Evidence of Circulation of Several HAV Genetic Variants and Emergence of Potential Antigenic Variants in an Endemo-Epidemic Country before Vaccine Introduction

Similar to several other countries in the world, the epidemiology of hepatitis A virus changed from high to intermediate endemicity level in Tunisia, which led to the occurrence of outbreaks. This study aimed to determine the genetic and antigenic variability of HAV strains circulating in Tunisia during the last few years. Genotyping using complete VP1 gene and VP1-2A junction confirmed the predominance of genotype IA, with co-circulation of several genetic and antigenic variants. Phylogenetic analysis including Tunisian and strains from other regions of the world showed the presence of at least two IA-variants within IA subgenotype. Amino-acid analysis showed several mutations in or close to epitope regions in the VP1-region. This study provides a baseline on the genetic and antigenic variability of HAV circulating strains before the introduction of vaccination into the national immunization schedule.     

Molecular Characterization of Closely Related H6N2 Avian Influenza Viruses Isolated from Turkey,Egypt, and Uganda

Genetic analysis of circulating avian influenza viruses (AIVs) in wild birds at different geographical regions during the same period could improve our knowledge about virus transmission dynamics in natural hosts, virus evolution as well as zoonotic potential. Here, we report the genetic and molecular characterization of H6N2 influenza viruses isolated from migratory birds in Turkey, Egypt, and Uganda during 2017–2018. The Egyptian and Turkish isolates were genetically closer to each other than they were to the virus isolated from Uganda. Our results also suggest that multiple reassortment events were involved in the genesis of the isolated viruses. All viruses contained molecular markers previously associated with increased replication and/or pathogenicity in mammals. The results of this study indicate that H6N2 viruses carried by migratory birds on the West Asian/East African and Mediterranean/Black Sea flyways have the potential to transmit to mammals including humans. Additionally, adaptation markers in these viruses indicate the potential risk for poultry, which also increases the possibility of human exposure to these viruses.     

Targeting the Complement Serine Protease MASP-2 as a Therapeutic Strategy for Coronavirus Infections

MASP-2, mannose-binding protein-associated serine protease 2, is a key enzyme in the lectin pathway of complement activation. Hyperactivation of this protein by human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 has been found to contribute to aberrant complement activation in patients, leading to aggravated lung injury with potentially fatal consequences. This hyperactivation is triggered in the lungs through a conserved, direct interaction between MASP-2 and coronavirus nucleocapsid (N) proteins. Blocking this interaction with monoclonal antibodies and interfering directly with the catalytic activity of MASP-2, have been found to alleviate coronavirus-induced lung injury both in vitro and in vivo. In this study, a virtual library of 8736 licensed drugs and clinical agents has been screened in silico according to two parallel strategies. The first strategy aims at identifying direct inhibitors of MASP-2 catalytic activity, while the second strategy focusses on finding protein-protein interaction inhibitors (PPIs) of MASP-2 and coronaviral N proteins. Such agents could represent promising support treatment options to prevent lung injury and reduce mortality rates of infections caused by both present and future-emerging coronaviruses. Forty-six drug repurposing candidates were purchased and, for the ones selected as potential direct inhibitors of MASP-2, a preliminary in vitro assay was conducted to assess their interference with the lectin pathway of complement activation. Some of the tested agents displayed a dose-response inhibitory activity of the lectin pathway, potentially providing the basis for a viable support strategy to prevent the severe complications of coronavirus infections.     

HIV-1 Envelope Conformation,Allostery, and Dynamics

The HIV-1 envelope glycoprotein (Env) mediates host cell fusion and is the primary target for HIV-1 vaccine design. The Env undergoes a series of functionally important conformational rearrangements upon engagement of its host cell receptor, CD4. As the sole target for broadly neutralizing antibodies, our understanding of these transitions plays a critical role in vaccine immunogen design. Here, we review available experimental data interrogating the HIV-1 Env conformation and detail computational efforts aimed at delineating the series of conformational changes connecting these rearrangements. These studies have provided a structural mapping of prefusion closed, open, and transition intermediate structures, the allosteric elements controlling rearrangements, and state-to-state transition dynamics. The combination of these investigations and innovations in molecular modeling set the stage for advanced studies examining rearrangements at greater spatial and temporal resolution.     

Perioperative identifications of non-palpable pulmonary nodules: a narrative review

Early detection of lung cancer is the key to improving treatment and prognosis of this disease, and the advent of advances in computed tomography (CT) imaging and national screening programs have improved the detection rate of very small pulmonary lesions. As such, the management of this sub-centimetric and often sub-solid lesions has become quite challenging for clinicians, especially for choosing the most suitable diagnostic method. In clinical practice, to fulfill this diagnostic yield, transthoracic needle biopsy (TTNB) is often the first choice especially for peripheral nodules. For lesions for which TTNB could present technical difficulties or failed, other diagnostic strategies are needed. In this case, video-assisted thoracic surgery (VATS) is the gold standard to reach the diagnosis of lung nodules suspect of being malignant. Nonetheless it’s often not easy the identification of such lesions during VATS because of their little dimensions, non-firm consistency, deep localization. In literature various marking techniques have been described, in order to improve intraoperative nodules detection and to reduce conversion rate to thoracotomy: CT-guided hookwire positioning, methylene blue staining, intra-operative ultrasound and electromagnetic navigation bronchoscopy are the most used. The scientific evidence on this matter is weak because there are no randomized clinical trials but only case series on single techniques with no comparison on efficacy, so there are no guidelines to refer. From this standing, in this article we conducted a narrative review of the existing literature on the subject, with the aim of outlining a framework as complete as possible. We analyzed strengths and weaknesses of the main techniques reported, so as to allow the clinician to orient himself with greater ease.     

低分子肝素钙联合双抗治疗进展性缺血性脑卒中疗效观察

目的：观察低分子肝素钙联合双抗治疗进展性缺血性脑卒中的临床效果。方法将100例进展性缺血性脑卒中患者随机分为观察组和对照组各50例。观察组采用氯吡格雷及拜阿司匹林与低分子肝素钙联合治疗,对照组采用血塞通常规治疗。观察2组患者治疗前后纤维蛋白原（Fg）水平、凝血酶原时间（PT）及神经功能缺损评分变化。结果观察组治疗总有效率为94％高于对照组的70％,差异有统计学意义（P ﹤0.05）;2组疗前 Fg、PT 比较差异无统计学意义（P ﹥0.05）,疗后2周,观察组 Fg 水平低于对照组,PT 大于对照组,差异均有统计学意义（P ﹤0.05）;治疗前2组患者神经功能缺损评分比较差异无统计学意义（P ﹥0.05）,治疗后观察组神经功能缺损评分低于对照组（P ﹤0.05）。结论采用低分子肝素钙联合双抗血小板治疗进展性缺血性脑卒中,可改善神经神经功能缺损情况,提高临床治疗效果,改善脑微循环,对改善患者预后有非常重要的价值。     

精准医疗时代下制药行业的挑战和机遇

精准医疗是一种基于病人特定分子标志物的医疗模式,不同于目前针对一般病人的循证医学模式。简要介绍了精准医疗的发展历史和美国的精准医疗计划,提出对制药行业的挑战主要在于:新药产品研发的复杂程度加大、较小的市场容量下研发投入难以回报、配套政策的滞后,给制药行业带来的机会在于:疾病细分导致药物创新需求增加、老药和失败药物面临重生的机遇、中小企业竞争的优势上升、延伸产业发展空间巨大,并针对性地提出了发展策略和建议。     

皮下注射低分子肝素钙预防烧伤植皮后深静脉血栓形成的效果评价

目的：评估皮下注射低分子肝素钙对预防烧伤植皮后深静脉血栓(DVT)形成的效果。方法选取2013年1月~2014年12月本院收治的79例烧伤后需植皮的患者,其中皮下注射低分子肝素钙预DVT患者41例设为治疗组。植皮术后仅使用红外线治疗仪照射,硫酸镁热敷,活动肌肉组织等基础措施的38例为对照组。统计血浆D-二聚体(D-dimer)浓度、血小板计数、植皮成活率、创面愈合时间、感染病例数、组织器官出血病例数和DVT形成数等指标。结果治疗组术后第3、7、11、15 d的血浆D-dimer浓度均低于对照组(P<0.05);对照组的血栓形成率为10.5%,明显高于治疗组的0(P<0.05);两组术前1 d的D-dimer浓度、血小板计数,植皮成活率、创面愈合时间、感染及出血发生率差异无统计学意义(P>0.05)。结论皮下注射低分子肝素钙对预防烧伤植皮术后患者DVT形成有一定的临床意义。