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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is enriched in transcripts associated with psychiatri

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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医患同在一个屋檐下

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英国医学杂志中文版 2016年第3期19卷 130-131页

作者： helen macdonald 李丹麑 The BMJ and GPLondon 中华医学会学术会务部

“要是医生有更多的时间与患者相处就好了——患者得到更细致的治疗．医生获得更强烈的成就感。”这是真理还是误区？全科医生Rangan Chatterjee暂停了每天只留给每位患者10分钟的预约门诊，打算亲身验证这个设想：他参与BBC的Doctor in... 详细信息

“要是医生有更多的时间与患者相处就好了——患者得到更细致的治疗．医生获得更强烈的成就感。”这是真理还是误区？全科医生Rangan Chatterjee暂停了每天只留给每位患者10分钟的预约门诊，打算亲身验证这个设想：他参与BBC的Doctor in the House节目录制，每天和患者住在一起，

关键词： Doctor in the House 医患双方心理辅导问诊形式变革

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World Journal of Emergency Medicine 2024年第4期15卷 256-262页

作者： Jie Er Janice Soo Yuan helen Zhang Gek Hsiang Lim Fatimah Lateef Department of Emergency Medicine Singapore General HospitalSingapore 168753Singapore Health Services Research Unit Singapore General HospitalSingapore168753Singapore

BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention.METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed.RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission.CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.

关键词： Cycling Injuries Emergency department

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SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C

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World Journal of Pediatrics 2024年第2期20卷 143-152页

作者： Andres F.Moreno Rojas Emelia Bainto helen Harvey Adriana H.Tremoulet Jane C.Burns Kirsten B.Dummer Department of Pediatrics Division of Pediatric CardiologyUniversity of California San Diegoand Rady Children’s Hospital3020 Children’s Way MC 5004San DiegoCA 92123USA Kawasaki Disease Research Center La JollaCAUSA Department of Pediatrics Division of Pediatric Critical CareUniversity of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA Department of Pediatrics University of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA

Background Recent infection with SARS‑CoV-2 in children has been associated with multisystem inflammatory syndrome in children(MIS-C).SARS‑CoV-2 has undergone different mutations.Few publications exist about specific variants and their correlation with the severity of MIS-C.Methods This was a single-center,retrospective study including all patients admitted with MIS-C at Rady Children’s Hospital-San Diego between May 2020 and March 2022.Local epidemiologic data,including viral genomic information,were obtained from public records.Demographics,clinical presentation,laboratory values,and outcomes were obtained from electronic medical records.Results The analysis included 104 pediatric patients.Four MIS-C waves were identified.Circulating variants in San Diego during the first wave included clades 20A to C.During the second wave,there were variants from clades 20A to C,20G,21C(Epsilon),20I(Alpha),and 20J(Gamma).The third wave had Delta strains(clades 21A,21I,and 21J),and the fourth had Omicron variants(clades 21K,21L,and 22C).MIS-C presented with similar symptoms and laboratory findings across all waves.More patients were admitted to the pediatric intensive care unit(PICU)(74%)and required inotropic support(63%)during the second wave.None of the patients required mechanical circulatory support,and only two required invasive ventilatory support.There was no mortality.Conclusions The various strains of SARS-CoV-2 triggered MIS-C with differing severities,with the second wave having a more severe clinical course.Whether the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

关键词： Complications COVID-19 MIS-C SARS-CoV-2 variants

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鹰

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疯狂英语（新悦读） 2015年第6期 37-41页

作者： helen macdonald 小狐

英国剑桥大学自然学家海伦·麦克唐纳所写的回忆录《鹰》可以说是2014年英国出版界的一本"奇书"。它不光享受着书评界一致的好评,几乎得到了所有媒体的盛赞,被多家媒体如《卫报》、《经济学人》等列入年度好书榜,还获得大众的认可,成为... 详细信息

英国剑桥大学自然学家海伦·麦克唐纳所写的回忆录《鹰》可以说是2014年英国出版界的一本"奇书"。它不光享受着书评界一致的好评,几乎得到了所有媒体的盛赞,被多家媒体如《卫报》、《经济学人》等列入年度好书榜,还获得大众的认可,成为畅销书。

关键词：经济学人《卫报》塞缪尔麦克唐纳大学讲师双筒望远镜一本苍头燕雀乌鸫 morning

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旨在实现更好医疗照护的循证医学声明针对患者照护研究中存在系统偏倚、浪费、错误和欺诈的回应

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英国医学杂志中文版 2017年第9期20卷 485-487页

作者： Heneghan Carl Mahtani Kamal R Goldacre Ben Godlee Fiona macdonald helen Jarvies Duncan 徐畅邓可(译者) 孙鑫(审校者) Centre for Evidence Based Medicine University of Oxford UK The BMJ London UK 四川大学华西医院中国循证医学中心

知情决策需要临床医师和患者识别并整合相关证据。但是，当前众多证据的可信度值得怀疑，较少研究真正能够解决患者的重要问题，可用于医患知情共同决策（inform share ddecision）的证据缺乏，他们如何能实现知情决策呢？

关键词：医疗照护医学声明患者医疗卫生行业

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疗愈

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作者： (英)海伦·麦克唐纳(helen macdonald)

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Predictors and Complications of Prematurity in Two Health Facilities in Fako Division, Southwest Region, Cameroon

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Open Journal of Pediatrics 2024年第3期14卷 630-644页

作者： Naiza Monono Verla Sissi Kamo helen Nguepong Vianney Nana Njamen Department of Internal Medicine and Paediatrics Faculty of Health Sciences University of Buea Buea Cameroon Regional Hospital Limbe Southwest Region Cameroon Department of Paediatrics Faculty of Medicine and Biomedical Sciences University of Garoua Garoua Cameroon Department of Obstetrics and Gynaecology Faculty of Health Sciences University of Buea Buea Cameroon

Background: Prematurity is the leading cause of neonatal mortality. Most preterm births can be associated to an identifiable risk factor. In Cameroon, especially in the Southwest Region, there is limited data regarding prematurity associated risk factors. The aim of this study was to evaluate the risk factors and complications of prematurity in two health facilities in the Fako division, the BRH and RHL. Methods: A hospital based retrospective case control study was done from the 1st of January 2021 to 28th of February 2022. We assessed the gestational ages at which preterm birth occurred and their short-term outcome using a structured pretested questionnaire to collect data from files. Data was analyzed using Statistical Package for Social Sciences (SPSS) version 26. Results: The minimum sample size was 137 preterms. 45.5% of cases were born between 34 and increased the risk of having a preterm birth meanwhile being married (AOR: 0.410;95% CI: 0.217 - 0.773;p = 0.006) decreased the risk. Hospital complications were neonatal infection 103 (51.5%), respiratory distress 79 (39.5%) and neonatal jaundice 61 (30.50%). Among the cases, 97 (48.50%) stayed in the hospital for 2 to 4 weeks and 177 (88.5%) were discharged alive. Conclusions: Modifiable factors that increased the risk of prematurity were advanced maternal age, secondary level of education, rural residence, and prenatal alcohol consumption. Being married decreased the risk. The most common hospital complications in both the cases and controls were neonatal infection, respiratory distress syndrome and neonatal jaundice.

关键词： Prematurity Gestational Age Risk Factors Complications Outcome

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旨在实现更好医疗照护的循证医学声明

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中国医院院长 2017年第21期13卷 22-23页

作者： Carl Heneghan Kamal R Mahtani Ben Goldacre Fiona Godlee helen macdonald Duncan Jarvies 徐畅邓可 Centre for Evidence Based Medicine University of Oxford UK

针对患者照护研究中存在系统偏倚、浪费、错误和欺诈的回应。知情决策需要临床医师和患者识别并整合相关证据。但是,当前众多证据的可信度值得怀疑,较少研究真正能够解决患者的重要问题,可用于医患知情共同决策（inform shared decisio... 详细信息

针对患者照护研究中存在系统偏倚、浪费、错误和欺诈的回应。知情决策需要临床医师和患者识别并整合相关证据。但是,当前众多证据的可信度值得怀疑,较少研究真正能够解决患者的重要问题,可用于医患知情共同决策（inform shared decision）的证据缺乏,他们如何能实现知情决策呢？大量研究存在设计不合理或实施不规范的问题。这些研究的结果很多被选择性报告或未报告。

关键词：医疗照护循证医学临床医师患者证据知情可信度

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医生中的利益冲突 "网片丑闻"表明:实施利益冲突注册至关重要

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英国医学杂志中文版 2020年第12期23卷 689-690页

作者： helen macdonald Margaret McCartney Carl Heneghan Fiona Godlee 季媛媛(译) The BMJ LondonUK Centre for Evidence Based Medicine University of OxfordOxfordUK 中华医学杂志英文版

一项由Julia Cumberledge教授主持开展的独立药品和医疗设备安全性审查研究,调查了英国卫生系统如何回应对激素妊娠试验Primodos、妊娠期间服用抗癫痫药物丙戊酸钠,以及盆腔网片负面结果的报道。该研究提出的9项建议中包含:英国医学总会... 详细信息

一项由Julia Cumberledge教授主持开展的独立药品和医疗设备安全性审查研究,调查了英国卫生系统如何回应对激素妊娠试验Primodos、妊娠期间服用抗癫痫药物丙戊酸钠,以及盆腔网片负面结果的报道。该研究提出的9项建议中包含:英国医学总会(GMC)注册制度"应扩大至包含所有医生存在的经济性及非经济性利益清单,公众有权了解这些内容"。研究组广泛听取了患者意见,其中一位患者表示:"我们应知晓临床医生是否存在与药品或医疗设备厂商之间的经济性或非经济性利益,这样我们才能对选择接受哪位医生的诊疗及何种治疗做出明智选择。"

关键词：非经济性利益冲突卫生系统妊娠试验抗癫痫药物丙戊酸钠明智选择注册制度

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