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BACKGROUND: The relationship between smoking and suicide remains controversial. METHOD: A total of 16 282 twin pairs born before 1958 in Finland and alive in 1974 were queried with detailed health and smoking questionnaires in 1975 and 1981, with response rates of 89% and 84%. Smoking status and dose, marital, employment, and socio-economic status, and indicators of psychiatric and somatic illness were assessed at both time points. Emergent psychiatric and medical illness and vital status, including suicide determined by forensic autopsy, were evaluated over 35-year follow-up through government registries. The association between smoking and suicide was determined in competing risks hazard models. In twin pairs discordant for smoking and suicide, the prospective association between smoking and suicide was determined using a matched case-control design. RESULTS: Smokers had a higher cumulative suicide incidence than former or never smokers. Heavy smokers had significantly higher suicide risk [hazard ratio (HR) 3.47, 95% confidence interval (CI) 2.31-5.22] than light smokers (HR 2.30, 95% CI 1.61-3.23) (p = 0.017). Compared with never smokers, smokers, but not former smokers, had increased suicide risk (HR 2.56, 95% CI 1.43-4.59), adjusting for depressive symptoms, alcohol and sedative-hypnotic use, and excluding those who developed serious somatic or psychiatric illness. In twin pairs discordant for smoking and suicide, suicide was more likely in smokers [odds ratio (OR) 6.0, 95% CI 2.06-23.8]. CONCLUSIONS: Adults who smoked tobacco were more likely to die by suicide, with a large, dose-dependent effect. This effect remained after consideration of many known predictors of suicide and shared familial effects, consistent with the hypothesis that exposure to tobacco smoke increases the risk of suicide.
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Fumar Cigarrillos/epidemiología , Sistema de Registros/estadística & datos numéricos , Suicidio/estadística & datos numéricos , Adolescente , Adulto , Anciano , Fumar Cigarrillos/efectos adversos , Femenino , Finlandia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Riesgo , Adulto JovenRESUMEN
BACKGROUND: Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness. METHOD: The analysis sample included 24 436 twins aged 40-90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms. RESULTS: Women reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2 s.d. above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness. CONCLUSIONS: Findings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.
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Depresión/etiología , Depresión/genética , Interacción Gen-Ambiente , Estado de Salud , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Depresión/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Escandinavos y Nórdicos/epidemiología , Factores SexualesRESUMEN
Because sustained physical activity is important for a healthy life, this paper examined whether a greater diversity of sport activities during adolescence predicts higher levels of leisure-time physical activity (LTPA) in adulthood. From sport activity participation reported by 17-year-old twins, we formed five groups: 1, 2, 3, 4, and 5+ different sport activities. At follow-up in their mid-thirties, twins were divided into four activity classes based on LTPA, including active commuting. Multinomial regression analyses, adjusted for several confounders, were conducted separately for male (N=1288) and female (N=1770) participants. Further, conditional logistic regression analysis included 23 twin pairs discordant for both diversity of sport activities in adolescence and LTPA in adulthood. The diversity of leisure-time sport activities in adolescence had a significant positive association with adulthood LTPA among females. Membership in the most active adult quartile, compared to the least active quartile, was predicted by participation in 2, 3, 4, and 5+ sport activities in adolescence with odds ratios: 1.52 (P=.11), 1.86 (P=.02), 1.29 (P=.39), and 3.12 (P=5.4e-05), respectively. Within-pair analyses, limited by the small sample of twins discordant for both adolescent activities and adult outcomes, did not replicate the association. A greater diversity of leisure-time sport activities in adolescence predicts higher levels of LTPA in adulthood in females, but the causal nature of this association remains unresolved.
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Ejercicio Físico , Actividades Recreativas , Deportes , Adolescente , Adulto , Femenino , Finlandia , Humanos , Estudios Longitudinales , Masculino , Adulto JovenRESUMEN
Smoking is a major risk factor for several somatic diseases and is also emerging as a causal factor for neuropsychiatric disorders. Genome-wide association (GWA) and candidate gene studies for smoking behavior and nicotine dependence (ND) have disclosed too few predisposing variants to account for the high estimated heritability. Previous large-scale GWA studies have had very limited phenotypic definitions of relevance to smoking-related behavior, which has likely impeded the discovery of genetic effects. We performed GWA analyses on 1114 adult twins ascertained for ever smoking from the population-based Finnish Twin Cohort study. The availability of 17 smoking-related phenotypes allowed us to comprehensively portray the dimensions of smoking behavior, clustered into the domains of smoking initiation, amount smoked and ND. Our results highlight a locus on 16p12.3, with several single-nucleotide polymorphisms (SNPs) in the vicinity of CLEC19A showing association (P<1 × 10(-6)) with smoking quantity. Interestingly, CLEC19A is located close to a previously reported attention-deficit hyperactivity disorder (ADHD) linkage locus and an evident link between ADHD and smoking has been established. Intriguing preliminary association (P<1 × 10(-5)) was detected between DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) ND diagnosis and several SNPs in ERBB4, coding for a Neuregulin receptor, on 2q33. The association between ERBB4 and DSM-IV ND diagnosis was replicated in an independent Australian sample. Recently, a significant increase in ErbB4 and Neuregulin 3 (Nrg3) expression was revealed following chronic nicotine exposure and withdrawal in mice and an association between NRG3 SNPs and smoking cessation success was detected in a clinical trial. ERBB4 has previously been associated with schizophrenia; further, it is located within an established schizophrenia linkage locus and within a linkage locus for a smoker phenotype identified in this sample. In conclusion, we disclose novel tentative evidence for the involvement of ERBB4 in ND, suggesting the involvement of the Neuregulin/ErbB signalling pathway in addictions and providing a plausible link between the high co-morbidity of schizophrenia and ND.
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Comportamiento de Búsqueda de Drogas , Fenotipo , Fumar/genética , Fumar/psicología , Tabaquismo/genética , Tabaquismo/psicología , Estudios de Cohortes , Familia , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Receptor ErbB-4/genética , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genéticaRESUMEN
Disbudding causes pain-related distress and behavioral changes in calves. Local anesthesia and non-steroidal anti-inflammatory drugs are effective for treating disbudding-related pain. Dairy producers play a key role in whether or not calves to be disbudded are properly medicated. Pain and distress related to disbudding of calves often remains untreated. Thus, we conducted this study to characterize perceptions and practices of dairy producers on disbudding and disbudding-related pain management. A questionnaire was sent to 1,000 randomly selected Finnish dairy producers (response rate: 45%). Our aim was to investigate producer perceptions about disbudding-related pain, the perceived need for pain alleviation before disbudding, and how these perceptions affect the valuing and use of pain alleviation before disbudding. More than 70% of Finnish dairy farms disbud their calves. Producers who ranked disbudding-related pain and need for pain alleviation higher called a veterinarian to medicate calves before disbudding more often than producers who ranked disbudding pain and need for pain alleviation lower. Among respondents who disbudded calves on their farms, 69% stated that disbudding caused severe pain, 63% stated that pain alleviation during disbudding is important, and 45% always had a veterinarian medicate their calves before disbudding. Producers with a herd healthcare agreement with their veterinarian estimated disbudding-related pain to be higher and had a veterinarian medicate calves more often than producers without such an agreement. Producers with tiestall systems and producers who did not use disbudding valued pain alleviation prior to disbudding higher than producers with freestalls and producers who used disbudding.
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Bienestar del Animal , Bovinos/fisiología , Industria Lechera/normas , Cuernos/cirugía , Manejo del Dolor/veterinaria , Veterinarios , Anestesia Local/veterinaria , Crianza de Animales Domésticos/métodos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Conducta Animal , Industria Lechera/métodos , Finlandia , Humanos , Leche/metabolismo , Dolor/prevención & control , Dolor/veterinaria , Encuestas y CuestionariosRESUMEN
Objectives: To investigate the longitudinal trends of decompressive craniectomy (DC) following traumatic brain injury (TBI) or stroke and explore whether the timing of cranial reconstruction affected revision or removal rates using Hospital Episode Statistics (HES) between 2014 and 2019. Design: Retrospective observational cohort study using HES. The time frame definitions mirror those often used in clinical practice. Setting: HES data from neurosurgical centres in England. Participants: HES data related to decompressive craniectomy procedures and cranioplasty following TBI or stroke between 2014 and 2019. Main outcome measures: The primary outcome was the timing and rate of revision/removal compared with cranioplasty within <12 weeks to ≥12 weeks. Results: There were 4627 DC procedures, of which 1847 (40%) were due to head injury, 1116 (24%) were due to stroke, 728 (16%) were due to other cerebrovascular diagnoses, 317 (7%) had mixed diagnosis and 619 (13%) had no pre-specified diagnoses. The number of DC procedures performed per year ranged from 876 in 2014-2015 to 967 in 2018-2019. There were 4466 cranioplasty procedures, with 309 (7%) revisions and/or removals during the first postoperative year. There was a 33% increase in the overall number of cranioplasty procedures performed within 12 weeks, and there were 1823 patients who underwent both craniectomy and cranioplasty during the study period, with 1436 (79%) having a cranioplasty within 1 year. However, relating to the timing of cranial reconstruction, there was no evidence of any difference in the rate of revision or removal surgery in the early timing group (6.5%) compared with standard care (7.9%) (adjusted HR 0.93, 95% CIs 0.61 to 1.43; p=0.75). Conclusions: Overall number of craniectomies and the subsequent requirements for cranioplasty increased steadily during the study period. However, relating to the timing of cranial reconstruction, there was no evidence of an overall difference in the rate of revision or removal surgery in the early timing group.
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In 2009, the number of foodborne norovirus outbreaks in Finland seemed markedly high, and many outbreaks seemed to be linked to imported frozen raspberries. We reviewed the data regarding all notified foodborne outbreaks in 2009 in Finland in order to assess the magnitude of the problem and to summarize the information on raspberry-linked outbreaks. Between March and August, 13 norovirus outbreaks affecting about 900 people could be linked to imported frozen raspberries. Two raspberry samples corresponding to two batches of raspberries were positive for norovirus. These two batches proved to have been the likely source in six of the 13 outbreaks. Analytical studies had not been conducted for six outbreaks, and virological test results were inconclusive in two. However, combining epidemiological and microbiological methods often enabled finding the source, as exemplified in investigation of a large school outbreak. To ensure prompt control measures in similar situations in the future, both aspects of outbreak investigations should be strengthened.
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Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Alimentos Congelados/virología , Frutas/virología , Gastroenteritis/epidemiología , Norovirus/aislamiento & purificación , Rosaceae/virología , Infecciones por Caliciviridae/virología , Heces/virología , Finlandia/epidemiología , Microbiología de Alimentos , Gastroenteritis/virología , Humanos , Incidencia , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
AIMS: To study the bidirectional relationships between life satisfaction (LS) and alcohol use. METHODS: Health questionnaires were administered in 1975, 1981 and 1990 to a population-based sample of healthy Finnish twins aged 18-45 at baseline (n = 14,083). These included a LS scale and three indicators for adverse alcohol use: binge drinking, passing out and high consumption (women/men ≥400/800 g/month). In longitudinal analyses, logistic regression, pair-wise case-control analyses and growth models were applied. RESULTS: All alcohol indicators increased the age-adjusted risk of becoming dissatisfied regardless of study period [binge drinking odds ratio (OR)(1975-1990 )= 1.29; 95% confidence interval (CI) 1.12-1.50; high consumption OR(1975-1990 )= 1.60; 1.29-1.99 and passing out OR(1981-1990 )= 2.01; 1.57-2.57]. Also, the dissatisfied had an increased subsequent risk for adverse alcohol use. The risk for passing out due to drinking (OR(1975-1990 )= 1.50; 1.22-1.86) was increased regardless of study period, while high consumption (OR(1975-1981 )= 1.97; 1.40-2.77; OR(1981-1990 )= 2.48; 1.50-4.12) and binge drinking (OR(1975-1981 )= 1.37; 1.12-1.67) showed some variation by the study period. Predictions remained after multiple adjustments. Longitudinally, high consumption predicted dissatisfaction somewhat more strongly than vice versa. The change/levels within the whole range of LS and alcohol consumption were only slightly associated in the entire study population. CONCLUSION: Life dissatisfaction and adverse alcohol use reciprocally predict each other prospectively. The heavier the alcohol use the stronger the relationship.
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Consumo de Bebidas Alcohólicas/psicología , Modelos Estadísticos , Satisfacción Personal , Gemelos/psicología , Adolescente , Adulto , Femenino , Finlandia , Estudios de Seguimiento , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , AutoinformeRESUMEN
No previous studies on the association of smoking behaviour with disability retirement due to register verified chronic obstructive pulmonary disease (COPD) exist. This 30-yr follow-up study examined how strongly aspects of cigarette smoking predict disability retirement due to COPD. The study population consisted of 24,043 adult Finnish twins (49.7% females) followed from 1975 to 2004. At baseline the participants had responded to a questionnaire. Information on retirement was obtained from the Finnish pension registers. Smoking strongly predicted disability retirement due to COPD. In comparison to never-smokers, age adjusted hazard ratio (HR) for current smokers was 22.0 (95% CI 10.0-48.5) and for smokers with ≥ 12 pack-yrs was 27.3 (95% CI 12.6-59.5). Similar estimates of risk were observed in within-pair analyses of twin pairs discordant for disability retirement due to COPD. Among discordant monozygotic pairs those with disability pension due to COPD were more often current smokers. The effect of early smoking onset (< 18 yrs) on the risk of disability retirement due to COPD remained after adjustment for the amount smoked (HR 1.70, 95% CI 1.08-2.68). Smoking strongly predicts disability retirement due to COPD. Preventive measures against disability retirement and other harmful consequences of tobacco smoking should receive greater emphasis.
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Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Fumar , Adulto , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/etiología , RiesgoRESUMEN
UNLABELLED: In this prospective study, 87 children were followed up from birth to 14 months with data on maternal vitamin D status during the pregnancy. Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. INTRODUCTION: Intrauterine nutritional deficits may have permanent consequences despite improved nutritional status postnatally. We evaluated the role of prenatal and postnatal vitamin D status on bone parameters in early infancy. METHODS: Eighty-seven children were followed from birth to 14 months. Background data were collected with a questionnaire and a 3-day food record. At 14 months bone variables were measured with peripheral computed tomography (pQCT) from the left tibia. Serum 25-OHD and bone turnover markers were determined. Findings were compared with maternal vitamin D status during pregnancy. RESULTS: The children were divided into two groups based on vitamin D status during pregnancy. Despite discrepant S-25-OHD at baseline (median 36.3 vs. 52.5 nmol/l, p < 0.001), the values at 14 months were similar (63 vs. 66 nmol/l, p = 0.58) in Low D and High D. Serum 25-OHD increased more in Low D (p < 0.001) despite similar total intake of vitamin D (mean 12.3 µg/day). In Low D, tibial bone mineral content (BMC) was lower at birth but BMC gain was greater (multivariate analysis of variance [MANOVA]; p = 0.032) resulting in similar BMC at 14 months in the two groups. In High D, tibial total bone cross-sectional area was higher at baseline; the difference persisted at 14 months (MANOVA; p = 0.068). Bone mineral density (BMD) and ΔBMD were similar in the two groups. CONCLUSIONS: Postnatal vitamin D supplementation improved vitamin D status but only partly eliminated the differences in bone variables induced by maternal vitamin D status during the fetal period. Further attention should be paid to improving vitamin D status during pregnancy.
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Desarrollo Óseo/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Tibia/crecimiento & desarrollo , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitaminas/uso terapéutico , Densidad Ósea , Dieta , Suplementos Dietéticos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , Tibia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Vitamina D/uso terapéuticoRESUMEN
BACKGROUND: Clinically ascertained reports suggest that boys and girls with attention deficit hyperactivity disorder (ADHD) may differ from each other in their vulnerability to substance use problems. METHOD: A total of 1545 Finnish adolescents were assessed for DSM-IV-based ADHD symptoms by their parents and classroom teachers using standardized rating scales at age 11-12 years. At age 14, substance use disorders and psychiatric co-morbidity were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism, providing DSM-III-R/DSM-IV diagnoses for Axis I disorders. At age 17.5, substance use was assessed by multi-item questionnaire. RESULTS: Although baseline ADHD symptoms were less common among females, they were more predictive of adverse substance use outcomes once conduct disorder and previous substance use were controlled for. Only in females were baseline ADHD symptoms significant predictors of alcohol abuse and dependence and illicit drug use at age 14. At the age of 17.5, parents' reports of inattentiveness and hyperactivity were significant predictors for frequent alcohol use in both sexes, but they were more predictive of frequent alcohol and illicit drug use in girls. Impulsivity in teachers' ratings predicted frequent alcohol use and illicit drug use in boys. Parental reports of inattentiveness in their 11-/12-year-old daughters were a consistent predictor for illicit drug use across adolescence. CONCLUSIONS: Inattentiveness and hyperactivity may be more predictive of alcohol use disorders and maladaptive patterns of alcohol and illicit drug use among girls than boys. The importance of these behavioural symptoms should be assessed further in the community, as they could jeopardize adolescents' successful transitioning into adult roles.
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Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastornos Relacionados con Sustancias/etiología , Adolescente , Factores de Edad , Trastorno por Déficit de Atención con Hiperactividad/psicología , Niño , Femenino , Humanos , Entrevista Psicológica , Masculino , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Factores Sexuales , Fumar/psicología , Trastornos Relacionados con Sustancias/psicología , Encuestas y CuestionariosRESUMEN
Human aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983-1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one-3-hydroxybutyrate, a ketone body produced during fasting-showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated (age 14) aggression were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher aggression (self-rated) was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.
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Ácido 3-Hidroxibutírico/sangre , Agresión , Adolescente , Adulto , Teorema de Bayes , Biomarcadores/sangre , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Gemelos , Adulto JovenRESUMEN
This study investigated the effect of voriconazole, an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4, and itraconazole, an inhibitor of CYP3A4, on the pharmacokinetics and pharmacodynamics of meloxicam. Twelve healthy volunteers in a crossover study ingested 15 mg of meloxicam without pretreatment (control), after voriconazole pretreatment, and after itraconazole pretreatment. The plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B(2) (TxB(2)) generation were monitored. Compared to the control phase, voriconazole increased the mean area under the plasma concentration-time curve from 0 to 72 h (AUC(0-72)) of meloxicam by 47% (P < 0.001) and prolonged its mean half-life (t(1/2)) by 51% (P < 0.01), without affecting its mean peak concentration (C(max)). In contrast, itraconazole decreased the mean AUC(0-72) and C(max) of meloxicam by 37% (P < 0.001) and by 64% (P < 0.001), respectively, and prolonged its t(1/2) and time to C(max). The plasma protein unbound fraction of meloxicam was unchanged by voriconazole and itraconazole. Lowered plasma meloxicam concentrations during the itraconazole phase were associated with decreased pharmacodymic effects of meloxicam, as observed by weaker inhibition of TxB(2) synthesis compared to the control and voriconazole phases. Voriconazole increases plasma concentrations of meloxicam, whereas itraconazole, unexpectedly, decreases plasma meloxicam concentrations, possibly by impairing its absorption.
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Antiinflamatorios no Esteroideos/sangre , Antifúngicos/farmacología , Itraconazol/farmacología , Pirimidinas/farmacología , Tiazinas/sangre , Tiazoles/sangre , Triazoles/farmacología , Adulto , Coagulación Sanguínea/efectos de los fármacos , Estudios Cruzados , Ciclooxigenasa 1/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Interacciones Farmacológicas , Genotipo , Semivida , Humanos , Masculino , Meloxicam , Unión Proteica , Tromboxano B2/biosíntesis , Voriconazol , Adulto JovenRESUMEN
We describe a cluster of norovirus outbreaks affecting about 200 people in Southern Finland in September and October 2009. All outbreaks occurred after consumption of imported raspberries from the same batch intended for the catering sector. Human norovirus genotype GI.4 was found in frozen raspberries. The berries were served in toppings of cakes in separate catering settings or mixed in curd cheese as a snack for children in a daycare center. The relative risk for consumption of the berry dish was 3.0 (p Asunto(s)
Infecciones por Caliciviridae/epidemiología
, Brotes de Enfermedades/estadística & datos numéricos
, Contaminación de Alimentos/estadística & datos numéricos
, Frutas/microbiología
, Gastroenteritis/epidemiología
, Infecciones por VIH/epidemiología
, Norovirus
, Análisis por Conglomerados
, Femenino
, Finlandia/epidemiología
, Congelación
, Humanos
, Incidencia
, Masculino
, Vigilancia de la Población/métodos
, Medición de Riesgo
, Factores de Riesgo
RESUMEN
A family cluster of three cases of type E botulism were identified in south-east France in September 2009. The suspected food source of infection was a vacuum packed hot-smoked whitefish of Canadian origin purchased by the family during a visit to Finland and consumed several weeks later in France on the day prior to symptom onset. No leftover fish was available to confirm this hypothesis. Vacuum packed hot-smoked whitefish has previously been associated with cases of type E botulism in multiple countries, including Finland, Germany, the United States and Israel.
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Botulismo/epidemiología , Clostridium botulinum tipo E/aislamiento & purificación , Brotes de Enfermedades , Microbiología de Alimentos , Conservación de Alimentos , Salmonidae/microbiología , Adolescente , Animales , Bioensayo , Botulismo/transmisión , Canadá , Finlandia , Manipulación de Alimentos/métodos , Manipulación de Alimentos/normas , Embalaje de Alimentos , Francia/epidemiología , Humanos , Ratones , Persona de Mediana Edad , Cuadriplejía/etiología , Refrigeración , TemperaturaRESUMEN
BACKGROUND: We recently showed that bone morphogenetic protein 7 (BMP7) is overexpressed in primary breast tumors. Here we explored the clinical significance of BMP7 expression in breast cancer. MATERIALS AND METHODS: This study included 483 breast cancer patients with complete clinicopathological information and up to 15 years of follow-up. Samples contained 241 lobular carcinomas, 242 ductal carcinomas, and 40 local recurrences. BMP7 protein expression was determined using immunohistochemistry. RESULTS: BMP7 was expressed in 47% of the primary tumor samples and 13% of the local recurrences. The primary tumors expressed BMP7 more often than the corresponding local recurrences (P = 0.004). BMP7 expression was dependent on the tumor subtype; 57% of the lobular carcinomas but only 37% of the ductal carcinomas were BMP7 positive (P = 0.0001). BMP7 expression was associated with accelerated bone metastasis formation (P = 0.040), especially in ductal carcinomas (P = 0.033), and multivariate analysis confirmed that BMP7 is an independent prognostic indicator for early bone metastasis development (P = 0.032). CONCLUSION: BMP7 is clearly associated with bone metastasis formation and thus might have clinical utility in identification of patients with increased risk of bone metastasis. This is the first time that bone inducing factor BMP7 has been linked to the bone metastasis process in breast cancer.
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Proteínas Morfogenéticas Óseas/metabolismo , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/secundario , Recurrencia Local de Neoplasia/patología , Factor de Crecimiento Transformador beta/metabolismo , Adulto , Anciano , Análisis de Varianza , Biomarcadores de Tumor/análisis , Proteína Morfogenética Ósea 7 , Proteínas Morfogenéticas Óseas/genética , Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/genética , Carcinoma Lobular/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Factor de Crecimiento Transformador beta/genéticaRESUMEN
Escherichia coli strains that cause sepsis and meningitis in neonatal infants carry S fimbriae that bind to sialyl galactoside units of cell surface glycoproteins. To investigate the possible role of S fimbriae in determining the tissue tropism of neonatal meningitis, we have studied the presence of binding sites for S fimbriae in different tissues of the neonatal rat which is susceptible to meningitis caused by S-fimbriated E. coli. Purified S fimbriae were incubated on cryostat sections of different rat organs and their binding was assessed by indirect immunofluorescence. In the brain of the neonatal rat, S fimbriae specifically bound to the luminal surfaces of the vascular endothelium and of the epithelium lining the choroid plexuses and brain ventricles. The binding was completely inhibited by the trisaccharide NeuAc alpha 2-3Gal beta 1-4Glc, a receptor analogue of S fimbriae, and by a preceding neuraminidase treatment of the sections. A recombinant E. coli strain expressing S fimbriae adhered in large numbers to the same tissue sites in the neonatal brain sections as did the purified fimbriae, whereas the non-fimbriated host strain and a recombinant strain expressing P fimbriae did not adhere to brain tissues. The results suggest that adhesion of S-fimbriated bacteria to the binding sites observed in the neonatal brain has a pathogenetic role during bacterial invasion from circulation into the cerebrospinal fluid.
Asunto(s)
Encéfalo/metabolismo , Escherichia coli/metabolismo , Fimbrias Bacterianas/metabolismo , Meningitis/metabolismo , Receptores Inmunológicos/análisis , Animales , Animales Recién Nacidos/metabolismo , Encéfalo/patología , Ventrículos Cerebrales/metabolismo , Ventrículos Cerebrales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Epitelio/metabolismo , Epitelio/patología , Meningitis/patología , Ratas , Ratas EndogámicasRESUMEN
Understanding molecular processes that link comorbid traits such as addictions and mental disorders can provide novel therapeutic targets. Neuregulin signaling pathway (NSP) has previously been implicated in schizophrenia, a neurodevelopmental disorder with high comorbidity to smoking. Using a Finnish twin family sample, we have previously detected association between nicotine dependence and ERBB4 (a neuregulin receptor), and linkage for smoking initiation at the ERBB4 locus on 2q33. Further, Neuregulin3 has recently been shown to associate with nicotine withdrawal in a behavioral mouse model. In this study, we scrutinized association and linkage between 15 036 common, low frequency and rare genetic variants in 10 NSP genes and phenotypes encompassing smoking and alcohol use. Using the Finnish twin family sample (N=1998 from 740 families), we detected 66 variants (representing 23 LD blocks) significantly associated (false discovery rate P<0.05) with smoking initiation, nicotine dependence and nicotine withdrawal. We comprehensively annotated the associated variants using expression (eQTL) and methylation quantitative trait loci (meQTL) analyses in a Finnish population sample. Among the 66 variants, we identified 25 eQTLs (in NRG1 and ERBB4), 22 meQTLs (in NRG3, ERBB4 and PSENEN), a missense variant in NRG1 (rs113317778) and a splicing disruption variant in ERBB4 (rs13385826). Majority of the QTLs in blood were replicated in silico using publicly available databases, with additional QTLs observed in brain. In conclusion, our results support the involvement of NSP in smoking behavior but not in alcohol use and abuse, and disclose functional potential for 56 of the 66 associated single-nucleotide polymorphism.
Asunto(s)
Neurregulinas/metabolismo , Receptor ErbB-4/genética , Fumar/genética , Anciano , Femenino , Finlandia/epidemiología , Ligamiento Genético , Humanos , Masculino , Persona de Mediana Edad , Neurregulina-1/genética , Nicotina , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Transducción de Señal/genética , Fumar/psicología , Síndrome de Abstinencia a Sustancias , Tabaquismo/genética , Tabaquismo/psicología , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genéticaRESUMEN
BACKGROUND: An increasing frequency of snacks has been observed in meal pattern studies. Snacks can alter the diet because of their high-energy density and low-nutrient content or on the contrary. OBJECTIVE: The prominence of snacks in energy intake and food consumption was assessed. DESIGN: Dietary data were collected for 2007 adults by using a computer-assisted 48-h dietary recall in the national FINDIET 2002 survey. Energy intakes and food consumption were aggregated for snacks and for main meals. RESULTS: Daily energy was mostly derived from main meals comprising traditional mixed dishes, milk and bread. However, a snack-dominating meal pattern was observed in 19% of men and 24% of women. This meal pattern was associated with urbanization in both genders and with physical work in men. Higher sucrose intake and lower intake of micronutrients were typical of the snack-dominating meal pattern compared to the others. CONCLUSIONS: As snacks appear to have a higher energy density and a lower content of micronutrients than main meals, a snack-dominating meal pattern is inadvisable. However, further studies are needed to examine the association between meal pattern and health status.