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1.
Cogn Emot ; 37(6): 1132-1143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37337975

RESUMO

Sleep has a profound effect on our mood, but insight in the mechanisms underlying this association is still lacking. We tested whether emotion regulation is a mediator in the relationship between fragmented sleep and mood disturbance. The effect of fragmented sleep on the emotion regulation strategies, including cognitive reappraisal, distraction, acceptance and suppression ability, was assessed. We further tested whether the use of these strategies, as well as rumination and self-criticism, mediated the association between fragmented sleep and negative and positive affect. Participants (N = 69) wore an actiwatch and filled in a sleep diary for 12 consecutive nights. They had one control night and one sleep fragmentation night. Emotion regulation ability was assessed with an experimental task. Usage of emotion regulation strategies and negative and positive affect were assessed four times during the day with a survey after the control and sleep fragmentation night. Cognitive reappraisal, distraction, acceptance and suppression ability did not differ between the sleep fragmentation and control condition. However, participants reported higher usage of rumination and distraction after the sleep fragmentation night and rumination significantly mediated the negative association between fragmented sleep and negative affect.


Assuntos
Regulação Emocional , Humanos , Regulação Emocional/fisiologia , Privação do Sono/psicologia , Afeto/fisiologia , Sono , Emoções/fisiologia
2.
Behav Genet ; 49(3): 286-297, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30810878

RESUMO

The interrelations among well-being, neuroticism, and depression can be captured in a so-called well-being spectrum (3-phenotype well-being spectrum, 3-WBS). Several other human traits are likely linked to the 3-WBS. In the present study, we investigate how the 3-WBS can be expanded. First, we constructed polygenic risk scores for the 3-WBS and used this score to predict a series of traits that have been associated with well-being in the literature. We included information on loneliness, big five personality traits, self-rated health, and flourishing. The 3-WBS polygenic score predicted all the original 3-WBS traits and additionally loneliness, self-rated health, and extraversion (R2 between 0.62% and 1.58%). Next, using LD score regression, we calculated genetic correlations between the 3-WBS and the traits of interest. From all candidate traits, loneliness and self-rated health were found to have the strongest genetic correlations (rg = - 0.79, and rg= 0.64, respectively) with the 3-WBS. Lastly, we use Genomic SEM to investigate the factor structure of the proposed spectrum. The best model fit was obtained for a two-factor model including the 5-WBS traits, with two highly correlated factors representing the negative- and positive end of the spectrum. Based on these analyses we propose to include loneliness and self-rated health in the WBS and use a 5-phenotype well-being spectrum in future studies to gain more insight into the determinants of human well-being.


Assuntos
Herança Multifatorial/genética , Personalidade/genética , Qualidade de Vida/psicologia , Depressão , Extroversão Psicológica , Feminino , Estudos de Associação Genética/métodos , Envelhecimento Saudável , Humanos , Estilo de Vida , Solidão/psicologia , Masculino , Testes Neuropsicológicos , Neuroticismo , Fenótipo
3.
Behav Genet ; 49(3): 298, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30900060

RESUMO

In the original version of this article, unfortunately, in the acknowledgement section "National Institutes of Health (NIH, R37 AG033590-08) to J Cacioppo" was omitted. This has been corrected by publishing this erratum.

4.
Mol Psychiatry ; 23(9): 1911-1919, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28972577

RESUMO

Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies. In this largest-ever GWAS meta-analysis for nicotine dependence and the largest-ever cross-ancestry GWAS meta-analysis for any smoking phenotype, we reconfirmed the well-known CHRNA5-CHRNA3-CHRNB4 genes and further yielded a novel association in the DNA methyltransferase gene DNMT3B. The intronic DNMT3B rs910083-C allele (frequency=44-77%) was associated with increased risk of nicotine dependence at P=3.7 × 10-8 (odds ratio (OR)=1.06 and 95% confidence interval (CI)=1.04-1.07 for severe vs mild dependence). The association was independently confirmed in the UK Biobank (N=48,931) using heavy vs never smoking as a proxy phenotype (P=3.6 × 10-4, OR=1.05, and 95% CI=1.02-1.08). Rs910083-C is also associated with increased risk of squamous cell lung carcinoma in the International Lung Cancer Consortium (N=60,586, meta-analysis P=0.0095, OR=1.05, and 95% CI=1.01-1.09). Moreover, rs910083-C was implicated as a cis-methylation quantitative trait locus (QTL) variant associated with higher DNMT3B methylation in fetal brain (N=166, P=2.3 × 10-26) and a cis-expression QTL variant associated with higher DNMT3B expression in adult cerebellum from the Genotype-Tissue Expression project (N=103, P=3.0 × 10-6) and the independent Brain eQTL Almanac (N=134, P=0.028). This novel DNMT3B cis-acting QTL variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Tabagismo/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Alelos , População Negra/genética , DNA (Citosina-5-)-Metiltransferases/fisiologia , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Fumar/genética , População Branca/genética , DNA Metiltransferase 3B
5.
Mol Psychiatry ; 22(1): 82-88, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27021816

RESUMO

By running gene and pathway analyses for several smoking behaviours in the Tobacco and Genetics Consortium (TAG) sample of 74 053 individuals, 21 genes and several chains of biological pathways were implicated. Analyses were carried out using the HYbrid Set-based Test (HYST) as implemented in the Knowledge-based mining system for Genome-wide Genetic studies software. Fifteen genes are novel and were not detected with the single nucleotide polymorphism-based approach in the original TAG analysis. For quantity smoked, 14 genes passed the false discovery rate of 0.05 (corrected for multiple testing), with the top association signal located at the IREB2 gene (P=1.57E-37). Three genomic loci were significantly associated with ever smoked. The top signal is located at the noncoding antisense RNA transcript BDNF-AS (P=6.25E-07) on 11p14. The SLC25A21 gene (P=2.09E-08) yielded the top association signal in the analysis of smoking cessation. The 19q13 noncoding RNA locus exceeded the genome-wide significance in the analysis of age at initiation (P=1.33E-06). Pathways belonging to the Neuronal system pathways, harbouring the nicotinic acetylcholine receptor genes expressing the α (CHRNA 1-9), ß (CHRNB 1-4), γ, δ and ɛ subunits, yielded the smallest P-values in the pathway analysis of the quantity smoked (lowest P=4.90E-42). Additionally, pathways belonging to 'a subway map of cancer pathways' regulating the cell cycle, mitotic DNA replication, axon growth and synaptic plasticity were found significantly enriched for genetic variants in ever smokers relative to never smokers (lowest P=1.61E-07). In addition, these pathways were also significantly associated with the quantity smoked (lowest P=4.28E-17). Our results shed light on one of the world's leading causes of preventable death and open a path to potential therapeutic targets. These results are informative in decoding the biological bases of other disease traits, such as depression and cancers, with which smoking shares genetic vulnerabilities.


Assuntos
Fumar/genética , Uso de Tabaco/genética , Feminino , Predisposição Genética para Doença/genética , Variação Genética/genética , Genoma , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Proteína 2 Reguladora do Ferro/genética , Masculino , Proteínas de Transporte da Membrana Mitocondrial/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Nicotínicos/genética , Fumar/psicologia , Abandono do Hábito de Fumar , Nicotiana , Tabagismo/genética
6.
Behav Genet ; 46(3): 378-88, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26324285

RESUMO

Maternal smoking during pregnancy (SDP) is associated with increased risk of externalizing and internalizing behaviors in offspring. Two explanations (not mutually exclusive) for this association are direct causal effects of maternal SDP and the effects of genetic and environmental factors common to parents and offspring which increase smoking as well as problem behaviors. Here, we examined the associations between parental SDP and mother rated offspring externalizing and internalizing behaviors (rated by the Child Behavior Checklist/2-3) at age three in a population-based sample of Dutch twins (N = 15,228 pairs). First, as a greater effect of maternal than of paternal SDP is consistent with a causal effect of maternal SDP, we compared the effects of maternal and paternal SDP. Second, as a beneficial effect of quitting smoking before pregnancy is consistent with the causal effect, we compared the effects of SDP in mothers who quit smoking before pregnancy, and mothers who continued to smoke during pregnancy. All mothers were established smokers before their pregnancy. The results indicated a greater effect of maternal SDP, compared to paternal SDP, for externalizing, aggression, overactive and withdrawn behavior. Quitting smoking was associated with less externalizing, overactive behavior, aggression, and oppositional behavior, but had no effect on internalizing, anxious depression, or withdrawn behavior. We conclude that these results are consistent with a causal, but small, effect of smoking on externalizing problems at age 3. The results do not support a causal effect of maternal SDP on internalizing behaviors.


Assuntos
Transtornos do Comportamento Infantil/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Criança , Feminino , Humanos , Masculino , Fenótipo , Gravidez , Análise de Regressão , Gêmeos
7.
Behav Genet ; 46(3): 304-14, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26410687

RESUMO

There are three types of monozygotic (MZ) twins. MZ twins can either share one chorion and one amnion, each twin can have its own amnion, or MZ twins can-like dizygotic twins-each have their own chorion and amnion. Sharing the same chorion may create a more similar/dissimilar prenatal environment and bias heritability estimates, but most twin studies do not distinguish between these three types of MZ twin pairs. The aim of this paper is to investigate the effect of chorion sharing on the similarity within MZ twin pairs for a large number of traits. Information on chorion status was obtained for the Netherlands twin register (NTR) by linkage to the records from the database of the dutch pathological anatomy national automated archive (PALGA). Record linkage was successful for over 9000 pairs. Effect of chorion type was tested by comparing the within-pair similarity between monochorionic (MC) and dichorionic (DC) MZ twins on 66 traits including weight, height, motor milestones, child problem behaviors, cognitive function, wellbeing and personality. For only 10 traits, within-pair similarity differed between MCMZ and DCMZ pairs. For traits influenced by birth weight (e.g. weight and height in young children) we expected that MC twins would be more discordant. This was found for 5 out of 13 measures. When looking at traits where blood supply is important, we saw MCMZ twins to be more concordant than DCMZ's for 3 traits. We conclude that the influence on the MZ twin correlation of the intra-uterine prenatal environment, as measured by sharing a chorion type, is small and limited to a few phenotypes. This implies that the assumption of equal prenatal environment of mono- and DC MZ twins, which characterizes the classical twin design, is largely tenable.


Assuntos
Córion/fisiologia , Padrões de Herança/genética , Estudos em Gêmeos como Assunto , Gêmeos/genética , Feminino , Humanos , Masculino , Gravidez
8.
Mol Psychiatry ; 20(10): 1232-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25469926

RESUMO

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.


Assuntos
Dissonias/genética , Sono/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Autorrelato , População Branca/genética
9.
Ultrasound Obstet Gynecol ; 46(6): 718-23, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25652890

RESUMO

OBJECTIVE: Although cerclage has been shown to reduce the risk of recurrent preterm birth in a high-risk patient population, the mechanism by which this occurs is not well understood. Our objective was to evaluate whether cerclage affects the rate of cervical shortening taking into account exposure to 17-hydroxyprogesterone and vaginal progesterone. METHODS: This was a retrospective cohort study of women who had serial cervical length measurements due to a history of spontaneous preterm delivery. Demographic data, obstetric history, progesterone administration, delivery information and serial cervical length measurements were collected. The rate of cervical shortening was compared in women with and without cerclage. Subgroup analyses were performed to compare rates of cervical shortening by indication for cerclage (history indicated vs ultrasound indicated) and outcome in the current pregnancy (cerclage vs no cerclage among those who delivered preterm). RESULTS: A total of 414 women were included of whom 32.4% (n = 134) had a cerclage. There was no difference in the rate of cervical shortening between the cerclage (0.8 mm/week) and no-cerclage (1.0 mm/week, P = 0.43) groups. The rates of cervical shortening among history-indicated and ultrasound-indicated cerclage groups were similar (0.9 vs 1.3 mm/week, respectively, P = 0.2). Among patients with a preterm delivery in the index pregnancy, the rates of cervical shortening among those with (1.31 mm/week) and without (1.28 mm/week, P = 0.78) cerclage were also similar. CONCLUSION: Cervical shortening among women with cerclage occurs at a similar rate to that among women without a cerclage, regardless of indication for cerclage or pregnancy outcome.


Assuntos
Cerclagem Cervical/efeitos adversos , Medida do Comprimento Cervical , Colo do Útero/diagnóstico por imagem , Trabalho de Parto Prematuro/prevenção & controle , Incompetência do Colo do Útero/cirurgia , 17-alfa-Hidroxiprogesterona/administração & dosagem , Adulto , Colo do Útero/cirurgia , Feminino , Humanos , Trabalho de Parto Prematuro/diagnóstico por imagem , Trabalho de Parto Prematuro/etiologia , Gravidez , Resultado da Gravidez , Gravidez de Alto Risco , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Progesterona/análise , Estudos Retrospectivos , Incompetência do Colo do Útero/diagnóstico por imagem , Vagina/química , Vagina/diagnóstico por imagem
10.
J Eur Acad Dermatol Venereol ; 29(12): 2349-55, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26337069

RESUMO

BACKGROUND: Topical therapies are the mainstay of treatment for psoriasis vulgaris. The fixed combination of calcipotriol (Cal) 50 µg/g plus betamethasone 0.5 mg/g (as dipropionate; BD) is a first-line topical treatment and available as a gel or ointment. The use of these fixed combination products was compared in PRO-long, a long-term noninterventional study, for which interim results (4 and 12 weeks) have previously been reported. OBJECTIVE: To describe and compare patients' perspectives on the fixed combination gel and ointment formulations; to include efficacy, adherence behaviour, treatment satisfaction and health-related quality of life (HRQoL) aspects during long-term real-life psoriasis management. METHODS: PRO-long was a multicentre, prospective, observational, 52-week study of patients prescribed fixed combination Cal/BD gel or ointment in clinical practice. For final analysis the following were assessed at weeks 24, 36 and 52: differences in the proportion of patients with 'mild'/'very mild' disease according to patient's global assessment of disease severity, adherence behaviour, treatment satisfaction (nine-item treatment satisfaction questionnaire for medication) and HRQoL (Skindex-29). RESULTS: Patients (n = 328) were prescribed once-daily Cal/BD gel (n = 152) or ointment (n = 176). At week 52, a higher proportion of patients reported that the severity of their psoriasis was 'mild'/'very mild' vs. baseline (gel: 60.2 vs. 47.1%; ointment: 58.8 vs. 42.4%), with greater treatment satisfaction reported in patients using gel vs. those using ointment. A higher proportion of patients found the gel 'easy' to use compared with the ointment (66.7 vs. 45.2%). Daily application of treatment took ≤ 5 min for 86.1% of patients using gel and 71.0% of patients using ointment. CONCLUSION: This real-life study has demonstrated similar effectiveness between the Cal/BD formulations. However, over a 52-week treatment period, patients reported greater treatment satisfaction with the gel, which was considered easier to use, faster to apply and overall a more convenient product.


Assuntos
Anti-Inflamatórios/administração & dosagem , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Betametasona/administração & dosagem , Calcitriol/administração & dosagem , Criança , Combinação de Medicamentos , Feminino , Géis , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Pomadas , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
11.
Psychol Med ; 44(12): 2673-83, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24957628

RESUMO

BACKGROUND: Cross-sectional and longitudinal studies have shown a positive association between attention deficit hyperactivity disorder (ADHD) and problematic alcohol use in adults. To what extent this association is explained by genetic and environmental factors is largely unknown. METHOD: Data on ADHD and alcohol consumption were collected by self-report in 6024 adult Dutch twins. ADHD symptoms were assessed by three subscales of the Conners' Adult ADHD Rating Scales - Self-Report: Screening Version (CAARS-S:SV): inattentiveness, hyperactivity and the ADHD index (ADHD-I). Problem drinking was defined as at least two self-reported alcohol-related problems on the CAGE questionnaire. Structural equation modelling was applied to the bivariate twin data to estimate genetic and environmental influences. RESULTS: Heritability of ADHD symptoms ranged between 32% and 40% and heritability of problem drinking was 50%. The positive correlation between ADHD symptoms and problem drinking was confirmed in this general population sample, with phenotypic correlations between 0.20 and 0.28 and genetic correlations between 0.39 and 0.50. Phenotypic correlations are primarily (61-100%) explained by genetic influences with non-shared environmental influences explaining the remaining covariance. No significant quantitative or qualitative gender differences in covariance structure were found. CONCLUSIONS: This study convincingly shows that ADHD symptoms and problem drinking are moderately but significantly correlated in adults and that genetic correlations are primarily underlying this association. This suggests that early interventions are required to prevent adolescents with ADHD from developing problematic levels of alcohol use. Furthermore, clinicians who treat alcohol-dependent patients should be aware that the patient may have a co-morbid condition of ADHD; integrated interventions are required.


Assuntos
Transtornos Relacionados ao Uso de Álcool/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Doenças em Gêmeos/genética , Adulto , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos Relacionados ao Uso de Álcool/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Comorbidade , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/etiologia , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Autorrelato
12.
J Eur Acad Dermatol Venereol ; 28(12): 1723-31, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24533503

RESUMO

BACKGROUND: Psoriasis is most often treated using topical therapies such as the once-daily fixed combination of calcipotriol and betamethasone dipropionate, which is available as a gel and an ointment. To date, there have been no direct comparisons of patient perspectives on the two formulations. OBJECTIVE: To describe and compare patients' perspectives on calcipotriol and betamethasone gel and ointment formulations, including real-life effectiveness, adherence behaviour, treatment satisfaction and health-related quality of life (QoL), during long-term psoriasis vulgaris management, according to interim findings from the PRO-long study. METHODS: PRO-long is a multicentre, prospective, observational, 52-week cohort study in patients prescribed fixed-combination calcipotriol (50 µg/g) and betamethasone (0.5 mg/g; as dipropionate) gel or ointment for long-term psoriasis management. Difference in effectiveness at 4 and 12 weeks was assessed by comparing the proportion of patients with controlled (mild or very mild) disease, according to the Patient's Global Assessment. Additional patient questionnaires were used to assess adherence behaviour, treatment satisfaction (nine-item Treatment Satisfaction Questionnaire for Medication) and health-related QoL (Skindex-29). RESULTS: A total of 156 patients were included in the analysis. In single items of the adherence behaviour and treatment satisfaction questionnaires, patients preferred the gel over the ointment as convenient, easy to use and fast to apply. Post hoc analysis demonstrated significant differences between gel and ointment for convenience and application time. More patients had controlled disease at week 12 with gel (71.9%) vs. ointment (65.7%); however, the difference was not statistically significant (primary end point; P = 0.40). CONCLUSION: This interim analysis supports fixed-combination calcipotriol and betamethasone gel as more convenient, easier to use and faster to apply than the ointment formulation in real-life conditions according to patients with psoriasis vulgaris. Furthermore, a numerical difference in patient-reported real-life effectiveness was seen in favour of the gel, although this was not statistically significant.


Assuntos
Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Betametasona/administração & dosagem , Betametasona/uso terapêutico , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Esquema de Medicação , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Satisfação do Paciente , Estudos Prospectivos , Psoríase/fisiopatologia , Psoríase/psicologia , Qualidade de Vida , Adulto Jovem
13.
Mol Psychiatry ; 17(11): 1116-29, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21876539

RESUMO

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).


Assuntos
Moléculas de Adesão Celular/genética , Café/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Ingestão de Líquidos/genética , Estudo de Associação Genômica Ampla/métodos , Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Cafeína/farmacologia , Linhagem Celular , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/genética , Humanos , Masculino , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , População Branca/genética
14.
J Microsc ; 249(2): 124-35, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23252774

RESUMO

In traditional cancer diagnosis, (histo)pathological images of biopsy samples are visually analysed by pathologists. However, this judgment is subjective and leads to variability among pathologists. Digital scanners may enable automated objective assessment, improved quality and reduced throughput time. Nucleus detection is seen as the corner stone for a range of applications in automated assessment of (histo)pathological images. In this paper, we propose an efficient nucleus detector designed with machine learning. We applied colour deconvolution to reconstruct each applied stain. Next, we constructed a large feature set and modified AdaBoost to create two detectors, focused on different characteristics in appearance of nuclei. The proposed modification of AdaBoost enables inclusion of the computational cost of each feature during selection, thus improving the computational efficiency of the resulting detectors. The outputs of the two detectors are merged by a globally optimal active contour algorithm to refine the border of the detected nuclei. With a detection rate of 95% (on average 58 incorrectly found objects per field-of-view) based on 51 field-of-view images of Her2 immunohistochemistry stained breast tissue and a complete analysis in 1 s per field-of-view, our nucleus detector shows good performance and could enable a range of applications in automated assessment of (histo)pathological images.


Assuntos
Núcleo Celular/ultraestrutura , Histocitoquímica/métodos , Processamento de Imagem Assistida por Computador/métodos , Microscopia/métodos , Inteligência Artificial , Automação/métodos , Humanos , Imuno-Histoquímica/métodos , Neoplasias/diagnóstico
15.
J Microsc ; 250(3): 166-78, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23550616

RESUMO

Malaria is a worldwide health problem with 225 million infections each year. A fast and easy-to-use method, with high performance is required to differentiate malaria from non-malarial fevers. Manual examination of blood smears is currently the gold standard, but it is time-consuming, labour-intensive, requires skilled microscopists and the sensitivity of the method depends heavily on the skills of the microscopist. We propose an easy-to-use, quantitative cartridge-scanner system for vision-based malaria diagnosis, focusing on low malaria parasite densities. We have used special finger-prick cartridges filled with acridine orange to obtain a thin blood film and a dedicated scanner to image the cartridge. Using supervised learning, we have built a Plasmodium falciparum detector. A two-step approach was used to first segment potentially interesting areas, which are then analysed in more detail. The performance of the detector was validated using 5,420 manually annotated parasite images from malaria parasite culture in medium, as well as using 40 cartridges of 11,780 images containing healthy blood. From finger prick to result, the prototype cartridge-scanner system gave a quantitative diagnosis in 16 min, of which only 1 min required manual interaction of basic operations. It does not require a wet lab or a skilled operator and provides parasite images for manual review and quality control. In healthy samples, the image analysis part of the system achieved an overall specificity of 99.999978% at the level of (infected) red blood cells, resulting in at most seven false positives per microlitre. Furthermore, the system showed a sensitivity of 75% at the cell level, enabling the detection of low parasite densities in a fast and easy-to-use manner. A field trial in Chittagong (Bangladesh) indicated that future work should primarily focus on improving the filling process of the cartridge and the focus control part of the scanner.


Assuntos
Automação Laboratorial/métodos , Processamento de Imagem Assistida por Computador/métodos , Malária Falciparum/diagnóstico , Microscopia/métodos , Parasitemia/diagnóstico , Parasitologia/métodos , Plasmodium falciparum/citologia , Bangladesh , Plasmodium falciparum/isolamento & purificação , Sensibilidade e Especificidade
17.
Tijdschr Psychiatr ; 55(8): 585-97, 2013.
Artigo em Holandês | MEDLINE | ID: mdl-23964004

RESUMO

BACKGROUND: Early alcohol initiation is strongly associated with increased alcohol consumption and alcohol abuse/dependence in adulthood. The mechanisms that underlie this association are unclear. AIM: To examine whether there is a causal link between early alcohol initiation and later alcohol consumption. METHOD: Survey data were collected from twin pairs (age range 18-80) included in the Netherlands Twin Register (NTR). A discordant twin design was used to examine the origin of the link between early alcohol initiation and adult alcohol consumption. Within monozygotic pairs (82-143 pairs), twins who started drinking early were compared to their brother/sister who started drinking later, on frequency of alcohol use, weekly alcohol consumption, number of alcohol intoxications, excessive drinking, alcohol abuse/-dependence, and hazardous drinking. By drawing comparisons within monozygotic pairs, we were able to control for the effects of genes/shared environment. Additional analyses examined the effects of age, sex, and in-/exclusion of lifelong abstainers. RESULTS: Within monozygotic twin pairs, the twin who had started drinking early did not differ significantly from his/her brother/sister with respect to future alcohol consumption. Results were independent of age, sex, and in-/exclusion of lifelong abstainers. CONCLUSION: Early alcohol initiation did not have significant causal effects on subsequent alcohol consumption in adulthood and may be an indicator of a predisposition for alcohol consumption. Campaigns aimed at raising the minimum age for alcohol initiation will possibly have only a limited effect on adult alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Gêmeos Monozigóticos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/epidemiologia , Alcoolismo/etiologia , Alcoolismo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fatores de Risco , Meio Social , Adulto Jovem
20.
J Small Anim Pract ; 63(10): 776-783, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35840129

RESUMO

OBJECTIVES: To report the clinical presentation, complications, and long-term outcomes of cats treated for perineal hernia with modified internal obturator muscle transposition. METHODS: The medical records of cats surgically treated for perineal hernia between 2013 and 2019 were reviewed and an owner questionnaire was conducted to determine long-term outcome. RESULTS: Thirty-six cats were included in the study: 34 had bilateral and two unilateral hernias. Of these 36, 24 (67%) were male neutered with a median age of 10 (range: 1 to 18) years. The complication rate was low, however, one cat experienced a major postoperative complication: rectal prolapse requiring revision surgery 48 hours postsurgery. Short-term outcomes were available for 32 of 36 (89%) cats. Of the 32, 23 were examined 6 weeks postoperatively, and a telephonic consultation was performed for an additional nine of 32. Of the 23 cats examined directly, none had recurrence. Overall 12 of 32 experienced short-term postoperative tenesmus which resolved in nine of 12 (75%). Long-term outcomes were available for 31 of 36 cats (86%), with a median of 18.5 (6 to 89) months follow-up. A good outcome was achieved in 23 of 31 (74%) whereas three of 31 (10%) had fair outcomes and five of 31 (16%) had a poor outcome. Of the five cats with a poor outcome, two required subtotal colectomy to manage clinical signs related to megacolon, two were euthanised following a return of clinical signs, and one developed unilateral recurrence. CLINICAL SIGNIFICANCE: Perineal hernia should be considered in cats presenting with tenesmus or recurrent obstipation. Surgical treatment of perineal hernias in cats can result in good owner-assessed long-term outcome.


Assuntos
Doenças do Gato , Hérnia Abdominal , Animais , Doenças do Gato/cirurgia , Gatos , Colectomia/veterinária , Feminino , Hérnia Abdominal/veterinária , Herniorrafia/veterinária , Masculino , Complicações Pós-Operatórias/veterinária , Estudos Retrospectivos , Resultado do Tratamento
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