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1.
PLoS One ; 16(7): e0253052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34197483

RESUMO

Whole grains have been associated with numerous beneficial health outcomes and are recommended in Canada's Food Guide; however, there is little research on whole grains specific to Canada. Therefore, the objective of this study was to characterize the association between Canadians' WG intake and nutrients, food groups and diet quality and to understand top sources of WG in the diets of Canadians. We used data from the Canadian Community Health Survey 2015: a cross-sectional survey that collected information on diet (using a 24-hour recall) and health from 20,487 Canadians 1 year and older. We classified study participants according to their WG intake: non-WG (n = 10,883) and three groups based on age-specific tertiles of WG intake, low-WG (n = 3,322), mid-WG (n = 3,180), and high-WG (n = 3,102). Results were analyzed using population-based survey methods and were adjusted for energy, age, gender, overweight/obesity, income, and supplement use. We found differences in nutrients and food groups by WG group: there was a significant linear trend across groups of increasing WG for increased fiber (children and adults), vitamin B6 (children), thiamin (adults), potassium (children and adults), zinc (adults), calcium (children and adults), iron (children and adults), magnesium (children and adults), fruit (adults), and legumes, nuts and seeds (adults); and decreased total fat (adults), saturated fat (adults), folate (children and adults), refined grains (adults and children), and meat and poultry (adults) intake. We found that there were no differences in total sugar or sodium intake across WG intake groups. The high WG intake group for both children and adults had higher diet quality, measured by the Nutrient Rich Food Index 9.3, compared to non-WG eaters. The top 2 food sources of WG across WG intake groups for children and adults were whole grain oat and high fiber breakfast cereal and whole grain and whole wheat bread. Other top sources of WG included rice, bread products, other breakfast cereals, salty snacks, cereal grains and flours, pasta, and sweet snacks. This research supports recommendations to increase WG foods intake as a means to improve diet quality of Canadians.


Assuntos
Inquéritos sobre Dietas , Dieta/métodos , Fibras na Dieta/análise , Grãos Integrais , Adolescente , Adulto , Canadá , Criança , Pré-Escolar , Estudos Transversais , Ingestão de Alimentos , Humanos , Lactente , Obesidade , Autorrelato , Adulto Jovem
2.
Trials ; 22(1): 8, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407804

RESUMO

OBJECTIVES: The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge. TRIAL DESIGN: Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation. PARTICIPANTS: Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends. EXCLUSION CRITERIA: 1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study. INTERVENTION AND COMPARATOR: Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care). MAIN OUTCOMES: The primary outcome is health-related quality of life (HRQoL) - PROMIS® 29+2 Profile v2.1 (PROPr) - measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation. RANDOMISATION: Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system. BLINDING (MASKING): To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm. TRIAL STATUS: Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021. TRIAL REGISTRATION: ISRCTN:11466448 , 23rd November 2020 FULL PROTOCOL: The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.


Assuntos
COVID-19/reabilitação , Terapia por Exercício/métodos , Intervenção Baseada em Internet/economia , Sistemas de Apoio Psicossocial , Encaminhamento e Consulta/economia , Adulto , COVID-19/diagnóstico , COVID-19/psicologia , COVID-19/virologia , Análise Custo-Benefício , Terapia por Exercício/economia , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido
3.
Mult Scler ; 26(12): 1476-1485, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33063621

RESUMO

BACKGROUND: The role of omega-3 fatty acid in multiple sclerosis (MS) susceptibility is unclear. OBJECTIVE: To determine whether fish/seafood intake or genetic factors that regulate omega-3 fatty acids levels are associated with MS risk. METHODS: We examined the association of fish and shrimp consumption and 13 tag single nucleotide polymorphisms (SNPs) in FADS1, FADS2, and ELOV2 with risk of MS in 1153 individuals from the MS Sunshine Study, a case-control study of incident MS or clinically isolated syndrome (CIS), recruited from Kaiser Permanente Southern California. RESULTS: Consuming fish/seafood at least once a week or at least once a month with regular fish oil use was associated with 44% reduced odds of MS/CIS (adjusted OR = 0.56; 95% CI = 0.41-0.76; p = 0.0002) compared with consuming fish/seafood less than once a month and no fish oil supplementation. Two FADS2 SNPs (rs174611 and rs174618) were independently associated with a lower risk of MS (adjusted ORs = 0.74, 0.79, p = 0.0056, 0.0090, respectively). Association of FADS2 SNPs with MS risk was confirmed in an independent dataset. CONCLUSION: These findings suggest that omega-3 fatty acid intake may be an important modifiable risk factor for MS. This is consistent with the other known health benefits of fish consumption and complementary genetic studies supporting a key role for omega-3 regulation.


Assuntos
Ácidos Graxos Ômega-3 , Esclerose Múltipla , Estudos de Casos e Controles , Dessaturase de Ácido Graxo Delta-5 , Dieta , Humanos , Esclerose Múltipla/genética , Fatores de Risco , Alimentos Marinhos
4.
Internet Interv ; 20: 100310, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32140427

RESUMO

AIM: To examine the efficacy of transdiagnostic internet-delivered cognitive behavioural therapy (iCBT), mindfulness-enhanced iCBT, and stand-alone online mindfulness training compared with a usual care control group (TAU) for clinical anxiety and depression. METHOD: Individuals (N = 158) with a DSM-5 diagnosis of a depressive and/or anxiety disorder were randomised to one of the three clinician-guided online interventions, or TAU over a 14-week intervention period. The primary outcomes were self-reported depression (PHQ-9) and anxiety (GAD-7) severity at post-treatment. Secondary outcomes included adherence rates, functional impairment (WHODAS-II), general distress (K-10), and diagnostic status at the 3-month follow-up (intervention groups). RESULTS: All three programs achieved significant and large reductions in symptoms of depression (g = 0.89-1.53), anxiety (g = 1.04-1.40), and distress (g = 1.25-1.76); and medium to large reductions in functional impairment (g = 0.53-0.98) from baseline to post-treatment and 3-month follow-up. Intention-to-treat linear mixed models showed that all three online programs were superior to usual care at reducing symptoms of depression (g = 0.89-1.18) and anxiety (g = 1.00-1.23). CONCLUSION: Transdiagnostic iCBT, mindfulness-enhanced iCBT and online mindfulness training are more efficacious for treating depression and anxiety disorders than usual care, and represent an accessible treatment option for these disorders.

5.
Public Health Nutr ; 23(12): 2165-2178, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31957633

RESUMO

OBJECTIVE: Ready-to-eat (RTE) cereal is an important source of nutrients in the American diet. Recent regulatory changes to labelling requirements may impact the fortification of RTE cereal. We used an evidence-based approach to optimize the fortification of RTE cereal considering current dietary patterns and nutrition policy. DESIGN: A US modelling study of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. The percentage of the population below the Estimated Average Requirement (EAR) and above the Upper Tolerable Intake Level (UL) was modelled under three scenarios: baseline, zero fortification and optimized fortification. SETTING: USA. PARTICIPANTS: Toddlers aged 1-3 years, n 559; children aged 4-12 years, n 1540; adolescents aged 13-18 years, n 992; and adults aged ≥19 years, n 576. RESULTS: Comparing current with optimized fortification, nutrient/100 g RTE cereal decreased for vitamin A, thiamin, riboflavin, niacin, vitamin B6, folic acid, vitamin B12, Ca and Fe (by 2-82 %). The amount of vitamins C and D increased (by 13 and 50 %, respectively). Among RTE cereal eaters, these changes resulted in modest increases in the percentage of the population aged ≥1 year below the EAR (+0·5 to +11·5 percentage points). Decreases were observed in the percentage of the population above the UL. CONCLUSIONS: Fortification of RTE cereal can be optimized to provide key nutrients and minimize the percentage of the population below the EAR and above the UL. Dietary intake modelling is useful to ensure that RTE cereal continues to help the population meet their nutrient needs.


Assuntos
Dieta , Grão Comestível , Alimentos Fortificados , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Modelos Teóricos , Inquéritos Nutricionais , Estados Unidos , Vitaminas/administração & dosagem
6.
Nutrients ; 11(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443588

RESUMO

Ready-to-eat (RTE) cereal is a popular food among children. However, there are no recent data on the associations between RTE cereal consumption and dietary outcomes in the U.S. Therefore, we sought to investigate how RTE cereal was associated with nutrient and food group intakes and overall dietary quality among children aged 0.5 to 17 years using the latest data from the National Health and Nutrition Examination Survey (NHANES 2015-2016). Thirty-six percent of children reported consuming RTE cereal. RTE cereal eaters consumed the same number of calories as non-eaters but had higher intakes of total carbohydrates, total sugar, fiber, calcium, iron, magnesium, potassium, zinc, vitamin A, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, and vitamin D, as well as lower intakes of total fat and saturated fat (p ≤ 0.0007). We also found that children who consumed RTE cereal had 29% higher total dairy intake (p < 0.0001) and 61% higher whole grain intake (p < 0.0001). Lastly, children who ate RTE cereal had higher diet quality than the children that did not eat RTE cereal, as shown by Healthy Eating Index 2015 total score (52.6 versus 47.7, p < 0.0001). Therefore, consumption of whole-grain fortified RTE cereals should be encouraged as part of healthy dietary patterns for children.


Assuntos
Desjejum , Fenômenos Fisiológicos da Nutrição Infantil , Grão Comestível , Fast Foods/análise , Estado Nutricional , Valor Nutritivo , Adolescente , Comportamento do Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Fatores Etários , Criança , Comportamento Infantil , Pré-Escolar , Estudos Transversais , Ingestão de Energia , Comportamento Alimentar , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Inquéritos Nutricionais , Recomendações Nutricionais , Estados Unidos
7.
Internet Interv ; 13: 41-50, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30206518

RESUMO

Transdiagnostic internet-delivered cognitive behavioural therapies (iCBT) are effective for treating anxiety and depression, but there is room for improvement. In this study we developed a new Mindfulness-Enhanced iCBT intervention by incorporating formal and informal mindfulness exercises within an existing transdiagnostic iCBT program for mixed depression and anxiety. We examined the acceptability, feasibility, and outcomes of this new program in a sample of 22 adults with anxiety disorders and/or major depression. Participants took part in the 7-lesson clinician-guided online intervention over 14 weeks, and completed measures of distress (K-10), anxiety (GAD-7), depression (PHQ-9), mindfulness (FFMQ) and well-being (WEMBWS) at pre-, mid-, post-treatment, and three months post-treatment. Treatment engagement, satisfaction, and side-effects were assessed. We found large, significant reductions in distress (Hedges g = 1.55), anxiety (g = 1.39), and depression (g = 1.96), and improvements in trait mindfulness (g = 0.98) and well-being (g = 1.26) between baseline and post-treatment, all of which were maintained at follow-up. Treatment satisfaction was high for treatment-completers, with minimal side-effects reported, although adherence was lower than expected (59.1% completed). These findings show that it is feasible to integrate online mindfulness training with iCBT for the treatment of anxiety and depression, but further research is needed to improve adherence. A randomised controlled trial is needed to explore the efficacy of this program.

8.
Nutrients ; 10(3)2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29495467

RESUMO

Multiple sclerosis (MS) incidence and serum 25-hydroxyvitamin D (25OHD) levels vary by race/ethnicity. We examined the consistency of beneficial effects of 25OHD and/or sun exposure for MS risk across multiple racial/ethnic groups. We recruited incident MS cases and controls (blacks 116 cases/131 controls; Hispanics 183/197; whites 247/267) from the membership of Kaiser Permanente Southern California into the MS Sunshine Study to simultaneously examine sun exposure and 25OHD, accounting for genetic ancestry and other factors. Higher lifetime ultraviolet radiation exposure (a rigorous measure of sun exposure) was associated with a lower risk of MS independent of serum 25OHD levels in blacks (adjusted OR = 0.53, 95% CI = 0.31-0.83; p = 0.007) and whites (OR = 0.68, 95% CI = 0.48-0.94; p = 0.020) with a similar magnitude of effect that did not reach statistical significance in Hispanics (OR = 0.66, 95% CI = 0.42-1.04; p = 0.071). Higher serum 25OHD levels were associated with a lower risk of MS only in whites. No association was found in Hispanics or blacks regardless of how 25OHD was modeled. Lifetime sun exposure appears to reduce the risk of MS regardless of race/ethnicity. In contrast, serum 25OHD levels are not associated with MS risk in blacks or Hispanics. Our findings challenge the biological plausibility of vitamin D deficiency as causal for MS and call into question the targeting of specific serum 25OHD levels to achieve health benefits, particularly in blacks and Hispanics.


Assuntos
População Negra , Hispânico ou Latino , Esclerose Múltipla/etnologia , Luz Solar , Deficiência de Vitamina D/etnologia , Vitamina D/sangue , Adulto , Alelos , Índice de Massa Corporal , California/epidemiologia , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Técnicas de Genotipagem , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Raios Ultravioleta , Vitamina D/administração & dosagem , Deficiência de Vitamina D/complicações , População Branca , Adulto Jovem
9.
Matern Child Nutr ; 14(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28464549

RESUMO

The double burden of malnutrition, defined by the coexistence of undernutrition and overweight, is well documented in low- and middle-income countries. However, the mechanisms by which employment may be related to maternal and child weight status in low- and middle-income countries are not well understood. We conducted in-depth interviews among 20 mothers who participated in Project MIEL, a contemporary trial which evaluated the effects of an integrated micronutrient supplement and parenting intervention in rural Guatemala. We utilized semi-structured interviews to explore the pathways by which maternal employment might influence bodyweight. Interviews were structured to explore the factors that mothers considered when deciding whether or not to participate in the labor force and how mothers perceived the influence of employment on determinants of their own bodyweight and that of their children. Themes were used to develop a conceptual framework. Mothers described four pathways through which employment could lead to changes in weight status: changes in food purchasing; improved household well-being; changes in time allocation; and psychological effects. Mothers described purchasing increased quantities and more varied types of food, as well as the purchase of energy-dense foods. Less time to devote to food preparation resulted in mothers preparing quicker meals and relying on substitute childcare. Mothers also expressed feelings of worry and neglect in relation to being employed, and perceived that these feelings would affect weight. A better understanding of these mechanisms is important for developing policies and programs to support women in the workplace and also reducing maternal and child overweight in Guatemala.


Assuntos
Peso Corporal , Emprego , Mães/psicologia , Mulheres Trabalhadoras/psicologia , Adulto , Saúde da Criança , Pré-Escolar , Culinária/métodos , Ingestão de Energia , Características da Família , Feminino , Alimentos/economia , Preferências Alimentares/psicologia , Guatemala , Humanos , Lactente , Masculino , Refeições/psicologia , Micronutrientes/administração & dosagem , Sobrepeso/psicologia , Pobreza , População Rural , Fatores Socioeconômicos
10.
Sci Eng Ethics ; 23(6): 1775-1790, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28000093

RESUMO

The mining and energy industries present unique challenges to engineers, who must navigate sometimes competing responsibilities and codes of conduct, such as personal senses of right and wrong, professional ethics codes, and their employers' corporate social responsibility (CSR) policies. Corporate social responsibility (CSR) is the current dominant framework used by industry to conceptualize firms' responsibilities to their stakeholders, yet has it plays a relatively minor role in engineering ethics education. In this article, we report on an interdisciplinary pedagogical intervention in a petroleum engineering seminar that sought to better prepare engineering undergraduate students to critically appraise the strengths and limitations of CSR as an approach to reconciling the interests of industry and communities. We find that as a result of the curricular interventions, engineering students were able to expand their knowledge of the social, rather than simply environmental and economic dimensions of CSR. They remained hesitant, however, in identifying the links between those social aspects of CSR and their actual engineering work. The study suggests that CSR may be a fruitful arena from which to illustrate the profoundly sociotechnical dimensions of the engineering challenges relevant to students' future careers.


Assuntos
Atitude , Engenharia/ética , Ética nos Negócios , Indústrias Extrativas e de Processamento/ética , Petróleo , Responsabilidade Social , Estudantes , Currículo , Engenharia/educação , Ética Profissional , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino
11.
Internet Interv ; 9: 25-37, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30135834

RESUMO

Major Depressive Disorder (MDD) is a leading cause of the Global Burden of Disease. Cognitive Behavioural Therapy (CBT) is an effective treatment for MDD, but access can be impaired due to numerous barriers. Internet-delivered CBT (iCBT) can be utilised to overcome treatment barriers and is an effective treatment for depression, but has never been compared to bibliotherapy. This Randomised Controlled Trial (RCT) included participants meeting diagnostic criteria for MDD (n = 270) being randomised to either: iCBT (n = 61), a CBT self-help book (bCBT) (n = 77), a meditation self-help book (bMED) (n = 64) or wait-list control (WLC) (n = 68). The primary outcome was the Patient Health Questionnaire 9-item scale (PHQ-9) at 12-weeks (post-treatment). All three active interventions were significantly more effective than WLC in reducing depression at post-treatment, but there were no significant differences between the groups. All three interventions led to large within-group reductions in PHQ-9 scores at post-treatment (g = 0.88-1.69), which were maintained at 3-month follow-up, although there was some evidence of relapse in the bMED group (within-group g [post to follow-up] = 0.09-1.04). Self-help based interventions could be beneficial in treating depression, however vigilance needs to be applied when selecting from the range of materials available. Replication of this study with a larger sample is required.

12.
J Affect Disord ; 178: 131-41, 2015 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-25805405

RESUMO

BACKGROUND: Accruing evidence suggests that positive imagery-based cognitive bias modification (CBM) could have potential as a standalone targeted intervention for depressive symptoms or as an adjunct to existing treatments. We sought to establish the benefit of this form of CBM when delivered prior to Internet cognitive behavioral therapy (iCBT) for depression METHODS: A randomized controlled trial (RCT) of a 1-week Internet-delivered positive CBM vs. an active control condition for participants (N=75, 69% female, mean age=42) meeting diagnostic criteria for major depression; followed by a 10-week iCBT program for both groups. RESULTS: Modified intent-to-treat marginal and mixed effect models demonstrated no significant difference between conditions following the CBM intervention or the iCBT program. In both conditions there were significant reductions (Cohen׳s d .57-1.58, 95% CI=.12-2.07) in primary measures of depression and interpretation bias (PHQ9, BDI-II, AST-D). Large effect size reductions (Cohen׳s d .81-1.32, 95% CI=.31-1.79) were observed for secondary measures of distress, disability, anxiety and repetitive negative thinking (K10, WHODAS, STAI, RTQ). Per protocol analyses conducted in the sample of participants who completed all seven sessions of CBM indicated between-group superiority of the positive over control group on depression symptoms (PHQ9, BDI-II) and psychological distress (K10) following CBM (Hedges g .55-.88, 95% CI=-.03-1.46) and following iCBT (PHQ9, K10). The majority (>70%) no longer met diagnostic criteria for depression at 3-month follow-up. LIMITATIONS: The control condition contained many active components and therefore may have represented a smaller 'dose' of the positive condition. CONCLUSIONS: Results provide preliminary support for the successful integration of imagery-based CBM into an existing Internet-based treatment for depression.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/terapia , Imagens, Psicoterapia , Internet , Adulto , Feminino , Humanos , Masculino , Terapia Assistida por Computador , Resultado do Tratamento
13.
J Virol ; 88(10): 5533-42, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24599995

RESUMO

UNLABELLED: Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds-dihydrodibenzothiepines (DHBTs), identified through high-throughput screening-with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE: The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other compounds targeting the same cellular pathways, may have therapeutic potential for the treatment of dengue virus infections.


Assuntos
Antivirais/metabolismo , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Receptores de Dopamina D4/antagonistas & inibidores , Transdução de Sinais , Replicação Viral/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Sindbis virus/efeitos dos fármacos , Sindbis virus/fisiologia , Vírus do Nilo Ocidental/efeitos dos fármacos , Vírus do Nilo Ocidental/fisiologia
14.
Proc Natl Acad Sci U S A ; 110(43): 17308-13, 2013 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-24101514

RESUMO

DNA metabolism and processing frequently require transient or metastable DNA conformations that are biologically important but challenging to characterize. We use gold nanocrystal labels combined with small angle X-ray scattering to develop, test, and apply a method to follow DNA conformations acting in the Escherichia coli mismatch repair (MMR) system in solution. We developed a neutral PEG linker that allowed gold-labeled DNAs to be flash-cooled and stored without degradation in sample quality. The 1,000-fold increased gold nanocrystal scattering vs. DNA enabled investigations at much lower concentrations than otherwise possible to avoid concentration-dependent tetramerization of the MMR initiation enzyme MutS. We analyzed the correlation scattering functions for the nanocrystals to provide higher resolution interparticle distributions not convoluted by the intraparticle distribution. We determined that mispair-containing DNAs were bent more by MutS than complementary sequence DNA (csDNA), did not promote tetramer formation, and allowed MutS conversion to a sliding clamp conformation that eliminated the DNA bends. Addition of second protein responder MutL did not stabilize the MutS-bent forms of DNA. Thus, DNA distortion is only involved at the earliest mispair recognition steps of MMR: MutL does not trap bent DNA conformations, suggesting migrating MutL or MutS/MutL complexes as a conserved feature of MMR. The results promote a mechanism of mismatch DNA bending followed by straightening in initial MutS and MutL responses in MMR. We demonstrate that small angle X-ray scattering with gold labels is an enabling method to examine protein-induced DNA distortions key to the DNA repair, replication, transcription, and packaging.


Assuntos
Reparo de Erro de Pareamento de DNA , Ouro/química , Nanopartículas/química , Conformação de Ácido Nucleico , Espalhamento a Baixo Ângulo , Difração de Raios X/métodos , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Algoritmos , DNA Bacteriano/química , DNA Bacteriano/metabolismo , DNA Bacteriano/ultraestrutura , Proteínas de Escherichia coli/metabolismo , Cinética , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Proteínas MutL , Proteína MutS de Ligação de DNA com Erro de Pareamento/metabolismo , Nanopartículas/ultraestrutura , Ligação Proteica , Soluções
15.
Pediatr Dermatol ; 30(5): e94-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23406375

RESUMO

A needle-free system that delivers lidocaine to the dermis using pressurized gas is often used as an alternative anesthetic for venipuncture and intravenous catheterization in children. This case report illustrates the potential histologic artifacts that may arise when using a needleless device for a cutaneous punch biopsy. We suggest against using a needleless system for pediatric skin biopsies.


Assuntos
Anestesia Local/efeitos adversos , Anestesia Local/instrumentação , Artefatos , Lidocaína/administração & dosagem , Neutropenia/patologia , Anormalidades da Pele/patologia , Anestésicos Locais/administração & dosagem , Biópsia/métodos , Criança , Feminino , Humanos
16.
Appl Environ Microbiol ; 79(5): 1646-53, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23275510

RESUMO

Molecular tools that can provide an estimate of the in situ growth rate of Geobacter species could improve understanding of dissimilatory metal reduction in a diversity of environments. Whole-genome microarray analyses of a subsurface isolate of Geobacter uraniireducens, grown under a variety of conditions, identified a number of genes that are differentially expressed at different specific growth rates. Expression of two genes encoding ribosomal proteins, rpsC and rplL, was further evaluated with quantitative reverse transcription-PCR (qRT-PCR) in cells with doubling times ranging from 6.56 h to 89.28 h. Transcript abundance of rpsC correlated best (r(2) = 0.90) with specific growth rates. Therefore, expression patterns of rpsC were used to estimate specific growth rates of Geobacter species during an in situ uranium bioremediation field experiment in which acetate was added to the groundwater to promote dissimilatory metal reduction. Initially, increased availability of acetate in the groundwater resulted in higher expression of Geobacter rpsC, and the increase in the number of Geobacter cells estimated with fluorescent in situ hybridization compared well with specific growth rates estimated from levels of in situ rpsC expression. However, in later phases, cell number increases were substantially lower than predicted from rpsC transcript abundance. This change coincided with a bloom of protozoa and increased attachment of Geobacter species to solid phases. These results suggest that monitoring rpsC expression may better reflect the actual rate that Geobacter species are metabolizing and growing during in situ uranium bioremediation than changes in cell abundance.


Assuntos
Perfilação da Expressão Gênica/métodos , Geobacter/crescimento & desenvolvimento , Água Subterrânea/microbiologia , Proteínas Ribossômicas/biossíntese , Acetatos/metabolismo , Biodegradação Ambiental , DNA Bacteriano/química , DNA Bacteriano/genética , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Análise de Sequência de DNA , Urânio/metabolismo
17.
ISME J ; 7(2): 370-83, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23038171

RESUMO

The possibility of arsenic release and the potential role of Geobacter in arsenic biogeochemistry during in situ uranium bioremediation was investigated because increased availability of organic matter has been associated with substantial releases of arsenic in other subsurface environments. In a field experiment conducted at the Rifle, CO study site, groundwater arsenic concentrations increased when acetate was added. The number of transcripts from arrA, which codes for the α-subunit of dissimilatory As(V) reductase, and acr3, which codes for the arsenic pump protein Acr3, were determined with quantitative reverse transcription-PCR. Most of the arrA (>60%) and acr3-1 (>90%) sequences that were recovered were most similar to Geobacter species, while the majority of acr3-2 (>50%) sequences were most closely related to Rhodoferax ferrireducens. Analysis of transcript abundance demonstrated that transcription of acr3-1 by the subsurface Geobacter community was correlated with arsenic concentrations in the groundwater. In contrast, Geobacter arrA transcript numbers lagged behind the major arsenic release and remained high even after arsenic concentrations declined. This suggested that factors other than As(V) availability regulated the transcription of arrA in situ, even though the presence of As(V) increased the transcription of arrA in cultures of Geobacter lovleyi, which was capable of As(V) reduction. These results demonstrate that subsurface Geobacter species can tightly regulate their physiological response to changes in groundwater arsenic concentrations. The transcriptomic approach developed here should be useful for the study of a diversity of other environments in which Geobacter species are considered to have an important influence on arsenic biogeochemistry.


Assuntos
Arsênio/metabolismo , Genes Bacterianos , Geobacter/metabolismo , Água Subterrânea/química , Urânio/metabolismo , Acetatos/química , Arseniato Redutases/genética , Biodegradação Ambiental , Colorado , Regulação Bacteriana da Expressão Gênica , Geobacter/genética , Transcriptoma
18.
Int J Sport Nutr Exerc Metab ; 20(5): 409-17, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20975109

RESUMO

The purpose of this study was to investigate the ability of whey-protein and leucine supplementation to enhance physical and cognitive performance and body composition. Thirty moderately fit participants completed a modified Air Force fitness test, a computer-based cognition test, and a dual-energy X-ray-absorptiometry scan for body composition before and after supplementing their daily diet for 8 wk with either 19.7 g of whey protein and 6.2 g leucine (WPL) or a calorie-equivalent placebo (P). Bench-press performance increased significantly from Week 1 to Week 8 in the WPL group, whereas the increase in the P group was not significant. Push-up performance increased significantly for WPL, and P showed a nonsignificant increase. Total mass, fat-free mass, and lean body mass all increased significantly in the WPL group but showed no change in the P group. No differences were observed within or between groups for crunches, chin-ups, 3-mile-run time, or cognition. The authors conclude that supplementing with whey protein and leucine may provide an advantage to people whose performance benefits from increased upper body strength and/or lean body mass.


Assuntos
Cognição/efeitos dos fármacos , Exercício Físico/fisiologia , Leucina/farmacologia , Proteínas do Leite/farmacologia , Músculo Esquelético/efeitos dos fármacos , Absorciometria de Fóton , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/fisiologia , Adulto , Análise de Variância , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Cognição/fisiologia , Proteínas Alimentares/metabolismo , Proteínas Alimentares/farmacologia , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Leucina/metabolismo , Masculino , Militares , Proteínas do Leite/metabolismo , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Proteínas do Soro do Leite
19.
Phytopathology ; 100(2): 127-33, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20055646

RESUMO

ABSTRACT Breakdown of sugar beet Rz1-mediated resistance against Beet necrotic yellow vein virus (BNYVV) infection was previously found, by reverse genetics, to be caused by a single mutation in its p25 gene. The possibility of alternative breaking mutations, however, has not been discarded. To explore the natural diversity of BNYVV in the field and its effects on overcoming Rz1, wild-type (WT) and resistance-breaking (RB) p25 genes from diverse production regions of North America were characterized. The relative titer of WT p25 was inversely correlated with disease expression in Rz1 plants from Minnesota and California. In Minnesota, the predominant WT p25 encoded the A(67)C(68) amino acid signature whereas, in California, it encoded A(67)L(68). In both locations, these WT signatures were associated with asymptomatic BNYVV infections of Rz1 cultivars. Further analyses of symptomatic resistant plants revealed that, in Minnesota, WT A(67)C(68) was replaced by V(67)C(68) whereas, in California, WT A(67)L(68) was replaced by V(67)L(68). Therefore, V(67) was apparently critical in overcoming Rz1 in both pathosystems. The greater genetic distances between isolates from different geographic regions rather than between WT and RB from the same location indicate that the underlying C to U transition originated independently in both BNYVV lineages.


Assuntos
Beta vulgaris/virologia , Genes Virais , Interações Hospedeiro-Patógeno , Vírus de Plantas/genética , Evolução Biológica , California , Variação Genética , Genótipo , Minnesota , Vírus de Plantas/patogenicidade , Mutação Puntual
20.
Int J Circumpolar Health ; 68(5): 421-32, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20044961

RESUMO

OBJECTIVES: The Inuit of Nunavik in northern Quebec have a lower risk for ischemic heart disease (IHD) compared to Caucasian populations. Acylation stimulating protein (ASP), which is involved in the storage of dietary fat, may play a role. The objective of the study was to determine plasma concentration of ASP in an Inuit and a southern Quebec Caucasian population. STUDY DESIGN: This is a cross-sectional study evaluating the relationship between ASP and dietary factors, such as retinol, whose intake is higher in the Inuit. As well, concentrations of ASP were evaluated in relationship to components of the metabolic syndrome. METHODS: Medical history was collected via a questionnaire and anthropometric measurements and blood samples were collected. RESULTS: ASP was significantly higher in both the Inuit men and women compared to Caucasian men (66.1 +/- 4.1 nM vs 27.5 +/- 2.5 nM, p < 0.0001) and women (71.8 +/- 3.8 nM vs 29.4 +/- 1.3 nM, p < 0.0001). In addition, ASP significantly correlated with total retinol (r = 0.17, p = 0.02) and free retinol (r = 0.15, p = 0.04) in Inuit men but not with other distinctive dietary markers such as omega-3 fatty acids. CONCLUSIONS: Inuit men and women have higher ASP which was unrelated to the number of risk factors for IHD that were present.


Assuntos
Adipocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Isquemia Miocárdica/sangue , Isquemia Miocárdica/etnologia , Vitamina A/sangue , Acilação , Adulto , Idoso , Pesos e Medidas Corporais , Complemento C3 , Estudos Transversais , Feminino , Humanos , Inuíte , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Quebeque/epidemiologia , Fatores Sexuais , População Branca
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