Mutation analysis in 16 patients with mtDNA depletion

Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutations. The current study suggest that scanning the TK2, DGUOK, SLC25A19, and NT5M genes is likely to help about 10% of MDS families in terms of genetic counseling. Also, our findings indicate that genotype-phenotype correlations are not straightforward in MDS.     

Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

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Involvement of the open-source community in combating the worldwide COVID-19 pandemic: a review

Abstract

The ongoing COVID-19 pandemic is unprecedented in the modern age both due to its scale and its disruption to daily life throughout the world. Widespread social isolation and restrictions in the age of modern communicative technology, coupled with some early successes for makers, have united the open-source community towards a common goal in a way not previously seen. Local hospitals and care facilities are turning to makers to print essential consumable parts, such as simple visors, while in the hardest hit areas, critical pieces of medical technology are being fabricated. While important and effective innovations are appearing almost daily, there are also some worrying trends towards hobbyists attempting manufacture of complex medical devices with little understanding of the clinical or scientific rationale behind their design. The nature of the open-source community, an area of intensive innovation, fluidity, and experimentation, jars with the exacting standards of medical device regulation. Here, we review the involvement of rapid prototyping and the open-source community in the key areas of personal protective equipment (PPE), diagnostics, critical care technology, and information acquisition and sharing, highlighting where makers and hackers have clashed with medical device regulations, and areas where the system has worked well to facilitate change.     

Human urinary excretion of doxifluridine and metabolites during a 5-day chemotherapeutic schedule using fluorine-19 nuclear magnetic resonance spectrometry

The urinary excretion of doxifluridine (5 dFUrd) and its metabolites was determined during five days of chemotherapy using fluorine-19 nuclear magnetic resonance spectrometry. The daily urinary excretion of 5 dFUrd and its metabolites was high (-100% of the 5 dFUrd administered) and nearly constant through out the treatment. By far the major excreted compounds were unchanged 5 dFUrd and -fluoro--alanine which made up respectively -40% and -50% of the total. Neither accumulation of 5 dFUrd nor significant modifications in its metabolism were observed during the treatment.     

新型冠状病毒肺炎患者出院后核酸检测阳性临床特征及原因综述

从新型冠状病毒肺炎(coronavirus disease 2019, COVID-19)暴发以来,研究发现COVID-19康复患者在出院后在14 d隔离管理或健康监测期间有样本采集核酸检测再次出现新型冠状病毒阳性(复阳)的情况,国内外相关研究报道越来越多。本研究采用文献查阅综述的方法,旨在综合描述COVID-19复阳者临床人口学特征、可能影响因素以及传播风险,为COVID-19患者出院管理、医疗资源救治分配和传播风险控制提供综合科学的建议。     

Specifics of chronic fatigue syndrome coping strategies identified in a French flash survey during the COVID-19 containment

The COVID-19 pandemic has focused health systems on supporting patients affected by this virus. Meanwhile in the community, many other contained patients could only use self-care strategies, especially in countries that have set up a long and strict containment such as France. The study aimed to compare coping strategies deployed by patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS; a poorly recognised syndrome) to those with better known and referenced chronic conditions. An online flash survey was conducted during the containment period in partnership with French Patients Organizations including ME/CFS national association. Therefore, ‘Brief COPE’ version of Lazarus and Folkman's Ways of Coping Check List has been adapted to the specificity of the containment. The survey was e-distributed in France from 15 April to 11 May 2020. Differences of coping strategies were analyzed using Wilcoxon–Mann–Withney test. Amongst 637 responses, 192 were complete, presenting a wide variety of diseases, including 93 ME/CFS. The latter have significantly different coping strategies than recognised diagnosed diseases patients: similar uses of emotion focused coping but less uses of seek social support and problem-focused copings. In conclusion, coping strategies are different for those who deal with the daily experience of ME/CFS, highly disabling chronic condition with diagnostic ambiguity, low degree of medical and social recognition and without treatment. Better understanding of those strategies is needed to provide the means for health promotion researchers, managers and clinicians, to accompany those patients.     

及时开展新冠疫情防控与大规模核酸检测的卫生经济学评价

目的 对广州市于第二波新冠疫情及时开展疫情防控以及大规模核酸检测进行卫生经济学评价。方法 基于全社会角度,从相关部门及文献中收集数据,对广州市的所有常住居民构建改进SEIR模型,通过构建不同情景,分析真实世界情景及疫情防控措施分别推迟3天与7天的情景下的结果产出值,并对广州市四轮大规模核酸检测行成本效益分析。结果 真实世界情境下,本轮疫情的总经济负担约为344.02亿元人民币。与及时开展疫情防控措施相比,推迟3天开展疫情防控措施会带来1 391例累计确诊病例、43例死亡以及额外的141.91亿元人民币的经济负担。而推迟7天开展疫情防控措施会带来26 237例累计确诊病例、882例死亡以及额外的294.62亿元人民币的经济负担。四轮大规模核酸检测的净收益为221.82亿元人民币,效益成本比为24.23。结论 面对疫情时及时开展疫情防控措施能够极大地减少经济负担,且进行大规模核酸检测具有良好的经济性。     

Diagnostics and Treatments of COVID-19: A Living Systematic Review of Economic Evaluations

ObjectivesAs healthcare systems continue to respond to the COVID-19 pandemic, cost-effectiveness evidence will be needed to identify which tests and treatments for COVID-19 offer value for money. We sought to review economic evaluations of diagnostic tests and treatments for COVID-19, critically appraising the methodological approaches used and reporting cost-effectiveness estimates, using a “living” systematic review approach.MethodsKey databases (including MEDLINE, EconLit, Embase) were last searched on July 12, 2021. Gray literature and model repositories were also searched. Only full economic evaluations published in English were included. Studies were quality assessed and data were extracted into standard tables. Results were narratively summarized. The review was completed by 2 reviewers independently, with disagreements resolved through discussion with a senior reviewer.ResultsOverall, 3540 records were identified, with 13 meeting the inclusion criteria. After quality assessment, 6 were excluded because of very severe limitations. Of the 7 studies included, 5 were cost-utility analyses and 2 were cost-effectiveness analyses. All were model-based analyses. A total of 5 evaluated treatments (dexamethasone, remdesivir, hypothetical) and 2 evaluated hypothetical testing strategies. Cost-effectiveness estimates were sensitive to the treatment effect on survival and hospitalization, testing speed and accuracy, disease severity, and price.ConclusionsPresently, there are few economic evaluations for COVID-19 tests and treatments. They suggest treatments that confer a survival benefit and fast diagnostic tests may be cost effective. Nevertheless, studies are subject to major evidence gaps and take inconsistent analytical approaches. The evidence may improve for planned updates of this “living” review.     

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

Between a hygiene rock and a hygienic hard place: Avoiding SARS-CoV-2 while needing environmental exposures for immunity

Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers.Lay Summary: Hygiene related to sewer systems and other technology can have adverse effects on immune function, and is distinct from personal hygiene practices such as hand washing and social distancing. Dealing with the drawbacks of hygiene must be undertaken without compromising the protection from infectious disease imposed by hygiene.