Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.     

There is a difference in functional ankle stability between different types of footwear in male athletes: A cross-sectional study

ContextLateral ankle sprains (LAS) are among the most common injuries in sports, with a poor long – term prognosis due to high chronicity and recurrence rates. Chronic ankle instability (CAI) results up to 40% of people that endured a first – time LAS.ObjectiveThe aim of this study was to compare ankle stability between groups characterised by the use of different types of footwear during their sport activities.DesignCross-sectional study.SettingFirm training surface, local sport clubs.ParticipantsFifty - one male subjects were recruited, distributed in four groups based on the type of footwear they use during their sport activities.Main outcome measuresAll subjects performed four clinical ankle stability tests, and completed the Dutch version of the Cumberland Ankle Instability Tool (CAIT) and Profile of Mood States (POMS). All clinical ankle stability tests were performed barefoot.ResultsSubjects performing their sport activities barefoot scored better than subjects performing their sport with shoes at the multiple hop test (p = .002 to .047) and executed the figure–of–8 hop test significantly faster than subjects with submalleolar ankle support (AS) (p = .019). Subjects with submalleolar AS and studs showed significantly better results than subjects with supramalleolar AS on the CAIT– score (p = .024, p = .030) and the side– hop test (p = .050, p = .045). They also scored significantly better than subjects with submalleolar AS for the side – hop test (p = .032), foot – lift test (p = .019) and figure–of 8 hop test (p = .011).ConclusionBarefoot sports performing subjects appear to have better ankle stability compared to subjects performing their sports with shoe support. Subjects performing sports with high AS appear to have worst ankle stability.Level of evidence: Level III, Cross–sectional study.     

French translation and validation of the Cumberland Ankle Instability Tool,an instrument for measuring functional ankle instability

BackgroundAnkle sprains are one of the most common musculoskeletal injuries, and can lead to chronic ankle instability (CAI). The Cumberland Ankle Instability Tool (CAIT) measures a subset of CAI, functional ankle instability (FAI). Because no French version existed, we set out to translate and validate the CAIT in French.MethodsThe CAIT was translated using a forward-backward methodology. We examined its psychometric properties and calculated a cut-off score for FAI in a sample of 102 subjects (median age 22 years).ResultsThe CAIT was translated without significant problems. The CAIT-F can discriminate between those with and without FAI (p < 0.001), with a cut-off score of ≤ 23 points. The test-retest reliability is excellent (ICC = 0.960), as is the internal consistency (α = 0.885). Construct validity was confirmed. No floor or ceiling effects were detected among subjects with FAI.ConclusionsThe CAIT is now available in French, and is a valid and reliable instrument.     

Early experience unpredictability in child development as a model for understanding the impact of the COVID-19 pandemic: A translational neuroscience perspective

Extensive evidence links adverse experiences during childhood to a wide range of negative consequences in biological, socioemotional, and cognitive development. Unpredictability is a core element underlying most forms of early adversity; it has been a focus of developmental research for many years and has been receiving increasing attention recently. In this article, we propose a conceptual model to describe how unpredictable and adverse early experiences affect children’s neurobiological, behavioral, and psychological development in the context of the COVID-19 pandemic. We first highlight the critical role of unpredictability in child development by reviewing existing conceptual models of early adversity as they relate to subsequent development across the lifespan. Then, we employ a translational neuroscience framework to summarize the current animal- and human-based evidence on the neurobiological alterations induced by early experience unpredictability. We further argue that the COVID-19 pandemic serves as a global “natural experiment” that provides rare insight to the investigation of the negative developmental consequences of widespread, clustered, and unpredictable adverse events among children. We discuss how the pandemic helps advance the science of unpredictable early adverse experiences. As unpredictability research continues to grow, we highlight several directions for future studies and implications for policymaking and intervention practices.     

Can tibio-femoral kinematic and kinetic parameters reveal poor functionality and underlying deficits after total knee replacement? A systematic review

BackgroundExtensive efforts have been made to understand joint kinematics and kinetics in total knee arthroplasty (TKA) in subjects with satisfactory outcomes during daily functional activities and clinical tests, but it remains unclear whether such movement characteristics hold the potential to indicate the underlying aetiology of unsatisfactory or bad TKA outcomes.PurposeTo investigate which kinematic and kinetic parameters assessed during passive clinical tests and functional activities of daily living are associated with poor functionality and underlying deficits after total knee replacement.MethodsWe focused on studies characterizing the kinematic or kinetic parameters of the knee joint that are associated with poor clinical outcome after TKA. Seventeen articles were included for the review, and kinematic and kinetic data from 719 patients with minimal follow up of 6 months were extracted and analyzed.ResultsPassive posterior translation at 90° flexion exhibited good potential for differentiating stable and unstable TKAs. Anterior-posterior (A-P) translation of the medial condyle at 0–30° and 30–60° flexion, A-P translation of the lateral condyle at 60–90° during closed chain exercises, as well as knee extension moment during stair ascent and descent, knee abduction moment during stair descent, knee internal rotation moment and plantar flexion moment during walking, 2nd peak ground reaction force during stair ascent and walking showed the greatest promise as functional biomarkers for a dissatisfied/poor outcome knee after TKA.ConclusionIn this study, we systematically reviewed the state-of-the-art knowledge of kinematics and kinetics associated with functional deficits, and found 11 biomechanical parameters that showed promise for supporting decision making in TKA.     

微创经皮骨盆前环内固定术治疗不稳定性骨盆前环损伤患者的效果

目的:观察微创经皮骨盆前环内固定术治疗不稳定性骨盆前环损伤患者的效果。方法:选取77例不稳定性骨盆前环损伤患者作为研究对象,按随机数字表法将其分为对照组38例与观察组39例。对照组采用开放性骨盆前环外固定术治疗,观察组采用微创经皮骨盆前环内固定术治疗,比较两组疾病相关指标水平、并发症发生率和治疗效果。结果:观察组手术时间长于对照组,骨痂形成时间短于对照组,术中出血量少于对照组,差异均有统计学意义(P<0.05);两组并发症发生率比较,差异无统计学意义(P>0.05);观察组优良率为97.44%(38/39),明显高于对照组的84.21%(32/39),差异有统计学意义(P<0.05)。结论:微创经皮骨盆前环内固定术治疗不稳定性骨盆前环损伤患者可提高优良率,缩短骨痂形成时间,以及减少术中出血量的效果优于开放性骨盆前环外固定术治疗,但手术时间会延长。     

动力髋螺钉与股骨近端髓内钉治疗不稳定型股骨粗隆间骨折的临床比较

目的：比较动力髋螺钉（ DHS）和股骨近端髓内钉（ PFNA）两种内固定治疗不稳定型股骨粗隆间骨折的临床疗效。方法自2008年5月至2013年4月间对95例老年股骨粗隆间不稳定型骨折患者进行回顾性研究,患者分为DHS组45例与PFNA组50例,比较两组的手术时间,术中出血量,下地行走时间,骨折愈合时间及髋关节功能等数据。结果 PFNA组和DHS组在手术时间,术中出血量,下地行走时间有显著差异,而在骨折愈合时间无明显差异,对于不稳定型股骨粗隆间骨折, PFNA组的髋关节功能优良率高于DHS组。结论对于不稳定的股骨粗隆间骨折,PFNA系统具有出血少,手术时间短,恢复快等的优点。