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Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S.pneumoniae

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Synthetic and Systems biotechnology 2017年第1期2卷 49-58页

作者： allison e.b.turner Jonas e.Gerson Helen Y.So Daniel J.Krasznai Adrienne J.St.Hilaire Donald F.Gerson Vaccine Research and Development PnuVax Incorporated Headquarters134 Albert St.KingstonOntarioK7L 3V2Canada Vaccine Research and Development PnuVax Incorporated Laboratories6000 Royalmount Ave.MontrealQuebecH4P 2T1Canada

Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6b,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

关键词： Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation

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Preoperative virtual video visits only:a convenient option that should be offered to caregivers beyond the pandemic

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World Journal of Pediatric Surgery 2022年第3期5卷 169-175页

作者： Danielle Dougherty allison R Thompson Karen elizabeth Speck erin e Perrone Section of Pediatric Surgery Department of SurgeryUniversity of Michigan Health SystemAnn ArborMichiganUSA Department of Health behavior and Health education University of Michigan School of Public HealthAnn ArborMIUSA

Objective During the COVID-19 pandemic,our group implemented preoperative video visits(VVs)to limit physical contact.The aim of this study was to determine caregivers’and providers’perceptions of this practice and to determine feasibility for continuation.Methods All patients who had only a preoperative VV prior to an elective surgery were identified from March-October 2020.Caregivers,surgeons,and clinic staff were surveyed about their experiences.Results Thirty-four preoperative VVs were followed by an elective surgery without a preceding in-person visit.Of the 31 caregiver surveys completed,the majority strongly agreed that the VV was more convenient(87%,n=27).eighty-one percent(n=25)strongly agreed or agreed that the VV saved them money.Ninety-four percent(n=29)strongly agreed or agreed that they would choose the VV option again.Caregivers saved an average travel distance of 60.3 miles one way(range 6.1-480).Of the 13/17 providers who responded,77%(n=10)expressed that the practice should continue.Conclusions Virtual health became a necessity during the pandemic,and caregivers were overwhelmingly satisfied.Continuing VVs as an option beyond the pandemic may be a reasonable and effective way to help eliminate some of the hurdles that impede healthcare-seeking behavior and should be offered.

关键词： convenient beyond eliminate

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Newfound physiological function of FAIM protein offers hope of novel disease-modifying therapy for Alzheimer's disease

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Neural Regeneration Research 2023年第12期18卷 2677-2679页

作者： allison Rbalaj Hiroaki Kaku Department of Investigative Medicine Western Michigan University Homer Stryker M.D.School of MedicineKalamazooMIUSA

Introduction of Fas apoptosis inhibitory molecule(FAIM): FAIM was originally discovered in FASresistant mouse primary b lymphocytes in 1999, and was thought of as a FAS-apoptosis inhibitor based on overexpression studies(Schneider et al., 1999). FAIM is an approximately 20 k Da intracellular protein, but a subsequent study identified an alternatively spliced form.

关键词： al. Alzheimer lymphocytes

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Autism spectrum disorders in adolescence and adulthood: Long-term outcomes and relevant issues for treatment and research

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Science China(Life Sciences) 2015年第10期58卷 1010-1015页

作者： allison b.RATTO Gary b.MeSIbOV Department of Psychology University of North Carolina at Chapel Hill Department of Psychiatry University of North Carolina at Chapel Hill

The advances in research and treatment of autism spectrum disorders(ASD) over the past three decades have focused largely on early childhood and school-age years. Although ASD is a lifelong condition, there has been relatively little attention paid to ASD during the adolescent and adulthood periods. As the population of those with ASD continues to rise and age, the need to provide research and treatment for this group has become increasingly evident. This paper reviews the current literature available on symptoms, functioning, and treatment of adolescents and adults with ASD, as well as the unique issues that arise for individuals with ASD after childhood. Adulthood outcomes for ASD are generally poor, even for those with average to above average cognitive ability. Further research and additional clinical resources are needed for this rapidly increasing group.

关键词：成年期治疗自闭青春期谱系 ASD 学龄儿童认知能力

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时钟与电网

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科技纵览 2024年第3期 78-78页

作者： allison Marsh 不详

1916年10月23日,位名叫亨利·e.沃伦(Henry e.Warren)的工程师在位于波士顿的爱迪生电气照明公司的L街发电站安装了一台电钟,悄然间彻底改变了电力传输。这个主站时钟保持了一种非常特殊的时间类型,它结合使用了同步自启动电机和钟摆来... 详细信息

1916年10月23日,位名叫亨利·e.沃伦(Henry e.Warren)的工程师在位于波士顿的爱迪生电气照明公司的L街发电站安装了一台电钟,悄然间彻底改变了电力传输。这个主站时钟保持了一种非常特殊的时间类型,它结合使用了同步自启动电机和钟摆来将发电站的交流电稳定地保持在每秒60个周期的频率。随着越来越多的发电站采用电钟,频率调节让它们得以共享电力并建立一个相互连接的电网。直到20世纪40年代末,沃伦电钟公司的站钟管理着美国95%以上的电力线路。

关键词：电气照明电力线路电力传输发电站频率调节启动电机交流电爱迪生

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Ketamine use disorder:preclinical,clinical,and neuroimaging evidence to support proposed mechanisms of actions

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Intelligent Medicine 2022年第2期2卷 61-68页

作者： Leah Vines Diana Sotelo allison Johnson evan Dennis Peter Manza Nora D.Volkow Gene-Jack Wang Laboratory of Neuroimaging National Institute on Alcohol Abuse and AlcoholismNational Institutes of Health10 Center DrRm B2L124BethesdaMarylandUnited States

Ketamine,a noncompetitive N-methyl-D-aspartate(NMDA)receptor antagonist,has been exclusively used as an anesthetic in medicine and has led to new insights into the pathophysiology of neuropsychiatric disorders.Clinical studies have shown that low subanesthetic doses of ketamine produce antidepressant effects for individuals with depression.However,its use as a treatment for psychiatric disorders has been limited due to its reinforcing effects and high potential for diversion and misuse.Preclinical studies have focused on understanding the molecular mechanisms underlying ketamine’s antidepressant effects,but a precise mechanism had yet to be elucidated.Here we review different hypotheses for ketamine’s mechanism of action including the direct inhibition and disinhibition of NMDA receptors,aminomethylphosphonic acid receptors(AMPAR)activation,and heightened activation of monoaminergic systems.The proposed mechanisms are not mutually exclusive,and their combined influence may exert the observed structural and functional neural impairments.Long term use of ketamine induces brain structural,functional impairments,and neurodevelopmental effects in both rodents and humans.Its misuse has increased rapidly in the past 20 years and is one of the most common addictive drugs used in Asia.The proposed mechanisms of action and supporting neuroimaging data allow for the development of tools to identify‘biotypes’of ketamine use disorder(KUD)using machine learning approaches,which could inform intervention and treatment.

关键词： Ketamine Neuroimaging N-methyl-D-aspartate Dopamine Serotonin Glutamatergic Gamma-aminobutyric acid

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Journal of Sport and Health Science 2022年第6期11卷 716-724页

作者： Zachary Yukio Kerr Avinash Chandran Aliza K.Nedimyer allison e.Rothschild Melissa C.Kay Paula Gildner K.Hunter byrd Juliet K Haarbauer-Krupa Johna K.Register-Mihalik Department of exercise and Sport Science University of North Carolina at Chapel HillChapel HillNC 27599-8700USA Matthew Gfeller Sport-Related Traumatic brain Injury Research Center University of North CarolinaChapel HillNC 27599-8700USA Injury Prevention Research Center University of North CarolinaChapel HillNC 27510USA Human Movement Science Curriculum University of North CarolinaChapel HillNC 27599-8700USA Department of Health behavior Gillings School of Public HealthUniversity of North CarolinaChapel HillNC 27599-7400USA School of Health Professions University of Southern MississippiHattiesburgMS 39406USA National Center for Injury Prevention and Control Centers for Disease Control and PreventionAtlantaGA 30341USA

Objective:Parents may use various information sources to obtain information about sport-related concussions(SRC).This study examined SRCrelated information sources used by parents of United States middle school children(age:10-15 years).Methods:A panel of 1083 randomly selected U.S.residents,aged≥18 years and identifying as parents of middle school children,completed an online questionnaire capturing parental and child characteristics,and utilization and perceived trustworthiness of various sources of SRC-related information.Multivariable logistic regression models identified factors associated with utilizing each source.Adjusted odds ratios(OR)with 95%confidence intervals(95%CIs)excluding 1.00 were deemed significant.Results:Doctors/healthcare providers(49.9%)and other healthcare-related resources(e.g.,Centers for Disease Control and Prevention,WebMD)(37.8%)were common SRC-related information sources;64.0%of parents utilized≥1 of these sources.both sources were considered“very”or“extremely”trustworthy for SRC-related information among parents using these sources(doctors/healthcare providers:89.8%;other healthcare-related resources:70.9%).A 10-year increase in parental age was associated with higher odds of utilizing doctors/healthcare providers(adjusted odd ratio(OR_(adjusted))=1.09,95%CI:1.02-1.16)and other healthcare-related resources(OR_(adjusted)=1.11,95%CI:1.03-1.19).The odds of utilizing doctors/healthcare providers(OR_(adjusted)=0.58,95%CI:0.40-0.84)and other healthcare-related resources(OR_(adjusted)=0.64,95%CI:0.44-0.93)were lower among parents whose middle school children had concussion histories versus the parents of children who did not have concussion histories.Conclusion:One-third of parents did not report using doctors/healthcare providers or other healthcare-related resources for SRC-related information.Factors associated with underutilization of these sources may be targets for future intervention.Continuing education for healthcare providers and educational opportunities for parents should high

关键词： Information seeking Media use Traumatic brain injury

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Macrophage polarization in response to wear particles in vitro

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Cellular & Molecular Immunology 2013年第6期10卷 471-482页

作者： Joseph K Antonios Zhenyu Yao Chenguang Li allison J Rao Stuart b Goodman Orthopaedic Research Laboratories Department of Orthopaedic Surgery Stanford University School of Medicine Stanford CA USA

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant （periprosthetic osteolysis）. Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory （M 1） macrophage phenotype rather than an anti-inflammatory pro-tissue healing （M2） macrophage phenotype. While it has been shown that interleukin-4 （IL-4） selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through I L-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate （PMMA） particles, lipopolysaccharide （LPS） and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase （iNOS） production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M 1 phenotype rather than to uncommitted （MO） macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

关键词： IL-4 macrophage polarization osteolysis PMMA particles total joint replacement

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PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function

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Nano Research 2020年第3期13卷 736-744页

作者： elizabeth e.Sweeney Preethi b.balakrishnan allison b.Powell Allan bowen Indra Sarabia Rachel A.burga R.brad Jones Alberto bosque C.Russell Y.Cruz Rohan Fernandes The George Washington Cancer Center The George Washington UniversityWashingtonDC20052USA Center for Cancer and Immunology Research Children’s National Health SystemWashingtonDC20010USA Department of Microbiology Immunologyand Tropical MedicineThe George Washington UniversityWashingtonDC20052USA Infectious Disease Division Weill Cornell Medical CollegeNew YorkNY10065USA View author publications Department of Medicine The George Washington UniversityWashingtonDC20052USA

Natural killer(NK)cells are attractive effector cells of the innate immune system against human immunodeficiency virus(HIV)and cancer.However,NK cell therapies are limited by the fact that target cells evade NK cells,for example,in latent reservoirs(in HIV)or through upregulation of inhibitory signals(in cancer).To address this limitation,we describe a biodegradable nanoparticlebased“priming”approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells.We present poly(lactic-co-glycolic acid)(PLGA)nanodepots(NDs)that co-encapsulate prostratin,a latency-reversing agent,and anti-CD25(aCD25),a cell surface binding antibody,to enhance primary NK cell function against HIV and cancer.We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs(termed Pro-aCD25-NDs).Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs.The NDs successfully released both active prostratin and anti-CD25,and with controllable release kinetics.When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells,the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25,and other controls.These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.

关键词： poly(lactic-co-glycolic acid)(PLGA)nanodepots natural killer(NK)cells human immunodeficiency virus(HIV) cancer latency-reversing agent antibody

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Suicide transport blockade of motor neuron survival generates a focal graded injury and functional deficit

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Neural Regeneration Research 2021年第7期16卷 1281-1287页

作者： allison S.Liang Joanna e.Pagano Christopher A.Chrzan Randall D.McKinnon Department of Neurosurgery Rutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA Member The Cancer Institute of New JerseyNew BrunswickNJUSA

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small rodents.Retrograde axonal transport of a pro-apoptotic phosphatidylinosotol 3'-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug administered.Motor neuron loss was detected by choline acetyltransferase(ChAT) immunostaining and with a transgenic thy1-eGFP marker.The short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus tracer.Using quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 μg wortmannin, relative to sham controls, and remained low after 90 days.Smaller effects were observed with 200 ng and 100 ng wortmannin.Wortmannin also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 days.Treated mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit test.Controls rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 months.Thus the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and repair.The efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral sclerosis.All procedures were performed at Rutgers under established Institutional Animal Care and Use protocols(eIACUC_TR201800022, approved on March 20, 2018).

关键词： amyotrophic lateral sclerosis injury motor function motor neuron PI3'kinase sciatic nerve suicide transport wortmannin

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