New associations of classic acute macular neuroretinopathy

PURPOSE: To describe novel underlying associations of classic acute macular neuroretinopathy (AMN). METHODS: Multimodal imaging case series evaluating patients with classic AMN lesions and previously unreported underlying aetiologies. RESULTS: Six patients were included (five women, one man, mean age 30±7 years). Mean distance best corrected visual acuity at initial presentation was 0.21±0.3 logMAR (mean Snellen acuity: 20/30, range 20/15-20/100) and at last follow-up visit 0.09±0.17 logMAR (Snellen acuity: 20/20, range 20/15-20/60). All cases but one had bilateral lesions and showed typical parafoveal hyporeflective lesions on infrared imaging, which corresponded to the hyper-reflectivity in the Henle's layer with attenuation of the external limiting membrane, the ellipsoid zone and interdigitation zone. Underlying diseases included thrombocytopenia and anaemia associated with dengue fever, acute lymphoblastic leukaemia, chronic kidney disease and ulcerative colitis, while Valsalva-like manoeuvre was found to be a potential trigger. Other novel associations included the use of lisdexamphetamine. CONCLUSIONS: Classic AMN may be associated with leukaemia, dengue fever, ulcerative colitis and chronic kidney disease, probably as a result of chorioretinal hypoxia in the setting of thrombocytopenia and anaemia. Adrenergic agonists such as lisdexamphetamine may also contribute to the manifestation of AMN.

Numerical Magnitude Skills in 6-Years-Old Children: Exploring Specific Associations with Components of Executive Function

Little is known about how children learn to associate numbers with their corresponding magnitude and about individual characteristics contributing to performance differences on the numerical magnitude tasks within a relatively homogenous sample of 6-year-olds. The present study investigated the relationships between components of executive function and two different numerical magnitude skills in a sample of 162 kindergartners. The Symbolic Number Line was predicted by verbal updating and switching, whereas the Symbolic Magnitude Comparison was predicted by inhibition. Both symbolic tasks were predicted by visuo-spatial updating. Current findings suggest that visuo-spatial updating underlies young children’s retrieval and processing of numbers’ magnitude.

Changes in blood lipids and their associations with changes in measures of height, weight and body mass index from age 8 to 18 years: Project Heartbeat!

A variety of studies indicate that the process of athrosclerosis begins in childhood. There was limited information on the association of the changes in anthropometric variables to blood lipids in school age children and adolescents. Previous longitudinal studies of children typically with insufficient frequency of observation could not provide sound inference on the dynamics of change in blood lipids. The aims of this analysis are (1) to document the sex- and ethnic-specific trajectory and velocity curves of blood lipids (TC, LDL-C, HDL-C and TG); (2) to evaluate the relationship of changes in anthropometric variables, such as height, weight and BMI, to blood lipids from age 8 to 18 years. ^ Project HeartBeat! is a longitudinal study designed to examine the patterns of serial change in major cardiovascular risk factors. Cohort of three different age levels, 8, 11 and 14 years at baseline, with a total of 678 participants were enrolled. Each member of these cohorts was examined three times per year for up to four years. ^ Sex- and ethnic-specific trajectory and velocity curves of blood lipids; demonstrated the complex and polyphasic changes in TC, LDL-C, HDL-C and TG longitudinally. The trajectory curves of TC, LDL-C and HDL-C with age showed curvilinear patterns of change. The velocity change in TC, HDL-C and LDL-C showed U-shaped curves for non-Blacks, and nearly linear lines in velocity of TG for both Blacks and non-Blacks. ^ The relationship of changes in anthropometric variables to blood lipids was evaulated by adding height, weight, or BMI and associated interaction terms separately to the basic age-sex models. Height or height gain had a significant negative association with changes in TC, LDL-C and HDL-C. Weight or BMI gain showed positive associations with TC, LDL-C and TC, and a negative relationship with HDL-C. ^ Dynamic changes of blood lipids in school age children and adolescents observed from this analysis suggested that using fixed screening criteria under the current NCEP guidelines for all ages 2–19 may not be appropriate for this age group. The association of increasing BMI or weight to an adverse blood lipid profile found in this analysis also indicated that weight or BMI monitoring could be a future intervention to be implemented in the pediatric population. ^

Functional and physical associations of beta1 integrins in the activation of human T lymphocytes

Adhesion involves interactions between cells or cells with extracellular matrix components and is a fundamental process for all multicellular organisms as well as many pathogenic microbes. Integrins are heterodimeric transmembrane proteins that function as adhesion molecules and transduce signals between the extracellular environment and the intracellular cytoskeletal machinery. β1 integrin subfamily is highly expressed on T lymphocytes and mediates cell spreading, adhesion and coactivation. T lymphocytes have an important role in the regulation and homeostasis of the immune system therefore, the goals of this study were to first to investigate β1 integrin interaction with fibronectin binding protein A (FnbpA), a surface protein expressed on gram-negative bacteria Staphylococcus aureus. Second, characterize the association and function of a non-integrin surface protein, CD98, with β1 integrins on T lymphocytes. ^ FnbpA binds to fibronectin (FN), also a ligand for α5β1 and α4β1 integrins on T lymphocytes. Since both bacterial proteins FnbpA and T cell integrins utilize FN, it was of interest to determine the effects FnbpA on T cell activation. Results demonstrated that recombinant FnbpA (rFnbpA) coimmobilized with OKT3 mediated T cell coactivation in a soluble FN-dependent manner. Integrin α5β1 was identified as the main integrin utilized by Staphylococcus aureus FnbpA from studies using soluble antibodies to inhibit T cell proliferation and parallel plate flow chamber assays. The mechanism of rFnbpA-mediated coactivation was one that used soluble FN as a bridge between rFnbpA and integrin α5β1 on the T lymphocyte. ^ Since integrins are utilized by T lymphocytes and bacterial proteins, it was of interest to identify proteins involved in integrin regulation. Anti-CD98 mAb 80A10 was identified and characterized from a screen to identify surface proteins involved in integrin signaling and functions. CD98 is a non-integrin protein that was sensitive to integrin inhibition in human T lymphocyte aggregation and activation, thus suggested that CD98 shared a common signaling pathway with integrins. These results led to the question of whether CD98 physically associates with β1 integrins. Fluorescence microscopy and biochemical analysis determined that CD98 is specifically associated with β1 integrin on human T lymphocytes and may be part of a larger multimolecular signaling complex. ^

Adherence to a lifestyle physical activity program: Trends over time and associations with processes of change and physical activity

Research on lifestyle physical activity interventions suggests that they help individuals meet the new recommendations for physical activity made by the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM). The purpose of this research was to describe the rates of adherence to two lifestyle physical activity intervention arms and to examine the association between adherence and outcome variables, using data from Project PRIME, a lifestyle physical activity intervention based on the transtheoretical model and conducted by the Cooper Institute of Aerobics Research, Dallas, Texas. Participants were 250 sedentary healthy adults, aged 35 to 70 years, primarily non-Hispanic White, and in the contemplation and preparation stages of readiness to change. They were randomized to a group (PRIME G) or a mail- and telephone-delivered condition (PRIME C). Adherence measures included attending class (PRIME G), completing a monthly telephone call with a health educator (PRIME C), and completing homework assignments and self-monitoring minutes of moderate- to vigorous physical activity (both groups). In the first results paper, adherence over time and between conditions was examined: Attendance in group, completing the monthly telephone call, and homework completion decreased over time, and participants in PRIME G were more likely to complete homework than those in PRIME C. Paper 2 aimed to determine whether the adherence measures predicted achievement of the CDC/ACSM physical activity guideline. In separate models for the two conditions, a latent variable measuring adherence was found to predict achievement of the guideline. Paper 3 examined the association between adherence measures and the transtheoretical model's processes of change within each condition. For both, participants who completed at least two thirds of the homework assignments improved their use of the processes of change more than those who completed less than that amount. These results suggest that encouraging adherence to a lifestyle physical activity intervention, at least among already motivated volunteers, may increase the likelihood of beneficial changes in the outcomes. ^

Physiogenomic Analysis of Weight Loss Induced by Dietary Carbohydrate Restriction

ABSTRACT : BACKGROUND : Diets that restrict carbohydrate (CHO) have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. METHODS : We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy). A total of 27 single nucleotide polymorphisms (SNPs) were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. RESULTS : Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF), hepatic glycogen synthase (GYS2), cholesteryl ester transfer protein (CETP) and galanin (GAL) genes were significantly associated with weight loss. CONCLUSION : A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

Community Trails in Community Context: GIS Analysis of Associations between Trail and Neighborhood Characteristics

This research examines the site and situation characteristics of community trails as landscapes promoting physical activity. Trail segment and neighborhood characteristics for six trails in urban, suburban, and exurban towns in northeastern Massachusetts were assessed from primary Global Positioning System (GPS) data and from secondary Census and land use data integrated in a geographic information system (GIS). Correlations between neighborhood street and housing density, land use mix, and sociodemographic characteristics and trail segment characteristics and amenities measure the degree to which trail segment attributes are associated with the surrounding neighborhood characteristics.

Family Court Judges' Training, Background, and Child Development Knowledge: Associations with Child Custody Decision Making

Family court judges are often asked to make inferences about - or directly interview children to ascertain - children's custody preferences and their maturity to express such preferences. These estimates of children's developmental maturity are important to the judges' considerations of children's "best interests" in custody cases. The research literature describing family court judges' background, education, training, and knowledge about child development is scant. With appropriate child development knowledge, judges should be better able to identify the developmental stages at which children have the cognitive and social capabilities to communicate directly their placement wishes or concerns. The current study is the first to examine judges' estimates of - and actual tests of - their child development knowledge, their training/education, and their application of this knowledge to their decisions to involve children as participants in contested custody cases.

The Associations Between Social, Behavioral, and Health Risk Factors on a High School Student’s Decision to Pursue Post High School Plans

Background: Due to the relationship between SES and health, pursuing post high-school plans can lead to better future health outcomes for the student. The current paper assesses how behavioral and health risk factors, and family and social support, effect a student’s decision to pursue post high school plans. Methods: Data from the Youth Behavioral Component of the 2007 Connecticut School Health Survey were analyzed. Composite measures of exposure to/participation in violent behavior, mental and physical health, family/social support and substance abuse were created. The effects of these domains on the decision to pursue post high-school plans were assessed using logistic regression. Data were stratified by socioeconomic status. Results: Low SES students were more likely than high SES students to be doubtful for post high-school plans. Cocaine abuse emerged as the risk factor that put low SES students at the highest odds of not pursuing post high-school plans, followed by involvement in violent/aggressive behavior, and receiving less family/social support than their peers. Similar findings regarding violence and family/social support were found in the high SES group. Findings regarding substance abuse in the high SES group were not statistically significant. Discussion: Prevention programs regarding violence and substance abuse may have the added benefit of increasing the likelihood that high school students will make post high school plans. Preventing cocaine use among low SES students may be of particular importance. Violence prevention measures should be tailored to the target group. Adequate family/social support emerged as an encouraging factor for post high school plans.

Diabetes genes and risk of prostate cancer in the Atherosclerosis Risk in Communities study

Prostate cancer (PrCa) is a leading cause of morbidity and mortality, yet the etiology remains uncertain. Meta-analyses show that PrCa risk is reduced by 16% in men with type 2 diabetes (T2D), but the mechanism is unknown. Recent genome-wide association studies and meta-analyses have found single nucleotide polymorphisms (SNPs) that consistently predict T2D risk. We evaluated associations of incident PrCa with 14 T2D SNPs in the Atherosclerosis Risk in Communities (ARIC) study. From 1987-2000, there were 397 incident PrCa cases ascertained from state or local cancer registries among 6,642 men (1,560 blacks and 5,082 whites) aged 45-64 years at baseline. Genotypes were determined by TaqMan assay. Cox proportional hazards models were used to assess the association between PrCa and increasing number of T2D risk-raising alleles for individual SNPs and for genetic risk scores (GRS) comprised of the number of T2D risk-raising alleles across SNPs. Two-way gene-gene interactions were evaluated with likelihood ratio tests. Using additive genetic models, the T2D risk-raising allele was associated with significantly reduced risk of PrCa for IGF2BP2 rs4402960 (hazard ratio [HR]=0.79; P=0.07 among blacks only), SLC2A2 rs5400 (race-adjusted HR=0.85; P=0.05) and UCP2 rs660339 (race-adjusted HR=0.84; P=0.02), but significantly increased risk of PrCa for CAPN10 rs3792267 (race-adjusted HR=1.20; P=0.05). No other SNPs were associated with PrCa using an additive genetic model. However, at least one copy of the T2D risk-raising allele for TCF7L2 rs7903146 was associated with reduced PrCa risk using a dominant genetic model (race-adjusted HR=0.79; P=0.03). These results imply that the T2D-PrCa association may be partly due to shared genetic variation, but these results should be verified since multiple tests were performed. When the combined, additive effects of these SNPs were tested using a GRS, there was nearly a 10% reduction in risk of PrCa per T2D risk-raising allele (race-adjusted HR=0.92; P=0.02). SNPs in IGF2BP2, KCNJ11 and SLC2A2 were also involved in multiple synergistic gene-gene interactions on a multiplicative scale. In conclusion, it appears that the T2D-PrCa association may be due, in part, to common genetic variation. Further knowledge of T2D gene-PrCa mechanisms may improve understanding of PrCa etiology and may inform PrCa prevention and treatment.^

Identification of diabetic retinopathy genes through a genome-wide association study among Mexican-Americans from Starr County, Texas

To identify genetic susceptibility loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas completed detailed physical and ophthalmologic examinations including fundus photography for diabetic retinopathy grading. 103 individuals with moderate-to-severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy were defined as cases for this study. DNA samples extracted from study subjects were genotyped using the Affymetrix GeneChip® Human Mapping 100K Set, which includes 116,204 single nucleotide polymorphisms (SNPs) across the whole genome. Single-marker allelic tests and 2- to 8-SNP sliding-window Haplotype Trend Regression implemented in HelixTreeTM were first performed with these direct genotypes to identify genes/regions contributing to the risk of severe diabetic retinopathy. An additional 1,885,781 HapMap Phase II SNPs were imputed from the direct genotypes to expand the genomic coverage for a more detailed exploration of genetic susceptibility to diabetic retinopathy. The average estimated allelic dosage and imputed genotypes with the highest posterior probabilities were subsequently analyzed for associations using logistic regression and Fisher's Exact allelic tests, respectively. To move beyond these SNP-based approaches, 104,572 directly genotyped and 333,375 well-imputed SNPs were used to construct genetic distance matrices based on 262 retinopathy candidate genes and their 112 related biological pathways. Multivariate distance matrix regression was then used to test hypotheses with genes and pathways as the units of inference in the context of susceptibility to diabetic retinopathy. This study provides a framework for genome-wide association analyses, and implicated several genes involved in the regulation of oxidative stress, inflammatory processes, histidine metabolism, and pancreatic cancer pathways associated with severe diabetic retinopathy. Many of these loci have not previously been implicated in either diabetic retinopathy or diabetes. In summary, CDC73, IL12RB2, and SULF1 had the best evidence as candidates to influence diabetic retinopathy, possibly through novel biological mechanisms related to VEGF-mediated signaling pathway or inflammatory processes. While this study uncovered some genes for diabetic retinopathy, a comprehensive picture of the genetic architecture of diabetic retinopathy has not yet been achieved. Once fully understood, the genetics and biology of diabetic retinopathy will contribute to better strategies for diagnosis, treatment and prevention of this disease.^

Cross-cultural equivalence and associations among food insecurity and parental influences of children's fruit and vegetable consumption

Over the past several decades, the prevalence of obesity has dramatically increased. Cause for concern has increased because overweight and obesity are major contributors to morbidity and mortality. Intervention research aimed at reducing the prevalence of obesity has identified the family, specifically the parent, as a key component of the home environment. However, findings from dietary behavior change interventions have been disheartening because few studies have reported meaningful change, suggesting methodological and/or measurement issues within the intervention process. A lack of appropriate mediators and cross-cultural equivalence may partially explain the reason for little change.^ The study aims were to (1) evaluate the psychometric properties and assess the cross cultural equivalence of the Food Insecurity Scale (paper 1) and the modified Parent Feeding Practices Questionnaire (paper 2) and to assess the overall relationships among food insecurity, parent mediators, and parent behaviors towards children's dietary behavior (paper 3) through structural equation modeling and tests of invariance. The study aims were accomplished through conducting secondary analyses using baseline data from English- and Spanish-speaking Hispanic women who participated in the Healthy Families: Step by Step (BHF) study.^ Results indicated that although the FIS and the mPFPQ exhibited sound psychometric properties, the instruments exhibited a lack of invariance across language spoken groups. The lack of invariance was more pronounced in the FIS. Results also supported the theoretical framework identifying parent's perceived barriers and self-efficacy as mediators of parent's behaviors toward improving children's health eating. Results did not suggest that the relationships were moderated by food insecurity.^ In conclusion, the identification of differential item functioning in food insecurity and parent feeding practices may be beneficial in enhancing tailored interventions through the incorporation of cultural differences into the change mechanisms. However, future research needs to be conducted to determine if the lack of invariance demonstrates the existence of item bias or if it is a reflection of true difference among the language spoken groups. Additionally, obesity intervention studies targeting parent/family barriers and parent self-efficacy to provide/encourage healthy diets may result in an increase in parent behaviors which promote healthy eating behaviors among children. Future research should also examine a more complete causal pathway to determine whether parental changes in the mediators ultimately lead to an increase in healthy dietary behavior among children.^

Associations between vaccination and childhood cancers in Texas counties

Background. In Dr. Mel Greaves "delayed-infection hypothesis," postponed exposure to common infections increases the likelihood of childhood cancer. Hygienic advancements in developed countries have reduced children's exposure to pathogens and children encounter common infectious agents at an older age with an immune system unable to deal with the foreign antigens. Vaccinations may be considered to be simulated infections as they prompt an antigenic response by the immune system. Vaccinations may regulate the risk of childhood cancer by modulating the immune system. The aim of the study was to determine if children born in Texas counties with higher levels of vaccination coverage were at a reduced risk for childhood cancer.^ Methods. We conducted a case-control study to examine the risk of childhood cancers, specifically leukemia, brain tumors, and non-Hodgkin lymphoma, in relation to vaccination rates in Texas counties. We utilized a multilevel mixed-effects regression model of the individual data from the Texas Cancer Registry (TCR) with group-level exposure data (i.e., the county- and public health region-level vaccination rates).^ Results. Utilizing county-level vaccination rates and controlling for child's sex, birth year, ethnicity, birth weight, and mother's age at child's birth the hepatitis B vaccine revealed negative associations with developing all cancer types (OR = 0.81, 95% CI: 0.67–0.98) and acute lymphoblastic leukemia (ALL) (OR = 0.63, 95% CI: 0.46–0.88). The decreased risk for ALL was also evident for the inactivated polio vaccine (IPV) (OR = 0.67, 95% CI: 0.49–0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44-0.87). Using public health region vaccine coverage levels, an inverse association between the Haemophilus influenzae type b (Hib) vaccine and ALL (OR: 0.58; 95% CI: 0.42–0.82) was present. Conversely, the measles, mumps, and rubella (MMR) vaccine resulted in a positive association with developing non-Hodgkin lymphoma (OR = 2.81, 95% CI: 1.27–6.22). ^

Determining associations and assessing methodological issues in a case-control study of hazardous air pollutants and neural tube defects

Recent studies have reported positive associations between maternal exposures to air pollutants and several adverse birth outcomes. However, there have been no assessments of the association between environmental hazardous air pollutants (HAPs) such as benzene, toluene, ethylbenzene, and xylene (BTEX) and neural tube defects (NTDs) a common and serious group of congenital malformations. Before examining this association, two important methodological questions must be addressed: (1) is maternal residential movement likely to result in exposure misclassification and (2) is it appropriate to lump defects of the neural tube, such as anencephaly and spina bifida, into a composite disease endpoint (i.e., NTDs). ^ Data from the National Birth Defects Prevention Study and Texas Birth Defects Registry were used to: (1) assess the extent to which change of residence may result in exposure misclassification when exposure is based on the address at delivery; (2) formally assess heterogeneity of the associations between known risk factors for NTDs, using polytomous logistic regression; and (3) conduct a case-control study assessing the association between ambient air levels of BTEX and the risk of NTDs among offspring. ^ Regarding maternal residential mobility, this study suggests address at delivery was not significantly different from using address at conception when assigning quartile of benzene exposure (OR 1.0, 95% CI 0.9, 1.3). On the question of effect heterogeneity among NTDs, the effect estimates for infant sex P = 0.017), maternal body mass index P = 0.016), and folate supplementation P = 0.050) were significantly different for anencephaly and spina bifida, suggesting it is often more appropriate to assess potential risk factors among subgroups of NTDs. For the main study question on the association between environmental HAPs and NTDs, mothers who have offspring with isolated spina bifida are 2.4 times likely to live in areas with the highest benzene levels (95% CI 1.1, 5.0). However, no other significant associations were observed.^ This project is the first to include not only an assessment of the relationship between environmental levels of BTEX and NTDs, but also two separate studies addressing important methodological issues associated with this question. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes. ^