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This study investigates children's problem-solving activities during mobile learning in an outdoor summer camp setting. We designed a mobile application to support children on trails at a nature center to apply strategies for decision making about tree life cycles. We analyzed video records of 10 groups (9 dyads and 1 triad) of children (ages 9–12) using primarily a thematic qualitative analysis of learning episodes. We analyzed how children used problem-solving strategies to identify and capture the tree cycle with the help of mobile tablets. We found that our mobile learning experience and its external representations supported the following: (1) engagement in deep learning in the natural setting as evidenced by coordinating decisions with photographic evidence; (2) use of procedural or tactical strategies to approach the problem; and (3) use of real-time decision making strategies about tree life cycles. [ABSTRACT FROM AUTHOR]

Background: African American patients disproportionately experience uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma. Objective: We sought to determine the degree to which African American patients respond to ICS medication and whether the level of response is influenced by other factors, including genetic ancestry. Methods: Patients aged 12 to 56 years who received care from a large health system in southeast Michigan and who resided in Detroit were recruited to participate if they had a diagnosis of asthma. Patients were treated with 6 weeks of inhaled beclomethasone dipropionate, and pulmonary function was remeasured after treatment. Ancestry was determined by genotyping ancestry-informative markers. The main outcome measure was ICS responsiveness defined as the change in prebronchodilator FEV1 over the 6-week course of treatment. Results: Among 147 participating African American patients with asthma, average improvement in FEV1 after 6 weeks of ICS treatment was 11.6%. The mean proportion of African ancestry in this group was 78.4%. The degree of baseline bronchodilator reversibility was the only factor consistently associated with ICS responsiveness, as measured by both an improvement in FEV1 and patient-reported asthma control (P = .001 and P = .021, respectively). The proportion of African ancestry was not significantly associated with ICS responsiveness. Conclusions: Although baseline pulmonary function parameters appear to be associated with the likelihood to respond to ICS treatment, the proportion of genetic African ancestry does not. This study suggests that genetic ancestry might not contribute to differences in ICS controller response among African American patients with asthma. [ABSTRACT FROM AUTHOR]

Purpose: Fat absorption may play a crucial role in colorectal carcinogenesis by determining intra-colonic exposure to potentially carcinogenic lipid metabolites.Methods: We conducted a population-based case-control study that included 1163 cases and 1501 controls to examine whether individuals who carry genetic variants associated with lower lipid absorption have a higher risk of colorectal cancer. Using Taqman assay, we determined FABP2 alanine (A)/threonine (T) polymorphism at codon 54 in exon-2 and APOE isoforms. Multivariable odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression models, assuming FABP2 A54 and APO non-E4 as high risk alleles.Results: We found no associations with either of the polymorphisms. The OR associated with FABP2 A54 homozygotes compared with the others was 1.01 (95% CI; 0.86-1.45) and that for non-ApoE4 carriers compared with carries was 0.95 (95% CI; 0.80-1.13). However, there was a statistically significant negative interaction between total fat intake and FABP2 AA genotypes (p=0.025), indicating that the risk of colorectal cancer associated with this polymorphism is higher in the subjects with lower fat intake.Conclusions: These results suggest that these SNPs may not be useful in predicting colorectal cancer risk in populations with high fat intake. [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. Methods: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. Results: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (χ2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 (P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN (P = .0169) and TIMP3 (P = .0023) in cases with a family history of AAA. Conclusions: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual’s risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA. [Copyright &y& Elsevier]

Summary: The possibility that androgens contribute to the male advantage typically found on measures of spatial cognition has been investigated using a variety of approaches. To date, evidence to support the notion that androgens affect spatial cognition in healthy young adults is somewhat equivocal. The present study sought to clarify the association between testosterone (T) and spatial performance by extending measurements of androgenicity to include both measures of circulating T as well as an androgen receptor-specific genetic marker. The aims of this study were to assess the contributions of sex, T, and androgen receptor CAG repeat number (CAGr) on virtual Morris water task (vMWT) performance in a group of healthy young men and women. The hypothesis that men would outperform women on vMWT outcomes was supported. Results indicate that CAGr may interact with T to impact navigation performance and suggest that consideration of androgen receptor sensitivity is an important consideration in evaluating hormone–behavior relationships. [ABSTRACT FROM AUTHOR]

Background: Resistin-like molecules (RELM) are expressed in many tissues and among those, RELMβ is most abundantly expressed in the colon. Based on animal studies, RELMβ is induced by high fat diets, obesity, and intestinal microflora and may play a role in insulin resistance and intestinal inflammation. In the present study, we evaluated whether RELMβ could be measured in human plasma and the influence of selected host and behavioral factors on RELMβ levels, including known risk factors for colorectal cancer.Methods: The subjects for this pilot study were derived from healthy controls who participated in a population-based case-control study of colorectal cancer in Metropolitan Detroit. The subjects were 45-80 years of age without history of cancer or colorectal resection.Results: RELMβ was present in human plasma, with levels in the range of 0.08-0.26 ng/mL. Lower RELMβ levels were found in subjects with non-Caucasian race, lower pack-years of smoking, and higher physical activity index scores. Other variables such as dietary intakes, gender, obesity, use of non-steroidal anti-inflammatory agents and history of polyps were not associated with RELMβ levels.Conclusions: The direct association of RELMβ with smoking and inverse association with physical activity, both of which are risk factors for colon cancer, indicates that RELMβ may be involved in mediating the effects of these two lifestyle factors on risk of colon cancer. [ABSTRACT FROM AUTHOR]

Abstract: The F344 rat rapidly forms large prolactinomas in response to chronic estrogen treatment. To identify genes expressed in the course of this estrogen induced pituitary tumor growth, we performed microarray analysis on the F344 rat pituitary after chronic estrogen treatment and on untreated controls. At a significance level set to minimize type I error, some 72 genes were found to be differentially expressed between estrogen treated and untreated. Of those genes, 70 have not been reported previously as being affected by estrogen in the F344 rat pituitary. Since many other investigators have studied the effect of estrogen on specific gene expression in rat pituitary, we also examined the mRNA expression of the 36 genes that have been previously reported as having their expression affected by estrogen in the rat pituitary. Of these, 13 were found to have their expression affected by estrogen treatment in the same direction as had been reported by others. [Copyright &y& Elsevier]

Objective: To conduct a phase II trial of the combination of carboplatin, prednisone, and everolimus in metastatic castrate-resistant prostate cancer (mCRPC) as mTOR inhibition can overcome resistance to chemotherapy in prostate cancer.Methods: Patients with progressive mCRPC pretreated with docetaxel-based regimen were eligible. Performance status of 0-1 and adequate bone marrow, renal, and liver function were required. Primary end point was time to progression. Treatment consisted of carboplatin (starting dose equal to area under the curve (AUC of 5) intravenously every 21 days along with oral everolimus 5 mg once daily and prednisone 5 mg twice daily.Results: Twenty-six patients were enrolled with median age of 69 years with 8 patients of African American origin. Grade 3 or 4 thrombocytopenia or neutropenia in 4 of 6 initial patients required dose adjustment of carboplatin to AUC of 4 for subsequent patients. There were no pharmacokinetic interactions between carboplatin and everolimus. The median time to progression was 2.5 months (90% confidence interval [CI], 1.8-4.3 months), and median overall survival was 12.5 months (90% CI, 7.7-18.7 months). Of 10 patients, 8 that demonstrated positive nuclear phosphorylated AKT (pAKT) staining on immunohistochemistry progressed within 9 weeks, whereas 2 patients with negative staining continued without progression for prolonged durations of 30 and 48 weeks. TSC1 gene mutations did not correlate with clinical outcome.Conclusion: The addition of the mTOR inhibitor everolimus to carboplatin demonstrated minimal clinical efficacy in metastatic prostate cancer. pAKT testing warrants further evaluation as a predictive marker of response to everolimus therapy. [ABSTRACT FROM AUTHOR]

Abstract: Aging is associated with appearance of white matter hyperintensities (WMH) on MRI scans. Vascular risk and inflammation, which increase with age, may contribute to white matter deterioration and proliferation of WMH. We investigated whether circulating biomarkers and genetic variants associated with elevated vascular risk and inflammation are associated with WMH volume in healthy adults (144 volunteers, 44–77years of age). We examined association of WMH volume with age, sex, hypertension, circulating levels of total plasma homocysteine (tHcy), cholesterol (low-density lipoprotein), and C-reactive protein (CRP), and four polymorphisms related to vascular risk and inflammation: Apolipoprotein ε (ApoE ε2,3,4), Angiotensin-Converting Enzyme insertion/deletion (ACE I/D), methylenetetrahydrofolate reductase (MTHFR) C677T, C-reactive protein (CRP)-286C>A>T, and interleukin-1β (IL-1β) C-511T. We found that larger WMH volume was associated with advanced age, hypertension, and elevated levels of homocysteine and CRP but not with low-density lipoprotein levels. Homozygotes for IL-1β-511T allele and carriers of CRP-286T allele that are associated with increased inflammatory response had larger WMH than the other allelic combinations. Carriers of the APOE ε2 allele had larger frontal WMH than ε3 homozygotes and ε4 carriers did. Thus, in healthy adults, who are free of neurological and vascular disease, genetic variants that promote inflammation and elevated levels of vascular risk biomarkers can contribute to brain abnormalities. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. [Copyright &y& Elsevier]

Abstract: Executive functions (EF) evidence significant age-related declines, but the mechanisms underpinning those changes are unclear. In this study, we focus on two potential sources of variation: a physiological indicator of vascular health, and genetic variants related to vascular functions. In a sample of healthy adults (n =158, ages 18–81), we examine the effects of age, pulse pressure, and two polymorphisms (comt val158met and ace insertion/deletion) on working memory and cognitive flexibility. Results indicate that in addition to often-replicated age differences, the alleles of two polymorphisms that promote vasoconstriction (comt val and ace D) and reduced availability of dopamine in neocortical synapses (comt val), negatively impact virtually all aspects of EF tasks that involve working memory. In some cases, suppression of cognitive performance is limited to men or necessitates a combination of both risk-associated alleles. After accounting for genetic and age-related variation, pulse pressure had no additional effect on EF. These findings suggest that in healthy adults, the effects of genetic risk factors significantly modulate the course of cognitive aging. [Copyright &y& Elsevier]

Background: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer.Methods: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action.Results: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR)=2.34, 95% confidence interval (CI) 1.23-4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P=0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR=3.00, 95%CI 1.29-6.99).Conclusion: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases. [ABSTRACT FROM AUTHOR]