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1.
Vaccines (Basel) ; 9(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916180

RESUMO

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

2.
Sci Rep ; 11(1): 9040, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907221

RESUMO

The nontuberculous mycobacteria (NTM) Mycobacterium avium is a clinically significant pathogen that can cause a wide range of maladies, including tuberculosis-like pulmonary disease. An immunocompromised host status, either genetically or acutely acquired, presents a large risk for progressive NTM infections. Due to this quietly emerging health threat, we evaluated the ability of a recombinant fusion protein ID91 combined with GLA-SE [glucopyranosyl lipid adjuvant, a toll like receptor 4 agonist formulated in an oil-in-water stable nano-emulsion] to confer protection in both C57BL/6 (wild type) and Beige (immunocompromised) mouse models. We optimized an aerosol challenge model using a clinical NTM isolate: M. avium 2-151 smt, observed bacterial growth kinetics, colony morphology, drug sensitivity and histopathology, characterized the influx of pulmonary immune cells, and confirmed the immunogenicity of ID91 in both mouse models. To determine prophylactic vaccine efficacy against this M. avium isolate, mice were immunized with either ID91 + GLA-SE or bacillus Calmette-Guérin (BCG). Immunocompromised Beige mice displayed a delayed influx of innate and adaptive immune cells resulting in a sustained and increased bacterial burden in the lungs and spleen compared to C57BL/6 mice. Importantly, both ID91 + GLA-SE and BCG vaccines significantly reduced pulmonary bacterial burden in both mouse strains. This work is a proof-of-concept study of subunit vaccine-induced protection against NTM.


Assuntos
Vacina BCG/administração & dosagem , Modelos Animais de Doenças , Hospedeiro Imunocomprometido/imunologia , Mycobacterium avium/patogenicidade , Tuberculose/prevenção & controle , Vacinas de Subunidades/administração & dosagem , Animais , Vacina BCG/imunologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium avium/metabolismo , Tuberculose/imunologia , Tuberculose/microbiologia , Vacinação , Vacinas de Subunidades/imunologia
3.
NPJ Vaccines ; 6(1): 47, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785745

RESUMO

To generate an inexpensive readily manufactured COVID-19 vaccine, we employed the LVS ΔcapB vector platform, previously used to generate potent candidate vaccines against Select Agent diseases tularemia, anthrax, plague, and melioidosis. Vaccines expressing SARS-CoV-2 structural proteins are constructed using the LVS ΔcapB vector, a highly attenuated replicating intracellular bacterium, and evaluated for efficacy in golden Syrian hamsters, which develop severe COVID-19-like disease. Hamsters immunized intradermally or intranasally with a vaccine co-expressing the Membrane and Nucleocapsid proteins and challenged 5 weeks later with a high dose of SARS-CoV-2 are protected against severe weight loss and lung pathology and show reduced viral loads in the oropharynx and lungs. Protection correlates with anti-Nucleocapsid antibody. This potent vaccine should be safe; inexpensive; easily manufactured, stored, and distributed; and given the high homology between Membrane and Nucleocapsid proteins of SARS-CoV and SARS-CoV-2, potentially serve as a universal vaccine against the SARS subset of pandemic causing ß-coronaviruses.

4.
Am J Occup Ther ; 74(3): 7403205160p1-7403205160p9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365322

RESUMO

IMPORTANCE: If occupational therapy is to play an important role in improving population health, it is important to understand how academic programs are preparing new occupational therapists for this role. OBJECTIVE: To determine current and desired coverage of population health concepts in entry-level occupational therapy programs. DESIGN: Online survey administered to occupational therapy program directors. SETTING: Higher education institutions. PARTICIPANTS: Survey invitations were sent to all 182 entry-level occupational therapy program directors in Spring 2018. MEASURES: Questionnaire responses were used to calculate current and desired curriculum coverage of 23 population health domains. RESULTS: Of 182 program directors, 60 (33.0%) responded. Respondents agreed that 21 of 23 population health domains should be included in entry-level occupational therapy programs, and 11 of the domains had moderate or better coverage in their current programs. The largest gaps between current and desired coverage were found in global health issues, population health informatics, environmental health, and organization of health systems. CONCLUSIONS AND RELEVANCE: Occupational therapy faculty can use these results to further develop the population health content of their programs. WHAT THIS ARTICLE ADDS: Although the occupational therapy profession advocates for the role of occupational therapists in the improvement of population health, little information is available about how to prepare new occupational therapists for this role. This study addresses this gap by presenting occupational therapy program directors' assessments of current and desired levels of population health content within their programs.


Assuntos
Currículo , Terapia Ocupacional/educação , Saúde da População , Humanos , Inquéritos e Questionários
5.
PLoS One ; 15(2): e0228327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32059005

RESUMO

Chronic wasting disease (CWD) continues to spread or be recognized in the United States, Canada, and Europe. CWD is diagnosed by demonstration of the causative misfolded prion protein (PrPCWD) in either brain or lymphoid tissue using immunodetection methods, with immunohistochemistry (IHC) recognized as the gold standard. In recent years, in vitro amplification assays have been developed that can detect CWD prion seeding activity in tissues, excreta, and body fluids of affected cervids. These methods potentially offer earlier and more facile detection of CWD, both pre- and post-mortem. Here we provide a longitudinal profile of CWD infection progression, as assessed by both real-time quaking-induced conversion (RT-QuIC) and IHC on serial biopsies of mucosal lymphoid tissues of white-tailed deer orally exposed to low doses of CWD prions. We report that detection of CWD infection by RT-QuIC preceded that by IHC in both tonsil and recto-anal lymphoid tissue (RAMALT) in 14 of 19 deer (74%). Of the 322 biopsy samples collected in post-exposure longitudinal monitoring, positive RT-QuIC results were obtained for 146 samples, 91 of which (62%) were concurrently also IHC-positive. The lower frequency of IHC positivity was manifest most in the earlier post-exposure periods and in biopsies in which lymphoid follicles were not detected. For all deer in which RT-QuIC seeding activity was detected in a tonsil or RAMALT biopsy, PrPCWD was subsequently or concurrently detected by IHC. Overall, this study (a) provides a longitudinal profile of CWD infection in deer after low yet infectious oral prion exposure; (b) illustrates the value of RT-QuIC for sensitive detection of CWD; and (c) demonstrates an ultimate high degree of correlation between RT-QuIC and IHC positivity as CWD infection progresses.


Assuntos
Imuno-Histoquímica , Técnicas de Amplificação de Ácido Nucleico/métodos , Doença de Emaciação Crônica/patologia , Administração Oral , Animais , Cervos , Progressão da Doença , Estudos Longitudinais , Tecido Linfoide/metabolismo , Tecido Linfoide/patologia , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , Proteínas Priônicas/genética , Proteínas Priônicas/metabolismo , Príons/administração & dosagem , Doença de Emaciação Crônica/metabolismo
6.
PLoS One ; 14(8): e0221654, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31461493

RESUMO

The diagnosis of chronic wasting disease (CWD) relies on demonstration of the disease-associated misfolded CWD prion protein (PrPCWD) in brain or retropharyngeal lymph node tissue by immunodetection methods, e.g. ELISA and immunohistochemistry (IHC). The success of these methods relies on a quality sample of tissues, which requires both anatomical knowledge and considerable dissection to collect. As the prevalence of CWD continues to increase globally, the development of fast and cost-effective methods to detect the disease is vital to facilitate CWD detection and surveillance. To address these issues, we have evaluated third eyelids from CWD-infected deer and elk using real-time quaking induced conversion (RT-QuIC). We identified prion seeding activity in third eyelids in 24 of 25 (96%) CWD-infected white-tailed deer (Odocoileus virginianus). We detected RT-QuIC positivity in the third eyelid as early as 1 month after experimental CWD exposure. In addition, we identified prion seeding activity in third eyelids of 18 of 25 (72%) naturally exposed asymptomatic CWD-positive rocky mountain elk (Cervus canadensis nelson). We compared CWD detection by RT-QuIC and IHC in third eyelid, retropharyngeal lymph node, and brain in 10 deer in early symptomatic stage of disease. IHC detected PrPCWD deposition in third eyelid lymphoid follicles in 5 of 10 deer (50%) whereas third eyelids of all 10 animals were positive by RT-QuIC. This difference reflected in part a lower requirement for lymphoid follicle presence for seeding activity detection by RT-QuIC. In conclusion, RT-QuIC analysis of the third eyelid, an easily accessed tissue, has potential to advance CWD detection and testing compliance.


Assuntos
Bioensaio/métodos , Sistemas Computacionais , Cervos/fisiologia , Pálpebras/patologia , Doença de Emaciação Crônica/diagnóstico , Animais
7.
J Alzheimers Dis ; 53(1): 161-70, 2016 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-27104905

RESUMO

BACKGROUND: Effective programs for promoting physical activity are needed for those with cognitive impairment. OBJECTIVE: To test the feasibility of mobile Health (mHealth) technology-supported physical activity prescription from a tertiary care memory clinic. METHODS: This feasibility study was designed as a 16-week randomized, crossover trial of a physical activity prescription: 8 weeks of intervention, 8 weeks of baseline or maintenance phase data collection. We recruited 2 cohorts: 21 individuals with Alzheimer-related cognitive impairment (mean age 72.3 (5.2), 9 females), and 9 individuals with normal cognition (mean age 69.6 (5.8), 8 females). We gave each cohort an mHealth accelerometer-based physical activity prescription to double number of steps taken. Our primary outcomes were feasibility and safety. Our secondary outcomes were change in weekly steps taken, Dementia Quality of Life Scale, Self-efficacy Scale, 6-minute Walk, and mini-Physical Performance Test. RESULTS: Set-up and use of the device was not a barrier to participation. However, only 62% of participants with cognitive impairment completed the intervention. The cohort with cognitive impairment did not change their weekly step count above Week 1. All participants in the cohort with normal cognition were able to set up and use their device and increased their weekly step count above Week 1. There were no differences between Week 1 and Week 8 for any secondary measures in either cohort. CONCLUSIONS: Setup and daily use of mHealth technology appears to be feasible for a person with cognitive impairment with the help of a partner, but increasing daily step counts over 8 weeks was not achieved. Future work needs to assess alternative activity prescription goals or additional support for patients and their partners.


Assuntos
Instituições de Assistência Ambulatorial , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/reabilitação , Exercício Físico/fisiologia , Promoção da Saúde/métodos , Acelerometria , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervenção Médica Precoce/métodos , Estudos de Viabilidade , Feminino , Humanos , Internet/estatística & dados numéricos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Fatores de Tempo
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