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1.
J Exp Med ; 217(9)2020 09 07.
Article in English | MEDLINE | ID: mdl-32584412

ABSTRACT

Dengue is a major public health concern in the tropical and subtropical world, with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of subunit vaccine approaches, and nonstructural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non-mouse-adapted DENV2 strains that are highly virulent. Exogenous administration of purified NS1 also failed to worsen in vivo vascular leakage in sublethally infected mice. Neither method of NS1 immune neutralization changed the disease outcome of a chimeric strain expressing a vascular leak-potent NS1. Instead, virus chimerization involving the prME structural region indicated that these proteins play a critical role in driving in vivo fitness and virulence of the virus, through induction of key proinflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain dependent, which warrants reevaluation of NS1 as a universal dengue vaccine candidate.


Subject(s)
Dengue Virus/pathogenicity , Viral Nonstructural Proteins/metabolism , Animals , Antibodies, Viral/immunology , Antibody-Dependent Enhancement/immunology , Capillary Permeability , Chimera , Cytokines/metabolism , Dengue/blood , Dengue/immunology , Dengue/virology , Dengue Virus/immunology , Dengue Virus/isolation & purification , Disease Models, Animal , Immunity , Immunization , Immunoglobulin G/blood , Mice , Receptor, Interferon alpha-beta/deficiency , Receptor, Interferon alpha-beta/metabolism , Severity of Illness Index , Viremia/immunology , Virulence
2.
Int J Pharm Pract ; 24(3): 160-9, 2016 May.
Article in English | MEDLINE | ID: mdl-26671003

ABSTRACT

OBJECTIVES: To investigate pharmacists' herbal/nutrient weight loss complementary medicine (WLCM) practices in the context of other pharmacist weight management support practices (provision of lifestyle advice, orlistat and meal replacement treatments); and gain insight into their attitudes, recommendations, information and education needs. METHODS: Pharmacists from a randomly selected sample of 214 community pharmacies from different socioeconomic areas in the Greater Brisbane region, Australia, were invited to complete a survey to explore their weight management practices, with a specific focus on herbal/nutrient WLCM practices. Data collected from the sample group represented pharmacist practices within the metropolitan Greater Brisbane region. KEY FINDINGS: This survey achieved a 51% response rate. During weight management consultations, a high proportion of customers (37%) sought advice from community pharmacists relating to WLCMs relative to other weight management practices; however, only a small proportion (10%) of pharmacists recommended them. Most were also found to be using resources that may not be evidence-based or do not provide sufficient WLCMs' information. CONCLUSION: Study results highlight the need for pharmacy professional bodies to develop evidence-based continuing education programmes to assist consumers with popular and widely available WLCMs products.


Subject(s)
Complementary Therapies , Education, Pharmacy , Health Knowledge, Attitudes, Practice , Herbal Medicine , Pharmacists/psychology , Weight Loss/drug effects , Adult , Attitude of Health Personnel , Female , Food , Humans , Male , Middle Aged , Patient Education as Topic , Professional Role , Young Adult
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