Neighborhood Characteristics and Elevated Blood Pressure in Older Adults

IMPORTANCE: The local environment remains an understudied contributor to elevated blood pressure among older adults. Untargeted approaches can identify neighborhood conditions interrelated with racial segregation that drive hypertension disparities. OBJECTIVE: To evaluate independent associations of sociodemographic, economic, and housing neighborhood factors with elevated blood pressure. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, the sample included Health and Retirement Study participants who had between 1 and 3 sets of biennial sphygmomanometer readings from 2006 to 2014 or 2008 to 2016. Statistical analyses were conducted from February 5 to November 30, 2021. EXPOSURES: Fifty-one standardized American Community Survey census tract variables (2005-2009). MAIN OUTCOMES AND MEASURES: Elevated sphygmomanometer readings over the study period (6-year period prevalence): a value of at least 140 mm Hg for systolic blood pressure and/or at least 90 mm Hg for diastolic blood pressure. Participants were divided 50:50 into training and test data sets. Generalized estimating equations were used to summarize multivariable associations between each neighborhood variable and the period prevalence of elevated blood pressure, adjusting for individual-level covariates. Any neighborhood factor associated (Simes-adjusted for multiple comparisons P ≤ .05) with elevated blood pressure in the training data set was rerun in the test data set to gauge model performance. Lastly, in the full cohort, race- and ethnicity-stratified associations were evaluated for each identified neighborhood factor on the likelihood of elevated blood pressure. RESULTS: Of 12 946 participants, 4565 (35%) had elevated sphygmomanometer readings (median [IQR] age, 68 [63-73] years; 2283 [50%] male; 228 [5%] Hispanic or Latino, 502 [11%] non-Hispanic Black, and 3761 [82%] non-Hispanic White). Between 2006 and 2016, a lower likelihood of elevated blood pressure was observed (relative risk for highest vs lowest tertile, 0.91; 95% CI, 0.86-0.96) among participants residing in a neighborhood with recent (post-1999) in-migration of homeowners. This association was precise among participants with non-Hispanic White and other race and ethnicity (relative risk, 0.91; 95% CI, 0.85-0.97) but not non-Hispanic Black participants (relative risk, 0.97; 95% CI, 0.85-1.11; P = .48 for interaction) or Hispanic or Latino participants (relative risk, 0.84; 95% CI, 0.65-1.09; P = .78 for interaction). CONCLUSIONS AND RELEVANCE: In this cohort study of older adults, recent relocation of homeowners to a neighborhood was robustly associated with reduced likelihood of elevated blood pressure among White participants but not their racially and ethnically marginalized counterparts. Our findings indicate that gentrification may influence later-life blood pressure control

Gender and ethnic disparities contributing to overweight in California adolescents

To explore differences in health behaviors and factors contributing to overweight among 12 to 17 year olds in California. Data from the 2005 California Health Interview Survey for 3,315 adolescents self-identified as Latino, Asian, or white were reviewed. Adolescents reported their weight, height, gender, ethnicity, parents’ educational level, household income, physical activity, sedentary activity, breakfast consumption, and family meals. Overall 34% of boys and 22% of girls in this study were overweight (>85th percentile for age and gender). Approximately 38% of Latinos, 25% of whites, and 16% of Asians were overweight. Latinos were more than twice as likely to be overweight as whites (2.07) and Asians (2.53). Younger adolescents (12–13 years old) and adolescents whose family income is less than 200% of the federal poverty level were more likely to be overweight. Low level of parental education is a risk factor for Latino and Asian girls and white and Latino boys. White girls with a lower socioeconomic status and white boys with more than 2 h daily of television, video, and computer time were more likely to be overweight. Results suggest gender and ethnic variations in factors that contribute to overweight in California adolescents. To influence the current overweight epidemic, clinicians must develop culturally sensitive and gender-specific interventions that address the unique needs of an ethnically diverse adolescent population

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Food Literacy while Shopping: Motivating Informed Food Purchasing Behaviour with a Situated Gameful App

Establishing healthy eating patterns early in life is critical and has implications for lifelong health. Situated interventions are a promising approach to improve eating patterns. How- ever, HCI research has emphasized calorie control and weight loss, potentially leading consumers to prioritize caloric in- take over healthy eating patterns. To support healthy eating more holistically, we designed a gameful app called Pirate Bri’s Grocery Adventure (PBGA) that seeks to improve food literacy—meaning the interconnected combination of food- related knowledge, skills, and behaviours that empower an individual to make informed food choices—through a situated approach to grocery shopping. Findings from our three-week field study revealed that PBGA was effective for improving players’ nutrition knowledge and motivation for healthier food choices and reducing their impulse purchases. Our findings highlight that nutrition apps should promote planning and shopping based on balance, variety, and moderation

The p53 Inhibitor MDM2 Facilitates Sonic Hedgehog-Mediated Tumorigenesis and Influences Cerebellar Foliation

Disruption of cerebellar granular neuronal precursor (GNP) maturation can result in defects in motor coordination and learning, or in medulloblastoma, the most common childhood brain tumor. The Sonic Hedgehog (Shh) pathway is important for GNP proliferation; however, the factors regulating the extent and timing of GNP proliferation, as well as GNP differentiation and migration are poorly understood. The p53 tumor suppressor has been shown to negatively regulate the activity of the Shh effector, Gli1, in neural stem cells; however, the contribution of p53 to the regulation of Shh signaling in GNPs during cerebellar development has not been determined. Here, we exploited a hypomorphic allele of Mdm2 (Mdm2puro), which encodes a critical negative regulator of p53, to alter the level of wild-type MDM2 and p53 in vivo. We report that mice with reduced levels of MDM2 and increased levels of p53 have small cerebella with shortened folia, reminiscent of deficient Shh signaling. Indeed, Shh signaling in Mdm2-deficient GNPs is attenuated, concomitant with decreased expression of the Shh transducers, Gli1 and Gli2. We also find that Shh stimulation of GNPs promotes MDM2 accumulation and enhances phosphorylation at serine 166, a modification known to increase MDM2-p53 binding. Significantly, loss of MDM2 in Ptch1+/− mice, a model for Shh-mediated human medulloblastoma, impedes cerebellar tumorigenesis. Together, these results place MDM2 at a major nexus between the p53 and Shh signaling pathways in GNPs, with key roles in cerebellar development, GNP survival, cerebellar foliation, and MB tumorigenesis

Introduction: Toward an Engaged Feminist Heritage Praxis

We advocate a feminist approach to archaeological heritage work in order to transform heritage practice and the production of archaeological knowledge. We use an engaged feminist standpoint and situate intersubjectivity and intersectionality as critical components of this practice. An engaged feminist approach to heritage work allows the discipline to consider women’s, men’s, and gender non-conforming persons’ positions in the field, to reveal their contributions, to develop critical pedagogical approaches, and to rethink forms of representation. Throughout, we emphasize the intellectual labor of women of color, queer and gender non-conforming persons, and early white feminists in archaeology

Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Bostonia: The Boston University Alumni Magazine. Volume 14

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Phenotypic Characterization of <i>EIF2AK4</i> Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of &lt;1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation. </jats:sec