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1.
Am J Vet Res ; : 1-10, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38821117

RESUMO

OBJECTIVE: To describe the CT findings of Australian dogs and cats with nasal cryptococcosis over a 12-year period. ANIMALS: 12 dogs and 9 cats diagnosed with nasal cryptococcosis from 2008 through 2020. METHODS: CT findings were compared among enrolled cases from Australian veterinary referral centers. Disease severity was compared between a subset of patients with cryptococcal speciation performed (n = 6 dogs; n = 3 cats) and geographic domicile. RESULTS: Dogs demonstrated diffuse disease affecting numerous nasal regions and sinuses. Cats displayed more focal nasal and nasopharyngeal disease. Dogs were more likely to have a nasal mass, whereas cats were more likely to have a nasopharyngeal mass. Cribriform plate lysis was common in dogs but not observed in cats. Sinonasal osteolysis was a common feature in both species. Mandibular lymph nodes were commonly enlarged in dogs, whereas in cats, the retropharyngeal lymph nodes were more likely enlarged. There was no obvious difference in disease severity or lesion distribution in relation to the causal species of Cryptococcus, although to determine if this finding is robust, an appropriately powered prospective study is warranted. CLINICAL RELEVANCE: There are numerous studies describing the clinical features, treatment, and outcomes of dogs and cats with cryptococcosis. To the best of our knowledge, there is only 1 previous study describing the CT features of nasal cryptococcosis, undertaken in one part of North America. Our study describes the CT features of nasal Cryptococcus sp in an Australian canine and feline cohort, adding new pertinent observations while reinforcing reported radiological observations.

2.
Stat Methods Med Res ; 33(6): 981-995, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623615

RESUMO

The focus of precision medicine is on decision support, often in the form of dynamic treatment regimes, which are sequences of decision rules. At each decision point, the decision rules determine the next treatment according to the patient's baseline characteristics, the information on treatments and responses accrued by that point, and the patient's current health status, including symptom severity and other measures. However, dynamic treatment regime estimation with ordinal outcomes is rarely studied, and rarer still in the context of interference - where one patient's treatment may affect another's outcome. In this paper, we introduce the weighted proportional odds model: a regression based, approximate doubly-robust approach to single-stage dynamic treatment regime estimation for ordinal outcomes. This method also accounts for the possibility of interference between individuals sharing a household through the use of covariate balancing weights derived from joint propensity scores. Examining different types of balancing weights, we verify the approximate double robustness of weighted proportional odds model with our adjusted weights via simulation studies. We further extend weighted proportional odds model to multi-stage dynamic treatment regime estimation with household interference, namely dynamic weighted proportional odds model. Lastly, we demonstrate our proposed methodology in the analysis of longitudinal survey data from the Population Assessment of Tobacco and Health study, which motivates this work. Furthermore, considering interference, we provide optimal treatment strategies for households to achieve smoking cessation of the pair in the household.


Assuntos
Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/estatística & dados numéricos , Abandono do Hábito de Fumar/métodos , Características da Família , Modelos Estatísticos , Medicina de Precisão/estatística & dados numéricos , Pontuação de Propensão
3.
Popul Health Metr ; 22(1): 6, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594706

RESUMO

BACKGROUND: Targeted marketing of menthol cigarettes in the US influences disparities in the prevalence of menthol smoking. There has been no analysis of sub-national data documenting differences in use across demographic subgroups. This study estimated trends in the prevalence of menthol use among adults who smoke in the nine US census divisions by sex, age, and race/ethnicity from 2002 to 2020. METHODS: Data from 12 waves of the US ITC Survey were used to estimate the prevalence of menthol cigarette use across census divisions and demographic subgroups using multilevel regression and post-stratification (n = 12,020). Multilevel logistic regression was used to predict the prevalence of menthol cigarette use in 72 cross-classified groups of adults who smoke defined by sex, age, race/ethnicity, and socioeconomic status; division-level effects were fit with a random intercept. Predicted prevalence was weighted by the total number of adults who smoke in each cross-classified group and aggregated to divisions within demographic subgroup. Estimates were validated against the Tobacco Use Supplement to the Current Population Survey (TUS-CPS). RESULTS: Overall modeled prevalence of menthol cigarette use was similar to TUS-CPS estimates. Prevalence among adults who smoke increased in each division from 2002 to 2020. By 2020, prevalence was highest in the Middle (46.3%) and South Atlantic (42.7%) and lowest in the Pacific (25.9%) and Mountain (24.2%) divisions. Prevalence was higher among adults aged 18-29 (vs. 50+) and females (vs. males). Prevalence among non-Hispanic Black people exceeded 80% in the Middle Atlantic, East North Central, West North Central, and South Atlantic in all years and varied most among Hispanic people in 2020 (Pacific: 26.5%, New England: 55.1%). CONCLUSIONS: Significant geographic variation in the prevalence of menthol cigarette use among adults who smoke suggests the proposed US Food and Drug Administration (FDA) menthol cigarette ban will exert differential public health benefits and challenges across geographic and demographic subgroups.


Assuntos
Mentol , Produtos do Tabaco , Adulto , Feminino , Humanos , Masculino , Censos , Prevalência , Fumar/epidemiologia , Controle do Tabagismo , Estados Unidos/epidemiologia , Adolescente , Adulto Jovem
4.
J Sch Nurs ; : 10598405241226805, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291656

RESUMO

School nurses encountered many workplace struggles while providing care during the COVID-19 pandemic. Several struggles involved organizational support, including having sufficient time, resources, compensation, and school leadership support. The purpose of this mixed methods study was to explore the experiences of school nurses working during the COVID-19 pandemic as they related to sufficient time to complete COVID-related activities, sufficient COVID-19 resources, compensation, and perceived organizational (school leadership) support. We obtained data from 1,564 National Association of School Nurses members regarding respondent characteristics, school characteristics, measures of organizational support, and qualitative perceived organizational support using a 17-question survey. Perceptions of having sufficient time to complete COVID-related tasks and infringement of these tasks on routine activities were worse for those with greater years of experience and education. Compensation for additional COVID-related work was more favorable for LPNs. School leaders should be aware of their role in bolstering organizational support and its impact.

5.
Addiction ; 119(5): 885-897, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38186201

RESUMO

BACKGROUND AND AIMS: Nicotine vaping products (NVPs) can potentially help adult tobacco users quit smoking. This study evaluated how adult consumers compare the costs between NVPs and cigarettes. METHOD: We used data from the US arm of the 2016-2020 International Tobacco Control Four Country Smoking and Vaping (ITC 4CV) surveys to perform a multinomial logit model with two-way fixed effects to measure how perceived cost comparisons are associated with NVP and cigarette taxes, use patterns, NVP device types and individual sociodemographic factors. RESULTS: Higher cigarette taxes are associated with a greater likelihood of perceiving NVPs and cigarettes as costing the same for the overall population and among people who exclusively smoke, and a lower likelihood of perceiving NVPs as more expensive among people who exclusively vape, compared with lower cigarette taxes. Pre-filled cartridge and tank users are more likely to perceive NVPs as less expensive than cigarettes, compared with people who use other types of NVPs. The associations between taxes and perceived cost comparison were more pronounced among males, younger and low-income populations. CONCLUSIONS: Higher cigarette taxes are associated with perceived financial incentives for nicotine vaping products (NVPs) over cigarettes, whereas NVP taxes are not associated with perceived cost comparison between NVPs and cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adulto , Masculino , Humanos , Estados Unidos , Vaping/epidemiologia , Nicotina , Controle do Tabagismo , Custos e Análise de Custo
6.
Vet Q ; 44(1): 1-9, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38288972

RESUMO

Feline infectious peritonitis (FIP) is a potentially fatal coronavirus-driven disease of cats. Treatment with nucleoside analogue GS-441524 and or prodrug remdesivir (RDV) have produced remission in both experimentally induced and naturally occurring FIP, yet information regarding metabolism of RDV into GS-441524 in cats is scarce. This study assessed possible phase I metabolism of RDV in cats, utilising an in vitro feline microsome model with in vitro t1/2 and in vitro Clint calculated using the substrate depletion method. A previously validated high-performance liquid chromatography (HPLC) fluorescence method was utilised for detection and analysis of RDV and GS-441524. Qualitative yield of RDV and intermediate metabolite GS-441524 were determined following microsome incubation, then compared to whole blood and plasma incubations. In vitro microsome incubation resulted in rapid depletion of RDV, though it did not appear to resemble a conventional phase I-dependent reaction in cats, as it is in humans and dogs. Depletion of RDV into GS-441524 was demonstrated in whole blood in vitro, suggesting cats convert RDV to GS-441524, likely via blood esterases, as observed in mice and rats. RDV metabolism is unlikely to be impacted by impaired liver function in cats. Furthermore, as RDV depletes within minutes, whereas GS-441524 is very stable, whole blood or plasma GS-441524 concentrations, rather than plasma RDV concentrations, are more appropriate for therapeutic drug monitoring (TDM) in cats receiving RDV.


Assuntos
Monofosfato de Adenosina , Adenosina , Alanina , Doenças do Gato , Infecções por Coronavirus , Peritonite Infecciosa Felina , Animais , Gatos , Adenosina/análogos & derivados , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Doenças do Gato/tratamento farmacológico , Infecções por Coronavirus/veterinária , Peritonite Infecciosa Felina/tratamento farmacológico , Plasma
7.
J Am Vet Med Assoc ; 262(4): 1-12, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38096664

RESUMO

OBJECTIVE: To describe the imaging findings in Australian cats and dogs with CNS cryptococcosis. ANIMALS: 23 cases (10 cats; 13 dogs) with CNS cryptococcosis and brain MRI or CT studies available to review. METHODS: Retrospective, multi-institutional case series. Brain MRI or CT studies were reviewed by a board-certified radiologist. Imaging findings were described and the differences between cats and dogs explored. RESULTS: Morphologic features were consistent with extra-axial lesions in all (n = 13) dogs and either intra-axial (5/10) or extra-axial (4/10) lesions in cats, with 1 cat having no detectable lesions in low-field brain MRI scans. Meningeal abnormalities were most common, followed by forebrain and cerebellar lesions. Intracranial MRI lesions were typically T2 hyperintense and T1 hypo- to isointense. Four cases had T2 hypointense lesions affecting the brain, sinonasal cavity, or regional lymph nodes. Intracranial CT lesions were mostly soft tissue attenuating. Contrast enhancement was present in all cases with contrast series available, with ring enhancement shown only in cats. Osteolysis was more common in dogs than cats, particularly affecting the cribriform plate. All 13 dogs and many (6/10) cats had at least 1 lesion affecting sinonasal or contiguous tissues, and locoregional lymphadenomegaly was common (7/10 cats; 11/13 dogs). CLINICAL RELEVANCE: Imaging lesions in cryptococcal meningoencephalitis were extra-axial in dogs but could be intra-axial or extra-axial in cats. Careful examination for extracranial lesions (sinonasal, retrobulbar, facial soft tissue, tympanic bullae, or locoregional lymph nodes) is important to provide alternative safe biopsy sites. T2 hypointense lesions, while rare, should prompt consideration of cryptococcosis.


Assuntos
Doenças do Gato , Criptococose , Doenças do Cão , Gatos , Cães , Animais , Estudos Retrospectivos , Austrália/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/veterinária , Criptococose/diagnóstico por imagem , Criptococose/veterinária , Tomografia Computadorizada por Raios X/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia , Doenças do Gato/diagnóstico por imagem , Doenças do Gato/patologia
8.
BMJ Open ; 13(11): e073027, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914306

RESUMO

INTRODUCTION: In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data. METHODS AND ANALYSIS: Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated. ETHICS AND DISSEMINATION: Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups.


Assuntos
Demência , Transtornos Neurocognitivos , Humanos , Estudos Longitudinais , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/epidemiologia , Envelhecimento , Demência/diagnóstico , Demência/epidemiologia , Algoritmos , Nova Escócia , Estudos Observacionais como Assunto
9.
Vet Q ; 43(1): 1-9, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37556736

RESUMO

The adenosine analogue GS-441524 has demonstrated efficacy in treatment of feline infectious peritonitis (FIP). With no commercially registered formulations of GS-441524 available, global focus shifted to its pro-drug remdesivir, as it became more accessible throughout the COVID-19 pandemic. This study developed and validated a simple liquid chromatography equipped with a fluorescence detector to quantify plasma concentrations of GS-441524 applicable for routine therapeutic monitoring of remdesivir or GS-441524 therapy for FIP infected cats. A Waters X-Bridge C18, 5 µm, 150 × 4.6 mm, column was used and mixtures of 20 mM ammonium acetate (pH 4.5) with acetonitrile of 5% and 70% were prepared for gradient mobile phase. With a simple protein precipitation using methanol to clean plasma sample, GS-441524 was monitored at excitation and emission wavelengths of 250 nm and 475 nm, respectively. Using an external standard, the lowest and highest limits of quantification were 19.5 ng/mL to 10,000 ng/mL, respectively. The intra- and inter day trueness of the quality controls (QCs) were within 10% of their nominal concentrations and intra- and inter day precision of the QCs (expressed as the coefficient of variation) ranged from 1.7 to 5.7%, This assay was able to quantify plasma trough levels of GS-441524 (23.7-190.1 ng/mL) after the administration of remdesivir (9.9-15.0 mg/kg BW, IV or SC) in FIP cats (n = 12). Accordingly, this study generated an alternative and cost-effective way to quantify GS-441524 in feline biological fluids at least up to 24 hr after administrations of remdesivir.


Assuntos
COVID-19 , Doenças do Gato , Peritonite Infecciosa Felina , Gatos , Animais , Cromatografia Líquida de Alta Pressão/veterinária , Cromatografia Líquida de Alta Pressão/métodos , COVID-19/veterinária , Pandemias , Peritonite Infecciosa Felina/tratamento farmacológico
10.
J Vet Intern Med ; 37(5): 1772-1783, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37439383

RESUMO

BACKGROUND: Nucleoside analog GS-441524 is effective in treating cats with feline infectious peritonitis (FIP). Investigation into the use of parent nucleotide analog remdesivir (GS-5734) is needed. OBJECTIVES: To assess efficacy and tolerability of remdesivir with or without transition to GS-441524 in cats with FIP and document clinical and clinicopathologic progression over 6 months. ANIMALS: Twenty-eight client-owned cats with FIP. METHODS: Cats were prospectively recruited between May 2021 and May 2022. An induction dosage of remdesivir 10 to 15 mg/kg intravenously or subcutaneously q24h was utilized for 4 doses, with a maintenance dosage of remdesivir (6-15 mg/kg SC) or GS-441524 (10-15 mg/kg per os) every 24 hours continued for at least 84 days. Laboratory testing, veterinary, and owner assessments were recorded. RESULTS: Twenty-four cats survived to 6 months (86%). Three cats died within 48 hours. Excluding these, survival from 48 hours to 6 months was 96% (24/25). Remission was achieved by day 84 in 56% (14/25). Three cats required secondary treatment for re-emergent FIP. Remission was achieved in all 3 after higher dosing (15-20 mg/kg). Adverse reactions were occasional site discomfort and skin irritation with remdesivir injection. Markers of treatment success included resolution of pyrexia, effusions, and presenting signs of FIP in the first half of treatment and normalization of globulin concentration, and continued body weight gains in the latter half of the treatment period. CONCLUSIONS AND CLINICAL IMPORTANCE: Parenteral administration of remdesivir and oral administration of GS-441524 are effective and well-tolerated treatments for FIP. Early emphasis on clinical, and later emphasis on clinicopathologic response, appears prudent when monitoring treatment efficacy.


Assuntos
Doenças do Gato , Coronavirus Felino , Peritonite Infecciosa Felina , Humanos , Gatos , Animais , Peritonite Infecciosa Felina/tratamento farmacológico , Exsudatos e Transudatos , Doenças do Gato/tratamento farmacológico
11.
Gynecol Oncol Rep ; 47: 101210, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37273764

RESUMO

Objective: The primary objective of this study was to estimate the prevalence of cannabis use in patients with gynecologic malignancies and to describe patterns of cannabis use. Secondary objectives included identifying sources of cannabis information used by patients. Methods: This is a single institution cross sectional survey conducted in Calgary, Alberta. Patients with a current or prior gynecologic cancer diagnosis were considered for inclusion. Planned analysis included descriptive statistics of patient demographics, and the patterns of cannabis use were described using frequencies and proportions. Results: Forty-six patients participated in the survey. The most common disease sites were ovarian cancer and uterine cancer, with the majority of patients receiving chemotherapy as part of their treatment (n = 35). Seventeen participants were current cannabis users (37%). The most common symptoms participants used cannabis for were pain (9/17), anxiety (9/17), and insomnia (9/17).Most patients using cannabis did not have a prescription and obtained their cannabis from a recreational dispensary (11/17). Many participants using cannabis had not talked to their doctor about cannabis (9/17). Instead, the most common sources of information about cannabis were cannabis retailers (20/46), and friends/family (20/46). Over 50% of patients would be interested in discussing cannabis if their physician broached the subject (26/46). Conclusions: The results from this survey indicate that patients would like to talk to their oncologist about cannabis. Further research is needed to inform physician training and direct patient education to ensure that patients have access to unbiased, evidence-based information to make decisions about cannabis use.

12.
Gac Sanit ; 37: 102307, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37247520

RESUMO

OBJECTIVE: The ITC EUREST-PLUS Spain Survey is a longitudinal study of a representative sample of Spanish adult (≥18 years old) smokers. This protocol describes the methods of the 2021 follow-up survey. METHOD: The ITC EUREST-PLUS Survey, a prospective cohort study of a representative sample of smokers in six European countries, was conducted in 2016 (baseline) and 2018 (waves 1 and 2). The 2021 ITC EUREST-PLUS Spain Survey is a continuation of the Spanish cohort with a new interview in 2021 (wave 3). Lost participants were replaced with new smokers recruited using the same multi-stage sampling design. This latest follow-up aims to examine current patterns and transitions of tobacco use and to evaluate the impact of new tobacco-related policies. COMMENTS: The ITC EUREST-PLUS Spain Survey will provide recent information about the impact of tobacco control policies on smoking behaviour.


Assuntos
Fumantes , Fumar , Adulto , Humanos , Adolescente , Estudos Prospectivos , Estudos Longitudinais , Espanha , Fumar/epidemiologia
13.
BMC Public Health ; 23(1): 872, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37170234

RESUMO

BACKGROUND: Older adults have been disproportionately impacted by COVID-19 and related preventative measures undertaken during the pandemic. Given clear evidence of the relationship between loneliness and health outcomes, it is imperative to better understand if, and how, loneliness has changed for older adults during the COVID-19 pandemic, and whom it has impacted most. METHOD: We used "pre-pandemic" data collected between 2015-2018 (n = 44,817) and "during pandemic" data collected between Sept 29-Dec 29, 2020 (n = 24,114) from community-living older adults participating in the Canadian Longitudinal Study on Aging. Loneliness was measured using the 3-item UCLA Loneliness Scale. Weighted generalized estimating equations estimated the prevalence of loneliness pre-pandemic and during the pandemic. Lagged logistic regression models examined individual-level factors associated with loneliness during the pandemic. RESULTS: We found the adjusted prevalence of loneliness increased to 50.5% (95% CI: 48.0%-53.1%) during the pandemic compared to 30.75% (95% CI: 28.72%-32.85%) pre-pandemic. Loneliness increased more for women (22.3% vs. 17.0%), those in urban areas (20.8% vs. 14.6%), and less for those 75 years and older (16.1% vs. 19.8% or more in all other age groups). Loneliness during the pandemic was strongly associated with pre-pandemic loneliness (aOR 4.87; 95% CI 4.49-5.28) and individual level sociodemographic factors [age < 55 vs. 75 + (aOR 1.41; CI 1.23-1.63), women (aOR 1.34; CI 1.25-1.43), and no post-secondary education vs. post-secondary education (aOR 0.73; CI 0.61-0.86)], living conditions [living alone (aOR 1.39; CI 1.27-1.52) and urban living (aOR 1.18; CI 1.07-1.30)], health status [depression (aOR 2.08; CI 1.88-2.30) and having two, or ≥ three chronic conditions (aOR 1.16; CI 1.03-1.31 and aOR 1.34; CI 1.20-1.50)], health behaviours [regular drinker vs. non-drinker (aOR 1.15; CI 1.04-1.28)], and pandemic-related factors [essential worker (aOR 0.77; CI 0.69-0.87), and spending less time alone than usual on weekdays (aOR 1.32; CI 1.19-1.46) and weekends (aOR 1.27; CI 1.14-1.41) compared to spending the same amount of time alone]. CONCLUSIONS: As has been noted for various other outcomes, the pandemic did not impact all subgroups of the population in the same way with respect to loneliness. Our results suggest that public health measures aimed at reducing loneliness during a pandemic should incorporate multifactor interventions fostering positive health behaviours and consider targeting those at high risk for loneliness.


Assuntos
COVID-19 , Humanos , Feminino , Idoso , COVID-19/epidemiologia , Solidão , Pandemias , Estudos Longitudinais , Prevalência , Canadá/epidemiologia , Envelhecimento , Fatores de Risco
14.
J Cell Biol ; 222(6)2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37145332

RESUMO

While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap lines across the intact Drosophila nervous system. 97.5% of the genes studied showed discordance between the distribution of mRNA and the proteins they encode in at least one region of the nervous system. These data suggest that post-transcriptional regulation is very common, helping to explain the complexity of the nervous system. We also discovered that 68.5% of these genes have transcripts present at the periphery of neurons, with 9.5% at the glial periphery. Peripheral transcripts include many potential new regulators of neurons, glia, and their interactions. Our approach is applicable to most genes and tissues and includes powerful novel data annotation and visualization tools for post-transcriptional regulation.


Assuntos
Proteínas de Drosophila , RNA Mensageiro , Animais , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Fatores de Transcrição/metabolismo , RNA Mensageiro/genética , Processamento Pós-Transcricional do RNA
15.
RNA ; 29(7): 1020-1032, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37041032

RESUMO

The level of each RNA species depends on the balance between its rates of production and decay. Although previous studies have measured RNA decay across the genome in tissue culture and single-celled organisms, few experiments have been performed in intact complex tissues and organs. It is therefore unclear whether the determinants of RNA decay found in cultured cells are preserved in an intact tissue, and whether they differ between neighboring cell types and are regulated during development. To address these questions, we measured RNA synthesis and decay rates genome wide via metabolic labeling of whole cultured Drosophila larval brains using 4-thiouridine. Our analysis revealed that decay rates span a range of more than 100-fold, and that RNA stability is linked to gene function, with mRNAs encoding transcription factors being much less stable than mRNAs involved in core metabolic functions. Surprisingly, among transcription factor mRNAs there was a clear demarcation between more widely used transcription factors and those that are expressed only transiently during development. mRNAs encoding transient transcription factors are among the least stable in the brain. These mRNAs are characterized by epigenetic silencing in most cell types, as shown by their enrichment with the histone modification H3K27me3. Our data suggest the presence of an mRNA destabilizing mechanism targeted to these transiently expressed transcription factors to allow their levels to be regulated rapidly with high precision. Our study also demonstrates a general method for measuring mRNA transcription and decay rates in intact organs or tissues, offering insights into the role of mRNA stability in the regulation of complex developmental programs.


Assuntos
Drosophila , Fatores de Transcrição , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Drosophila/genética , Larva/genética , Larva/metabolismo , Encéfalo/metabolismo , Estabilidade de RNA
16.
Paediatr Child Health ; 28(1): 8-16, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36865761

RESUMO

Introduction: Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning. Methods: MEDLINE, EMBASE, PsychINFO, CINAHL, and Clinicaltrials.gov were searched. Observational studies comparing prenatal cannabis use to controls were included. Offspring neuro-behavioural outcomes were grouped in prespecified domains of (1) intelligence and (2) cognitive functioning. Random-effect models were performed for meta-analyses when at least three studies reported the same outcome. All others were summarized qualitatively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework was used to assess evidence certainty. Results: Of the 1982 reviewed studies (n = 523,107 patients), 28 were included. Significant heterogeneity and cohort redundancy limited meta-analysis. Very low-quality evidence from pooled analyses showed no significant associations between prenatal cannabis exposure and attention [standardized mean difference = -0.27 (95% CI = -0.60 to 0.07)], global intelligence quotient [-0.16 (-0.42 to 0.10)], reading [-0.05 (-0.29 to 0.20)], written comprehension [-0.09 (-0.40 to 0.22)], spelling [-0.04 (-0.26 to 0.17)], and mathematics [-0.01 (-0.15 to 0.13)]. No significant associations were found between prenatal cannabis exposure for all other outcomes. Individual studies reported significant differences between the heavy use groups and non-exposed, although this did not prove to be significant when outcomes were pooled. Conclusions: The current review did not find a clear association between prenatal cannabis use and offspring neuro-behavioural outcomes. However, evidence was low quality and heterogenous. Further prospective investigation is needed to elucidate any potential association between prenatal cannabis use and long-term neuro-developmental outcomes.

17.
Commun Med (Lond) ; 3(1): 36, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906677

RESUMO

BACKGROUND: Symptom persistence in non-hospitalized COVID-19 patients, also known as Long COVID or Post-acute Sequelae of COVID-19, is not well characterized or understood, and few studies have included non-COVID-19 control groups. METHODS: We used data from a cross-sectional COVID-19 questionnaire (September-December 2020) linked to baseline (2011-2015) and follow-up (2015-2018) data from a population-based cohort including 23,757 adults 50+ years to examine how age, sex, and pre-pandemic physical, psychological, social, and functional health were related to the severity and persistence of 23 COVID-19-related symptoms experienced between March 2020 and questionnaire completion. RESULTS: The most common symptoms are fatigue, dry cough, muscle/joint pain, sore throat, headache, and runny nose; reported by over 25% of participant who had (n = 121) or did not have (n = 23,636) COVID-19 during the study period. The cumulative incidence of moderate/severe symptoms in people with COVID-19 is more than double that reported by people without COVID-19, with the absolute difference ranging from 16.8% (runny nose) to 37.8% (fatigue). Approximately 60% of male and 73% of female participants with COVID-19 report at least one symptom persisting >1 month. Persistence >1 month is higher in females (aIRR = 1.68; 95% CI: 1.03, 2.73) and those with multimorbidity (aIRR = 1.90; 95% CI: 1.02, 3.49); persistence >3 months decreases by 15% with each unit increase in subjective social status after adjusting for age, sex and multimorbidity. CONCLUSIONS: Many people living in the community who were not hospitalized for COVID-19 still experience symptoms 1- and 3-months post infection. These data suggest that additional supports, for example access to rehabilitative care, are needed to help some individuals fully recover.


Some people who develop COVID-19 experience persistence of symptoms. Here, we aimed to understand the factors associated with the severity and persistence of these symptoms in adults 50 years and older living in the community who had COVID-19. Using information provided by 23,757 participants from across Canada we compared the symptoms between those who had COVID-19 and those who did not. The number and severity of symptoms in participants who had COVID-19 was beyond what would be expected due to other causes. Over two-thirds of participants who had COVID-19 reported symptoms persisting for more than one month, and over half of the participants more than three months. Symptom persistence was higher in females, those with multiple chronic conditions, and lower perceived social status. This suggests that a substantial proportion of people who were not hospitalized for COVID-19 may require further healthcare assistance.

18.
Tob Control ; 32(2): 153-162, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-34548384

RESUMO

BACKGROUND: In February 2020, Canada implemented plain packaging without any changes to the size and content of health warning labels (HWLs), which were last updated in 2012 (pictorial HWLs on 75% of the pack front and back). This pre-post evaluation study assessed the impact of plain packaging in Canada on: (1) pack appeal; (2) HWL effectiveness; and (3) support for plain packaging. Additionally, a quasi-experimental design was used to assess the Canadian results relative to two comparator countries: Australia, where plain packaging (with new larger HWLs) was implemented in 2012, and the United States (USA), where plain packaging has not been implemented and the same text warnings have appeared on cigarette packs since 1985. METHODS: Data are from adult smokers who participated in the 2018 and/or 2020 International Tobacco Control Smoking and Vaping Surveys in Canada (n=4600), Australia (n=1834) and the USA (n=3046). Online surveys were conducted before (February to July 2018) and after (February to June 2020) the implementation of plain packaging in Canada. Adjusted regression analyses were conducted on weighted data. RESULTS: Plain packaging was associated with a significant increase in the percentage of Canadian smokers who did not like the look of their cigarette pack (2018: 28.6% vs 2020: 44.7%, p<0.001), whereas no change in pack appeal was observed among smokers in Australia and the USA over the same period. Plain packaging was not associated with changes in HWL effectiveness in Canada. Support for plain packaging increased significantly among Canadian smokers (2018: 25.6% vs 2020: 33.7%, p<0.001). CONCLUSIONS: Plain packaging in Canada substantially reduced pack appeal and increased support for the policy among adult smokers; however, there was no increase in the effectiveness of Canada's 8-year-old HWLs. The impact of plain packaging on health warning effectiveness may depend on the design of the warnings and length of time since implementation.


Assuntos
Abandono do Hábito de Fumar , Produtos do Tabaco , Vaping , Adulto , Humanos , Estados Unidos/epidemiologia , Criança , Fumantes , Rotulagem de Produtos/métodos , Canadá/epidemiologia , Fumar/epidemiologia , Embalagem de Produtos/métodos , Inquéritos e Questionários , Prevenção do Hábito de Fumar
19.
OTJR (Thorofare N J) ; 43(1): 109-118, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35481376

RESUMO

Occupational therapists support the occupational participation of people who are dying yet remain underutilized in end-of-life care. The purpose of this article was to explore how occupational therapists develop their role in end-of-life care to provide strategies to address underutilization. Using a grounded-theory method, semi-structured interviews were conducted with 21 occupational therapists. Three themes emerged which demonstrate participants' role development process. Participants' experiences with dying (Close Experience of Loss) often instilled the importance of end-of-life care. Led by these convictions (Willing to Do It), participants developed skills for end-of-life care. Reflecting on their experiences and treatment outcomes (Making a Difference), participants self-validated their role. The Model of Occupational Therapists' Role Development in End-of-Life Care captured this process. Personal experiences and critical self-reflection may provide an adaptive means to drive role development and appropriately increase end-of-life care occupational therapy utilization.


Assuntos
Terapia Ocupacional , Assistência Terminal , Humanos , Terapeutas Ocupacionais , Pesquisa Qualitativa
20.
Tob Control ; 32(6): 734-738, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-35483720

RESUMO

INTRODUCTION: Between 2015 and 2018, Canada banned menthol cigarettes. This study pooled data from two pre-post cohort studies (the Ontario Menthol Ban Study, and the International Tobacco Control Policy Evaluation (ITC) Canada Survey, conducted in seven provinces) to derive more precise estimates of the impact of Canada's menthol ban on quitting and to apply these estimates to project the impact of a menthol ban in the USA. METHODS: Weighted multivariable logistic analyses compared post-ban quit success of menthol smokers with non-menthol smokers (for daily smokers and for all (daily + non-daily) smokers), controlling for sex, age, ethnicity, education, baseline smoking status, baseline cigarettes per day and study regions. Projections to the USA were created by multiplying the effect size of the Canadian menthol ban on quitting (percentage of increased quitting among menthol smokers) by the number of menthol smokers overall and among African Americans, from the 2019 National Survey on Drug Use and Health. RESULTS: After the menthol cigarette ban, menthol smokers were more likely than non-menthol smokers to have quit smoking among daily smokers (difference=8.0%; 95% CI: 2.4% to 13.7%,p=0.005) and all (daily+non-daily) smokers (difference=7.3%; 95% CI: 2.1% to 12.5%,p=0.006). The projected number of smokers who would quit after a US menthol ban would be 789 724 daily smokers (including 199 732 African Americans) and 1 337 988 daily+non-daily smokers (including 381 272 African Americans). CONCLUSIONS: This pooled analysis of Canada's menthol cigarette ban provides the foundation for estimating the impact of menthol bans in the USA and other countries. Projections suggest that a US menthol cigarette ban would have a substantial impact on increasing quitting.


Assuntos
Abandono do Hábito de Fumar , Produtos do Tabaco , Humanos , Estados Unidos/epidemiologia , Mentol , Fumantes , Ontário/epidemiologia
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