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1.
Nicotine Tob Res ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616654

RESUMO

INTRODUCTION: Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs. METHODS: Eighty participants who typically smoked menthol cigarettes completed this clinical lab study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following one-week of substituting their preferred MCA for their UBMC, participants completed a 90-min concurrent-choice self-administration task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the lab with subsequent response effort for UBMCs on the concurrent-choice task. RESULTS: Three demand indices for UBMC were positively associated with UBMC response effort: Essential Value (EV; p=.02), Omax (p=.02), and breakpoint (p=.04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p=.03), Pmax (p=.04), Omax (p=.03), and breakpoint (p=.03). Subjective effects captured by the mCEQ were not associated with response effort. CONCLUSIONS: Demand indices reflecting Persistence (i.e., sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (i.e., addiction potential) of combustible tobacco products similar to the longer self-administration task. IMPLICATIONS: In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of cigarette purchase task efficiently capture information on the relative reinforcing value of usual brand menthol cigarettes and plausible alternative tobacco products, similar to a 90-min in-laboratory self-administration task.

2.
Nat Microbiol ; 9(5): 1231-1243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649413

RESUMO

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.


Assuntos
Mucosa , Infecções por Poxviridae , Eliminação de Partículas Virais , Animais , Feminino , Mucosa/virologia , Infecções por Poxviridae/transmissão , Infecções por Poxviridae/virologia , Infecções por Poxviridae/veterinária , Humanos , Replicação Viral , Modelos Animais de Doenças , Roedores/virologia , Masculino , Ratos , Vagina/virologia , Surtos de Doenças
3.
J Infect Dis ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38487996

RESUMO

The most recent Sudan virus (SUDV) outbreak in Uganda was first detected in September 2022 and resulted in 164 laboratory-confirmed cases and 77 deaths. There are no approved vaccines against SUDV. Here, we investigated the protective efficacy of ChAdOx1-biEBOV in cynomolgus macaques using a prime or a prime-boost regimen. ChAdOx1-biEBOV is a replication-deficient simian adenovirus vector encoding SUDV and Ebola virus (EBOV) glycoproteins (GPs). Intramuscular vaccination induced SUDV and EBOV GP-specific IgG responses and neutralizing antibodies. Upon challenge with SUDV, vaccinated animals showed signs of disease like those observed in control animals, and no difference in survival outcomes were measured among all three groups. Viral load in blood samples and in tissue samples obtained after necropsy were not significantly different between groups. Overall, this study highlights the importance of evaluating vaccines in multiple animal models and demonstrates the importance of understanding protective efficacy in both animal models and human hosts.

4.
Addict Behav ; 152: 107975, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38309240

RESUMO

BACKGROUND: Nicotine vaping is more prevalent among U.S. adults with disabilities compared to those without disabilities. However, less is known about nicotine vaping among adolescents (12-17 years) and young adults (18-25 years) by disability status. METHODS: Using data from a sample of 24,722 adolescents and young adults (AYAs) from the 2021 National Survey on Drug Use and Health, we conducted descriptive and multivariable analyses to estimate the national prevalence of nicotine vaping by disability type and examined major depressive episodes (MDEs) as a risk factor for nicotine vaping. RESULTS: A greater proportion of AYAs with disabilities engaged in past-month nicotine vaping compared to those without a disability (13.9 % vs 9.6 %, p = 0.0001). Also, when MDE was excluded from the model, AYAs with any disability had higher odds of nicotine vaping (AOR = 1.41; 95 % CI 1.15, 1.74) than those without a disability. However, disability status was no longer significant when MDE was included (AOR = 1.16; 95 % CI 0.91, 1.46) in the model. CONCLUSIONS: The higher prevalence of nicotine vaping among AYAs with disabilities suggests that tailored messages may be needed to communicate health risks and adverse outcomes of e-cigarette use. Also, MDE is associated with nicotine vaping among AYA populations. This information can be helpful to school nurses, counselors, and mental health professionals in their screening of major depression as a risk factor for e-cigarette use.


Assuntos
Transtorno Depressivo Maior , Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , Adolescente , Adulto Jovem , Vaping/psicologia , Transtorno Depressivo Maior/epidemiologia , Prevalência , Fatores de Risco
5.
Elife ; 122024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38416804

RESUMO

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 hr), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10 µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 hr). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.


Assuntos
COVID-19 , SARS-CoV-2 , Cricetinae , Animais , Masculino , Mesocricetus , Aerossóis e Gotículas Respiratórios
6.
Prev Med Rep ; 38: 102593, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38283968

RESUMO

INTRODUCTION: Cigarette smoking is disproportionately high among lesbian, gay, and bisexual (LGB) adults. Yet, collapsing these identities into a monolith can disguise important within group disparities (e.g., lesbian/gay versus bisexual female). The purpose of this study is to report recent national prevalence estimates and trends of cigarette smoking behaviors and nicotine dependence by sexual identity and sex. METHODS: Data were from the 2015-2019 National Survey on Drug Use and Health (n = 210,392; adults 18+), a nationally representative, repeated cross-sectional study of substance use and mental health in the U.S. We examined bivariate and multivariable associations between sexual identity and cigarette smoking measures (i.e., former smoking, lifetime smoking, current smoking, current daily smoking, nicotine dependence) by sex. We also examined linear time trends in current and former smoking. Covariates included age, race/ethnicity, education, annual household income, and survey year. RESULTS: Bisexual women had the highest unadjusted prevalence of current smoking (31 %) and lowest of former smoking (25 %). LGB females and males had higher adjusted prevalence of current smoking, daily smoking, and nicotine dependence than heterosexual adults. Bisexual females and gay and bisexual males had lower adjusted prevalence of former smoking (adjusted prevalence ratio range: 0.78-0.85) than heterosexual counterparts. DISCUSSION: This is the first study to identify disproportionately low prevalence of former smoking among bisexual females. Paired with findings of high prevalence of current cigarette smoking and nicotine dependence, these data suggest that tobacco control interventions targeted toward bisexual females are urgently needed to reduce the burden of cigarette smoking among these individuals.

7.
J Adolesc Health ; 74(4): 764-773, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38043040

RESUMO

PURPOSE: To estimate the national prevalence of tobacco, marijuana, and alcohol use among U.S. adolescents (age 12-17) and young adults (aged 18-25; adolescents and young adults [AYAs]) with a disability and examine associations between disability and substance use from 2015 to 2019. METHODS: Data from the 2015-2019 National Survey on Drug Use and Health were used to estimate the prevalence of tobacco, marijuana, and alcohol use among AYAs with disabilities. Modified Poisson regression models evaluated linear time trends in past-month substance use and estimated adjusted prevalence ratios (aPRs) for past-month cigarette, any tobacco, alcohol, and marijuana use. RESULTS: Adolescents with any disability had a higher prevalence of past-month cigarette (aPR = 1.87; 95% CI 1.67-2.09), alcohol (aPR = 1.21; 95% CI 1.11-1.31), and marijuana use (aPR = 1.47; 95% CI 1.36-1.60) compared to those without disabilities. Cigarette smoking among adolescents decreased over this time period; however, the decline among adolescents without a disability was greater than those with any disability. Young adults with any disability had a higher prevalence of past-month cigarette (aPR = 1.42; 95% CI 1.35-1.48) and marijuana use (aPR = 1.39; 95% CI 1.34-1.45), but a lower prevalence of past-month alcohol use (aPR = 0.93; 95% CI 0.90-0.95) than those without disabilities. Alcohol use remained constant among young adults with any disability but decreased for those without disabilities. DISCUSSION: Population-level disparities in cigarette and marijuana use exist in AYAs with disabilities. Future studies should identify strategies tailored to AYAs with disabilities to encourage smoking cessation and prevent cannabis use disorder.


Assuntos
Fumar Maconha , Uso da Maconha , Transtornos Relacionados ao Uso de Substâncias , Uso de Tabaco , Consumo de Álcool por Menores , Adolescente , Adulto , Criança , Humanos , Adulto Jovem , Cannabis , Fumar Maconha/epidemiologia , Uso da Maconha/epidemiologia , Prevalência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Uso de Tabaco/epidemiologia , Pessoas com Deficiência
8.
Addict Behav ; 149: 107905, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37977010

RESUMO

INTRODUCTION: People with disabilities disproportionately use tobacco products. However, little is known about cessation interventions tailored for people with disabilities. The objective of this study was to conduct a systematic review of smoking cessation interventions for adults with disabilities. METHODS: Six electronic databases (Cochrane, CINAHL Plus [EBSCOhost], Embase [Ovid], Medline [Ovid], PsycINFO [Ovid], and Web of Science) were searched to identify eligible interventions for people with disabilities (e.g., vision, hearing, mobility, communication, cognition, self-care) through July 2023. Two independent coders evaluated the records and extracted data from studies that met inclusion criteria. Qualitative synthesis was conducted on the included studies in 2023. RESULTS: One randomized controlled trial and one nonrandomized study met the inclusion criteria. Both studies used mindfulness-based procedures to reduce cigarette use in adults with mild intellectual disability. The outcome was defined as self-reported cigarette use at follow-up, which ranged from 1 year to 3 years. Limited information was provided on how the interventions were tailored to meet the unique needs of people with disabilities in either study. CONCLUSION: Two interventions conducted in adults with mild intellectual disability showed promising results using mindfulness-based procedures; however, the studies did not address barriers reported by people with disabilities, nor tailor the interventions to meet the needs of the target population. Research is needed to address tobacco use disparities among people with a range of disabilities. Current cessation interventions would be enhanced by integrating disability identifiers alongside other demographic information in future studies and reporting subgroup analyses in adults with disabilities.


Assuntos
Pessoas com Deficiência , Deficiência Intelectual , Atenção Plena , Abandono do Hábito de Fumar , Adulto , Humanos , Terapia Comportamental , Abandono do Hábito de Fumar/métodos
9.
Tob Control ; 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37963771

RESUMO

INTRODUCTION: This study assessed the substitutability of plausible combustible menthol cigarette alternatives (MCAs) for usual brand menthol cigarettes (UBMCs) in adults who smoke menthol cigarettes. METHODS: Following three in-lab sampling sessions, 80 adults aged 21-50 who smoke menthol cigarettes chose their preferred MCA: (1) a menthol roll-your-own cigarette (mRYO), (2) a menthol filtered little cigar (mFLC) or (3) a non-menthol cigarette (NMC). Participants were instructed to completely substitute their preferred MCA for their UBMC for 1 week and complete daily diaries documenting adherence and subjective effects. At the final lab visit, participants completed concurrent choice and cross-price elasticity tasks with their substitute product and UBMC as the comparator. RESULTS: Most (65%) participants chose mRYO as their preferred product, followed by NMC and mFLC. Adherence to MCA was high for all products across the week (range: 63%-88%). Positive subjective effects for mRYO decreased over time but remained numerically higher than the other MCA products; craving reduction also decreased for NMC across phases. In the progressive ratio task, participants chose their UBMC in 61.7% of choices; this did not differ by preferred MCA, although the median breakpoint was highest for mRYO and similar for mFLC and NMC. Cross-price elasticity comparing UBMC and the preferred product indicated high substitutability of each MCA at phase 3 (I values -0.70 to -0.82). CONCLUSIONS AND RELEVANCE: mRYOs were the most preferred MCA among the study products, but all MCAs were acceptable substitutes for UBMC using behavioural and economic measures in a short-term trial period.Trial registration number NCT04844762.

10.
Nat Commun ; 14(1): 6592, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37852960

RESUMO

Limited data is available on the effect of vaccination and previous virus exposure on the nature of SARS-CoV-2 transmission and immune-pressure on variants. To understand the impact of pre-existing immunity on SARS-CoV-2 airborne transmission efficiency, we perform a transmission chain experiment using naïve, intranasally or intramuscularly AZD1222 vaccinated, and previously infected hamsters. A clear gradient in transmission efficacy is observed: Transmission in hamsters vaccinated via the intramuscular route was reduced over three airborne chains (approx. 60%) compared to naïve animals, whereas transmission in previously infected hamsters and those vaccinated via the intranasal route was reduced by 80%. We also find that the Delta B.1.617.2 variant outcompeted Omicron B.1.1.529 after dual infection within and between hosts in naïve, vaccinated, and previously infected transmission chains, yet an increase in Omicron B.1.1.529 competitiveness is observed in groups with pre-existing immunity against Delta B.1.617.2. This correlates with an increase in the strength of the humoral response against Delta B.1.617.2, with the strongest response seen in previously infected animals. These data highlight the continuous need to improve vaccination strategies and address the additional evolutionary pressure pre-existing immunity may exert on SARS-CoV-2.


Assuntos
COVID-19 , Vacinas , Animais , Cricetinae , Humanos , COVID-19/prevenção & controle , ChAdOx1 nCoV-19 , SARS-CoV-2
11.
Emerg Infect Dis ; 29(10): 2065-2072, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37735747

RESUMO

An outbreak of human mpox infection in nonendemic countries appears to have been driven largely by transmission through body fluids or skin-to-skin contact during sexual activity. We evaluated the stability of monkeypox virus (MPXV) in different environments and specific body fluids and tested the effectiveness of decontamination methodologies. MPXV decayed faster at higher temperatures, and rates varied considerably depending on the medium in which virus was suspended, both in solution and on surfaces. More proteinaceous fluids supported greater persistence. Chlorination was an effective decontamination technique, but only at higher concentrations. Wastewater was more difficult to decontaminate than plain deionized water; testing for infectious MPXV could be a helpful addition to PCR-based wastewater surveillance when high levels of viral DNA are detected. Our findings suggest that, because virus stability is sufficient to support environmental MPXV transmission in healthcare settings, exposure and dose-response will be limiting factors for those transmission routes.


Assuntos
Líquidos Corporais , Águas Residuárias , Humanos , Monkeypox virus/genética , Vigilância Epidemiológica Baseada em Águas Residuárias , DNA Viral
12.
EMBO Rep ; 24(8): e57003, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37424505

RESUMO

Misfolded Aß is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aß strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, tropism to specific brain regions, differential recruitment of Aß40 /Aß42 peptides, and induction of microglial and astroglial responses. Importantly, the aggregates induced by 2F and 3F are structurally different as determined by ssNMR. Our study analyzes the biological properties of purified Aß polymorphs that have been characterized at the atomic resolution level and provides relevant information on the pathological significance of misfolded Aß strains.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Proteólise
13.
BMJ Open ; 13(3): e066700, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36948548

RESUMO

INTRODUCTION: People with disabilities have a higher prevalence of cigarette smoking than people without disabilities. However, little information exists on smoking cessation interventions tailored to address the unique needs of people with disabilities. This paper describes a systematic review protocol to identify and evaluate tobacco smoking cessation interventions designed to improve outcomes for people with disabilities. METHODS AND ANALYSIS: We will conduct a systematic review of the literature using the procedures outlined by Cochrane. We will search four electronic databases (CINAHL Plus (EBSCO), Embase (Ovid), Medline (Ovid) and PsycINFO (Ovid)) with no date restriction to identify tobacco cessation interventions tailored to meet the needs of people with disabilities. We will extract data and assess risk of bias using the RoB2 and ROBINS-I for included studies using Covidence systematic review software. Quantitative and qualitative syntheses will summarise key study characteristics and outcomes with text, tables and forest plots; a meta-analysis will be conducted, if appropriate. ETHICS AND DISSEMINATION: Ethical approval is not required as there are no primary data associated with the study. Data will be disseminated through a peer-reviewed articles and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022337434.


Assuntos
Fumar Cigarros , Abandono do Hábito de Fumar , Envio de Mensagens de Texto , Humanos , Adulto , Abandono do Hábito de Fumar/métodos , Terapia Comportamental , Software , Literatura de Revisão como Assunto , Metanálise como Assunto
14.
J Am Coll Health ; : 1-5, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36595624

RESUMO

Objective: To explore the feasibility and utility of a tolerance break (T-Break) guide on young adults' cannabis use. Participants: Young adults aged 18-29 (n = 125) who were current cannabis users. Methods: Participants recruited through posters and listservs at various universities were offered the T-Break Guide-daily activities, advice, and encouragement-to help complete a 21-day cannabis break. Bivariate analyses examined associations between Guide use and follow-up measures. Results: Compared to non-Guide users, participants who used the Guide "a lot" were more likely to complete the 21-day abstinence break (84% vs. 57%), revise their personal definition of balance to mean less cannabis (84% vs. 62%), and plan a future break (32% vs. 11%). Conclusion: Use of this self-directed T-Break Guide may help young adults take a break from cannabis use and reduce future use. Further research using more rigorous designs to test the Guide's efficacy and assess longer-term maintenance of effects is needed.

15.
Drug Alcohol Depend ; 243: 109738, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36535098

RESUMO

INTRODUCTION: The prevalence of current cigarette smoking is higher in people with disabilities compared to those without. However, little is known about smoking status and trends in smoking by disability functioning domain. METHODS: Data from the 2015-2019 National Surveys on Drug Use and Health were used to estimate the prevalence of past-month and daily cigarette smoking, former smoking, and nicotine dependence for people with any disability and six disability functioning domains. Logistic regression models estimated the odds of each outcome by disability domain compared to no disability, adjusting for sociodemographic factors. RESULTS: From 2015-2019, the overall prevalence of current cigarette smoking (23.3% vs. 16.7%) and the proportion of those with nicotine dependence (14.6% vs 8.0%) was higher in people with any disability compared to those without (ps < 0.001). The prevalence of current cigarette smoking decreased while the prevalence of former cigarette smoking increased from 2015 to 2019 (ps < 0.05). People with any disability had higher odds of current smoking (AOR=1.20; 95% CI 1.16, 1.25) and similar odds of former smoking (AOR=1.00; 95% CI 0.95, 1.06) compared to people without disabilities. Odds of current and former smoking varied by domain. CONCLUSION: The prevalence of cigarette smoking among people with any disability decreased over time but remained higher than those without. People with any disability had similar odds of former smoking, though differences existed by disability domain. Future research should explore additional smoking and quit behaviors by disability functioning domain.


Assuntos
Fumar Cigarros , Pessoas com Deficiência , Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Tabagismo , Adulto , Humanos , Fumar Cigarros/epidemiologia , Tabagismo/epidemiologia , Prevalência
16.
bioRxiv ; 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36032963

RESUMO

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 h), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 h). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.

17.
NPJ Vaccines ; 7(1): 171, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543806

RESUMO

Nipah virus (NiV) is a highly pathogenic and re-emerging virus, which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal challenge with NiV Bangladesh (NiV-B) in hamsters. Here, we investigated the efficacy of ChAdOx1 NiV in the lethal African green monkey (AGM) NiV challenge model. AGMs were vaccinated either 4 weeks before challenge (prime vaccination), or 8 and 4 weeks before challenge with ChAdOx1 NiV (prime-boost vaccination). A robust humoral and cellular response was detected starting 14 days post-initial vaccination. Upon challenge, control animals displayed a variety of signs and had to be euthanized between 5 and 7 days post inoculation. In contrast, vaccinated animals showed no signs of disease, and we were unable to detect infectious virus in tissues and all but one swab. No to limited antibodies against fusion protein or nucleoprotein antigen could be detected 42 days post challenge, suggesting that vaccination induced a very robust protective immune response preventing extensive virus replication.

18.
JCI Insight ; 7(22)2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36509288

RESUMO

An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, models that develop severe disease are still needed. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding nonstructural protein 6 in open reading frame 1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID-19 and, as such, are uniquely suited to test viral countermeasures.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Animais , Vison , Pulmão/diagnóstico por imagem
19.
Tob Control ; 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424139

RESUMO

INTRODUCTION: The Food and Drug Administration (FDA) has issued proposed product standards banning menthol as a characterising flavour in cigarettes and cigars. The public health benefits of these product standards may be attenuated by the role of plausible substitutes in the marketplace. Therefore, the present study examined the addiction potential of plausible combustible menthol alternatives compared with usual brand menthol cigarettes (UBMC). METHODS: Ninety-eight adult menthol cigarette smokers completed four visits, smoking their UBMC at the first session and three menthol cigarette alternatives in random order at the subsequent visits: (1) a preassembled menthol roll-your-own (mRYO) cigarette using menthol pipe tobacco and mentholated cigarette tube, (2) a menthol filtered little cigar (mFLC) and (3) a non-menthol cigarette (NMC). Measures of smoking topography, exhaled carbon monoxide (CO), craving and withdrawal, subjective effects and behavioural economic demand indices were assessed. RESULTS: Compared with UBMC, menthol cigarette alternatives resulted in different puffing topography and CO exposure (except mRYO), and lower levels of positive subjective experience and behavioural economic demand indices. Among the alternative products, participants reported the highest level of positive subjective experience and higher demand for mRYO, compared with mFLC and NMC. Similarly, participants were significantly more likely to want to try again, purchase and use the mRYO product regularly compared with mFLC and NMC. CONCLUSIONS AND RELEVANCE: mRYO cigarettes were the most highly rated cigarette alternative among study products, suggesting their potential appeal as a menthol cigarette substitute and needed inclusion of menthol pipe tobacco and cigarette tubes in FDA's proposed ban.

20.
Sci Adv ; 8(46): eade1860, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36399566

RESUMO

Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Because of confounding factors in the human population, such as preexisting immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were up-regulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggest that, in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.

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