Behavioural impairment and oxidative stress by acute exposure of zebrafish to a commercial formulation of tebuconazole

Tebuconazole is a systemic follicular fungicide known to cause diverse problems in non-target organisms namely associated to the pure active ingredient. As such, the objective of this work was to evaluate developmental changes induced by a tebuconazole commercial formulation to a non-target animal model. Zebrafish embryos at ± 2 h post-fertilization were exposed to tebuconazole wettable powder concentrations (0.05, 0.5 and 5 mg L^-1) for 96 h with developmental toxicity assessed throughout the exposure period and biochemical parameters evaluated at the end of the exposure. Behavioural assessment (spatial exploration and response to stimuli) was conducted 24 h after the end of the exposure. While no developmental and physiological alterations were observed, exposure to tebuconazole resulted in an increased generation of reactive oxidative species at the 0.05 and 0.5 mg L^-1 concentrations and a decreased GPx activity at the 0.5 mg L^-1 concentration suggesting a potential protection mechanism. There was also a change in the avoidance-escape behaviour supporting an anxiolytic effect suggesting possible alterations in the central nervous system development demanding further studies.     

Sparkling plastic: Effects of exposure to glitter on the Mediterranean mussel Mytilus galloprovincialis

Microbeads and fragments have been widely studied, while glitter remains neglected by the literature although found in a variety product (e.g., body paints, nail polish, cosmetics, craft products). The main aim of this study was to assess the effects of different types and concentrations of glitter particles on Mytilus galloprovincialis after 7 days of exposure. The experiment was divided into a preliminary test and a confirmatory test. Our findings support the hypothesis for a link between concentration and type of glitter particles, percentage of recovery and oxidative stress in M. galloprovincialis. There was a significant correlation between particle length and percentage of particles recovered in water, suggesting that the digestive tract of M. galloprovincialis retains smaller particles more. In addition, we noted an increase in antioxidant defense induced by smaller particles. Moreover, certain types of glitter crumbled and shortened in length, resulting in higher levels of oxidative stress biomarkers. Finally, the star-shaped glitter particles had a different effect on oxidative stress biomarkers. Further studies are needed to clarify the toxic effects of glitter on aquatic organisms and to quantify its proportion to other microplastics in the environment.     

女性压力性尿失禁风险预测的研究进展

综述女性压力性尿失禁(stress urinary incontinence,SUI)风险预测的研究进展。指出女性SUI风险预测相关文献普遍存在风险预测工具和指标缺乏临床大样本验证,指标、纳入人群不统一的现象,风险预测模型存在构建过程未按报告规范进行,未进行完整的模型验证以及模型性能评价指标不规范的情况。未来研究可以在现有风险预测工具或模型的基础上进行改进、完善,以期为女性SUI风险预测提供参考。     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

Case Report: Transient Stress Hyperglycemia in the Patient With ST-Elevation Myocardial Infarction

Transient stress hyperglycemia in the setting of acute myocardial infarction is a frequent phenomenon. Its transient nature should not dissuade the clinician from management of elevated blood glucose in a patient after an ST-elevation myocardial infarction. This case presents an adult patient after an ST-elevation myocardial infarction with transient stress hyperglycemia and the evidence used to identify optimal pharmacologic management and secondary prevention.     

银杏叶制剂联合地塞米松在老年突聋治疗中对血清炎症指标的影响

目的: 探讨银杏叶制剂联合地塞米松在老年突聋治疗中对血清炎症指标的影响。方法: 按随机数字表法将我院2016年7月-2021年7月收治的102例老年突聋患者分入两组（各51例）。对照组用地塞米松治疗，治疗组加用银杏叶制剂治疗。观察两组治疗前后纯音听阈和血管内皮功能指标[超氧化物歧化酶（SOD）、脂质过氧化物（LPO）、一氧化氮（NO）]、血清炎症指标[肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、白细胞介素-6（IL-6）]，分析其疗效与不良反应。结果: 与对照组比较，治疗组总有效率更高（96.08％vs 82.35％）（χ2=4.993，P=0.025）；两组治疗后各频率点阈值均下降，且相比对照组，治疗组治疗后各频率点阈值更低（P<0.05）；治疗后两组SOD、NO水平均升高，LPO水平降低（P<0.05），且相比对照组，治疗组治疗后SOD、NO水平更高，LPO水平更低（P<0.05）；治疗后两组血清TNF-α、CRP、IL-6水平降低，且相比对照组，治疗组TNF-α、CRP、IL-6水平更低（P<0.05）；治疗组不良反应发生率5.88％，对照组为9.80％，两组比较差异无统计学意义（P=0.543，χ2=0.461）。结论: 银杏叶制剂联合地塞米松治疗老年突聋患者疗效理想，能恢复各频率点听力，安全可靠，推测改善患者血管内皮功能和炎症因子水平是其重要作用机制。     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Mobile daily diaries to characterize stressors and acute health symptoms in an environmental justice neighborhood

Low-income communities and communities of color face multiple, cumulative environmental and social burdens. Methods development in environmental justice research has largely focused on spatial and quantitative approaches. Less attention has been paid to developing methodologies that help collect information on everyday stressors and quality of life experiences for residents in overburdened communities. Mixed methods approaches can be one way to structure study designs that help consider how residents experience environmental and socioeconomic impacts in a localized community context. In neighborhoods burdened by cumulative stressors, traditional cross-sectional epidemiological research designs can also be challenging, as well as limited or narrow in their application. However, repeat sampling of measures within a vulnerable population can approach a quasi-experimental design and help consider variations within residents in a single neighborhood as well as better parse relationships between exposures and outcomes. Through a community-academic partnership with university partners, local community partners, and a local promotores de salud (community health workers) network, we pilot tested a novel mobile daily diary approach in both English and Spanish in an urban, predominantly immigrant community in South Los Angeles as a potential method to collect information on daily stress, environmental quality, and health status/symptoms. We collected resident responses via a once per day 7-day SMS/text messaging survey. We sought to gather granular data on daily resident experiences of air pollution and environmental hazards. Residents reported acute health symptoms and stressors, with repeat measures demonstrating how residents might rank, categorize, or cope with stressors. We find that residents in environmental justice communities record variation in their daily diary responses and document changes in environmental quality, stressors, and odors. Refining this type of method could enable a more rigorous examination of co-occurrences of environmental quality and acute health symptoms. This approach supports the inclusion of residents in the research process and helps more systematically integrate open-ended environmental health relevant data in environmental justice efforts. Used with measured data such as air monitoring or health measures, mixed methods generated data can help support efforts that aim to alleviate sources of daily stress, alongside efforts to reduce overall pollution burdens. Mobile daily diaries can be one way to capture variable responses to environmental quality, acute health symptoms, and stressors.