RESUMEN
OBJECTIVE: The aim was to examine the effects of low to moderate maternal alcohol consumption and binge drinking in early pregnancy on children's attention at 5 years of age. DESIGN: Prospective follow-up study. SETTING: Neuropsychological testing in four Danish cities 2003-2008. POPULATION: A cohort of 1628 women and their children sampled from the Danish National Birth Cohort. METHODS: Participants were sampled based on maternal alcohol consumption during pregnancy. At 5 years of age, the children were tested with the recently developed Test of Everyday Attention for Children at Five (TEACh-5). Parental education, maternal IQ, maternal smoking in pregnancy, the child's age at testing, gender, and tester were considered core confounding factors, whereas the full model also controlled the following potential confounding factors: maternal binge drinking or low to moderate alcohol consumption, age, body mass index (BMI), parity, home environment, postnatal smoking in the home, child's health status, and indicators for hearing and vision impairments. MAIN OUTCOME MEASURES: TEACh-5 attention scores. RESULTS: There were no significant effects on test performance in children of mothers drinking up to 8 drinks per week compared with children of mothers who abstained, but there was a significant association between maternal consumption of 9 or more drinks per week and risk of a low overall attention score (OR 3.50, 95% CI 1.15-10.68). No consistent or significant associations were observed between binge drinking and attention test scores. CONCLUSIONS: The findings suggest an effect of maternal consumption of 9 or more drinks per week on attention functions in children, but the study detected no effects of lower levels of maternal consumption and no consistent effects of maternal binge drinking.
Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Atención , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Preescolar , Dinamarca/epidemiología , Escolaridad , Etanol/envenenamiento , Femenino , Humanos , Inteligencia/fisiología , Masculino , Pruebas Neuropsicológicas , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Estudios ProspectivosRESUMEN
OBJECTIVES: To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception. DESIGN: Population-based follow-up study. SETTING: All children born alive in Denmark 1995-2003. PARTICIPANTS: 588,967 children born in Denmark from January 1995 to December 2003. Assisted conception was defined as in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection and ovulation induction (OI) with or without subsequent insemination. Children exposed to IVF or OI were identified in the IVF Register and in the Danish Drug Prescription Register. MAIN OUTCOME MEASURES: A diagnosis of ASD in the Danish Psychiatric Central Register. RESULTS: 33,139 (5.6%) of all children born in Denmark in 1995-2003 resulted from assisted conception, 225 of whom (0.68%) had a diagnosis of ASD. Of the 555,828 children born in this period after natural conception, 3394 (0.61%) had a diagnosis of ASD. The follow-up time was 4-13 years (median 9 years). In crude analyses, children born after assisted conception had an increased risk of a diagnosis of ASD: crude hazard rate ratio (HRR) 1.25 (95% CI 1.09 to 1.43). In analyses adjusting for maternal age, educational level, parity, smoking, birth weight and multiplicity, the risk disappeared: adjusted HRR 1.13. (95% CI 0.97 to 1.31). However, subgroup analyses that suggest possible associations in women who received follicle stimulating hormone indicate the need for further study. DISCUSSION: This population-based follow-up study found no risk of ASD in children born after assisted conception.
Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/etiología , Técnicas Reproductivas Asistidas/efectos adversos , Adulto , Niño , Trastornos Generalizados del Desarrollo Infantil/epidemiología , Preescolar , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Medición de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Earlier studies reported an increased cancer risk among patients with systemic sclerosis. Study size limitations and paucity of population-based study designs may have resulted in imprecise risk estimates. OBJECTIVES: To assess cancer risk among patients with systemic sclerosis in a nationwide follow-up study. METHODS: Patients with a first diagnosis of systemic sclerosis from 1977 to 2006 were identified from the nationwide Danish National Registry of Patients (DNRP), whose records encompass all hospitalizations and outpatient visits. Patients' DNRP records were linked to the Danish Cancer Registry. We compared their cancer incidence with that expected from cancer incidence in the general population, calculating standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Two thousand and forty patients with systemic sclerosis were identified and followed for 16,003 person-years, with a median follow-up time of 6·4 years (interquartile range 2·2-11·5). Among these patients, 222 cases of cancer were identified. The overall SIR for cancer was 1·5 (95% CI 1·3-1·7), with a gender-specific SIR of 2·2 (95% CI 1·7-2·8) for men and 1·3 (95% CI 1·1-1·6) for women. The most frequent cancers were smoking- and alcohol-related cancers including lung cancer (SIR = 1·6, 95% CI 1·2-2·0), haematological cancers (SIR = 2·5, 95% CI 1·5-4·0) and immune-related cancers (SIR = 1·4, 95% CI 1·0-1·9). CONCLUSIONS: Systemic sclerosis is a risk factor for cancer, particularly smoking- and alcohol-related cancers. Men with systemic sclerosis generally are at higher cancer risk than women. Both primary and secondary cancer preventive measures are needed in the care of patients with systemic sclerosis.
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Neoplasias/etiología , Esclerodermia Sistémica/complicaciones , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Cocarcinogénesis , Dinamarca/epidemiología , Métodos Epidemiológicos , Femenino , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/etiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Esclerodermia Sistémica/epidemiología , Factores Sexuales , Fumar/efectos adversos , Fumar/epidemiología , Adulto JovenRESUMEN
BACKGROUND: This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC). METHODS: This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception was defined as IVF, with or without ICSI, and ovulation induction (OI), with or without subsequent insemination. RESULTS: There were 33 139 (5.6%) children born in Denmark from 1995 to 2003 as a result of assisted conception and through to June 2009, 1146 (0.19%) children received a CP diagnosis. Children born after assisted conception had an increased risk of a CP diagnosis, crude hazard rate ratio (HRR) 1.90 (95% CI: 1.57-2.31) compared with NC children. Divided into IVF and OI children compared with NC children, the risk was HRR 2.34 (95% CI: 1.81-3.01) and HRR 1.55 (95% CI: 1.17-2.06), respectively. When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC. CONCLUSION: The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants consideration to enhance the long-term health of children born after IVF.
Asunto(s)
Parálisis Cerebral/epidemiología , Fertilización In Vitro , Recien Nacido Prematuro , Progenie de Nacimiento Múltiple , Adolescente , Adulto , Niño , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
The solubilities of heat-denatured and reduced, S-carboxymethylated proteins have been investigated in various organic solvents. Polar, protic solvents (formic acid, trifluoroacetic acid, 3-mercaptopropionic acid) were found to be good solvents for the denatured proteins (20-40 mg ml-1), and the solubilities of the reduced, S-carboxymethylated proteins were generally higher than those of the heat-denatured forms. Most other organic solvents were less effective in solubilizing the denatured proteins. Apolar solvents did not solubilise denatured proteins, but low solubilizing powers were observed for polar, aprotic solvents. Heat-denaturation was observed to result in the formation of large intermolecular aggregates, which, for ovalbumin and lysozyme, were formed by intermolecular S-S bonds, but for bovine serum albumin involved intermolecular isopeptide bonds.
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Proteínas/química , Electroforesis en Gel de Poliacrilamida , Compuestos Orgánicos , Desnaturalización Proteica , Solubilidad , SolventesRESUMEN
Calreticulin is a highly conserved protein with a relative molecular weight of 46,000, and is mainly located in the endoplasmic reticulum. Calreticulin was first characterized as a calcium-binding protein in the endoplasmic reticulum, but since then other functions of calreticulin have been characterized, including chaperone and lectin properties, and regulation of integrin and nuclear hormone receptor activity. We have investigated the interactions between purified human placental calreticulin and native and denatured proteins. Our results show that calreticulin binds to denatured proteins in a time- and pH-dependent manner, which at physiological pH is dependent on divalent cations. The binding was dependent on the state of the denatured protein, and was highly sensitive to the ionic composition of the environment, being strongly inhibited by phosphate-containing compounds. Calreticulin did not seem to distinguish between denatured glycosylated and non-glycosylated proteins, and was found to bind to native basic proteins, presumably by sheer electrostatic forces.
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Proteínas de Unión al Calcio/metabolismo , Chaperonas Moleculares/metabolismo , Ribonucleoproteínas/metabolismo , Animales , Proteínas Sanguíneas/metabolismo , Proteínas de Unión al Calcio/aislamiento & purificación , Calreticulina , Cationes Bivalentes , Bovinos , Cromatografía/métodos , Electroforesis en Gel de Poliacrilamida , Retículo Endoplásmico/química , Ensayo de Inmunoadsorción Enzimática , Humanos , Concentración de Iones de Hidrógeno , Chaperonas Moleculares/aislamiento & purificación , Unión Proteica , Ribonucleoproteínas/aislamiento & purificación , Sensibilidad y Especificidad , Sefarosa/análogos & derivadosRESUMEN
A solid phase conjugation method is described based on the preadsorption of proteins to aluminium hydroxide adjuvant followed by activation of the adsorbed carrier proteins with iodoacetic acid N-hydroxysuccinimidester or other conjugation reagents. Cysteine-containing peptides were coupled to the iodoacetic acid-activated carrier-adjuvant particles through their SH groups. No dialysis is required since the reaction product is isolated at each step of the procedure by a simple centrifugation and can easily be extensively washed between individual manipulations. The method generates peptide-carrier-adjuvant particles with sterically defined presentation of the peptides at the surface of the particles. When used for immunization of mice and rabbits the conjugates elicited high-titered specific anti-peptide sera, which reacted well with the parent protein in ELISA. The strongest reactions were with the denatured form of the parent protein. On immunoblots antisera to the N- and C-terminus of calreticulin recognized the same M, 52,000 protein.