Significance Level P-value Research Articles

Maternal preconception body mass index and offspring cord blood DNA methylation: Exploration of early life origins of disease

Maternal obesity is associated with a variety of common diseases in the offspring. One possible underlying mechanism could be maternal obesity induced alterations in DNA methylation. However, this hypothesis is yet to be tested. We performed epigenomic mapping of cord blood among 308 Black mother-infant pairs delivered at term at the Boston Medical Center using the Illumina HumanMethylation27 BeadChip. Linear regression and pathway analyses were conducted to evaluate the associations between DNA methylation levels and prepregnancy maternal BMI (<25, 25-30, ≥30 kg/m(2) ). The methylation levels of 20 CpG sites were associated with maternal BMI at a significance level of P-value <10(-4) in the overall sample, and boys and girls, separately. One CpG site remained statistically significant after correction for multiple comparisons (FDR corrected P-value = 0.04) and was annotated to a potential cancer gene, ZCCHC10. Some of the other CpG site annotated genes appear to be critical to the development of cancers and cardiovascular diseases (i.e., WNT16, C18orf8, ANGPTL2, SAPCD2, ADCY3, PRR16, ERBB2, DOK2, PLAC1). Significant findings from pathway analysis, such as infectious and inflammatory and lipid metabolism pathways, lends support for the potential impact of maternal BMI on the above stated disorders. This study demonstrates that prepregnancy maternal BMI might lead to alterations in offspring DNA methylation in genes relevant to the development of a range of complex chronic diseases, providing evidence of trans-generational influence on disease susceptibility via epigenetic mechanism.

Bone Markers in the Treatment of Cancer Related Bone Disease in Patients with Metastatic Breast Cancer

Bone metastases and treatment-induced osteoporosis are frequently the maincauses of morbidity in patients with malignancies. Monitoring the level of bone markers (markers of bone metabolism) has been fairly well mapped in osteoporosis, where medical procedures can be modified according to the kinetics of marker levels before an answer can be evaluated by densitometry and before the onset of fractures. In bone metastases the role of these levels is not clear. The metabolic markers of bone resorption under review in this set were s-Cross Laps (CTX) - a peptide that is a part of C - telopeptide, and N-terminal propeptide of collagen type 1 (P1NP). Material and methods: We monitored a group of 52 female patients with metastatic breastcancer. The patients received appropriate systemic treatment based on the immunohistochemistry of the tumor; the treatment consisted of hormone therapy or chemotherapy, and included parenteral bisphosphonates (ibandronate and zoledronic acid alternately). Routine biochemical tests and blood count done prior to the initiation of therapy also included taking laboratory markers of bone metabolism CTX and P1NP and measuring bone mineral density (according to T-score). These bone markers were then checked in three, six, nine and twelve months, and matched with the progress of the disease. Total monitoring time was fifteen months. Results: The patients in this set whose CTX value in the first sampling was less than 0.425 ran 8.5 times higher risk of death; the patients whose P1NP value reached more than 74 in the first collection ran 8.7 times higher risk of death. According to Cox proportional-hazards regression analysis for CTX, the significance level of p-value was 0.0452 and HR was 8.516 (95% CI 1.047 to 69.262), a difference which is not statistically significant. Regarding P1NP in Cox regression analysis, the significance level of p-value is 0.0433 and HR 8.673 (95% CI 1.067 to 70.520). Even this difference is therefore not statistically significant. When comparing the kinetics of marker levels, the difference is below statistical significance: p-value 0.6131 for P1NP and p-value 0.6357 for CTX. Conclusion: The results of this study confirm a correlation between the starting levels of CTX and P1NP with the overall survival rate, which corresponds to the other results presented in literature.

Lipodystrophy syndrome and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy

To describe lipid profile, body shape changes, and cardiovascular risk factors in children and adolescents infected with HIV/AIDS receiving highly active antiretroviral therapy. We investigated 43 children and adolescents being treated with this therapy at the outpatient clinic of pediatric infectious diseases of Instituto Fernandes Figueira/Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Values of total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides were determined. We also performed glucose tolerance test and analyzed body fat distribution, nutritional status, dietary intake, and family history of cardiovascular risk. The statistical analysis was performed using Student's t test. Significance level of p-value was lower than 0.05. We found lipid abnormality in 88.3% and body shape change in 13.9% of the cases. Nutritional status was adequate (81.3%) in most of the study population. Cholesterol intake in children older than 9 years was above the recommended value. Prevalence of dyslipidemia and, therefore, risk for cardiovascular diseases were high during the use of highly active antiretroviral therapy.

Síndrome da lipodistrofia e fatores de risco cardiovasculares em crianças e adolescentes infectados pelo HIV/AIDS em uso de terapia antirretroviral de alta potência

OBJETIVO: Descrever o perfil lipídico, alterações da conformação corporal e fatores de risco cardiovasculares em crianças e adolescentes infectados pelo HIV/AIDS, tratados com terapia antirretroviral de alta potência. MÉTODOS: Foram estudadas 43 crianças e adolescentes em uso dessa terapia atendidas no ambulatório de doenças infecciosas em Pediatria do Instituto Fernandes Figueira/Fundação Oswaldo Cruz, Rio de Janeiro (RJ). Foram realizadas dosagens de colesterol total, lipoproteína de alta densidade, lipoproteína de baixa densidade, triglicerídeos, teste de tolerância à glicose e avaliada a distribuição de gordura corporal, estado nutricional, ingestão dietética e história familiar de risco cardiovascular. As análises estatísticas foram realizadas com o teste t de Student. O nível de significância estatístico do p foi menor que 0,05. RESULTADOS: Observou-se alteração lipídica em 88,3% e de conformação corporal em 13,9% dos casos. O estado nutricional foi adequado na maioria (81,3%) da população do estudo. A ingestão de colesterol em crianças com mais de 9 anos foi acima do recomendado. CONCLUSÃO: A prevalência de dislipidemia e, consequentemente, o risco para doenças cardiovasculares foram altos durante o uso de terapia antirretroviral de alta potência.

Eating late in the evening is associated with childhood obesity in some age groups but not in all children: the relationship between time of consumption and body weight status in U.S. children

BackgroundSome studies in adults indicate a positive correlation between eating later in the day and overall energy intake as well as body weight status. Thus, the time of food intake may be a risk factor in childhood obesity. This study was designed to describe the proportion of energy consumed in the time from 4 pm to midnight measured in two-hour increments and to determine a potential association between the time of proportion of energy consumed and body weight status.MethodsDietary, anthropometric, and socio-demographic data of 2–18 year olds (N = 11,072) of the National Health and Nutrition Examination Survey (NHANES) 1999–2004 was examined to describe the proportion of total energy consumed within two-hour time periods between 4 pm and midnight. To examine the potential association between eating later in the day and body weight status, generalized estimating equations (GEE) models were used to quantify the effect of time trends (proportion of total energy consumed in each 2-hour time period from 4 pm to 11.59 pm) on body weight status. Analysis was conducted in the total sample and in subgroups stratified by sex, ethnic group (Non-Hispanic white, Non-Hispanic black, Mexican American, Other Hispanic, and Other Race including multi-racial) and age group (2–5, 6–11, and 12–18 year olds). Complex sample survey analysis were used to assess differences at a significance level of p-value < 0.05.ResultsProportion of energy consumed varied by sex, ethnic group, and age groups between 4 pm and 11.59 pm. Compared to healthy weight children, overweight school-age children consumed significantly higher while overweight adolescents consumed significantly lower proportions of total daily energy with each advancing two-hour time increment.ConclusionThe association between the circadian rhythm of eating and body weight status needs to be investigated further to examine the effect of time of consumption on the risk of childhood obesity. Especially longitudinal studies in diverse child populations would help elucidate the importance of time of eating on obesity.