lemniscus, uncinate fasciculus, and superior cerebellar peduncle. Aberrant associations between patterns of cognitive functions to white matter may be explained by dysmyelination.