Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

Reliability and criterion validity of two-dimensional movement assessments in those with patellofemoral pain

ObjectivesDetermine criterion validity and intra/inter-rater reliability of 2-dimensional (2D) knee frontal plane projection angle (kFPPA), hip frontal plane projection angle (hFPPA), and dynamic valgus index (DVI) during forward step-downs in those with patellofemoral pain (PFP).DesignCross-sectional.SettingUniversity research laboratory.Participants39 participants with PFP (34.18 ± 7.41years, 170± .1 cm, 81.03 ± 19.36 kg, duration of pain: 68.67 ± 85.08months, anterior knee pain scale: 80.49 ± 7.87, visual analog scale:2.08 ± 2.02)Main outcome measuresAverage 3D hip and knee sagittal, frontal, and transverse joint angles and 2D kFPPA, hFPPA, and DVI at maximum knee flexion were variables of interest. 3D DVI was calculated as the sum of hip and knee frontal and transverse angles. 2D kFPPA, hFPPA, and DVI were calculated by two raters independently on two occasions.ResultsIntra- and inter-rater reliability of all 2D angles were excellent. kFPPA was moderately correlated to 3D knee transverse angles. hFPPA was moderately correlated to 3D hip frontal and transverse angles and largely correlated to 3D DVI. 2D DVI was moderately correlated to hip transverse angles.ConclusionkFPPA, hFPPA, and DVI are reliable. hFPPA may be reflective of 3D hip and knee frontal and transverse motion during forward step-downs in those with PFP.     

Visualization of electrophysiological activity at the carpal tunnel area using magnetoneurography

ObjectiveTo establish a noninvasive method to measure the neuromagnetic fields of the median nerve at the carpal tunnel after electrical digital nerve stimulation and evaluate peripheral nerve function.MethodsUsing a vector-type biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields at the carpal tunnel were recorded after electrical stimulation of the index or middle digital nerve in five healthy volunteers. A novel technique for removing stimulus-induced artifacts was applied, and current distributions were calculated using a spatial filter algorithm and superimposed on X-ray.ResultsA neuromagnetic field propagating from the palm to the carpal tunnel was observed in all participants. Current distributions estimated from the magnetic fields had five components: leading and trailing components parallel to the conduction pathway, outward current preceding the leading component, inward currents between the leading and trailing components, and outward current following the trailing component. The conduction velocity and peak latency of the inward current agreed well with those of sensory nerve action potentials.ConclusionRemoving stimulus-induced artifacts enabled magnetoneurography to noninvasively visualize with high spatial resolution the electrophysiological neural activity from the palm to the carpal tunnel.SignificanceThis is the first report of using magnetoneurography to visualize electrophysiological nerve activity at the palm and carpal tunnel.     

针刺足运感区结合局部电针围刺治疗中风后尿失禁的临床观察

[目的]观察针刺足运感区结合局部电针围刺与常规针刺、常规针刺联合足运感区治疗中风后尿失禁的临床疗效差异。[方法]将90例患者随机分为治疗组、对照1组和对照2组,每组30例,治疗组予针刺足运感区结合膀胱体表相应投影区域电针围刺;对照1组参照全国高等中医药院校"十三五"规划教材《针灸治疗学》中有关"尿失禁"的治疗选穴;对照2组在对照1组的基础上联合足运感区针刺,每日上午行神经内科常规治疗,每日下午行中风后尿失禁的临床治疗,每次30 min,每周连续治疗6次,6次为1个疗程,疗程间休息1 d,共2个疗程。观察3组治疗前后尿失禁程度、尿失禁临床症状评分及日常生活活动能力量表(ADL)评分,并比较3组患者的临床疗效。[结果] 3组患者治疗后尿失禁程度、尿失禁临床症状评分及ADL评分均较前改善(均P0.05),治疗组对尿失禁程度及尿失禁临床症状评分的改善较其他两组更明显(P0.05),且治疗组和对照2组的ADL评分明显优于对照1组(P0.05)。治疗组总有效率为93.3%(30/28),优于对照1组76.7%(30/23)和对照2组83.3%(30/25,P0.05)。[结论]针刺足运感区结合局部电针围刺治疗中风后尿失禁疗效显著。     

Impact of dose reduction and the use of an advanced model-based iterative reconstruction algorithm on spectral performance of a dual-source CT system: A task-based image quality assessment

PurposeTo assess the impact of dose reduction and the use of an advanced modeled iterative reconstruction algorithm (ADMIRE) on image quality in low-energy monochromatic images from a dual-source dual energy computed tomography CT (DSCT) platform.Materials and methodsAcquisitions on an image-quality phantom were performed using DSCT equipment with 100/Sn150 kVp for four dose levels (CTDI_vol: 20/11/8/5mGy). Raw data were reconstructed for six energy levels (40/50/60/70/80/100 keV) using filtered back projection and two levels of ADMIRE (A3/A5). Noise power spectrum (NPS) and task-based transfer function (TTF) were calculated on virtual monoenergetic images (VMIs). Detectability index (d′) was computed to model the detection task of two enhanced iodine lesions as function of keV.ResultsNoise-magnitude was significantly reduced between 40 to 70 keV by ?56 ± 0% (SD) (range: ?56%–?55%) with FBP; ?56 ± 0% (SD) (?56%–?56%) with A3; and ?57 ± 1% (SD) (range: ?57%–?56%) with A5. The average spatial frequency of the NPS peaked at 70 keV and decreased as ADMIRE level increased. TTF values at 50% were greatest at 40 keV and shifted towards lower frequencies as the keV increased. The detectability of both lesions increased with increasing dose level and ADMIRE level. For the simulated lesion with iodine at 2 mg/mL, d’ values peaked at 70 keV for all reconstruction types, except for A3 at 20 mGy and A5 at 11 and 20 mGy, where d’ peaked at 60 keV. For the other simulated lesion, d’ values were highest at 40 keV and decreased beyond.ConclusionAt low keV on VMIs, this study confirms that iterative reconstruction reduces the noise magnitude, improves the spatial resolution and increases the detectability of enhanced iodine lesions.     

Antibody persistence and booster response following MenACWY-CRM vaccination in children as assessed by two different assay methods

BackgroundThe quadrivalent meningococcal conjugate vaccine MenACWY-CRM has been shown to be immunogenic and well-tolerated in infants and toddlers. We evaluated antibody persistence for up to 4 years after vaccination with MenACWY-CRM in the first years of life and response to a booster dose administered at 60 months of age.MethodsThis was phase 3b, open-label, multicenter extension trial (NCT01148017). We assessed by hSBA and rSBA the persistence of antibody responses to serogroups ACWY in 203 healthy 60-month-olds receiving 4 doses of MenACWY-CRM during infancy (ACWY-4 group), or 2 doses at 12/13 and 15 months or 1 dose at 18 months of age (ACWY-2 group). We administered a MenACWY-CRM dose to 224 primed and 45 naïve 60-month-olds and evaluated safety and antibody response 1 month later.ResultsAntibody persistence measured by both assays was higher in primed than naïve 60-month-olds. The percentages of primed children with hSBA titers ≥8 was low for serogroup A (6–25%) and moderate for serogroups C (27–43%), Y (69–74%) and W (56–69%). For all serogroups, hSBA antibody geometric mean titers (GMTs) tended to be higher in the ACWY-2 than the ACWY-4 group. Post-booster/single dose, ≥96% of primed and ≥73% of naïve children had hSBA titers ≥8 against each serogroup, and hSBA GMTs were higher in primed children. The booster dose was well-tolerated and no safety concern was identified. We further assessed persistence using rSBA across different age groups and detected no overall correlation between rSBA and hSBA titers.ConclusionsPrimary vaccination of infants/toddlers with MenACWY-CRM resulted in moderate antibody persistence against serogroups C, W and Y for up to 4 years after the last priming dose. Regardless of priming schedule, a MenACWY-CRM booster dose at 60 months of age induced a robust immune response against all serogroups and was well-tolerated in all children.     

Protection of White Leghorn chickens by recombinant fowlpox vector vaccine with an updated H5 insert against Mexican H5N2 avian influenza viruses

Despite decades of vaccination, surveillance, and biosecurity measures, H5N2 low pathogenicity avian influenza (LPAI) virus infections continue in Mexico and neighboring countries. One explanation for tenacity of H5N2 LPAI in Mexico is the antigenic divergence of circulating field viruses compared to licensed vaccines due to antigenic drift. Our phylogenetic analysis indicates that the H5N2 LPAI viruses circulating in Mexico and neighboring countries since 1994 have undergone antigenic drift away from vaccine seed strains. Here we evaluated the efficacy of a new recombinant fowlpox virus vector containing an updated H5 insert (rFPV-H5/2016), more relevant to the current strains circulating in Mexico. We tested the vaccine efficacy against a closely related subcluster 4 Mexican H5N2 LPAI (2010 H5/LP) virus and the historic H5N2 HPAI (1995 H5/HP) virus in White Leghorn chickens. The rFPV-H5/2016 vaccine provided hemagglutinin inhibition (HI) titers pre-challenge against viral antigens from both challenge viruses in almost 100% of the immunized birds, with no differences in number of birds seroconverting or HI titers among all tested doses (1.5, 2.0, and 3.1 log₁₀ mean tissue culture infectious doses/bird). The vaccine conferred 100% clinical protection and a significant decrease in oral and cloacal virus shedding from 1995 H5/HP virus challenged birds when compared to the sham controls at all tested doses. Virus shedding titers from vaccinated 2010 H5/LP virus challenged birds significantly decreased compared to sham birds especially at earlier time points. Our results confirm the efficacy of the new rFPV-H5/2016 against antigenic drift of LPAI virus in Mexico and suggest that this vaccine would be a good candidate, likely as a primer in a prime-boost vaccination program.     

Pediatric cardiac computed tomography angiography: Expert consensus from the Filiale de Cardiologie Pédiatrique et Congénitale (FCPC) and the Société Française d’Imagerie Cardiaque et Vasculaire diagnostique et interventionnelle (SFICV)

This article was designed to provide a pediatric cardiac computed tomography angiography (CCTA) expert panel consensus based on opinions of experts of the Société Française d’Imagerie Cardiaque et Vasculaire diagnostique et interventionnelle (SFICV) and of the Filiale de Cardiologie Pédiatrique Congénitale (FCPC). This expert panel consensus includes recommendations for indications, patient preparation, CTA radiation dose reduction techniques, and post-processing techniques. The consensus was based on data from available literature (original papers, reviews and guidelines) and on opinions of a group of specialists with extensive experience in the use of CT imaging in congenital heart disease. In order to reach high potential and avoid pitfalls, CCTA in children with congenital heart disease requires training and experience. Moreover, pediatric cardiac CCTA protocols should be standardized to acquire optimal images in this population with the lowest radiation dose possible to prevent unnecessary radiation exposure. We also provided a suggested structured report and a list of acquisition protocols and technical parameters in relation to specific vendors.     

The relationship between ankle dorsiflexion range of motion,frontal plane projection angle,and patellofemoral pain syndrome

BackgroundAnkle range of motion abnormalities have been often linked with alteration in knee kinematics leading to the development of patellofemoral pain syndrome (PFPS). Literature exploring the relationship between ankle dorsiflexion range of motion (DF ROM) and knee kinematics during functional tasks is scanty. This study aims to assess the relation between ankle DF ROM and frontal plane projection angle (FPPA), one of the knee kinematic variables, in individuals with and without PFPS during a step-down test.MethodsThis is a case-control study in which seventy PFPS patients and other 70 asymptomatic control subjects had their ankle DF ROM measured using an inclinometer with the knee flexed and extended. Their FPPA angles were measured using Kinovea software while doing the step-down test.ResultsWhen the two groups were compared, ankle DF ROM measured with the knee flexed was higher in the control group (33.15 ± 4.96) than in the PFPS group (30.20 ± 6.93) (p = 0.03). In both the PFPS group and the control group, the correlation between FPPA and ankle DF ROM with the knee flexed was statistically insignificant (p = 0.075 and 0.323 respectively).ConclusionDecreased ankle DF ROM can be one of the contributing factors to the development of PFPS in the context of greater dynamic knee valgus.