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Raymond Schinazi Discusses the Discovery of Early Antiretroviral Agents and Sofosbuvir Raymond Schinazi讨论早期抗逆转录病毒药物和索非布韦的发现
Q1 Medicine Pub Date : 2023-11-06 DOI: 10.20411/pai.v8i2.624
Michael M. Lederman, Neil Greenspan
In this interview, Raymond Schinazi, PhD, Hon DSc, talks about his career with Michael M. Lederman, MD, and Neil S. Greenspan, MD, PhD, senior editors of Pathogens and Immunity. Dr. Schinazi has invented numerous powerful antiviral agents including the antiretrovirals lamivudine (3TC) and emtricitabine (FTC) and was instrumental in the discovery of the anti-hepatitis C agent sofosbuvir. These drugs have saved millions of lives and, here, Dr. Schinazi shares in detail how these agents were invented, how they work, and how they are being applied. He also offers his thoughts about newer approaches to treat viral infections.
在这次采访中,Raymond Schinazi博士,Hon DSc,谈到了他与Michael M. Lederman医学博士和Neil S. Greenspan医学博士,病原体和免疫资深编辑的职业生涯。他发明了许多强大的抗病毒药物,包括抗逆转录病毒药物拉米夫定(3TC)和恩曲他滨(FTC),并在发现抗丙型肝炎药物sofosbuvir方面发挥了重要作用。这些药物挽救了数百万人的生命,在这里,Schinazi博士详细分享了这些药物是如何发明的,它们是如何工作的,以及它们是如何应用的。他还提出了他对治疗病毒感染的新方法的看法。
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引用次数: 0
Raymond Schinazi Discusses the Discovery of Early Antiretroviral Agents and Sofosbuvir. Raymond Schinazi讨论早期抗逆转录病毒药物和索非布韦的发现。
Q1 Medicine Pub Date : 2023-11-06 eCollection Date: 2023-01-01 DOI: 10.20411/pai.v8i1.624
Michael M Lederman, Neil S Greenspan
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引用次数: 0
The Evolution of Diagnostic Techniques in the Paleopathology of Tuberculosis: A Scoping Review. 结核病古病理学诊断技术的发展:范围界定综述。
Q1 Medicine Pub Date : 2023-10-18 eCollection Date: 2023-01-01 DOI: 10.20411/pai.v8i1.597
Veronica Papa, Francesco M Galassi, Elena Varotto, Andrea Gori, Mauro Vaccarezza

Tuberculosis (TB) is an ancient chronic infectious disease that remains a global health concern. In human remains, the most common and characteristic clinical signs are the skeletal modifications involving the spine, such as in Pott's disease. Diagnosing TB in ancient human remains is challenging. Therefore, in this systematic review, the authors investigated the studies assessing molecular diagnosis of Pott's disease in ancient human remains with the intention to survey the literature, map the evidence, and identify gaps and future perspectives on TB in paleopathology. Our systematic review offers a full contextualization of the history of Pott's disease in ancient times. Our search strategy was performed between August 2022 and March 2023. The authors initially identified 340 records, and 74 studies were finally included and assessed for qualitative analysis. Due to non-specific clinical signs associated with TB, how best to diagnose tuberculosis in human remains still represents a central point. Nevertheless, ancient DNA (aDNA) analysis, lipid biomarkers, and spoligotyping might be extremely useful tools in the study of TB in human remains. Moreover, we propose the extraction and study of immune response genes involved in innate and adaptive immunity versus Mycobacterium spp. as an innovative and vastly overlooked approach in TB paleopathology. Complementary methodologies should be integrated to provide the best approach to the study of TB in human remains.

肺结核是一种古老的慢性传染病,至今仍是全球健康问题。在人类遗骸中,最常见和最具特征性的临床症状是涉及脊椎的骨骼改变,例如Pott病。在古代人类遗骸中诊断结核病具有挑战性。因此,在这篇系统综述中,作者调查了评估古人类遗骸中Pott病分子诊断的研究,目的是调查文献,绘制证据图,并确定古病理学中结核病的差距和未来前景。我们的系统综述提供了古代波特病历史的完整背景。我们的搜索策略是在2022年8月至2023年3月之间执行的。作者最初确定了340份记录,74项研究最终被纳入并评估进行定性分析。由于与结核病相关的非特异性临床症状,如何最好地诊断人类遗骸中的结核病仍然是一个中心问题。然而,古代DNA(aDNA)分析、脂质生物标志物和孢子分型可能是研究人类遗骸中结核病的非常有用的工具。此外,我们建议提取和研究与对分枝杆菌的先天和适应性免疫有关的免疫反应基因。这是结核病古病理学中一种创新且被广泛忽视的方法。应整合补充方法,为研究人类遗骸中的结核病提供最佳方法。
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引用次数: 0
Genomic Characterization of 2 Cutibacterium acnes Isolates from a Surgical Site Infection Reveals Large Genomic Inversion. 从手术部位感染分离的2株痤疮杆菌的基因组特征揭示了大的基因组倒置。
Q1 Medicine Pub Date : 2023-10-05 eCollection Date: 2023-01-01 DOI: 10.20411/pai.v8i1.606
D Garrett Brown, Taylor A Wahlig, Angela Ma, Laura K Certain, Peter N Chalmers, Mark A Fisher, Daniel T Leung

Background: Cutibacterium acnes is a common commensal of human skin but may also present as an opportunistic pathogen in prosthetic joint and wound infections. Unfortunately, few complete genomes of C. acnes are publicly available, and even fewer are of isolates associated with infection. Here we report the isolation, characterization, and complete genomes of 2 C. acnes isolates from a surgical site infection of an elbow.

Methods: We used standard microbiological methods for phenotypic characterization and performed whole genome sequencing on 2 C. acnes isolates using a combination of short-read and long-read sequencing.

Results: Antibiotic susceptibility testing showed beta-lactamase negative and low minimal inhibitory concentrations to all antibiotics tested, with the exception of metronidazole. We assembled complete genomes of the 2 isolates, which are approximately 2.5 megabases in length. The isolates belong to the single-locus sequence type (SLST) H1 and the multi-locus sequence type (MLST) IB. Both isolates have similar composition of known virulence genes, and we found no evidence of plasmids but did find phage-associated genes. Notably, the 2 genomes are 99.97% identical but contain a large genomic inversion encompassing approximately half of the genome.

Conclusions: This is the first characterization of this large-scale genomic inversion in nearly identical isolates from the same wound. This report adds to the limited numbers of publicly available infection-associated complete genomes of C. acnes.

背景:痤疮皮肤杆菌是人类皮肤的常见共生菌,但也可能作为一种机会性病原体出现在人工关节和伤口感染中。不幸的是,很少有完整的痤疮梭菌基因组公开,与感染相关的分离株的基因组更少。在这里,我们报道了从肘部手术部位感染中分离出的2株痤疮梭菌的分离物、特征和完整基因组。方法:我们使用标准微生物学方法进行表型表征,并使用短读和长读测序相结合的方法对2个痤疮梭菌分离株进行全基因组测序。结果:除甲硝唑外,所有受试抗生素的药敏试验均显示β-内酰胺酶阴性,最低抑菌浓度较低。我们组装了这两个分离株的完整基因组,长度约为2.5兆碱基。分离株属于单基因座序列型(SLST)H1和多基因座序列类型(MLST)IB。这两种分离株的已知毒力基因组成相似,我们没有发现质粒的证据,但确实发现了噬菌体相关基因。值得注意的是,这两个基因组有99.97%的相同性,但包含大约一半基因组的大基因组反转。结论:这是首次在来自同一伤口的几乎相同的分离株中对这种大规模基因组倒置进行表征。这份报告增加了有限数量的可公开获得的与感染相关的痤疮梭菌完整基因组。
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引用次数: 0
Military Medicine and Medical Research as a Source of Inspiration and Innovation to Solve National Security and Health Challenges in the 21st Century. 军事医学和医学研究是解决21世纪国家安全和健康挑战的灵感和创新来源。
Q1 Medicine Pub Date : 2023-09-08 eCollection Date: 2023-01-01 DOI: 10.20411/pai.v8i1.596
Nanak S Dhillon, Nayeon Jeon, Umut A Gurkan, Anirban Sen Gupta, Robert A Bonomo, Lawrence F Drummy, Mei Zhang, Mark R Chance

The history of military medicine and research is rife with examples of novel treatments and new approaches to heal and cure soldiers and others impacted by war's devastation. In the 21st century, new threats, like climate change, are combined with traditional threats, like geopolitical conflict, to create novel challenges for our strategic interests. Extreme and inaccessible environments provide heightened risks for warfighter exposure to dangerous bacteria, viruses, and fungi, as well as exposure to toxic substances and extremes of temperature, pressure, or both providing threats to performance and eroding resilience. Back home, caring for our veterans is also a health-care priority, and the diseases of veterans increasingly overlap with the health needs of an aging society. These trends of climate change, politics, and demographics suggest performance evaluation and resilience planning and response are critical to assuring both warfighter performance and societal health. The Cleveland ecosystem, comprising several hospitals, a leading University, and one of the nation's larger Veteran's Health Administration systems, is ideal for incubating and understanding the response to these challenges. In this review, we explore the interconnections of collaborations between Defense agencies, particularly Air Force and Army and academic medical center-based investigators to drive responses to the national health security challenges facing the United States and the world.

军事医学和研究史上充斥着治愈士兵和其他受战争破坏影响的人的新疗法和新方法的例子。在21世纪,气候变化等新威胁与地缘政治冲突等传统威胁相结合,给我们的战略利益带来了新的挑战。极端和难以接近的环境增加了作战人员接触危险细菌、病毒和真菌的风险,也增加了接触有毒物质和极端温度、压力的风险,或两者都对性能和恢复力构成威胁。在国内,照顾退伍军人也是医疗保健的优先事项,退伍军人的疾病与老龄化社会的健康需求越来越重叠。气候变化、政治和人口统计的这些趋势表明,绩效评估、恢复力规划和应对对于确保作战人员的绩效和社会健康至关重要。克利夫兰的生态系统由几家医院、一所领先的大学和美国较大的退伍军人健康管理系统之一组成,是孵化和了解应对这些挑战的理想选择。在这篇综述中,我们探讨了国防机构之间的合作关系,特别是空军和陆军以及学术医疗中心的调查人员之间的合作,以推动应对美国和世界面临的国家卫生安全挑战。
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引用次数: 0
Immunohematologic Biomarkers in COVID-19: Insights into Pathogenesis, Prognosis, and Prevention. COVID-19免疫血液学生物标志物:发病机制、预后和预防的见解。
Q1 Medicine Pub Date : 2023-06-26 eCollection Date: 2023-01-01 DOI: 10.20411/pai.v8i1.572
David R Sweet, Michael L Freeman, David A Zidar

Coronavirus disease 2019 (COVID-19) has had profound effects on the health of individuals and on healthcare systems worldwide. While healthcare workers on the frontlines have fought to quell multiple waves of infection, the efforts of the larger research community have changed the arch of this pandemic as well. This review will focus on biomarker discovery and other efforts to identify features that predict outcomes, and in so doing, identify possible effector and passenger mechanisms of adverse outcomes. Identifying measurable soluble factors, cell-types, and clinical parameters that predict a patient's disease course will have a legacy for the study of immunologic responses, especially stimuli, which induce an overactive, yet ineffectual immune system. As prognostic biomarkers were identified, some have served to represent pathways of therapeutic interest in clinical trials. The pandemic conditions have created urgency for accelerated target identification and validation. Collectively, these COVID-19 studies of biomarkers, disease outcomes, and therapeutic efficacy have revealed that immunologic systems and responses to stimuli are more heterogeneous than previously assumed. Understanding the genetic and acquired features that mediate divergent immunologic outcomes in response to this global exposure is ongoing and will ultimately improve our preparedness for future pandemics, as well as impact preventive approaches to other immunologic diseases.

2019冠状病毒病(新冠肺炎)对全球个人健康和医疗系统产生了深远影响。尽管前线的医护人员一直在努力平息多波感染,但更大的研究界的努力也改变了这场疫情的格局。这篇综述将侧重于生物标志物的发现和其他努力,以确定预测结果的特征,并在这样做的过程中,确定不良结果的可能效应器和乘客机制。识别可测量的可溶性因子、细胞类型和预测患者病程的临床参数,将为研究免疫反应,特别是刺激,产生过度活跃但无效的免疫系统留下遗产。随着预后生物标志物的确定,一些已经在临床试验中代表了治疗兴趣的途径。新冠疫情条件迫切需要加快目标识别和验证。总之,这些关于生物标志物、疾病结果和治疗效果的新冠肺炎研究表明,免疫系统和对刺激的反应比以前假设的更为异质。了解在应对这种全球暴露时介导不同免疫结果的遗传和后天特征正在进行中,并将最终改善我们对未来流行病的准备,以及对其他免疫疾病的预防方法产生影响。
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引用次数: 2
A Community-Driven Framework to Prioritize the Use of Donated Human Biological Materials in the Context of HIV Cure-Related Research at the End of Life. 一个社区驱动的框架,在生命末期与艾滋病治疗相关的研究中优先使用捐赠的人类生物材料。
Q1 Medicine Pub Date : 2023-05-24 eCollection Date: 2023-01-01 DOI: 10.20411/pai.v8i1.583
Karine Dubé, Thomas J Villa, Jeff Taylor, Andy Kaytes, David J Moore, Susan J Little, Antoine Chaillon, Davey M Smith, Sara Gianella

Initiated in 2017 after extensive community engagement, the Last Gift program enrolls altruistic volunteers willing to donate their cells and tissues at the end of life to allow studies on HIV reservoir dynamics across anatomical sites. As the Last Gift team received tissue requests outside the scope of HIV cure research, we noticed the absence of guiding frameworks to help prioritize the use of altruistically donated human biological materials. In this commentary, we present a proposed framework for prioritizing the use of donated human biological materials within and outside the end-of-life (EOL) HIV cure research context, using the Last Gift study as an example. First, we discuss regulatory and policy considerations, and highlight key ethical values to guide prioritization decisions. Second, we present our prioritization framework and share some of our experiences prioritizing requests for donated human biological materials within and outside EOL HIV cure research.

经过广泛的社区参与,"最后的礼物 "计划于 2017 年启动,招募愿意在生命终结时捐献细胞和组织的利他主义志愿者,以便开展跨解剖部位的 HIV 储库动态研究。在 "最后的礼物 "团队收到艾滋病治愈研究范围之外的组织请求时,我们注意到缺乏指导框架来帮助确定利他捐赠的人类生物材料的优先使用顺序。在这篇评论中,我们以 "最后的礼物 "研究为例,提出了在生命终结(EOL)HIV 治愈研究范围内外优先使用捐赠人体生物材料的建议框架。首先,我们讨论了监管和政策方面的考虑因素,并强调了指导优先决策的关键伦理价值。其次,我们介绍了我们的优先排序框架,并分享了我们在生命末期 (EOL) HIV 治愈研究中和生命末期 (EOL) 以外的捐赠人体生物材料申请优先排序方面的一些经验。
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引用次数: 0
B-Cell Responses to Sars-Cov-2 mRNA Vaccines. b细胞对Sars-Cov-2 mRNA疫苗的应答
Q1 Medicine Pub Date : 2022-12-09 eCollection Date: 2022-01-01 DOI: 10.20411/pai.v7i2.550
Lela Kardava, Clarisa M Buckner, Susan Moir

Most vaccines against viral pathogens protect through the acquisition of immunological memory from long-lived plasma cells that produce antibodies and memory B cells that can rapidly respond upon an encounter with the pathogen or its variants. The COVID-19 pandemic and rapid deployment of effective vaccines have provided an unprecedented opportunity to study the immune response to a new yet rapidly evolving pathogen. Here we review the scientific literature and our efforts to understand antibody and B-cell responses to SARS-CoV-2 vaccines, the effect of SARSCoV-2 infection on both primary and secondary immune responses, and how repeated exposures may impact outcomes.

大多数针对病毒病原体的疫苗通过从产生抗体的长寿浆细胞和记忆B细胞获得免疫记忆来进行保护,记忆B细胞在遇到病原体或其变体时可以迅速做出反应。新冠肺炎大流行和有效疫苗的快速部署为研究对一种新的快速进化病原体的免疫反应提供了前所未有的机会。在这里,我们回顾了科学文献和我们为了解抗体和B细胞对严重急性呼吸系统综合征冠状病毒2型疫苗的反应、严重急性呼吸系冠状病毒2型感染对初级和次级免疫反应的影响,以及重复暴露可能如何影响结果所做的努力。
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引用次数: 0
Pandemics and the English Language: Concepts Critical for Conversing About COVID-19. 流行病和英语:讨论COVID-19的关键概念。
Q1 Medicine Pub Date : 2022-11-10 eCollection Date: 2022-01-01 DOI: 10.20411/pai.v7i2.542
Neil S Greenspan, Guillermo A Pereda

We consider the multiple senses of several key terms that are used to discuss the ongoing COVID-19 pandemic and clarify meanings of the corresponding concepts. Topics addressed include: 1) the meaning of immunity to an infectious agent in varying medical and scientific contexts, 2) the scientific factors that influenced the rapid generation and clinical implementation of safe and effective vaccines for COVID-19, 3) the difference between mutational abrogation of reactivity with B- or T-cell antigen receptors (immune escape) versus active interference with host immune mechanisms mediated by gene products encoded within the genome of the infectious agent (immune evasion), 4) the different ways by which the COVID-19 pandemic has "caused" deaths, and 5) briefly, the challenge of precisely defining the term pathogen.

我们考虑了用于讨论正在进行的COVID-19大流行的几个关键术语的多重含义,并澄清了相应概念的含义。讨论的主题包括:1)在不同的医学和科学背景下对感染原免疫的意义,2)影响安全有效的COVID-19疫苗快速生成和临床实施的科学因素,3)与B细胞或t细胞抗原受体反应性的突变消除(免疫逃逸)与由感染原基因组内编码的基因产物介导的对宿主免疫机制的主动干扰(免疫逃逸)之间的区别,4) COVID-19大流行“造成”死亡的不同方式,以及5)简单地说,准确定义病原体一词的挑战。
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引用次数: 0
Real-World Evidence on the Effectiveness of Plexiglass Barriers in Reducing Aerosol Exposure. 有机玻璃屏障减少气溶胶暴露有效性的真实证据。
Q1 Medicine Pub Date : 2022-11-04 eCollection Date: 2022-01-01 DOI: 10.20411/pai.v7i2.533
Jennifer L Cadnum, Annette L Jencson, Samir Memic, Andrew O Osborne, Maria M Torres-Teran, Brigid M Wilson, Abhishek Deshpande, Curtis J Donskey

Reprinted with permission, Cleveland Clinic Foundation ©2022. All Rights Reserved.

Background: Barriers are commonly installed in workplace situations where physical distancing cannot be maintained to reduce the risk for transmission of respiratory viruses. Although some types of barriers have been shown to reduce exposure to aerosols in laboratory-based testing, limited information is available on the efficacy of barriers in real-world settings.

Methods: In an acute care hospital, we tested the effectiveness of in-use plexiglass barriers in reducing exposure of staff to aerosolized particles. A nebulizer was used to release 5% NaCl aerosol 1 meter from staff members with and without the barrier positioned between the point of aerosol release and the hospital staff. Particle counts on the staff side of the barrier were measured using a 6-channel particle counter. A condensed moisture (fog) generating device was used to visualize the airflow patterns.

Results: Of 13 in-use barriers tested, 6 (46%) significantly reduced aerosol particle counts detected behind the barrier, 6 (46%) reduced particle counts to a modest, non-significant degree, and 1 (8%) significantly increased particle counts behind the barrier. Condensed moisture fog accumulated in the area where staff were seated behind the barrier that increased particle exposure, but not behind the other barriers. After repositioning the ineffective barrier, the condensed moisture fog no longer accumulated behind the barrier and aerosol exposure was reduced.

Conclusion: In real-world settings, plexiglass barriers vary widely in effectiveness in reducing staff exposure to aerosols, and some barriers may increase risk for exposure if not positioned correctly. Devices that visualize airflow patterns may be useful as simple tools to assess barriers.

经许可转载,克利夫兰诊所基金会©2022。版权所有。背景:通常在无法保持物理距离的工作场所设置屏障,以减少呼吸道病毒传播的风险。尽管某些类型的屏障在实验室测试中已被证明可以减少气溶胶暴露,但关于屏障在实际环境中的功效的信息有限。方法:在一家急症护理医院,我们测试了使用中的有机玻璃屏障在减少工作人员接触雾化颗粒方面的有效性。使用喷雾器在离工作人员1米远的地方释放5% NaCl气溶胶,在气溶胶释放点与医院工作人员之间有或没有屏障。使用6通道粒子计数器测量屏障工作人员侧的粒子计数。一个冷凝的水汽(雾)产生装置被用来可视化气流模式。结果:在测试的13个使用中的屏障中,6个(46%)显著减少了屏障后检测到的气溶胶颗粒计数,6个(46%)将颗粒计数减少到适度的、不显著的程度,1个(8%)显著增加了屏障后的颗粒计数。凝结的湿气雾积聚在工作人员坐在屏障后面的区域,增加了颗粒暴露,但没有在其他屏障后面。重新定位无效屏障后,凝聚的湿气雾不再积聚在屏障后面,气溶胶暴露减少。结论:在现实环境中,有机玻璃屏障在减少工作人员气溶胶暴露方面的有效性差异很大,如果放置不当,一些屏障可能会增加暴露风险。可视化气流模式的设备可能是评估障碍的简单工具。
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引用次数: 4
期刊
Pathogens and Immunity
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