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1.
Int J Med Inform ; 174: 105047, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36948062

RESUMO

BACKGROUND: Diet is key in preventing rapid infant weight gain but adherence to infant dietary recommendations is difficult to follow and low in adherence. OBJECTIVE: Develop and pilot test the "Baby-Feed" web application for parents and healthcare professionals to easily evaluate infant diets and provide immediate feedback to promote adherence to current infant dietary recommendations. METHODS: Baby-Feed was developed following the ADDIE (analysis, design, development, implementation, and evaluation) model. It was pilot tested among two clinicians and 25 parents of infants aged 4 to 12 months that had a scheduled well-child visit at a community health center in Miami. After 2 weeks of using Baby-Feed, parents completed a feasibility, acceptability, satisfaction, and usability questionnaire. Parents and clinicians were also asked to suggest improvements. Descriptive analysis included frequency and median (25th, 75th percentiles). One-sample binomial tests was used to evaluate if feasible, acceptable, satisfactory, and usable. RESULTS: Twenty-three parents completed the evaluation (all were mothers), 31.0 (26.0, 33.0) years-old, 96% Hispanic, 83% had ≥ high school education, with 1.5 (1.0, 2.0) children. Infants' age was 6.1 (4.0, 9.0) months and 57% were boys. Binomial tests indicated that most parents (greater than87%) agreed that Baby-Feed was easy to use, learn, quick, would use it again, rated it as 4/5 stars. They used it greater than 1 times per week (p < 0.001). Parents suggested improving the visuals (more icons, colors, and pictures) and images of portion sizes, highlighting missing fields, being able to view/open it on their phones, and adding recipes and more information. The two clinicians (a pediatrician and a physician assistant) suggested to be open-access and to add more infant nutrition information. CONCLUSION: Baby-Feed was feasible, usable, satisfactory, and acceptable. It could be used as a tool to easily evaluate infant diets in the healthcare setting to provide immediate feedback.


Assuntos
Dieta , Pais , Masculino , Lactente , Humanos , Adulto , Feminino , Inquéritos e Questionários , Instalações de Saúde , Atenção à Saúde
2.
J Forensic Leg Med ; 59: 36-38, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30130700

RESUMO

Although the past few years have seen a significant increase in the use of synthetic cannabinoids, very few fatalities have been reported whereby synthetic cannabinoids have contributed or were solely responsible for the death of an individual. We report a rapid death of an individual following ingestion of 5 F-PB-22 and 5 F-AKB-48. Case information and autopsy findings are presented. Post-mortem blood samples were obtained and 5 F-PB-22 and 5 F-AKB-48 were detected along with 311 mg/100 ml alcohol. The cause of death was certified as the effects of a combination of alcohol and synthetic cannabinoids (5 F-PB-22 and 5 F-AKB-48).


Assuntos
Canabinoides/intoxicação , Morte Súbita/etiologia , Drogas Desenhadas/intoxicação , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Canabinoides/sangue , Depressores do Sistema Nervoso Central/análise , Depressores do Sistema Nervoso Central/intoxicação , Drogas Desenhadas/análise , Etanol/análise , Etanol/intoxicação , Humanos , Masculino
3.
J Manipulative Physiol Ther ; 40(9): 635-642, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29229053

RESUMO

OBJECTIVE: The purpose of this study was to evaluate a chiropractic service for back pain patients integrated within a publicly funded, multidisciplinary, primary care community health center in Cambridge, Ontario, Canada. METHODS: Patients consulting for back pain of any duration were referred by their medical doctor or nurse practitioner for chiropractic treatment at the community health center. Patients completed questionnaires at baseline and at discharge from the service. Data were collected prospectively on consecutive patients between January 2014 and January 2016. RESULTS: Questionnaire data were obtained from 93 patients. The mean age of the sample was 49.0 ± 16.27 years, and 66% were unemployed. More than three-quarters (77%) had had their back pain for more than a month, and 68% described it as constant. According to the Bournemouth Questionnaire, Bothersomeness, and global improvement scales, a majority (63%, 74%, and 93%, respectively) reported improvement at discharge, and most (82%) reported a significant reduction in pain medication. More than three-quarters (77%) did not visit their primary care provider while under chiropractic care, and almost all (93%) were satisfied with the service. According to the EuroQol 5 Domain questionnaire, more than one-third of patients (39%) also reported improvement in their general health state at discharge. CONCLUSION: Implementation of an integrated chiropractic service was associated with high levels of improvement and patient satisfaction in a sample of patients of low socioeconomic status with subacute and chronic back pain.


Assuntos
Centros Comunitários de Saúde/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Pessoal de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Dor Lombar/reabilitação , Manipulação Quiroprática , Adulto , Idoso , Canadá , Serviços de Saúde Comunitária/normas , Serviços de Saúde Comunitária/tendências , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Dor Lombar/diagnóstico , Masculino , Pessoa de Meia-Idade , Ontário , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos
4.
Am J Clin Nutr ; 106(3): 736-746, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28793995

RESUMO

Background: A low-calorie diet (LCD) reduces fat mass excess, improves insulin sensitivity, and alters adipose tissue (AT) gene expression, yet the relation with clinical outcomes remains unclear.Objective: We evaluated AT transcriptome alterations during an LCD and the association with weight and glycemic outcomes both at LCD termination and 6 mo after the LCD.Design: Using RNA sequencing (RNAseq), we analyzed transcriptome changes in AT from 191 obese, nondiabetic patients within a multicenter, controlled dietary intervention. Expression changes were associated with outcomes after an 8-wk LCD (800-1000 kcal/d) and 6 mo after the LCD. Results were validated by using quantitative reverse transcriptase-polymerase chain reaction in 350 subjects from the same cohort. Statistical models were constructed to classify weight maintainers or glycemic improvers.Results: With RNAseq analyses, we identified 1173 genes that were differentially expressed after the LCD, of which 350 and 33 were associated with changes in body mass index (BMI; in kg/m2) and Matsuda index values, respectively, whereas 29 genes were associated with both endpoints. Pathway analyses highlighted enrichment in lipid and glucose metabolism. Classification models were constructed to identify weight maintainers. A model based on clinical baseline variables could not achieve any classification (validation AUC: 0.50; 95% CI: 0.36, 0.64). However, clinical changes during the LCD yielded better performance of the model (AUC: 0.73; 95% CI: 0.60, 0.87]). Adding baseline expression to this model improved the performance significantly (AUC: 0.87; 95% CI: 0.77, 0.96; Delong's P = 0.012). Similar analyses were performed to classify subjects with good glycemic improvements. Baseline- and LCD-based clinical models yielded similar performance (best AUC: 0.73; 95% CI: 0.60, 0.86). The addition of expression changes during the LCD improved the performance substantially (AUC: 0.80; 95% CI: 0.69, 0.92; P = 0.058).Conclusions: This study investigated AT transcriptome alterations after an LCD in a large cohort of obese, nondiabetic patients. Gene expression combined with clinical variables enabled us to distinguish weight and glycemic responders from nonresponders. These potential biomarkers may help clinicians understand intersubject variability and better predict the success of dietary interventions. This trial was registered at clinicaltrials.gov as NCT00390637.


Assuntos
Tecido Adiposo/metabolismo , Glicemia/metabolismo , Restrição Calórica , Dieta Redutora , Resistência à Insulina , Obesidade/genética , Transcriptoma , Adulto , Área Sob a Curva , Biomarcadores/metabolismo , Peso Corporal , Manutenção do Peso Corporal , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Obesidade/metabolismo , Obesidade/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Redução de Peso/genética
5.
Psychoneuroendocrinology ; 85: 88-95, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28843169

RESUMO

Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n=5705) and saliva levels (n=1717), as well as diurnal saliva levels (n=1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n=12,597) and saliva cortisol (n=7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0-13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations.


Assuntos
Estudo de Associação Genômica Ampla , Hidrocortisona/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Países Baixos , Saliva/química
6.
J Clin Endocrinol Metab ; 102(8): 2751-2761, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28482007

RESUMO

Context: Although calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals. Objective: To identify biomarkers of successful weight control during a dietary intervention (DI). Design, Setting, and Participants: Adipose tissue (AT) transcriptomes were compared between 21 obese individuals who either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using quantitative reverse transcription polymerase chain reaction and protein levels of potential circulating biomarkers measured by enzyme-linked immunosorbent assay. Intervention: Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet. Outcome Measure: Weight changes at the end of the DI. Results: We evaluated six genes that had altered expression during DI, encode secreted proteins, and have not previously been implicated in weight control (EGFL6, FSTL3, CRYAB, TNMD, SPARC, IGFBP3), as well as genes for which baseline expression differed between those with good and poor weight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored AT messenger RNA expression; all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals who went on to have good weight control. Expression quantitative trait loci analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified in which transforming growth factor ß1 (TGF-ß1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-ß1 inhibitor. Conclusions: We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.


Assuntos
Restrição Calórica , Obesidade/dietoterapia , RNA Mensageiro/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio , Moléculas de Adesão Celular , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Proteínas Relacionadas à Folistatina/genética , Proteínas Relacionadas à Folistatina/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Análise em Microsséries , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Osteonectina/genética , Osteonectina/metabolismo , Polimorfismo Genético , Locos de Características Quantitativas , Reação em Cadeia da Polimerase em Tempo Real , Fator de Crescimento Transformador beta1/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Cadeia B de alfa-Cristalina/genética , Cadeia B de alfa-Cristalina/metabolismo
7.
Chiropr Man Therap ; 24: 18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27280015

RESUMO

BACKGROUND: Research in various medical fields demonstrates a consistent and positive association between clinical outcomes and the quality of the therapeutic alliance between the patient and clinician. The aim of this study was to explore how well chiropractors and their patients in The Netherlands perceive the quality of their working relationship. METHODS: A nationwide survey of chiropractors and their patients was conducted in The Netherlands, using a validated Dutch translation of the Working Alliance Inventory (WAV-12). Data were collected over a 5-week period in September-October 2014. Both patients and chiropractors were requested to reflect on 12 statements about to how well they perceived their collaboration in reaching consensus on treatment goals and treatment strategies, and how well they perceived the existence of an affective bond in their working relationship. A 5-point Likert scale was used to answer each question. Higher ratings reflected a more positive perception of the therapeutic alliance. Furthermore, levels of agreement between patients' and chiropractors' perceptions of the quality of their therapeutic alliance were determined. RESULTS: In total, 207 working relationships between patients and their chiropractor were analysed. The quality of the therapeutic alliance was perceived as being very positive for both patients (n = 183, mean 49.14 ± 7.12) and chiropractors (n = 202, mean 50.48 ± 4.97). There was no difference in patients' perceptions whether treated by a male or female chiropractor, nor in relation to the chiropractor's years of experience. Nevertheless, poor agreement was found between perceptions of patients and chiropractors in the same relationship (ICC = 0.13). CONCLUSIONS: Both patients and chiropractors perceived the quality of the therapeutic alliance as being very positive. Despite these positive results, patient and chiropractor pairs perceived the level of collaboration in order to reach agreement on treatment goals and strategies and the quality of their affective bond very differently. Clinically, these results suggest that chiropractors should, during the course of treatment, continue to collaborate with their patient and frequently verify whether their patient continues to agree with the treatment goals and treatment plan applied to further develop, improve and maintain a positive therapeutic alliance.

8.
Int J Epidemiol ; 45(6): 1927-1937, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-25979724

RESUMO

Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.


Assuntos
Estatura/genética , Doença das Coronárias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/sangue , Doença das Coronárias/sangue , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Análise da Randomização Mendeliana/métodos , Estudos Observacionais como Assunto , Polimorfismo de Nucleotídeo Único , Testes de Função Respiratória , Fatores de Risco , Acidente Vascular Cerebral/sangue , Triglicerídeos/sangue
9.
BMC Musculoskelet Disord ; 16: 234, 2015 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-26338033

RESUMO

BACKGROUND: Modic changes (MC) have been linked with low back pain (LBP) and worse outcomes from some treatments. No studies have investigated the impact that MCs may have on patient outcomes from lumbar facet injections. Therefore, the purpose of this study is to investigate whether the presence of Modic changes is related to 'improvement' in patients undergoing imaging-guided lumbar facet injection therapy. METHODS: Outcomes from 226 patients with MRI scans within 3 months of their imaging-guided lumbar facet injections were investigated to determine whether MCs are related to 'improvement' post injection. At 1 day, 1 week and 1 month post injection the Patients Global Impression of Change scale answers were collected by postal questionnaire. This was the primary outcome measure. The numerical rating scale for pain data was collected prior to treatment and at the same post injection time points. The MRI scans were independently evaluated by two examiners for the presence/absence of Modic changes and the type of Modic change if present. Kappa statistics were used for reliability of diagnosis analysis. Chi-squared test and logistic regression analysis tested MCs with 'improvement'. RESULTS: Intra- and inter-examiner reliability for the diagnosis of MCs was Kappa = 0.77 and 0.74. Intra- and inter-examiner reliability for categorizing MCs was K = 0.77 and K = 0.78. At 1 month post injection 45.2 % of patients without MCs reported clinically relevant 'improvement' compared to 34.2 % of patients with MC I and 32.1 % of patients with MC II. However, this did not reach statistical significance. Logistic regression found that Modic changes were not predictive of 'improvement'. CONCLUSIONS: There was a tendency for patients without MCs to have better outcomes but this did not reach statistical significance. The reliability of diagnosing MCs was substantial.


Assuntos
Dor Lombar/diagnóstico , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética/tendências , Medição da Dor/tendências , Articulação Zigapofisária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Injeções Intra-Articulares , Dor Lombar/tratamento farmacológico , Vértebras Lombares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Estudos Prospectivos , Adulto Jovem , Articulação Zigapofisária/efeitos dos fármacos
10.
J Forensic Leg Med ; 33: 82-90, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26048504

RESUMO

The challenge of interpreting post-mortem drug concentrations is well documented and relies on appropriate sample collection, knowledge of case circumstances as well as reference to published tables of data, whilst taking into account the known issues of post-mortem drug redistribution and tolerance. Existing published data has evolved from simple data tables to those now including sample origin and single to poly drug use, but additional information tends to be specific to those reported in individual case studies. We have developed a Bayesian network framework to assign a likelihood of fatality based on the contribution of drug concentrations whilst taking into account the pathological findings. This expert system has been tested against casework within the coronial jurisdiction of Sunderland, UK. We demonstrate in this pilot study that the Bayesian network can be used to proffer a degree of confidence in how deaths may be reported in cases when drugs are implicated. It has also highlighted the potential for deaths to be reported according to the pathological states at post-mortem when drugs have a significant contribution that may have an impact on mortality statistics. The Bayesian network could be used as complementary approach to assist in the interpretation of post-mortem drug concentrations.


Assuntos
Funções Verossimilhança , Intoxicação/diagnóstico , Mudanças Depois da Morte , Adulto , Concentração Alcoólica no Sangue , Causas de Morte , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Toxicologia Forense/métodos , Humanos , Masculino , Entorpecentes/efeitos adversos , Entorpecentes/análise , Preparações Farmacêuticas/análise , Projetos Piloto , Reino Unido , Adulto Jovem
11.
Nature ; 518(7538): 197-206, 2015 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-25673413

RESUMO

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.


Assuntos
Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Obesidade/genética , Obesidade/metabolismo , Adipogenia/genética , Adiposidade/genética , Fatores Etários , Metabolismo Energético/genética , Europa (Continente)/etnologia , Feminino , Predisposição Genética para Doença/genética , Ácido Glutâmico/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Grupos Raciais/genética , Sinapses/metabolismo
12.
Chiropr Man Therap ; 22(1): 32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25309721

RESUMO

BACKGROUND: The use of patient-reported questionnaires to collect information on costs associated with routine healthcare services, such as chiropractic, represents a less labour intensive alternative to retrieving these data from patient files. The aim of this paper was to compare patient-report versus patient files for the collection of data describing healthcare usage in chiropractic clinics. METHODS: As part of a prospective single cohort multi-centre study, data on the number of visits made to chiropractic clinics determined using patient-reported questionnaires or as recorded in patient files were compared three months following the start of treatment. These data were analysed for agreement using the Intraclass Correlation Coefficient (ICC) and the 95% Limits of Agreement. RESULTS: Eighty-nine patients that had undergone chiropractic care were included in the present study. The two methods yielded an ICC of 0.83 (95% CI = 0.75 to 0.88). However, there was a significant difference between the data collection methods, with an average of 0.6 (95% CI = 0.25 to 1.01) additional visits reported in patient files. The 95% Limits of Agreement ranged from 3 fewer visits to 4 additional visits in patient files relative to the number of visits recalled by patients. CONCLUSION: There was some discrepancy between the number of visits made to the clinic recalled by patients compared to the number recorded in patient files. This should be taken into account in future evaluations of costs of treatments.

13.
PLoS Genet ; 10(7): e1004474, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25010111

RESUMO

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.


Assuntos
Estudo de Associação Genômica Ampla , Hidrocortisona/sangue , Transcortina/genética , alfa 1-Antitripsina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Exoma/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único/genética , Ligação Proteica , Transcortina/metabolismo , alfa 1-Antitripsina/metabolismo
14.
J Can Chiropr Assoc ; 58(1): 6-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24587491
15.
J Clin Endocrinol Metab ; 99(1): 160-168, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24092834

RESUMO

CONTEXT: Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary-adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11ß-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue. OBJECTIVE: We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans. DESIGN: This was a randomized, single-blinded, crossover study. SETTING: The study was conducted at a hospital research facility. PARTICIPANTS: Eight normal-weight healthy men participated in the study. INTERVENTIONS: Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol. OUTCOME MEASURES AND RESULTS: Plasma cortisol increased similarly after all macronutrient meals (by ∼90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11ß-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance. CONCLUSIONS: Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and glucocorticoids and the contrasting effects of certain diets on postprandial metabolism.


Assuntos
Glândulas Suprarrenais/metabolismo , Ingestão de Alimentos/fisiologia , Hidrocortisona/sangue , Período Pós-Prandial , Tecido Adiposo/metabolismo , Adulto , Estudos Cross-Over , Alimentos , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Fígado/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Placebos , Método Simples-Cego , Adulto Jovem
16.
J Chiropr Educ ; 27(1): 40-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23519168

RESUMO

OBJECTIVE: The subject of research methods is not commonly covered in continuing professional development (CPD) courses in spite of its emphasis in undergraduate education. This initiative aimed to develop postgraduate research competency and recruit chiropractors to musculoskeletal research. METHODS: The program was delivered as a university-based program with 20 credits over seven contact weekends covering topics of evidence-based practice, research methods, statistics, ethics, resources, and funding. Students were assessed through assignments showing competency in critical literature review, case report writing, and production of a research protocol as the final assessment. Non-student participation for CPD points was possible. A student evaluation survey was completed after the end of the academic year. RESULTS: There were 26 participants: 16 as students handing in assignments, 10 as non-student participants for up to 94 CPD points. Three submitted a final protocol and two registered at a university PhD program. A network of research clinics was established for data collection for future multicenter studies. CONCLUSIONS: The program was well received by the participants and gave them the tools and resources to perform research. The two-level attendance system afforded a basis for setting up a network of research clinics with a fundamental understanding of optimal data collection. This initiative has shown that research skills can be revisited through CPD programs as part of evidence-based lifelong learning.

17.
PLoS One ; 8(2): e57310, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23468967

RESUMO

OBJECTIVE: We examined whether a panel of SNPs, systematically selected from genome-wide association studies (GWAS), could improve risk prediction of coronary heart disease (CHD), over-and-above conventional risk factors. These SNPs have already demonstrated reproducible associations with CHD; here we examined their use in long-term risk prediction. STUDY DESIGN AND SETTING: SNPs identified from meta-analyses of GWAS of CHD were tested in 840 men and women aged 55-75 from the Edinburgh Artery Study, a prospective, population-based study with 15 years of follow-up. Cox proportional hazards models were used to evaluate the addition of SNPs to conventional risk factors in prediction of CHD risk. CHD was classified as myocardial infarction (MI), coronary intervention (angioplasty, or coronary artery bypass surgery), angina and/or unspecified ischaemic heart disease as a cause of death; additional analyses were limited to MI or coronary intervention. Model performance was assessed by changes in discrimination and net reclassification improvement (NRI). RESULTS: There were significant improvements with addition of 27 SNPs to conventional risk factors for prediction of CHD (NRI of 54%, P<0.001; C-index 0.671 to 0.740, P = 0.001), as well as MI or coronary intervention, (NRI of 44%, P<0.001; C-index 0.717 to 0.750, P = 0.256). ROC curves showed that addition of SNPs better improved discrimination when the sensitivity of conventional risk factors was low for prediction of MI or coronary intervention. CONCLUSION: There was significant improvement in risk prediction of CHD over 15 years when SNPs identified from GWAS were added to conventional risk factors. This effect may be particularly useful for identifying individuals with a low prognostic index who are in fact at increased risk of disease than indicated by conventional risk factors alone.


Assuntos
Doença das Coronárias/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Public Health Nutr ; 16(8): 1427-35, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22958548

RESUMO

OBJECTIVE: FFQ are popular instruments for assessing dietary intakes in epidemiological studies but have not been validated for use in severely obese pregnancy. The aim of the present study was to compare nutrient intakes assessed by an FFQ with those obtained from a food diary among severely obese pregnant women. DESIGN: Comparison of an FFQ containing 170 food items and a food diary for 4 d (three weekdays and one weekend day); absolute agreement was assessed using the paired t test and relative agreement by Pearson/Spearman correlation, crossclassification into tertiles and weighted kappa values. SETTING: Antenatal metabolic clinic for severely obese women. SUBJECTS: Thirty-one severely obese (BMI at booking ≥ 40.0 kg/m2) and thirty-two lean control (BMI520.0­24.9 kg/m2) pregnant women. RESULTS: The findings showed that nutrient intakes estimated by the FFQ were significantly higher than those from the food diary; average correlation was 0.32 in obese and 0.43 in lean women. A mean of 48.5% of obese and 47.3% of lean women were correctly classified, while 12.9% (obese) and 10.0% (lean) were grossly misclassified. Weighted k values ranged from 20.04 to 0.79 in obese women and from 0.16 to 0.78 in lean women. CONCLUSIONS: Overall, the relative agreement between the FFQ and food diary was lower in the obese group than in the lean group, but was comparable with earlier studies conducted in pregnant women. The validity assessments suggest that the FFQ is a useful tool for ranking severely obese pregnant women according to the levels of their dietary intake.


Assuntos
Registros de Dieta , Comportamento Alimentar , Obesidade/metabolismo , Gravidez , Inquéritos e Questionários , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Avaliação Nutricional , Reprodutibilidade dos Testes , Escócia , Fatores Socioeconômicos , População Branca , Saúde da Mulher , Adulto Jovem
19.
Circ Cardiovasc Genet ; 5(6): 656-65, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23152477

RESUMO

BACKGROUND: Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. METHODS AND RESULTS: To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMT(mean), IMT(max), and IMT(mean-max)), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11,590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75 × 10(-7) for IMT(max); replication P=7.24×10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53 × 10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83 × 10(-4), n=82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). CONCLUSIONS: This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent.


Assuntos
Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/genética , Proteína Substrato Associada a Crk/genética , Loci Gênicos/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Fosfoproteínas/genética , Idoso , Alelos , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Fatores de Risco
20.
J Manipulative Physiol Ther ; 35(8): 600-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23158465

RESUMO

OBJECTIVE: The purpose of this study was to determine the efficacy of chiropractic manual therapy for infants with unexplained crying behavior and if there was any effect of parental reporting bias. METHODS: Infants with unexplained persistent crying (infant colic) were recruited between October 2007 and November 2009 at a chiropractic teaching clinic in the United Kingdom. Infants younger than 8 weeks were randomized to 1 of 3 groups: (i) infant treated, parent aware; (ii) infant treated, parent unaware; and (iii) infant not treated, parent unaware. The primary outcome was a daily crying diary completed by parents over a period of 10 days. Treatments were pragmatic, individualized to examination findings, and consisted of chiropractic manual therapy of the spine. Analysis of covariance was used to investigate differences between groups. RESULTS: One hundred four patients were randomized. In parents blinded to treatment allocation, using 2 or less hours of crying per day to determine a clinically significant improvement in crying time, the increased odds of improvement in treated infants compared with those not receiving treatment were statistically significant at day 8 (adjusted odds ratio [OR], 8.1; 95% confidence interval [CI], 1.4-45.0) and at day 10 (adjusted OR, 11.8; 95% CI, 2.1-68.3). The number needed to treat was 3. In contrast, the odds of improvement in treated infants were not significantly different in blinded compared with nonblinded parents (adjusted ORs, 0.7 [95% CI, 0.2-2.0] and 0.5 [95% CI, 0.1-1.6] at days 8 and 10, respectively). CONCLUSIONS: In this study, chiropractic manual therapy improved crying behavior in infants with colic. The findings showed that knowledge of treatment by the parent did not appear to contribute to the observed treatment effects in this study. Thus, it is unlikely that observed treatment effect is due to bias on the part of the reporting parent.


Assuntos
Cólica/terapia , Choro , Comportamento do Lactente , Manipulação Quiroprática/métodos , Cólica/diagnóstico , Intervalos de Confiança , Feminino , Humanos , Lactente , Masculino , Razão de Chances , Valores de Referência , Índice de Gravidade de Doença , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Reino Unido
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