Embryonic statistical analyses reveal 2 growth phenotypes in mouse models of Down syndrome.

BACKGROUND: Down syndrome is associated with several comorbidities, including intellectual disability, growth restriction, and congenital heart defects. The prevalence of Down syndrome-associated comorbidities is highly variable, and intellectual disability, although fully penetrant, ranges from mild to severe. Understanding the basis of this interindividual variability might identify predictive biomarkers of in utero and postnatal outcomes that could be used as endpoints to test the efficacy of future therapeutic interventions. OBJECTIVE: The main objective of this study was to examine if antenatal interindividual variability exists in mouse models of Down syndrome and whether applying statistical approaches to clinically relevant measurements (ie, the weights of the embryo, placenta, and brain) could define cutoffs that discriminate between subgroups of trisomic embryos. STUDY DESIGN: Three commonly used mouse models of Down syndrome (Dp(16)1/Yey, Ts65Dn, and Ts1Cje) and a new model (Ts66Yah) were used in this study. Trisomic and euploid littermate embryos were used from each model with total numbers of 102 for Ts66Yah, 118 for Dp(16)1/Yey, 92 for Ts65Dn, and 126 for Ts1Cje. Placental, embryonic, and brain weights and volumes at embryonic day 18.5 were compared between genotypes in each model. K-mean clustering analysis was applied to embryonic and brain weights to identify severity classes in trisomic embryos, and brain and placental volumetric measurements were compared between genotypes and classes for each strain. In addition, Ts66Yah embryos were examined for malformations because embryonic phenotypes have never been examined in this model. RESULTS: Reduced body and brain weights were present in Ts66Yah, Dp(16)1/Yey, and Ts65Dn embyos. Cluster analysis identified 2 severity classes in trisomic embryos-mild and severe-in all 4 models that were distinguishable using a putative embryonic weight cutoff of <0.5 standard deviation below the mean. Ts66Yah trisomic embryos develop congenital anomalies that are also found in humans with Down syndrome, including congenital heart defects and renal pelvis dilation. CONCLUSION: Statistical approaches applied to clinically relevant measurements revealed 2 classes of phenotypic severity in trisomic mouse models of Down syndrome. Analysis of severely affected trisomic animals may facilitate the identification of biomarkers and endpoints that can be used to prenatally predict outcomes and the efficacy of treatments.

Life under stay-at-home orders: a panel study of change in social interaction and emotional wellbeing among older Americans during COVID-19 pandemic.

BACKGROUND: Recent research has shown the mental health consequence of social distancing during the COVID-19 pandemic, but longitudinal data are relatively scarce. It is unclear whether the pattern of isolation and elevated stress seen at the beginning of the pandemic persists over time. This study evaluates change in social interaction over six months and its impact on emotional wellbeing among older adults. METHODS: We drew data from a panel study with six repeated assessments of social interaction and emotional wellbeing conducted monthly May through October 2020. The sample included a total of 380 White, Black and Hispanic participants aged 50 and over, of whom 33% had low income, who residing in fourteen U.S. states with active stay-at-home orders in May 2020. The analysis examined how change in living arrangement, in-person interaction outside the household, quality of relationship with family and friends, and perceived social support affected trajectories of isolation stress, COVID worry and sadness. RESULTS: While their living arrangements (Odds Ratio [OR] = 0.95, 95% Confidence Interval [CI] = 0.87, 1.03) and relationship quality (OR = 0.94, 95% CI = 0.82, 1.01) remained stable, older adults experienced fluctuations in perceived social support (linear Slope b = -1.42, s.e. = 0.16, p < .001, quadratic slope b = 0.50, s.e. = 0.08, p < .001, cubic slope b = -0.04, s.e. = 0.01, p < .001) and increases in in-person conversations outside the household (OR = 1.19, 95% CI = 1.09, 1.29). Living with a spouse/partner stabilized isolation stress (change in linear slope b = 1.16, s.e. = 0.48, p < .05, in quadratic slope b = -0.62, s.e. = 0.26, p < .05, and in cubic slope = 0.09, s.e. = 0.04, p < .05) and COVID worry (change in quadratic slope b = -0.66, s.e. = 0.32, p < .05 and in cubic slope = 0.09, s.e. = 0.04, p < .05) over time. Individuals with better relationship quality with friends had decreased sadness over time (OR = 0.90, 95% CI = 0.82, 0.99). Changes in social support were associated with greater fluctuations in isolation stress and COVID worry. CONCLUSIONS: During the pandemic, social interactions are protective and lack of stability in feeling supported makes older adults vulnerable to stress. Efforts should focus on (re)building and maintaining companionship and support to mitigate the pandemic's negative impact.

A Bayesian hierarchical logistic regression model of multiple informant family health histories.

BACKGROUND: Family health history (FHH) inherently involves collecting proxy reports of health statuses of related family members. Traditionally, such information has been collected from a single informant. More recently, research has suggested that a multiple informant approach to collecting FHH results in improved individual risk assessments. Likewise, recent work has emphasized the importance of incorporating health-related behaviors into FHH-based risk calculations. Integrating both multiple accounts of FHH with behavioral information on family members represents a significant methodological challenge as such FHH data is hierarchical in nature and arises from potentially error-prone processes. METHODS: In this paper, we introduce a statistical model that addresses these challenges using informative priors for background variation in disease prevalence and the effect of other, potentially correlated, variables while accounting for the nested structure of these data. Our empirical example is drawn from previously published data on families with a history of diabetes. RESULTS: The results of the comparative model assessment suggest that simply accounting for the structured nature of multiple informant FHH data improves classification accuracy over the baseline and that incorporating family member health-related behavioral information into the model is preferred over alternative specifications. CONCLUSIONS: The proposed modelling framework is a flexible solution to integrate multiple informant FHH for risk prediction purposes.

Activating Communal Coping Related to Diabetes Risk in Mexican-Heritage Families.

We investigate how interpersonal ties influence communication about type 2 diabetes risk and encouragement to maintain or adopt a healthy lifestyle between family members of Mexican heritage, after a family history-based risk assessment intervention. Results suggest that individuals are more likely to initiate risk communication with another family member if they are close to, already seek advice from, or discuss health with him or her. Risk communication precedes encouragement, which is initiated by the older generation of the family. Understanding the role of interpersonal relationships in Mexican-heritage families can help identify who best to target in future health behavior interventions.

Developing Shared Appraisals of Diabetes Risk Through Family Health History Feedback: The Case of Mexican-Heritage Families.

Background: Collecting complete and accurate family health history is critical to preventing type 2 diabetes. Purpose: We seek to identify the optimal risk feedback approach that facilitates risk communication between parents and their adult children and helps them develop shared appraisals of family history of type 2 diabetes. Methods: In a sample of parent-adult child dyads from 125 Mexican-heritage families residing in Houston, Texas, we examine change in parent-child dyadic (dis)agreement with respect to their shared family health history from baseline to 10 months after receipt of risk feedback generated by Family Healthware. A 2 × 2 factorial design is applied to test how the recipient (one parent or all family members) and the content (risk assessment with or without behavioral recommendations) of the feedback affect (dis)agreement through interpersonal ties, particularly dyadic risk communication. Results: Providing risk assessment without behavioral recommendations to the parent, but not the adult child, shifts the dyads toward agreement (relative risk ratio [RRR]= 1.78, 95% confidence interval [CI] [1.18-2.67]), by activating reciprocal risk communication between parents and children (RRR =2.70, 95% CI [1.81-4.03]). Dyads with close interpersonal ties are more likely to shift toward agreement (RRR = 3.09, 95% CI [1.89-5.07]). Conclusion: Programs aimed at improving family health history knowledge and accuracy of reports should tailor risk feedback strategically for better intervention effect and leverage a network approach in disease prevention among at-risk minority and/or immigrant populations. Trial Registration Number: NCT00469339.

Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes.

Macrolides antibiotics have been effectively used in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were determined from patients who were diagnosed with bronchiectasis isolated with or without P. aeruginosa and treated with azithromycin for 3-5 days. Azithromycin treatment enhanced bacterial clearance and attenuated lung injury in mice chronically infected with P. aeruginosa, which resulted from the inhibition of caspase-1-dependent IL-1ß and IL-18 secretion. In vitro, azithromycin and erythromycin inhibited NLRC4 and NLRP3 inflammasomes activation. Plasma IL-18 levels were higher in bronchiectasis patients with P. aeruginosa isolation compared with healthy controls. Azithromycin administration markedly decreased IL-18 secretion in bronchiectasis patients. The results of this study reveal that azithromycin and erythromycin exert a novel anti-inflammatory effect by attenuating inflammasomes activation, which suggests potential treatment options for inflammasome-related diseases.

Motivating Mexican American adults to share family history with healthcare providers.

Family history of metabolic conditions is a primary factor for clinicians to consider when administering preventive care. Sharing this information with healthcare providers proactively is therefore important to individual health outcomes. This brief report seeks to identify factors associated with sharing family history with healthcare providers in individuals of Mexican heritage. Data were obtained from a health education intervention study conducted during 2008-2010, which recruited 497 adult participants from 162 multigenerational households in Houston, Texas to receive family history-based risk feedback generated by Family Healthware™. Households were randomized to receive a pedigree of metabolic conditions or a pedigree coupled with supplementary information about one's personalized risk assessment and behavioral recommendations. Participants completed two follow-up surveys at three and ten months post intervention, respectively. Analysis based on 296 participants from 147 households who read but did not share their feedback at three-month follow-up suggests benefits of providing personalized risk assessment and tailored behavioral recommendations in addition to a simple pedigree. Participants receiving supplementary risk feedback are more likely to share it with family members at three-month follow-up, which is associated with increased sharing and willingness to share risk feedback with healthcare providers at ten-month follow-up. The findings highlight the importance of family relationships in medical information disclosure in Mexican American adults. Future interventions should capitalize on family relationships in health education and promotion programs for optimal prevention of metabolic conditions in at-risk populations.

Inter-Individual Variability in Trajectories of Functional Limitations by Race/Gender.

OBJECTIVE: Several theories emphasize that systematic interindividual divergence is a key feature of cohort aging and evidence for accumulative social inequality over the life course. While many have documented widening health gaps with age between subgroups, such divergence is only one aspect of the broader social inequality based on race and gender. This article examines patterns of interindividual variability in trajectories of functional limitations within each race/gender. METHODS: Using data from the Health and Retirement Study (HRS)'s HRS cohort (born 1931-1941), I estimate growth curves of functional limitations with Level 2 heteroscedasticity, allowing interindividual variability to differ across 4 groups: white men, black men, white women, and black women. I examine race/gender differences in the age-based pattern of interindividual variability using an interquartile range of estimated individual trajectories. RESULTS: Black men, white women, and black women have greater interindividual variability in functional limitations than do white men. Interindividual variability increases systematically with age at similar rates for all groups but black women. DISCUSSION: Functional limitations become more heterogeneous with age for the entire cohort and for white men, white women, and black men. Future research should identify life-course processes that generate the race and gender patterning of interindividual variability in late-life health.

Belief and behavior aspects of the EAT-26: The case of schoolgirls in Belize.

This study investigates components of eating attitudes in a sample of Belizean schoolgirls and argues for separate analysis of eating beliefs and eating behaviors using the EAT-26 in populations undergoing rapid cultural change. The EAT-26 was utilized in a novel manner, preserving the ethnographic and empirical distinction between belief and behavior components of eating attitudes. Participants included a sample of secondary schoolgirls (n = 80) undergoing acculturative stress. Participants reported more disordered eating beliefs than behaviors. Respondents having higher belief scores than behavior scores were more likely to prefer thinner body build and to be concerned about boys' assessments of their bodies. Girls with higher behavior scores were less likely to report eating when hungry and stopping when full. In conclusion, discriminant validity was found between attitudinal and behavioral aspects of the EAT-26 as evidenced by face validity and patterns in predicting body image preference and desired weight change. Such a distinction has implications for assessing risk for disordered eating among populations undergoing acculturative stress. Among such populations, while behavioral symptoms might be absent or present in subclinical levels, disordered beliefs associated with psychological distress or potential precursors to eating-disordered behavior might be detected and should be investigated further.

Racial differences in family health history knowledge of type 2 diabetes: exploring the role of interpersonal mechanisms.

Collecting complete and accurate family health history is critical to preventing type 2 diabetes. Whether there are any racial difference in family health history knowledge of type 2 diabetes and whether such differences are related to interpersonal mechanisms remain unclear. We seek to identify the interpersonal mechanisms that give rise to discrepancies in family health history knowledge of type 2 diabetes in families of different racial backgrounds. We analyze informant-dyad consensus with respect to shared family history of type 2 diabetes in 127 informants of 45 families in the greater Cincinnati area (white: 28 families, 78 informants; black/African-American: 17 families, 49 informants). We first document a difference in informant-dyad consensus by race and then test whether this difference can be explained by interpersonal ties, particularly health communication. Compared with their white counterparts, dyads in families of black/African-American background are more likely to have an uneven distribution of knowledge, with one informant knowing and the other not knowing his/her family health history. The racial difference is explained by dyads in families of black/African-American background having fewer reciprocal health communication ties. While associated with informant-dyad consensus, education, kinship ties, and closeness ties do not account for the observed racial difference. Activating health communication is a key to improving family health history knowledge, especially in families of black/African-American background. Researchers and clinicians should leverage communication ties in the family network for better collection and utilization of family health history in preventive services.

From Noise to Signal: The Age and Social Patterning of Intra-Individual Variability in Late-Life Health.

OBJECTIVES: Despite a long tradition of attending to issues of intra-individual variability in the gerontological literature, large-scale panel studies on late-life health disparities have primarily relied on average health trajectories, relegating intra-individual variability over time to random error terms, or "noise." This article reintegrates the systematic study of intra-individual variability back into standard growth curve modeling and investigates the age and social patterning of intra-individual variability in health trajectories. METHOD: Using panel data from the Health and Retirement Study, we estimate multilevel growth curves of functional limitations and cognitive impairment and examine whether intra-individual variability in these two health outcomes varies by age, gender, race/ethnicity, and socioeconomic status, using level-1 residuals extracted from the adjusted growth curve models. RESULTS: For both outcomes, intra-individual variability increases with age. Racial/ethnic minorities and individuals with lower socioeconomic status tend to have greater intra-individual variability in health. Relying exclusively on average health trajectories may have masked important "signals" of life course health inequality. DISCUSSION: The findings contribute to scientific understanding of the source of heterogeneity in late-life health and highlight the need to further investigate specific life course mechanisms that generate the social patterning of intra-individual variability in health status.

Intraindividual Variability in Late-Life Functional Limitations Among White, Black, and Hispanic Older Adults.

Consistent with the weathering hypothesis, many studies have captured racial/ethnic disparities in average functional health trajectories. The same mechanisms of social inequality that contribute to worse average health among minority adults may also contribute to greater fluctuations in their physical function at upper ages. Using panel data from the Health and Retirement Study, we examine patterns of intraindividual variability over time in trajectories of functional limitations for White, Black, and Hispanic older adults. Intraindividual variability increases with age for both Whites and Blacks and such increase is greater for Blacks. Hispanics have the greatest intraindividual variability but there is no age-based pattern. Socioeconomic status and comorbidity are associated with intraindividual variability for all race/ethnicity yet do not explain the age-based increase in intraindividual variability for Whites or Blacks. The findings suggest further nuances to the weathering hypothesis-social disadvantage can generate instability in physical function as minority adults age.

The Continued Eclipse of Heterogeneity in Gerontological Research.

OBJECTIVES: After a long history of neglect, diversity among older people and increasing heterogeneity with age are now familiar ideas in gerontological discourse. We take up the question of whether this increased attention is translating into the domain of empirical research. We replicate Nelson and Dannefer's (1992) review of the treatment of age-based variability in gerontological research, the most recent known assessment of the issue. METHOD: A sample of empirical studies was drawn from six gerontological journals to determine (a) whether measures of within-age variability were reported and/or discussed and (b) if reported, the observed age-based pattern of variability in the outcome(s). RESULTS: The majority of studies neither reported nor discussed age-based variability. Among those that did report, the great majority indicated either stability or increasing variability with age. Observed patterns varied by outcome type. Although a majority of analyses of psychological and social outcomes suggested that variability was stable across age, half of the analyses of biological/health outcomes indicated increasing variability. Overall, very few (3%) of studies suggested decreasing variability. DISCUSSION: Consistent with earlier reports of studies, researchers continue to focus on average differences between age groups, yet key issues in social gerontology require attention to intra-age variability.

Put the Family Back in Family Health History: A Multiple-Informant Approach.

INTRODUCTION: An accurate family health history is essential for individual risk assessment. This study uses a multiple-informant approach to examine whether family members have consistent perceptions of shared familial risk for four common chronic conditions (heart disease, Type 2 diabetes, high cholesterol, and hypertension) and whether accounting for inconsistency in family health history reports leads to more accurate risk assessment. METHODS: In 2012-2013, individual and family health histories were collected from 127 adult informants of 45 families in the Greater Cincinnati Area. Pedigrees were linked within each family to assess inter-informant (in)consistency regarding common biological family member's health history. An adjusted risk assessment based on pooled pedigrees of multiple informants was evaluated to determine whether it could more accurately identify individuals affected by common chronic conditions, using self-reported disease diagnoses as a validation criterion. Analysis was completed in 2015-2016. RESULTS: Inter-informant consistency in family health history reports was 54% for heart disease, 61% for Type 2 diabetes, 43% for high cholesterol, and 41% for hypertension. Compared with the unadjusted risk assessment, the adjusted risk assessment correctly identified an additional 7%-13% of the individuals who had been diagnosed, with a ≤2% increase in cases that were predicted to be at risk but had not been diagnosed. CONCLUSIONS: Considerable inconsistency exists in individual knowledge of their family health history. Accounting for such inconsistency can, nevertheless, lead to a more accurate genetic risk assessment tool. A multiple-informant approach is potentially powerful when coupled with technology to support clinical decisions.

Bronchiectasis in China.

Bronchiectasis is a common but long-neglected disease in China, causing a substantial disease burden both to patients and to society. The overall prevalence of physician-diagnosed bronchiectasis in people aged 40 years or older is estimated at 1.2% and is trending upward with aging of the population. The etiology of bronchiectasis has not been identified heretofore in more than 70% of patients in China, although pneumonia and tuberculosis still appear to be the most common causes of acquired bronchiectasis. Etiologies, comorbidities, and infecting organisms vary greatly across previously published epidemiological studies, resulting in considerable uncertainty. Little is known about the spectrum of severity of bronchiectasis in China. Presently, engagement of pulmonologists is largely limited to acute treatment of exacerbations of severe bronchiectasis. Based on limited available data and expert consensus, the first comprehensive guidelines for the diagnosis and treatment of bronchiectasis in China were published in 2012. Research to advance medical care for patients with this disease in China should focus on several priorities, including: standardization of diagnostic criteria with appropriate application of computed tomographic imaging; use of validated multidimensional grading systems to assess the severity of bronchiectasis; and epidemiological studies that are designed to measure mild to moderate as well as severe disease, and to represent the population beyond large urban centers. Better estimates of the true burden of bronchiectasis are needed to guide allocation of national medical resources and to implement public health strategies for prevention of the disease. Treatment should be expanded to include expert maintenance care of ambulatory patients in addition to treatment of exacerbations.

Can we capture the intersections? Older Black women, education, and health.

BACKGROUND: Race/ethnicity, gender, and socioeconomic status are the three most prominent factors to predict health outcomes. Despite the fact that persistent health inequalities are found between groups, we know little about how the interrelatedness of these social positions influences the health of older adults. PURPOSE: In this study, we apply a feminist intersectional approach to the study of health inequalities, treating social variables as multiplicative rather than additive to capture the mutually constitutive dimensions of race/ethnicity, gender, and education. METHODS: This paper makes use of data from the National Social Life, Health and Aging Project, a nationally representative sample of 3,005 community-dwelling U.S. adults aged 57 to 85 years old, to explore intersections of race, gender, and education. We use a combination of stratified analysis with an interaction term to test multiplicative effects. RESULTS: First, our findings confirm that Black women with less than a high school education have the poorest self-rated health. Second, at the bivariate level, we find highly educated White men are not the converse of lower educated Black women. Third, at the multivariate level, we find being Black and female has an effect on health beyond those already accounted for by race and gender. CONCLUSION: This research demonstrates the explanatory power of an intersectionality approach to deepen understanding of the overlapping, simultaneous production of health inequalities by race, class, and gender.