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。     

Silver Diamine Fluoride Protocol for Reducing Preventable Dental Hospitalisations in Victorian Children

IntroductionThis study was designed to assess whether a dental caries management protocol combining a single application of 38% silver diamine fluoride (SDF) with comprehensive oral health education will successfully divert high-risk children from dental treatment under dental general anaesthesia (DGA), arrest active caries in primary teeth, and improve parent-reported child oral health–related quality of life (OHRQoL).MethodsChildren aged 2 to 10 years, who attended two public dental agencies in Victoria, Australia, and were unable to tolerate restorative treatments in the clinic setting, elected to participate in either a 38% SDF intervention protocol or, alternatively, referral for DGA. Follow-up examinations were completed at 6 months to assess caries progression, decayed missing filled tooth index, PUFA index (pulpal involvement, ulceration, fistula, abscess), DGA referral rates, and OHRQoL (Early Childhood Oral Health Impact Scale [ECOHIS]).ResultsOf the total sample, 89.5% of children (n = 102) [mean (SD) age, 4.1 (1.0) years] with 401 active carious lesions elected to participate in the 38% SDF protocol; 10.5% (n = 12) of parents opted for referral for treatment under DGA. The proportion of active caries subsequently arrested at follow-up (number of arrested lesions/number of lesions treated) was 0.78 (95% CI, 0.69 to 0.87). There was an 88% reduction in referrals for DGA in eligible children over the 6-month period. The 38% SDF intervention group showed a significant improvement in ECOHIS scores at follow-up (P < .001).DiscussionAdoption of the 38% SDF intervention protocol resulted in a significant reduction in the rate of preventable dental hospitalisations. Most parents opted against referral for DGA. Parent-reported OHRQoL for children improved significantly.     

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.     

携带同源重组修复相关基因突变的消化道肿瘤的临床特点

目的:探讨消化道肿瘤中同源重组修复相关基因(homologous recombination repair related gene，HRR)突变的发生情况及临床意义。方法:共92例消化道肿瘤患者，79例患者进行了血液标本HRR检测，53例患者进行了组织标本HRR检测，40例患者同时行血液和组织的HRR基因检测，收集患者基因检测结果及临床相关资料。结果:在79例患者血液标本检测中发现10例（12.6%）有临床意义HRR突变，在53例患者组织标本检测中发现9例（17.0%）有临床意义HRR突变。40例同时行血液和组织的HRR基因检测患者中常见的有临床意义HRR突变为CDK12突变4例（10.0%）、ATM突变3例（7.5%）、BRCA1突变2例（5.0%）。13例有临床意义HRR突变患者中常见共存突变为TP53突变10例（76.9%）、APC突变5例（38.5%）、PIK3CA突变4例（30.8%）。40例患者中13例患者血液和/或组织中有临床意义HRR突变，27例患者血液和组织中均无任何临床意义HRR突变且两组相比，有临床意义HRR突变组肿瘤突变负荷（tumor mutational burden，TMB）为6.17(2.24～11.52)，而未携带HRR突变组TMB为0.4(0～3.75)，差异有统计学意义（P＜0.05）。40例患者组织检测中7例HRR有临床意义的突变，33例无HRR突变，血液检测中10例HRR有临床意义的突变，30例无HRR突变，一致性检验的Kappa值为0.333（P=0.031）。结论:携带有临床意义HRR突变的消化道肿瘤患者TMB更高，血液和组织检测HRR突变有较好的一致性。     

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.