Development of Dietary Patterns Spanning Infancy and Toddlerhood: Relation to Body Size,Composition and Metabolic Risk Markers at Three Years

Little is known about the development of dietary patterns during toddlerhood and the relation to growth and health. The study objective was to characterise the development of dietary patterns from 9–36 mo of age and investigate the association to body size, body composition and metabolic risk markers at 36 mo. Food records were filled out at 9, 18 and 36 mo of age (n = 229). Dietary patterns were identified by principal component analysis (PCA). Three dietary patterns were identified: Transition Food, Healthy Food and Traditional Food. The course of development in dietary patterns from 9–36 mo indicated tracking for a relatively large group of participants in the three patterns. Transition Food and Healthy Food were associated with some of the investigated outcomes. Children with lower adherence to the Transition Food pattern than average at 18 and 36 mo irrespectively of intake at 9 mo had higher BMI z-scores at 36 mo. Similar trend was identified for higher fat mass indices. Children with lower adherence to the Healthy Food pattern than average at all three ages compared to children with higher adherence to the Healthy Food pattern at the first two registrations, 9 and 18 mo had higher total cholesterol and LDL. Hence, this could represent undesirable development of dietary patterns in toddlers. In conclusion, development of dietary patterns can be exploratory characterised by PCA and related to potential cardiovascular risk markers in toddlers even within a relatively homogeneous population with a high socioeconomic status. The tracking of dietary patterns from 9 mo of age indicates a need for early and sustained promotion of healthy diets.     

运动障碍疾病与脑内金属铜、铁、钙沉积

在过去的20年,金属及其代谢过程对神经疾病的影响引起了神经科学家的极大兴趣。近年来大量文献报道,铁、铜、锰和锌作为重要的神经化学因子与目的蛋白相互作用导致了与疾病病理生理密切相关的反应。     

Luteinizing hormone levels are positively correlated with plasma amyloid-beta protein levels in elderly men

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.     

Dietary calcium and bone mineral density in premenopausal women with systemic lupus erythematosus

The primary objective of this study was to determine the relationship between dietary calcium intake and bone mineral density (BMD) in premenopausal women with systemic lupus erythematosus (SLE) on corticosteroids (CS). The secondary aim was to identify other risk factors for osteoporosis in these patients. A cross-sectional sample of patients attending the SLE Clinic at a teaching hospital was recruited. BMD was measured using dual-energy X-ray absorptiometry. Daily dietary calcium intake was assessed using a structured validated food frequency questionnaire, in which patients were asked to estimate their food intake based on their recent 2-month dietary habits. Sixty subjects were recruited with a mean age of 33.70±8.46 years. The median duration of CS use was 5.5 years (range 0.08–24). The median cumulative dose of steroids was 17.21 g (range 0.16–91.37). The median daily dietary calcium intake was 483 mg (range 78–2101). There was no significant correlation between calcium intake and BMD, even after correcting for CS use. There were also no correlations between BMD and the duration of SLE, cumulative CS use, duration of CS use, smoking, alcohol intake, and SLE disease activity index score. Twenty-eight (46.7%) patients had normal BMD, 28 (46.7%) had osteopenia, and four (6.6%) had osteoporosis. Duration of SLE significantly correlated with cumulative CS dosage. In conclusion, 6.7% of these Asian premenopausal SLE women had osteoporosis and only 46.7% had normal BMD. Daily dietary calcium intake did not correlate with BMD.     

Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition

Non-small cell lung cancers with activating mutations in the epidermal growth factor receptor (EGFR) are highly responsive to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. Such cancers are “addicted” to EGFR, and treatment with a TKI invariably leads to down-regulation of the PI3K-AKT-mTOR and MEK-ERK signaling pathways, resulting in apoptosis. Using a dual PI3K-mTOR inhibitor, NVP-BEZ235, we evaluated whether PI3K-mTOR inhibition alone induced apoptosis in these cancers. In contrast to HER2-amplified breast cancers, we found that PI3K-mTOR inhibition did not promote substantial apoptosis in the EGFR mutant lung cancers. However, blocking both PI3K-mTOR and MEK simultaneously led to apoptosis to similar levels as the EGFR TKIs, suggesting that down-regulation of these pathways may account for much of the apoptosis promoted by EGFR inhibition. In EGFR mutant lung cancers, down-regulation of both intracellular pathways converged on the BH3 family of proteins regulating apoptosis. PI3K inhibition led to down-regulation of Mcl-1, and MEK inhibition led to up-regulation of BIM. In fact, down-regulation of Mcl-1 by siRNA was sufficient to sensitize these cancers to single-agent MEK inhibitors. Surprisingly, an AKT inhibitor did not decrease Mcl-1 levels, and when combined with MEK inhibitors, failed to induce apoptosis. Importantly, we observed that the combination of PI3K-mTOR and MEK inhibitors effectively shrunk tumors in a transgenic and xenograft model of EGFR T790M-L858R cancers. These data indicate simultaneous inhibition of PI3K-mTOR and MEK signaling is an effective strategy for treating EGFR mutant lung cancers, including those with acquired resistance to EGFR TKIs.     

Proposed adjustments to pathologic staging of epithelial malignant pleural mesothelioma based on analysis of 354 cases

BACKGROUND:

Several pathologic staging systems for malignant pleural mesothelioma (MPM) have been published, but none of them provide optimal survival stratification or stage distribution among patients treated with surgery. Interpretation of prior studies that correlate pathologic factors with outcome has been confounded by the inclusion of patients undergoing differing surgical procedures and with varied tumor histology.

METHODS:

We examined pathologic characteristics, previously included in published studies, and explored correlations with outcome among patients with epithelioid MPM who underwent extrapleural pneumonectomy (EPP) at Brigham and Women's Hospital (BWH). Comparisons of survival among patients with and without each tumor or lymph node feature guided adjustments to the American Joint Commission on Cancer (AJCC)/International Union Against Cancer (UICC) classification criteria. Proportional hazards modeling of TN combinations guided adjustments to stage groupings.

RESULTS:

Three hundred fifty‐four patients were resectable by EPP and had complete pathologic data. Overall median survival was 18 months from surgery. By AJCC/UICC criteria, 233 (66%) patients were stage III, whereas by BWH criteria, 194 (55%) patients were stage III. T classification criteria were adjusted based on prevalence and relation to survival. N status correlated significantly with survival. Regrouping of TN combinations based on relative hazard and Kaplan‐Meier survival analysis resulted in improved stage distribution (stage I‐IV: 8%, 43%, 33%, 16%, respectively) and survival stratification (51, 26, 15, 8 months, respectively).

CONCLUSIONS:

Proposed adjustments to TNM staging criteria improved outcome stratification of patients with epithelial tumor histology who received surgical therapy by EPP and complete pathologic assessment. Determining relevance to other treatment or staging modalities will require verification in additional cohorts. Cancer 2010. © 2010 American Cancer Society.