A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

Medical practitioners’ educational competence about oral and oropharyngeal carcinoma: a systematic review and meta-analysis

Medical practitioners’ (MP) role is pivotal in primary prevention, early diagnosis, prompt referral and effective management of oral and oropharyngeal carcinomas (OC/OPC), which raises the importance of their effective OC/OPC education at all levels of medical education. The purpose of this systematic review was to summarise the available scientific evidence about their educational competence in dealing with OC/OPC. We made a systematic search of papers in the English language in MEDLINE, Scopus, Cochrane Library CENTRAL and CINAHL databases from their inception until December 2018. Overall, 23 cross-sectional and three interventional studies have been selected for the systematic review and 18 of these were included in the meta-analyses. Excluding tobacco use (synthesised estimate of 95% of respondents identified tobacco as an OC/OPC risk factor, 95% CI of synthesised estimate 92% to 97%) and alcohol consumption (65%, 95%CI 52% to 77%), less than half of MP (approximately) were knowledgeable about important OC/OPC risk factors including human papilloma virus (42%, 95% CI 30% to 54%), poor diet (34%, 95% CI 17% to 54%), and advancing age (45%, 95% CI 21% to 70%). There was a low to moderate level of awareness among MP regarding common precancerous oral lesions involving leukoplakia (56%, 95% CI 32% to 79%), erythroplakia (30%, 95% CI 8% to 58%), and oral lichen planus (13%, 95% CI 0 to 41%). Moderate knowledge was also recorded about frequent sites of OC development involving the tongue (48%, 95% CI 33% to 64%) and floor of the mouth (37%, 95% CI 19% to 57%). Most MP enquired about tobacco use (86%, 95% CI 74% to 96%), and alcohol consumption (73%, 95% CI 47% to 94%) during history taking, and expressed willingness to be given supplementary OC/OPC education (78%, 95% CI 54% to 96%), as well. With regard to the incidence of intraoral screening, 27% of MP (95% CI 12% to 46%) make an intraoral examination as a routine. Interestingly, studies from each continent yielded significantly different outcomes to some research questions in the review. From the MP’s perspective, clinical time restrictions and deficiencies in organised training were recognised as the main barriers towards their OC/OPC educational competence. The findings of this systematic review indicated the existence of deficiencies in knowledge and misconceptions, neglected preventive responsibilities, and associated barriers towards OC/OPC. A need for improved OC/OPC training at all levels of medical education is required to increase competence worldwide.     

母亲龋易感性与婴儿口腔微生物多样性关系的纵向探究

目的通过检查有龋及无龋母亲的口腔卫生状况,并通过随访收集其婴儿1个月(1月龄)及6个月(6月龄)的唾液样本测序分析,观察母亲患龋情况对其婴儿口腔微生物多样性的影响。方法通过筛查收集1月龄婴儿的唾液样本;于首次采样时记录母亲的口腔卫生状况,根据母亲患龋情况将婴儿分为母亲有龋组(简称有龋组)和母亲无龋组(简称无龋组),跟踪随访至婴儿6个月时再次收集唾液样本。通过高通量测序的方法,分析婴儿不同月龄微生物多样性的变化。结果本研究随访受试者10例(男6例,女4例),其中有龋组7例,无龋组3例,各组间的微生物群落多样性Shannon指数均无显著性差异(P>0.05)。无龋组婴儿1月龄至6月龄时微生物群落的物种组成有较大变化;有龋组婴儿在1月龄和6月龄时组内各样本间物种组成均差异较大;1月龄时两组微生物群落较相似,而至6月龄时两组婴儿唾液的物种组成已开始发生变化。结论有龋组婴儿口腔内菌群多样性总体高于无龋组,在1月龄至6月龄间婴儿口腔内微生物物种的多样性及丰度均有了不同程度的提高。     

Cytotoxicity of Chinese motherwort (YiMuCao) aqueous ethanol extract is non-apoptotic and estrogen receptor independent on human breast cancer cells

Background

Motherwort has been used as medicinal herb for many years in both China and Europe. In particular, Chinese motherwort has been commonly used to treat disorders of mammary gland in Chinese traditional medicine (TCM). Chinese motherwort aqueous extract (MAE) was previously reported to have anti-cancer activity in breast cancer cells with low potency (IC50s in a range of 8–40 mg/mL). However, treatment of motherwort ethanol extract in vivo markedly suppressed the development of uterine adenomyosis and mammary cancers in mice. Therefore, anti-cancer activity of Chinese motherwort, especially in a form of ethanol extract, needs to be confirmed further at cellular level.

Materials and methods

Aerial part of Chinese motherwort (Leonurus japonicus Houtt) dry powder is extracted with 70% ethanol and the chemical components were characterized with HPLC finger print as well as mass spectrometry. Cytotoxicity of the motherwort aqueous ethanol extract (MAEE) was analyzed with MTT assay on ER negative MDA-MB-231 and ER positive MCF-7 human breast cancer cell lines. Hoechst 33342 staining and flow cytometry were used to verify whether the cell death induced by MAEE is apoptosis in nature. Cell cycle status of MAEE treated cells were analyzed with flow cytometry.

Results

Our results showed that MAEE caused cell death in a dose-dependent and time-dependent fashion in both ER positive and negative breast cancer cells. Morphology, Hoechst 33342 staining and flow cytometry evidence all indicated the cell death is not in an apoptotic nature. Furthermore, low concentrations of MAEE caused cell cycle arrest at G2/M phase.

Conclusions

These data suggest that Chinese motherwort aqueous ethanol extract may effectively inhibit the proliferation of breast cancer cells through mechanisms of both cytotoxicity and cell cycle arrest. The cellular effects of MAEE are non-apoptotic and ER independent on breast cancer cells.     

Integrating the molecular and the population approaches to dementia research to help guide the future development of appropriate therapeutics

Dementia research over the last 50 years has expanded enormously and has greater international interest now than at any time in history. A variety of scientific approaches have been brought to bear on this complex disorder in which the syndrome of clinical features is its defining importance in societal terms. Little has emerged in terms of tangible benefits for people with dementia to date other than a hugely increased awareness at societal and governmental levels. One of the drivers for the increase in focus has been epidemiological evidence, which has provided background numbers for the justification of resources for dementia research. However it can be argued that this justification did not take into account the true meaning of the population evidence, drawing instead on preconceptions which were, at the time, the widely accepted interpretations of earlier evidence. Current evidence, along with the lack of single therapeutic successes, suggests that a clearer analysis is required which not only examines the value and applicability of existing knowledge, most particularly its generation and generalizability, but also where future investment should go for most likely benefit of populations. This includes a hard look at the pre-occupation of societies with single therapies, their place in the context of prevention more generally, particularly within aging populations, and how evidence is generated on likely impacts and their timeframes.     

Comparative evaluation of the impact of minimally invasive preparation vs. conventional straight‐line preparation on tooth biomechanics: a finite element analysis

Minimally invasive endodontics emphasizes preservation of a maximal amount of healthy tooth tissue. However, whether the tooth structure preserved by minimally invasive endodontics can maintain higher fracture resistance is unclear. This study aimed to compare the biomechanics on teeth after minimally invasive (MI) preparation and straight‐line (SL) preparation using finite element analysis. Six finite element analysis models of a mandibular first molar were constructed and divided into two groups (MI and SL). Two loads of 250 N, one vertically stimulating the vertical masticatory force and the other given 45° to the longitudinal axis of the tooth, were applied. Stresses in the teeth were calculated and analyzed. Under both vertical and 45° loads, the greatest stresses were located at the margin of the cavities on the occlusal surfaces. The stress concentration areas of teeth with minimally invasive access cavities were smaller than those of teeth prepared with straight‐line opening in coronal and cervical areas. The stress concentration points in the cervical areas increased with the increase of canal taper in the coronal third. Minimally invasive access preparation reduced the stress distribution in crown and cervical regions. A smaller taper cervical enlargement caused lower stress in the cervical region.