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1.
Drugs (Abingdon Engl) ; 30(3): 334-343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37587980

RESUMO

Increasing understanding of the risk and protective factors for adolescent nonmedical use of prescription drugs (NMUPD) could inform prevention efforts. Several correlates have been identified, including parental factors, perceptions about use and accessibility, social norms, and age. However, these constructs have rarely been simultaneously examined using paired data from parents and adolescents. We aimed to examine the relative influence of these correlates among dyads (N=349) of mothers and adolescent daughters. Using multiple logistic regression, daughters' past NMUPD and inclination for future NMUPD were regressed onto descriptive norms for friend use, perceived drug accessibility and risk of harm from use, daughter age, mothers' disapproval about use, mothers' past NMUPD and inclination for future NMUPD, and the mother-daughter relationship quality. Akaike weights and lasso regressions were also estimated to evaluate the relative importance of each correlate. Higher descriptive norms for friend use, older age, and mothers' inclination for NMUPD were risk factors for daughters' NMUPD, while a closer mother-daughter relationship and mothers' disapproving attitudes towards NMUPD were protective factors. The three analysis approaches were corroborative. Results suggest friend descriptive norms, mother-daughter relationship quality, and mothers' attitudes about NMUPD are important prevention targets.

2.
J Health Commun ; 27(6): 394-406, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35993376

RESUMO

In a social media campaign aimed at reducing mothers' permissiveness for indoor tanning (IT) by their teenage daughters, a secondary analysis of campaign engagement effects on IT outcomes was performed. Mothers (n = 869) with daughters aged 14-17 were recruited in 34 states that did not ban IT by minors under age 18 for a randomized trial with follow-up at 12 months (end of intervention) and 18 months (6 months after intervention) post-randomization. Daughters' (n = 469) baseline and follow-up responses were analyzed too. Mothers received a Facebook feed on adolescent health topics that included posts about preventing IT (intervention) or prescription drug misuse (control). Engagement was measured by extracting reactions (e.g., like, sad, etc.) and comments posted by mothers to the campaign posts. Overall, 76.4% of posts received a reaction and/or comment. Mothers who engaged with IT posts were less permissive of daughters' IT immediately at the conclusion of the campaign (permit IT: -0.39, p < .05; facilitate IT: -0.29, p < .05) and 6 months after intervention (permit IT: -0.32, p < .05; facilitate IT: -0.31, p < .05) than mothers who did not engage with posts. Engagement with posts was essential to the success of a social media campaign for preventing IT by minors by reducing mothers' permissiveness.


Assuntos
Mídias Sociais , Banho de Sol , Feminino , Adolescente , Humanos , Mães
3.
New Phytol ; 227(4): 1264-1276, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32285454

RESUMO

The identification of immune receptors in crop plants is time-consuming but important for disease control. Previously, resistance gene enrichment sequencing (RenSeq) was developed to accelerate mapping of nucleotide-binding domain and leucine-rich repeat containing (NLR) genes. However, resistances mediated by pattern recognition receptors (PRRs) remain less utilized. Here, our pipeline shows accelerated mapping of PRRs. Effectoromics leads to precise identification of plants with target PRRs, and subsequent RLP/K enrichment sequencing (RLP/KSeq) leads to detection of informative single nucleotide polymorphisms that are linked to the trait. Using Phytophthora infestans as a model, we identified Solanum microdontum plants that recognize the apoplastic effectors INF1 or SCR74. RLP/KSeq in a segregating Solanum population confirmed the localization of the INF1 receptor on chromosome 12, and led to the rapid mapping of the response to SCR74 to chromosome 9. By using markers obtained from RLP/KSeq in conjunction with additional markers, we fine-mapped the SCR74 receptor to a 43-kbp G-LecRK locus. Our findings show that RLP/KSeq enables rapid mapping of PRRs and is especially beneficial for crop plants with large and complex genomes. This work will enable the elucidation and characterization of the nonNLR plant immune receptors and ultimately facilitate informed resistance breeding.


Assuntos
Phytophthora infestans , Solanum , Sequência de Aminoácidos , Melhoramento Vegetal , Doenças das Plantas/genética , Receptores de Reconhecimento de Padrão
4.
Subst Use Misuse ; 55(1): 37-47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31526177

RESUMO

Background: Prescription drug abuse is a public health problem in the United States and the region of Appalachia, specifically. Primary care and addiction medicine-as possible points of access for prescription drugs with abuse potential and points of intervention for prescription drug abuse-are among the medical fields at its forefront. Little is known, however, about perceptions of prescription drug abuse across the two patient populations. Objectives: The objective of this qualitative analysis was to explore perceptions of the scale and context of prescription drug abuse among primary care and addiction medicine patients in Appalachia. Methods: As part of a mixed methods study, semi-structured interviews were conducted with 20 patients from primary care and addiction medicine in Central and South Central Appalachia from 2014 to 2015. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify themes. Results: Three themes were identified: (1) pervasiveness of prescription drug abuse, describing perceptions of its high prevalence and negative consequences; (2) routes and routine practices for prescription drug acquisition and distribution, describing perceptions of routes of access to prescription drugs and behaviors exhibited to acquire and distribute prescription drugs; and (3) rationales for prescription drug acquisition and distribution, describing perceptions of the two underlying reasons for these processes-tolerance/addiction and revenue source. Conclusions/Importance: Perceptions of prescription drug abuse among primary care and addiction medicine patients in Appalachia are multifaceted, especially regarding prescription drug acquisition and distribution. Clinical practice implications for mitigating prescription drug abuse are discussed.


Assuntos
Comportamento Aditivo/psicologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Medicamentos sob Prescrição , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Região dos Apalaches , Atitude , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/psicologia , Atenção Primária à Saúde , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estados Unidos , Adulto Jovem
5.
Subst Abus ; 41(1): 121-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31403901

RESUMO

Background: Provider-patient communication underpins many initiatives aimed at reducing the public health burden associated with prescription drug abuse in the United States. The purpose of this qualitative analysis was to examine the characteristics of provider-patient communication about prescription drug abuse from the perspective of prescribers. Methods: From 2014 to 2015, 10 semi-structured interviews were conducted with a purposive sample of prescribers from multiple professions and medical fields in Central and South Central Appalachia. The interviews were conducted using a guide informed by Social Cognitive Theory and community theory research, audio-recorded, and transcribed verbatim. Thematic analysis, facilitated by NVivo 10 software, was used to generate themes. Results: Prescribers described 3 primary communication patterns with patients related to prescription drug abuse-informative, counteractive, and supportive. Prescribers also reported multiple factors-personal (e.g., education, experiences, and feelings of tension) and environmental (e.g., relationship with a patient, clinical resources, and policies on controlled prescription drugs)-that affect provider-patient communication and, by association, delivery of patient care related to prescription drug abuse. Conclusions: The findings suggest that provider-patient communication about prescription drug abuse is multidimensional and dynamic, characterized by multiple communication patterns and contributory factors. They have implications for (1) research aimed at advancing theoretical understanding of prescriber prescription drug abuse communication behaviors with patients and (2) interventions aimed at strengthening prescriber prescription drug abuse communication behaviors with patients.


Assuntos
Analgésicos Opioides/uso terapêutico , Comunicação , Educação de Pacientes como Assunto , Relações Médico-Paciente , Padrões de Prática Médica , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
6.
New Phytol ; 221(3): 1634-1648, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30288743

RESUMO

The oomycete pathogens Phytophthora infestans and P. capsici cause significant crop losses world-wide, threatening food security. In each case, pathogenicity factors, called RXLR effectors, contribute to virulence. Some RXLRs are perceived by resistance proteins to trigger host immunity, but our understanding of the demographic processes and adaptive evolution of pathogen virulence remains poor. Here, we describe PenSeq, a highly efficient enrichment sequencing approach for genes encoding pathogenicity determinants which, as shown for the infamous potato blight pathogen Phytophthora infestans, make up < 1% of the entire genome. PenSeq facilitates the characterization of allelic diversity in pathogen effectors, enabling evolutionary and population genomic analyses of Phytophthora species. Furthermore, PenSeq enables the massively parallel identification of presence/absence variations and sequence polymorphisms in key pathogen genes, which is a prerequisite for the efficient deployment of host resistance genes. PenSeq represents a cost-effective alternative to whole-genome sequencing and addresses crucial limitations of current plant pathogen population studies, which are often based on selectively neutral markers and consequently have limited utility in the analysis of adaptive evolution. The approach can be adapted to diverse microbes and pathogens.


Assuntos
Genômica , Oomicetos/genética , Análise de Sequência de DNA/métodos , Alelos , Sequência de Bases , Genética Populacional , Genoma , Heterozigoto , Nucleotídeos/genética , Phytophthora infestans/genética , Polimorfismo Genético , Padrões de Referência
7.
Theor Appl Genet ; 132(4): 1283-1294, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30666393

RESUMO

KEY MESSAGE: The nematode resistance gene H2 was mapped to the distal end of chromosome 5 in tetraploid potato. The H2 resistance gene, introduced into cultivated potatoes from the wild diploid species Solanum multidissectum, confers a high level of resistance to the Pa1 pathotype of the potato cyst nematode Globodera pallida. A cross between tetraploid H2-containing breeding clone P55/7 and susceptible potato variety Picasso yielded an F1 population that segregated approximately 1:1 for the resistance phenotype, which is consistent with a single dominant gene in a simplex configuration. Using genome reduction methodologies RenSeq and GenSeq, the segregating F1 population enabled the genetic characterisation of the resistance through a bulked segregant analysis. A diagnostic RenSeq analysis of the parents confirmed that the resistance in P55/7 cannot be explained by previously characterised resistance genes. Only the variety Picasso contained functionally characterised disease resistance genes Rpi-R1, Rpi-R3a, Rpi-R3b variant, Gpa2 and Rx, which was independently confirmed through effector vacuum infiltration assays. RenSeq and GenSeq independently identified sequence polymorphisms linked to the H2 resistance on the top end of potato chromosome 5. Allele-specific KASP markers further defined the locus containing the H2 gene to a 4.7 Mb interval on the distal short arm of potato chromosome 5 and to positions that correspond to 1.4 MB and 6.1 MB in the potato reference genome.


Assuntos
Mapeamento Cromossômico , Resistência à Doença/genética , Solanum tuberosum/genética , Solanum tuberosum/parasitologia , Tetraploidia , Tylenchoidea/patogenicidade , Animais , Segregação de Cromossomos/genética , Cromossomos de Plantas/genética , Cruzamentos Genéticos , Genes Dominantes , Genes de Plantas , Loci Gênicos , Proteínas NLR/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Polimorfismo de Nucleotídeo Único/genética , Solanum tuberosum/imunologia
8.
J Exp Bot ; 69(7): 1545-1555, 2018 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-29385612

RESUMO

Following the often short-lived protection that major nucleotide binding, leucine-rich-repeat (NB-LRR) resistance genes offer against the potato pathogen Phytophthora infestans, field resistance was thought to provide a more durable alternative to prevent late blight disease. We previously identified the QTL dPI09c on potato chromosome 9 as a more durable field resistance source against late blight. Here, the resistance QTL was fine-mapped to a 186 kb region. The interval corresponds to a larger, 389 kb, genomic region in the potato reference genome of Solanum tuberosum Group Phureja doubled monoploid clone DM1-3 (DM) and from which functional NB-LRRs R8, R9a, Rpi-moc1, and Rpi_vnt1 have arisen independently in wild species. dRenSeq analysis of parental clones alongside resistant and susceptible bulks of the segregating population B3C1HP showed full sequence representation of R8. This was independently validated using long-range PCR and screening of a bespoke bacterial artificial chromosome library. The latter enabled a comparative analysis of the sequence variation in this locus in diverse Solanaceae. We reveal for the first time that broad spectrum and durable field resistance against P. infestans is conferred by the NB-LRR gene R8, which is thought to provide narrow spectrum race-specific resistance.


Assuntos
Resistência à Doença/genética , Phytophthora infestans/fisiologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Locos de Características Quantitativas , Solanum tuberosum/genética , Sequência de Bases , Mapeamento Cromossômico , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Alinhamento de Sequência , Solanum tuberosum/microbiologia
9.
Respir Res ; 19(1): 89, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-29747661

RESUMO

BACKGROUND: Asthmatics that are exposed to inhaled pollutants such as cigarette smoke (CS) have increased symptom severity. Approximately 25% of adult asthmatics are thought to be active smokers and many sufferers, especially in the third world, are exposed to high levels of inhaled pollutants. The mechanism by which CS or other airborne pollutants alter the disease phenotype and the effectiveness of treatment in asthma is not known. The aim of this study was to determine the impact of CS exposure on the phenotype and treatment sensitivity of rodent models of allergic asthma. METHODS: Models of allergic asthma were configured that mimicked aspects of the asthma phenotype and the effect of CS exposure investigated. In some experiments, treatment with gold standard asthma therapies was investigated and end-points such as airway cellular burden, late asthmatic response (LAR) and airway hyper-Reactivity (AHR) assessed. RESULTS: CS co-exposure caused an increase in the LAR but interestingly attenuated the AHR. The effectiveness of LABA, LAMA and glucocorticoid treatment on LAR appeared to be retained in the CS-exposed model system. The eosinophilia or lymphocyte burden was not altered by CS co-exposure, nor did CS appear to alter the effectiveness of glucocorticoid treatment. Steroids, however failed to reduce the neutrophilic inflammation in sensitized mice exposed to CS. CONCLUSIONS: These model data have certain parallels with clinical findings in asthmatics, where CS exposure did not impact the anti-inflammatory efficacy of steroids but attenuated AHR and enhanced symptoms such as the bronchospasm associated with the LAR. These model systems may be utilised to investigate how CS and other airborne pollutants impact the asthma phenotype; providing the opportunity to identify novel targets.


Assuntos
Asma/imunologia , Fumar Cigarros/imunologia , Modelos Animais de Doenças , Exposição por Inalação/efeitos adversos , Fenótipo , Animais , Asma/fisiopatologia , Fumar Cigarros/efeitos adversos , Fumar Cigarros/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Endogâmicos BN
10.
Theor Appl Genet ; 131(6): 1287-1297, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29560514

RESUMO

KEY MESSAGE: A broad-spectrum late blight disease-resistance gene from Solanum verrucosum has been mapped to potato chromosome 9. The gene is distinct from previously identified-resistance genes. We have identified and characterised a broad-spectrum resistance to Phytophthora infestans from the wild Mexican species Solanum verrucosum. Diagnostic resistance gene enrichment (dRenSeq) revealed that the resistance is not conferred by previously identified nucleotide-binding, leucine-rich repeat genes. Utilising the sequenced potato genome as a reference, two complementary enrichment strategies that target resistance genes (RenSeq) and single/low-copy number genes (Generic-mapping enrichment Sequencing; GenSeq), respectively, were deployed for the rapid, SNP-based mapping of the resistance through bulked-segregant analysis. Both approaches independently positioned the resistance, referred to as Rpi-ver1, to the distal end of potato chromosome 9. Stringent post-enrichment read filtering identified a total of 64 informative SNPs that corresponded to the expected ratio for significant polymorphisms in the parents as well as the bulks. Of these, 61 SNPs are located on potato chromosome 9 and reside within 27 individual genes, which in the sequenced potato clone DM locate to positions 45.9 to 60.9 Mb. RenSeq- and GenSeq-derived SNPs within the target region were converted into allele-specific PCR-based KASP markers and further defined the position of the resistance to a 4.3 Mb interval at the bottom end of chromosome 9 between positions 52.62-56.98 Mb.


Assuntos
Resistência à Doença/genética , Genes de Plantas , Doenças das Plantas/genética , Solanum/genética , Mapeamento Cromossômico , DNA de Plantas/genética , Diploide , Marcadores Genéticos , Phytophthora infestans , Doenças das Plantas/microbiologia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Solanum/microbiologia
11.
Respir Res ; 18(1): 55, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28399855

RESUMO

BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the current available therapies are effective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In the search to understand disease pathogenesis and find effective therapies hypotheses are often tested in animal models before progressing into clinical studies. However, current dogma is that animal model data is often not predictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challenge induced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal model systems. As the mouse is typically selected as preferred species for pre-clinical models, we wanted to characterise and probe the validity of a murine model exhibiting an allergen induced LAR. METHODS: C57BL/6 mice were sensitised with antigen and subsequently topically challenged with the same antigen. The role of AlumTM adjuvant, glucocorticoid, long acting muscarinic receptor antagonist (LAMA), TRPA1, CD4+ and CD8+ T cells, B cells, Mast cells and IgE were determined in the LAR using genetically modified mice and a range of pharmacological tools. RESULTS: Our data showed that unlike other features of asthma (e.g. cellular inflammation, elevated IgE levels and airway hyper-reactivity (AHR) the LAR required AlumTMadjuvant. Furthermore, the LAR appeared to be sensitive to glucocorticoid and required CD4+ T cells. Unlike in other species studied, the LAR was not sensitive to LAMA treatment nor required the TRPA1 ion channel, suggesting that airway sensory nerves are not involved in the LAR in this species. Furthermore, the data suggested that CD8+ T cells and the mast cell-B-cell - IgE axis appear to be protective in this murine model. CONCLUSION: Together we can conclude that this model does feature steroid sensitive, CD4+ T cell dependent, allergen induced LAR. However, collectively our data questions the validity of using the murine pre-clinical model of LAR in the assessment of future asthma therapies.


Assuntos
Antígenos/imunologia , Asma/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Imunidade Inata/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo
12.
Prev Sci ; 18(2): 131-140, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27549602

RESUMO

Youthful indoor tanning as few as ten sessions can increase the risk of melanoma by two to four times with each additional session adding another 2 % to the risk. Recent research estimates that indoor tanning can be linked to approximately 450,000 cases of skin cancer annually in the USA, Europe, and Australia. Despite these risks, indoor tanning remains popular with adolescents. This study tested the efficacy of a web-based skin cancer prevention intervention designed to reduce indoor tanning motivations in adolescent females. A nationally representative sample of 443 female teens was enrolled from an online panel into a two-arm, parallel group design, randomized controlled trial. Treatment participants received an appearance-focused intervention grounded in established health behavior change models. Controls viewed a teen alcohol prevention website. Outcome variables included willingness and intentions to indoor tan, willingness to sunless tan, and measures of indoor tanning attitudes and beliefs. The intervention decreased willingness and intentions to indoor tan and increased sunless tanning willingness relative to controls. We also examined indirect mechanisms of change through intervening variables (e.g., indoor tanning attitudes, norms, positive and negative expectancies) using the product of coefficient approach. The web-based intervention demonstrated efficacy in changing adolescent indoor tanning motivations and improving their orientation toward healthier alternatives. Results from the intervening variable analyses give guidance to future adolescent skin cancer prevention interventions.


Assuntos
Internet , Neoplasias Cutâneas/prevenção & controle , Banho de Sol/psicologia , Banho de Sol/tendências , Adolescente , Austrália , Feminino , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Intenção , Motivação
13.
Plant J ; 84(1): 111-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26255869

RESUMO

Combinations of histones carrying different covalent modifications are a major component of epigenetic variation. We have mapped nine modified histones in the barley seedling epigenome by chromatin immunoprecipitation next-generation sequencing (ChIP-seq). The chromosomal distributions of the modifications group them into four different classes, and members of a given class also tend to coincide at the local DNA level, suggesting that global distribution patterns reflect local epigenetic environments. We used this peak sharing to define 10 chromatin states representing local epigenetic environments in the barley genome. Five states map mainly to genes and five to intergenic regions. Two genic states involving H3K36me3 are preferentially associated with constitutive gene expression, while an H3K27me3-containing genic state is associated with differentially expressed genes. The 10 states display striking distribution patterns that divide barley chromosomes into three distinct global environments. First, telomere-proximal regions contain high densities of H3K27me3 covering both genes and intergenic DNA, together with very low levels of the repressive H3K27me1 modification. Flanking these are gene-rich interior regions that are rich in active chromatin states and have greatly decreased levels of H3K27me3 and increasing amounts of H3K27me1 and H3K9me2. Lastly, H3K27me3-depleted pericentromeric regions contain gene islands with active chromatin states separated by extensive retrotransposon-rich regions that are associated with abundant H3K27me1 and H3K9me2 modifications. We propose an epigenomic framework for barley whereby intergenic H3K27me3 specifies facultative heterochromatin in the telomere-proximal regions and H3K27me1 is diagnostic for constitutive heterochromatin elsewhere in the barley genome.


Assuntos
Cromatina/metabolismo , Heterocromatina/metabolismo , Histonas/metabolismo , Hordeum/metabolismo , Cromatina/genética , Imunoprecipitação da Cromatina , Epigênese Genética/genética , Heterocromatina/genética , Histonas/genética , Hordeum/genética
14.
Respir Res ; 17: 45, 2016 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-27112462

RESUMO

BACKGROUND: The incidence of asthma is increasing at an alarming rate and while the current available therapies are effective in the majority of patients they fail to adequately control symptoms at the more severe end of the disease spectrum. In the search to understand disease pathogenesis and find effective therapies animal models are often employed. As exposure to house dust mite (HDM) has a causative link, it is thought of as the allergen of choice for modelling asthma. The objective was to develop a HDM driven model of asthmatic sensitisation and characterise the role of key allergic effector cells/mediators. METHODS: Mice were sensitised with low doses of HDM and then subsequently challenged. Cellular inflammation, IgE and airway responsiveness (AHR) was assessed in wild type mice or CD4(+)/CD8(+) T cells, B cells or IgE knock out mice. RESULTS: Only those mice sensitised with HDM responded to subsequent low dose topical challenge. Similar to the classical ovalbumin model, there was no requirement for systemic alum sensitisation. Characterisation of the role of effector cells demonstrated that the allergic cellular inflammation and AHR was dependent on CD4(+) and CD8(+) T cells but not B cells or IgE. Finally, we show that this model, unlike the classic OVA model, appears to be resistant to developing tolerance. CONCLUSIONS: This CD4(+)/CD8(+) T cell dependent, HDM driven model of allergic asthma exhibits key features of asthma. Furthermore, we suggest that the ability to repeat challenge with HDM means this model is amenable to studies exploring the effect of therapeutic dosing in chronic, established disease.


Assuntos
Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Hipersensibilidade Respiratória/imunologia , Animais , Antígenos de Dermatophagoides/administração & dosagem , Asma/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/patologia
15.
Respir Res ; 17(1): 67, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27255083

RESUMO

BACKGROUND: Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals. METHODS: Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation. RESULTS: CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes. CONCLUSION: Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation.


Assuntos
Asma/metabolismo , Pulmão/metabolismo , Pneumonia/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Asma/induzido quimicamente , Asma/imunologia , Asma/prevenção & controle , Antígenos CD4/genética , Antígenos CD4/metabolismo , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Imunoglobulina E/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , Fenótipo , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/prevenção & controle , Pyroglyphidae/imunologia , Ratos Endogâmicos BN , Transdução de Sinais , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/deficiência , Canais de Cátion TRPV/genética
16.
Ann Behav Med ; 50(1): 48-57, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26370893

RESUMO

BACKGROUND: Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. PURPOSE: This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. METHODS: Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. RESULTS: Three subgroups were identified: a low risk, anti-tanning subgroup (18.6 %) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate risk aware social tanner subgroup (47.2 %) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high risk risky relaxation tanner subgroup (34.2 %) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the aware social tanner and risky relaxation tanner subgroups were significantly more likely to initiate indoor tanning in the following year. CONCLUSIONS: These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful.


Assuntos
Comportamento do Adolescente/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Banho de Sol/psicologia , Adolescente , Criança , Feminino , Humanos , Estudos Longitudinais , Assunção de Riscos
17.
Plant J ; 79(6): 981-92, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24947331

RESUMO

The low-recombining pericentromeric region of the barley genome contains roughly a quarter of the genes of the species, embedded in low-recombining DNA that is rich in repeats and repressive chromatin signatures. We have investigated the effects of pericentromeric region residency upon the expression, diversity and evolution of these genes. We observe no significant difference in average transcript level or developmental RNA specificity between the barley pericentromeric region and the rest of the genome. In contrast, all of the evolutionary parameters studied here show evidence of compromised gene evolution in this region. First, genes within the pericentromeric region of wild barley show reduced diversity and significantly weakened purifying selection compared with the rest of the genome. Second, gene duplicates (ohnolog pairs) derived from the cereal whole-genome duplication event ca. 60MYa have been completely eliminated from the barley pericentromeric region. Third, local gene duplication in the pericentromeric region is reduced by 29% relative to the rest of the genome. Thus, the pericentromeric region of barley is a permissive environment for gene expression but has restricted gene evolution in a sizeable fraction of barley's genes.


Assuntos
Evolução Molecular , Variação Genética , Genoma de Planta/genética , Hordeum/genética , Sequência de Bases , Duplicação Gênica , Expressão Gênica , Ontologia Genética , Heterocromatina/genética , Dados de Sequência Molecular , Recombinação Genética , Análise de Sequência de RNA
18.
Pulm Pharmacol Ther ; 29(2): 181-98, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24929072

RESUMO

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent respiratory diseases characterized by airway inflammation, airway obstruction and airway hyperresponsiveness. Whilst current therapies, such as ß-agonists and glucocorticoids, may be effective at reducing symptoms, they do not reduce disease progression. Thus, there is a need to identify new therapeutic targets. In this review, we summarize the potential of novel targets or tools, including anti-inflammatories, phosphodiesterase inhibitors, kinase inhibitors, transient receptor potential channels, vitamin D and protease inhibitors, for the treatment of asthma and COPD.


Assuntos
Asma/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Humanos , Inibidores de Fosfodiesterase/uso terapêutico , Inibidores de Proteases/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Canais de Potencial de Receptor Transitório/uso terapêutico , Vitamina D/uso terapêutico
20.
Cancer Epidemiol Biomarkers Prev ; 31(4): 885-892, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35064063

RESUMO

BACKGROUND: A social media campaign for mothers aimed at reducing indoor tanning (IT) by adolescent daughters reduced mothers' permissiveness toward IT in an immediate posttest. Whether the effects persisted at 6 months after the campaign remains to be determined. METHODS: Mothers (N = 869) of daughters ages 14-17 in 34 states without bans on IT by minors were enrolled in a randomized trial. All mothers received an adolescent health campaign over 12 months with posts on preventing IT (intervention) or prescription drug misuse (control). Mothers completed a follow-up at 18 months post-randomization measuring IT permissiveness, attitudes, intentions, communication, and behavior, and support for state bans. Daughters (n = 469; 54.0%) just completed baseline and follow-up surveys. RESULTS: Structural equation modeling showed that intervention-group mothers were less permissive of IT by daughters [unstandardized coefficient, -0.17; 95% confidence interval (CI), -0.31 to -0.03], had greater self-efficacy to refuse daughter's IT requests (0.17; 95% CI, 0.06-0.29) and lower IT intentions themselves (-0.18; 95% CI, -0.35 to -0.01), and were more supportive of bans on IT by minors (0.23; 95% CI, 0.02-0.43) than control-group mothers. Intervention-group daughters expressed less positive IT attitudes than controls (-0.16; 95% CI, 0.31 to -0.01). CONCLUSIONS: The social media campaign may have had a persisting effect of convincing mothers to withhold permission for daughters to indoor tan for 6 months after its conclusion. Reduced IT intentions and increased support for bans on IT by minors also persisted among mothers. IMPACT: Social media may increase support among mothers to place more restrictions on IT by minors.


Assuntos
Mídias Sociais , Banho de Sol , Adolescente , Feminino , Promoção da Saúde , Humanos , Mães , Núcleo Familiar
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