Differentiation Syndrome, a Side Effect From the Therapy of Acute Promyelocytic Leukemia.

Differentiation Syndrome is a complication of all-trans retinoic acid (ATRA) therapy in patients with acute promyelocytic leukemia (APML). It appears clinically as acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates. When symptoms develop, physicians are recommended to stop ATRA therapy to minimize complications and reduce mortality immediately. This case report describes a 67-year-old male who was diagnosed with acute promyelocytic leukaemia after he developed episodes of hematuria and easy bruising at home. After beginning a treatment regime of ATRA, steroids, and arsenic, the patient began to have symptoms of differentiation syndrome.

A Cumulative Deficit Laboratory Test-based Frailty Index: Personal and Neighborhood Associations.

OBJECTIVES: To explore the association between a newly developed cumulative laboratory-based frailty index (FI) and intrinsic (personal) and extrinsic (social, environmental) characteristics. DESIGN: Cross-sectional longitudinal study. SETTING: The third and fourth waves of the community-representative, five-county, 10-year Duke Established Populations for Epidemiologic Studies of the Elderly study, carried out in a health service-rich area. PARTICIPANTS: Cognitively intact survivors of the third wave (N = 1,740), who provided blood samples for standard laboratory work. MEASUREMENTS: Biomarkers (n = 28) were measured to develop a cumulative deficit laboratory test-based FI (Duke FI) derived from standard laboratory tests: SMAC-24 chemistry panel, high-density lipoprotein cholesterol panel, and complete blood count. Information was gathered on scales assessing intrinsic characteristics (personal locus of control, life satisfaction, self-esteem, depressive symptomatology) and extrinsic characteristics (support received from and provided to family and friends, stressful life events, neighborhood disadvantage). RESULTS: The newly developed Duke FI had content, construct, concurrent, and predictive validity. In addition to sex, race, and income, the Duke FI was associated at the intrinsic level with locus of control, self-esteem, life satisfaction, and depressive symptomatology (each P < .01) and at the extrinsic level with provision (P < .01) and with receipt of instrumental help (P < .10), social stressors (P < .03), and neighborhood disadvantage (P < .01) in unadjusted analysis; race fully explained neighborhood disadvantage. CONCLUSION: Intrinsic (personality) characteristics and personally close extrinsic characteristics (contacts with family and friends, personal stressors) are associated with laboratory test-based frailty, as is neighborhood disadvantage, although in this accessible, health service-rich environment, race fully explained association with neighborhood disadvantage, suggesting that interventions to reduce frailty in residents in such an environment should pay particular attention to characteristics that immediately affect the individual.

Neighborhood and Family Environment of Expectant Mothers May Influence Prenatal Programming of Adult Cancer Risk: Discussion and an Illustrative DNA Methylation Example.

Childhood stressors including physical abuse predict adult cancer risk. Prior research portrays this finding as an indirect mechanism that operates through coping behaviors, including adult smoking, or through increased toxic exposures during childhood. Little is known about potential direct causal mechanisms between early-life stressors and adult cancer. Because prenatal conditions can affect gene expression by altering DNA methylation, with implications for adult health, we hypothesize that maternal stress may program methylation of cancer-linked genes during gametogenesis. To illustrate this hypothesis, we related maternal social resources to methylation at the imprinted MEG3 differentially methylated regulatory region, which has been linked to multiple cancer types. Mothers (n = 489) from a diverse birth cohort (Durham, North Carolina) provided newborns' cord blood and completed a questionnaire. Newborns of currently married mothers showed lower (-0.321 SD, p < .05) methylation compared to newborns of never-married mothers, who did not differ from newborns whose mothers were cohabiting and others (adjusted for demographics). MEG3 DNA methylation levels were also lower when maternal grandmothers co-resided before pregnancy (-0.314 SD, p < .05). A 1-SD increase in prenatal neighborhood disadvantage also predicted higher methylation (-0.137 SD, p < .05). In conclusion, we found that maternal social resources may result in differential methylation of MEG3, which demonstrates a potential partial mechanism priming socially disadvantaged newborns for later risk of some cancers.

Maternal blood lead concentrations, DNA methylation of MEG3 DMR regulating the DLK1/MEG3 imprinted domain and early growth in a multiethnic cohort.

Prenatal exposure to lead (Pb) is known to decrease fetal growth; but its effects on postnatal growth and mechanistic insights linking Pb to growth are not clearly defined. Genomically imprinted genes are powerful regulators of growth and energy utilization, and may be particularly vulnerable to environmental Pb exposure. Because imprinting is established early and maintained via DNA methylation, we hypothesized that prenatal Pb exposure alters DNA methylation of imprinted genes resulting in lower birth weight and rapid growth. Pb was measured by inductively coupled plasma mass spectrometry (ICP-MS) in peripheral blood of 321 women of the Newborn Epigenetic STudy (NEST) obtained at gestation ~12 weeks. Linear and logistic regression models were used to evaluate associations between maternal Pb levels, methylation of differentially methylated regions (DMRs) regulating H19, MEG3, PEG3, and PLAGL1, measured by pyrosequencing, birth weight, and weight-for-height z score gains between birth and age 1yr, ages 1-2yrs, and 2-3yrs. Children born to women with Pb levels in the upper tertile had higher methylation of the regulatory region of the MEG3 DMR imprinted domain (ß= 1.57, se= 0.82, p= 0.06). Pb levels were also associated with lower birth weight (ß= -0.41, se= 0.15, p= 0.01) and rapid gains in adiposity (OR= 12.32, 95%CI=1.25-121.30, p= 0.03) by age 2-3 years. These data provide early human evidence for Pb associations with hypermethylation at the MEG3 DMR regulatory region and rapid adiposity gain-a risk factor for childhood obesity and cardiometabolic diseases in adulthood.

Chicago Residents' Perceptions of Air Quality: Objective Pollution, the Built Environment, and Neighborhood Stigma Theory.

Substantial research documents higher pollution levels in minority neighborhoods, but little research evaluates how residents perceive their own communities' pollution risks. According to "Neighborhood stigma" theory, survey respondents share a cultural bias that minorities cause social dysfunction, leading to over-reports of dysfunction in minority communities. This study investigates perceptions of residential outdoor air quality by linking objective data on built and social environments with multiple measures of pollution and a representative survey of Chicago residents. Consistent with the scholarly narrative, results show air quality is rated worse where minorities and poverty are concentrated, even after extensive adjustment for objective pollution and built environment measures. Perceptions of air pollution may thus be driven by neighborhood socioeconomic position far more than by respondents' ability to perceive pollution. The finding that 63.5% of the sample reported excellent or good air quality helps to explain current challenging in promoting environmental action.

Geographic clustering of elevated blood heavy metal levels in pregnant women.

BACKGROUND: Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) exposure is ubiquitous and has been associated with higher risk of growth restriction and cardiometabolic and neurodevelopmental disorders. However, cost-efficient strategies to identify at-risk populations and potential sources of exposure to inform mitigation efforts are limited. The objective of this study was to describe the spatial distribution and identify factors associated with Cd, Pb, Hg, and As concentrations in peripheral blood of pregnant women. METHODS: Heavy metals were measured in whole peripheral blood of 310 pregnant women obtained at gestational age ~12 weeks. Prenatal residential addresses were geocoded and geospatial analysis (Getis-Ord Gi* statistics) was used to determine if elevated blood concentrations were geographically clustered. Logistic regression models were used to identify factors associated with elevated blood metal levels and cluster membership. RESULTS: Geospatial clusters for Cd and Pb were identified with high confidence (p-value for Gi* statistic <0.01). The Cd and Pb clusters comprised 10.5 and 9.2 % of Durham County residents, respectively. Medians and interquartile ranges of blood concentrations (µg/dL) for all participants were Cd 0.02 (0.01-0.04), Hg 0.03 (0.01-0.07), Pb 0.34 (0.16-0.83), and As 0.04 (0.04-0.05). In the Cd cluster, medians and interquartile ranges of blood concentrations (µg/dL) were Cd 0.06 (0.02-0.16), Hg 0.02 (0.00-0.05), Pb 0.54 (0.23-1.23), and As 0.05 (0.04-0.05). In the Pb cluster, medians and interquartile ranges of blood concentrations (µg/dL) were Cd 0.03 (0.02-0.15), Hg 0.01 (0.01-0.05), Pb 0.39 (0.24-0.74), and As 0.04 (0.04-0.05). Co-exposure with Pb and Cd was also clustered, the p-values for the Gi* statistic for Pb and Cd was <0.01. Cluster membership was associated with lower education levels and higher pre-pregnancy BMI. CONCLUSIONS: Our data support that elevated blood concentrations of Cd and Pb are spatially clustered in this urban environment compared to the surrounding areas. Spatial analysis of metals concentrations in peripheral blood or urine obtained routinely during prenatal care can be useful in surveillance of heavy metal exposure.

A disadvantaged advantage in walkability: findings from socioeconomic and geographical analysis of national built environment data in the United States.

Urban form-the structure of the built environment-can influence physical activity, yet little is known about how walkable design differs according to neighborhood sociodemographic composition. We studied how walkable urban form varies by neighborhood sociodemographic composition, region, and urbanicity across the United States. Using linear regression models and 2000-2001 US Census data, we investigated the relationship between 5 neighborhood census characteristics (income, education, racial/ethnic composition, age distribution, and sex) and 5 walkability indicators in almost 65,000 census tracts in 48 states and the District of Columbia. Data on the built environment were obtained from the RAND Corporation's (Santa Monica, California) Center for Population Health and Health Disparities (median block length, street segment, and node density) and the US Geological Survey's National Land Cover Database (proportion open space and proportion highly developed). Disadvantaged neighborhoods and those with more educated residents were more walkable (i.e., shorter block length, greater street node density, more developed land use, and higher density of street segments). However, tracts with a higher proportion of children and older adults were less walkable (fewer street nodes and lower density of street segments), after adjustment for region and level of urbanicity. Research and policy on the walkability-health link should give nuanced attention to the gap between persons living in walkable areas and those for whom walkability has the most to offer.

The association of health and income in the elderly: experience from a southern state of Brazil.

OBJECTIVES: In high income, developed countries, health status tends to improve as income increases, but primarily through the 50(th)-66(th) percentile of income. It is unclear whether the same limitation holds in middle income countries, and for both general assessments of health and specific conditions. METHODS: Data were obtained from Brazil, a middle income country. In-person interviews with a representative sample of community residents age ≥ 60 (N=6963), in the southern state of Rio Grande do Sul, obtained information on demographic characteristics including household income and number of persons supported, general health status (self-rated health, functional status), depression, and seven physician-diagnosed, self-reported health conditions. Analyses used household income (adjusted for number supported and economies of scale) together with higher order income terms, and controlled for demographics and comorbidities, to ascertain nonlinearity between income and general and specific health measures. RESULTS: In fully controlled analyses income was associated with general measures of health (linearly with self-rated health, nonlinearly with functional status). For specific health measures there was a consistent linear association with depression, pulmonary disorders, renal disorders, and sensory impairment. For musculoskeletal, cardiovascular (negative association), and gastrointestinal disorders this association no longer held when comorbidities were controlled. There was no association with diabetes. CONCLUSION: Contrary to findings in high income countries, the association of household-size-adjusted income with health was generally linear, sometimes negative, and sometimes absent when comorbidities were controlled.

Neighborhood context and social disparities in cumulative biological risk factors.

OBJECTIVE: This study examines the role of neighborhood context in the accumulation of biological risk factors and racial/ethnic and socioeconomic disparities. METHODS: Data came from face-to-face interviews and blood sample collection on a probability sample of adults (n = 549) in the 2002 Chicago Community Adult Health Study. Following the approach of prior studies, we constructed an index of cumulative biological risk (CBR) by counting how many of eight biomarkers exceeded clinically defined criteria for "high risk": systolic and diastolic blood pressure, resting heart rate, hemoglobin A(1c), C-reactive protein, waist size, and total and high-density lipoprotein cholesterol. Data are presented as incidence rate ratios (IRRs) based on generalized linear models with a Poisson link function and population-average estimates with robust standard errors. RESULTS: Non-Hispanic blacks (n = 200), Hispanics (n = 149), and people with low (n = 134) and moderate (n = 275) level of education had significantly higher numbers of biological risks than their respective reference groups (IRR = 1.48, 1.59, 1.62, and 1.48, respectively, with p < .01). Black-white (p < .001) and Hispanic-white (p < .003) disparities in CBR remained significant after adjusting for individual-level socioeconomic position and behavioral factors, whereas individual-level controls substantially diminished the low/high (p < .069) and moderate/high (p < .042) educational differences. Estimating "within-neighborhood" disparities to adjust for neighborhood context fully explained the black-white gap in CBR (p < .542) and reduced the Hispanic-white gap to borderline significance (p < .053). Neighborhood affluence predicted lower levels of CBR (IRR = 0.82, p < .027), but neighborhood disadvantage was not significantly associated with CBR (IRR = 1.00, p < .948). CONCLUSIONS: Neighborhood environments seem to play a pivotal role in the accumulation of biological risk and disparities therein.