Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug resistant serotype 6C

BackgroundIn 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced free of charge in Brazil as part of the public immunization program. Here we investigated the carriage prevalence, colonization risk factors, capsular types, and antimicrobial resistance among pneumococcal isolates obtained from children in Brazil four years after routine PCV10 use.MethodsBetween September and December 2014, we conducted a cross-sectional study among children < 6 years old who attended one public and two private clinics in Niterói, RJ, Brazil to evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and capsular types were determined for all isolates.ResultsOf 522 children, 118 (22.6%) were pneumococcal carriers. Being ≥ 2 years old, attending childcare center, presenting with any symptoms, having acute or chronic respiratory disease, and residing in a slum were associated with pneumococcal carriage. The most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and 6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12–8.0 μg/ml and 0.012–1.0 μg/ml, respectively. The 33 (28%) erythromycin-resistant isolates (MICs of 1.5 to >256 μg/ml) displayed the cMLS_B (72.7%) or M (27.3%) phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were largely explained by the prevalence of multidrug resistant (MDR) serotype 6C isolates.ConclusionsEffects of universal childhood PCV10 use on carriage were evident, with the near elimination of PCV10 serotypes. The emergence of MDR serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor serotype 6C increase in invasive diseases is warranted.     

A Study of Expectations and the Marital Quality of Participants of a Marital Enrichment Seminar

This longitudinal study investigated the effects of expectations of effort of self and spouse on the marital quality of marital enrichment seminar participants. Self‐report measures of marital quality, expectations regarding effort put into implementing what was learned during the seminar, amount of perceived effort, and satisfaction with effort were administered before and after the seminar, as well as at a 2‐month follow‐up. Participants (147 women, 95 men) attended community‐based marital enrichment seminars in 12 U.S. cities. Multivariate path models indicated that larger discrepancies between expectations of effort postseminar and perceived effort at 2‐month follow‐up were associated with less satisfaction with perceived effort. Furthermore, participants' dissatisfaction in their spouses' effort had a negative effect on marital quality while controlling for initial marital quality, whereas dissatisfaction in their own effort did not. These findings highlight the possible detrimental effect that unmet spousal expectations can have. Implications for marital enrichment programs and couples therapy are discussed.     

基于网络药理学探讨补肾强督治偻方治疗强直性脊柱炎的作用机理

目的通过网络药理学方法探讨补肾强督治偻方治疗强直性脊柱炎的作用机理。方法运用中药系统药理学成分分析平台(BAT-MAN)数据库获取补肾强督治偻方的作用靶标基因,于CTD数据库中获取强直性脊柱炎疾病相对应的靶标基因,将两者取交集后获取疾病-药物蛋白靶基因,运用网络可视化软件STRING构建蛋白质间相互作用网络,并将结果进行网络可视化展示,通过网络结构和节点间加权重联系的计算分析算法筛选出重要的关键基因。借助DAVID在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和KEGG通路富集分析。最后在CTD数据库中获取关键基因于强直性脊柱炎的疾病治疗作用。结果补肾强督治偻方靶标基因与强直性脊柱炎疾病靶标基因的交集基因有705个。GO分析结果显示,补肾强督治偻方-强直性脊柱炎交集靶基因的生物功能主要包括基因表达的阳性调控、炎症反应、细胞增殖阳性调控等;信号通路富集结果显示,补肾强督治偻方-强直性脊柱炎交集靶基因的网络主要涉及肿瘤坏死因子信号通路、雌激素信号通路、T细胞受体信号通路等。获得关键基因23个,都与痛症、炎症性疾病及关节炎性疾病相关。结论补肾强督治偻方治疗强直性脊柱炎是多靶点、多通路、多选择的复杂机制过程,其机制多与抗炎和镇痛相关。     

An innovative medical school curriculum to enhance exposure to genetics and genomics: Updates and outcomes

PurposeIn 2011, we introduced an innovative parallel curriculum at Baylor College of Medicine, formerly called the Genetics Track Curriculum and now called the Genetics and Genomics Pathway, aimed at providing an opportunity for an enriched educational experience throughout medical school. In this report, we describe our 10-year experience with the program and highlight growth in enrollment as well as academic achievements of graduating students.MethodsWe reviewed the data of students enrolled in this pathway, including retention, satisfaction, student-driven curriculum changes, scholarly outcomes, and career outcomes.ResultsFrom September 2011 to June 2021, 121 students were enrolled in the Genetics and Genomics Pathway program. In total, 64 students (64/121 = 53%) left the program before graduating (the majority, after their first year). Of the 57 remaining students, 29 graduated (29/57, approximately 51%), and 4 of the 29 students (4/29 = 14%) matched into a genetics training program.ConclusionThis novel program serves as a mechanism for garnering increased interest and competence in medical genetics. The longitudinal nature of the program fosters enthusiasm for genetics and provides ample opportunity to develop valuable research skills. Given the ongoing shortage of providers in this field, such programs are vital to increase the size of the workforce and broaden the knowledge of providers in diverse fields.     

Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms

We report RNA‐Sequencing results on a cohort of patients with single suture craniosynostosis and demonstrate significant enrichment of heterozygous, rare, and damaging variants among key craniosynostosis‐related genes. Genetic burden analysis identified a significant increase in damaging variants in ATR, EFNA4, ERF, MEGF8, SCARF2, and TGFBR2. Of 391 participants, 15% were found to have damaging and potentially causal variants in 29 genes. We observed transmission in 96% of the affected individuals, and thus penetrance, epigenetics, and oligogenic factors need to be considered when recommending genetic testing in patients with nonsyndromic craniosynostosis.

     

富氧对海拔3 700m高原人体血液流变学的影响

目的探讨在高原建立富氧室对机体血液流变学的影响.方法在海拔3 700m高原室内充氧,使氧浓度提高为24%～25%.12名受试者在富氧条件下睡眠10h,出富氧室4h后,检测红细胞压积(HCT)、血液粘度(ηb)、血浆粘度(ηp)、还原粘度(ηr)、红细胞刚性指数(IR)、红细胞变形系数(TK)和血细胞聚集系数(VAl).结果富氧后较富氧前ηb、ηp、IR、TK和VAI均降低,有显著性差异(P<0.05),HCT、ηr无统计学意义(P>0.05).结论富氧10h可改善高原机体缺氧,并且增强机体的氧储备可持续4h以上.     

Evaluation of a novel kit (TF-Test) for the diagnosis of intestinal parasitic infections

Intestinal parasitic infections are currently a source of concern for Public Health agencies in developing and developed countries. Since three ovum‐and‐parasite stool examinations have been demonstrated to provide sensitive results, we designed a practical and economical kit (TF‐Test) that is now commercially available (Immunoassay Com. Ind. Ltda., São Paulo, Brazil). This kit allows the separate collection of three fecal specimens into a preservative solution. The specimens are then pooled, double‐filtered, and concentrated by a single rapid centrifugation process. The TF‐Test was evaluated in four different laboratories in a study using 1,102 outpatients and individuals living in an endemic area for enteroparasitosis. The overall sensitivity found using the TF‐Test (86.2–97.8%) was significantly higher (P<0.01) than the sensitivity of conventional techniques such as the Coprotest (NL Comércio Exterior Ltda, São Paulo, Brazil) and the combination of Lutz/Hoffman, Faust, and Rugai techniques (De Carli, Diagnóstico Laboratorial das Parasitoses Humanas. Métodos e Técnicas, 1994), which ranged from 48.3% to 75.9%. When the above combined three specimen technique was repeated with three specimens collected on different days, its sensitivity became similar (P>0.01) to that of the TF‐Test. The kappa index values of agreement for the TF‐Test were consistent (P<0.01), being higher and ranking in a better position than conventional techniques. The high sensitivity, cost/benefit ratio, and practical aspects demonstrate that the TF‐Test is suitable for individual diagnosis, epidemiological inquiries, or evaluation of chemotherapy in treated communities. J. Clin. Lab. Anal. 18:132–138, 2004. © 2004 Wiley‐Liss, Inc.     

固定化离子液体吸附分离八角茴香中莽草酸

目的 研究固定化离子液体（SILs）对八角茴香提取液中莽草酸的吸附分离性能,并分离制备莽草酸。方法 采用静态与动态吸附-解吸方法,研究SILs对莽草酸的吸附平衡和吸附动力学性能,并采用Freundlich型和Langmuir型方程拟合了303、313、323 K温度下的吸附等温线。结果 SILs对莽草酸具有良好的吸附特性,吸附等温线与Freundlich型和Langmuir型方程拟合效果均较好,且以Freundlich型方程拟合更佳。采用SILs对八角茴香中莽草酸进行富集分离,富集率为80.34%。结论 该方法简便易行、富集率高,可用于八角茴香提取液（物）中莽草酸的富集分离。     

Ultra-rapid cardiotoxicity of the hepatitis C virus protease inhibitor BILN 2061 in the urokinase-type plasminogen activator mouse

BACKGROUND & AIMS: Because current therapies for chronic hepatitis C virus (HCV) infections are suboptimal and associated with severe side effects, novel treatment options are needed. A small animal model has recently been developed to study HCV infections. To examine the usefulness of this human liver-urokinase-type plasminogen activator (uPA)(+/+) severe combined immune deficient (SCID) mouse for the development of HCV-targeted drugs, we evaluated the antiviral efficacy and safety of an HCV NS3-protease inhibitor, BILN 2061. METHODS: BILN 2061 was orally administered at clinical range doses for 4 days to SCID mice that differed in the presence of HCV infection, human hepatocyte grafts, and uPA zygosity. Treatment outcome was evaluated clinically, virologically, and morphologically. Using standard high-performance liquid chromatography-ultraviolet (HPLC-UV) methods and mass spectrometry, single-dose pharmacokinetics and multiple-dose drug exposures were analyzed. The (13)C-aminopyrine breath test was applied to compare in vivo liver function. RESULTS: A 4-day treatment with BILN 2061 of HCV genotype-1b infected chimeric animals reduced the viral load by >100-fold, but concomitant clinical and ultrastructural signs of cardiotoxicity appeared. BILN 2061 administration to uPA-transgenic mice induced mitochondrial swelling with aberrant cristae in cardiomyocytes, but not in skeletal muscle. Because both drug accumulation and liver function were identical in affected uPA-transgenic and nontransgenic SCID mice without cardiac involvement, the urokinase plasminogen activator transgene itself appears to be implicated. CONCLUSIONS: The human liver-uPA(+/+)SCID mouse is an interesting small animal model to evaluate the preclinical safety and efficacy of new antiviral compounds against HCV. The uPA-transgene increases the susceptibility of mice to BILN 2061-induced cardiotoxicity.     

Environmental enrichment enhances directional selectivity of primary auditory cortical neurons in rats

Environment enrichment (EE) has an important role in brain plasticity. Previous research has shown that EE increases the response strength of auditory cortical neurons, but it remains unknown whether EE can affect the directional selectivity of auditory neurons. In this study, rats were exposed to EE conditions during the developmental critical period (EE1) or after the critical period (EE2). By in vivo extracellular recording, we found that EE enhanced the directional selectivity of primary auditory cortical neurons in EE1 rats, which showed a sharper azimuth selectivity curve of auditory cortical neurons compared with normal rats. However, there was no significant difference in directional selectivity between the EE2 rats and age-matched control rats. Our findings indicate that early exposure to EE enhances the directional sensitivity of primary auditory cortical neurons. These results provide an insight into developmental plasticity in the auditory system.