The combined effect of motivational interviewing and wearable fitness trackers on motivation and physical activity in inactive adults: A randomized controlled trial.

Despite overwhelming adoption of wearable fitness trackers (WFT), it is unclear if they affect physical activity (PA) engagement or PA motivation. We hypothesized that combining a WFT with an effective intervention, motivational interviewing (MI), would positively influence both motivation and PA. A 12-week randomized controlled trial was conducted in 40 adults who did not meet PA recommendations. The four conditions were: a PA education (Educational control, n = 10), a WFT (WFT, n = 10), bi-weekly MI sessions (MI, n = 10), or both interventions (WFT+, n = 10). Motivation and PA were measured through an online survey and actigraphy pre- and post-intervention. Both the WFT+ and MI groups improved autonomous forms and decreased controlled forms of motivation. They also had higher basic psychological needs scores when compared to the Education group post-intervention. We detected no changes in PA. High autonomous motivation at baseline predicted higher post-intervention PA in the WFT+ group but predicted lower post-intervention PA in the WFT group. Results suggests that MI alone or with a WFT can improve basic psychological needs and autonomous forms of motivation for PA, but not PA participation. Individual differences in motivation at baseline may moderate the effect of a WFT on PA. This study was registered at clinicaltrials.gov (NCT490014).

Educational attainment of same-sex and opposite-sex dizygotic twins: An individual-level pooled study of 19 twin cohorts.

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (ß = -0.05 educational years, 95% CI -0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (ß = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.

Autonomous motivation and action planning are longitudinally associated with physical activity during adolescence and early adulthood.

We examined the associations of autonomous motivation, controlled motivation, and physical activity (PA) planning with PA participation over six years across the adolescent-to-adult transition. Participants from the NEXT Generation Health Study, a nationally representative cohort study of U.S. 10th graders (N=2785), completed surveys yearly from 2010 to 2016 (four years post-high school). This study used data from Waves 2 (W2) through 7 (W7). Data were analyzed using growth models accounting for the complex survey design and controlling for sex, race/ethnicity, and body mass index. A piecewise growth model with two pieces (Piece 1: W2-W4; Piece 2: W4-W7) indicated that PA declined during late adolescence (W2-W4) (b=-0.31, ß=-0.22, p<.001), but did not decline after the transition into early adulthood (W4-W7) (b=-0.08, ß=-0.04, p=.052). Autonomous motivation was positively associated with PA at all waves (b=0.23-0.33, ß=1.90-4.37, p<.001). Controlled motivation was only positively associated with PA at W3 (12th grade) (b=0.13, ß=1.54, p=.011). PA planning varied significantly between individuals and significantly predicted PA (b=0.44, ß=0.21, p<.001). Although PA decreased significantly during late adolescence, PA did not decrease significantly after transitioning into early adulthood (one to four years post-high school). Elevated autonomous motivation and PA planning were consistently and significantly associated with higher PA, suggesting that these may be useful intervention targets during this adolescent-to-adult transition.

Veterinary-prescribed physical activity promotes walking in healthy dogs and people.

BACKGROUND: Regular physical activity (PA) promotes health and can prevent and treat diseases among both humans and dogs. Unfortunately, most U.S. adults do not meet PA recommendations, and many dogs are also insufficiently active. Veterinary-prescribed PA programs have shown some success in increasing activity among overweight dogs, but the impacts of such programs have not yet been tested for efficacy among otherwise-healthy dogs and owners. In addition, although wearable devices that monitor PA and provide individuals with feedback (e.g., progress toward a daily step goal) can effectively increase human PA, it is unclear what impact similar wearable devices have on human and dog PA when the PA-monitoring devices are worn by dogs. The present study assessed the impact of an 8-week veterinary-prescribed PA program on activity and health among dogs and their owners, and randomized participants (n = 59) to two groups: one in which PA was measured but not visible to participants (n = 30), and one in which PA was measured and real time feedback was visible through a wearable device (n = 29). RESULTS: Participants in both groups showed significant PA increases over the course of the 8-week program. Biomedical testing performed at the veterinary clinic facilitated early diagnosis of systemic illness in one human participant. The frequency of hypertension in human participants decreased significantly from baseline to the end of the program (week 8). Other health indices (e.g., BMI in humans, body weight and BCS in dogs) improved, albeit not to a statistically significant extent, over the course of the program. There were no significant differences on the outcomes of interest between the two experimental conditions. CONCLUSIONS: Veterinary-prescribed PA programs appear promising for increasing PA among insufficiently active but otherwise healthy dogs as well as their owners. Additional testing of veterinary-prescribed PA is warranted, particularly at other types of veterinary clinics (e.g., private practices). Incorporating wearable devices permitting owners to track canine PA did not appear necessary for obtaining these benefits; however, additional studies investigating alternative devices or different time periods may be warranted.

C-reactive protein from dried blood spots: Application to household air pollution field studies.

Household air pollution (HAP) is estimated to be an important risk factor for cardiovascular disease, but little clinical evidence exists and collecting biomarkers of disease risk is difficult in low-resource settings. Among 54 Nicaraguan women with woodburning cookstoves, we evaluated cross-sectional associations between 48-hour measures of HAP (eg, fine particulate matter, PM2.5 ) and C-reactive protein (CRP) via dried blood spots; secondary analyses included seven additional biomarkers of systemic injury and inflammation. We conducted sub-studies to calculate the intraclass correlation coefficient (ICC) in biomarkers collected over four consecutive days in Nicaragua and to assess the validity of measuring biomarkers in dried blood by calculating the correlation with paired venous-drawn samples in Colorado. Measures of HAP were associated with CRP (eg, a 25% increase in indoor PM2.5 was associated with a 7.4% increase in CRP [95% confidence interval: 0.7, 14.5]). Most of the variability in CRP concentrations over the 4-day period was between-person (ICC: 0.88), and CRP concentrations were highly correlated between paired dried blood and venous-drawn serum (Spearman ρ = .96). Results for secondary biomarkers were primarily consistent with null associations, and the sub-study ICCs and correlations were lower. Assessing CRP via dried blood spots provides a feasible approach to elucidate the association between HAP and cardiovascular disease risk.

Early B Cell Factor 1 (EBF1) Regulates Glomerular Development by Controlling Mesangial Maturation and Consequently COX-2 Expression.

BACKGROUND: We recently showed the transcription factor Early B cell factor 1 (EBF1) is essential for the last stages of metanephric development, and that mice globally deficient in EBF1 display impaired maturation of peripheral glomeruli. EBF1 is present within multiple glomerular cell types, including the glomerular mesangium and podocytes. METHODS: To identify which cell type is driving the glomerular developmental defects in the global EBF1 knockout mice, we deleted EBF1 from the mesangium/pericytes (Foxd1-cre) or podocytes (Podocin-cre) in mice. RESULTS: Deletion of EBF1 from Foxd1 lineage cells resulted in hypoplastic kidneys, poorly differentiated peripheral glomeruli, and decreased proximal tubular mass in the outer cortex. Renal insufficiency was apparent at P21 when proteinuria presents, fibrosis of both the glomeruli and interstitium rapidly progresses, microthrombi appear, and hematuria develops. Approximately half of the Foxd1+, Ebf1fl/fl mice die before they are 3 months old. Mice with podocyte-targeted deletion of EBF1 exhibited no developmental abnormalities. Mice with Ebf1 deficiency in Foxd1 lineage cells shared characteristics with Ptgs2/COX-2-insufficient models, and mechanistic investigation revealed impaired calcineurin/NFATc1 activation and decreased COX-2 expression. Deletion of COX-2 from the interstitial/mesangial lineage displayed a less severe phenotype than EBF1 deficiency in mice. Overexpressing COX-2 in the EBF1-deficient mice, however, partially restored glomerular development. CONCLUSIONS: The results suggest that EBF1 regulates metanephric development at the last stages of glomerular maturation through its actions in the stromal progenitor (Foxd1+) lineage where it mediates proper regulation of calcineurin/NFAT signaling and COX-2 expression.

Exposure to household air pollution from biomass cookstoves and self-reported symptoms among women in rural Honduras.

Household air pollution from combustion of solid fuels is an important risk factor for morbidity and mortality, causing an estimated 2.6 million premature deaths globally in 2016. Self-reported health symptoms are a meaningful measure of quality of life, however, few studies have evaluated symptoms and quantitative measures of exposure to household air pollution. We assessed the cross-sectional association of self-reported symptoms and exposures to household air pollution among women in rural Honduras using stove type (traditional [n = 76]; cleaner-burning Justa [n = 74]) and 24-hour average personal and kitchen fine particulate matter (PM2.5) concentrations. The odds of prevalent symptoms were higher among women using traditional stoves vs Justa stoves (e.g. headache: odds ratio = 2.23; 95% confidence interval = 1.13-4.39). Associations between symptoms and measured PM2.5 were generally consistent with the null. These results add to the evidence suggesting reduced exposures and better health-related quality of life among women using cleaner-burning biomass stoves.

Household air pollution from biomass-burning cookstoves and metabolic syndrome, blood lipid concentrations, and waist circumference in Honduran women: A cross-sectional study.

BACKGROUND: Household air pollution from cooking with solid fuels affects nearly 3 billion people worldwide and is responsible for an estimated 2.5 million premature deaths and 77 million disability-adjusted life years annually. Investigating the effect of household air pollution on indicators of cardiometabolic disease, such as metabolic syndrome, can help clarify the pathways between this widespread exposure and cardiovascular diseases, which are increasing in low- and middle-income countries. METHODS: Our cross-sectional study of 150 women in rural Honduras (76 with traditional stoves and 74 with cleaner-burning Justa stoves) explored the effect of household air pollution exposure on cardiovascular disease risk factors. Household air pollution was measured by stove type and 24-h average kitchen and personal fine particulate matter [PM2.5] mass and black carbon concentrations. Health endpoints included non-fasting total cholesterol, high-density lipoprotein, calculated low-density lipoprotein, triglycerides, waist circumference to indicate abdominal obesity, and presence of metabolic syndrome (defined by current modified international guidelines: waist circumference ≥ 80 cm plus any two of the following: triglycerides > 200 mg/dL, HDL < 50 mg/dL, systolic blood pressure ≥ 130 mmHg, diastolic blood pressure ≥ 85 mmHg, or glycated hemoglobin > 5.6%). RESULTS: Forty percent of women met the criteria for metabolic syndrome. The prevalence ratio [PR] for metabolic syndrome (versus normal) per interquartile range increase in kitchen PM2.5 and kitchen black carbon was 1.16 (95% confidence interval [CI]: 1.01-1.34) per 312 µg/m3 increase in PM2.5, and 1.07 (95% CI: 1.03-1.12) per 73 µg/m3 increase in black carbon. There is suggestive evidence of a stronger effect in women ≥ 40 years of age compared to women < 40 (p-value for interaction = 0.12 for personal PM2.5). There was no evidence of associations between all other exposure metrics and health endpoints. CONCLUSIONS: The prevalence of metabolic syndrome among our study population was high compared to global estimates. We observed a suggestive effect between metabolic syndrome and exposure to household air pollution. These results for metabolic syndrome may be driven by specific syndrome components, such as blood pressure. Longitudinal research with repeated health and exposure measures is needed to better understand the link between household air pollution and indicators of cardiometabolic disease risk.

Exposure to household air pollution from biomass cookstoves and blood pressure among women in rural Honduras: A cross-sectional study.

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed cross-sectional associations of 24-hour mean concentrations of personal and kitchen fine particulate matter (PM2.5 ), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleaner-burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24-hour PM2.5 concentrations of 126 µg/m3 (77) and 360 µg/m3 (374), while Justa stove users' exposures were 66 µg/m3 (38) and 137 µg/m3 (194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7-4.3) per unit increase in natural log-transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3-8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0-2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups.

Study protocol for a stepped-wedge randomized cookstove intervention in rural Honduras: household air pollution and cardiometabolic health.

BACKGROUND: Growing evidence links household air pollution exposure from biomass-burning cookstoves to cardiometabolic disease risk. Few randomized controlled interventions of cookstoves (biomass or otherwise) have quantitatively characterized changes in exposure and indicators of cardiometabolic health, a growing and understudied burden in low- and middle-income countries (LMICs). Ideally, the solution is to transition households to clean cooking, such as with electric or liquefied petroleum gas stoves; however, those unable to afford or to access these options will continue to burn biomass for the foreseeable future. Wood-burning cookstove designs such as the Justa (incorporating an engineered combustion zone and chimney) have the potential to substantially reduce air pollution exposures. Previous cookstove intervention studies have been limited by stove types that did not substantially reduce exposures and/or by low cookstove adoption and sustained use, and few studies have incorporated community-engaged approaches to enhance the intervention. METHODS/DESIGN: We conducted an individual-level, stepped-wedge randomized controlled trial with the Justa cookstove intervention in rural Honduras. We enrolled 230 female primary cooks who were not pregnant, non-smoking, aged 24-59 years old, and used traditional wood-burning cookstoves at baseline. A community advisory board guided survey development and communication with participants, including recruitment and retention strategies. Over a 3-year study period, participants completed 6 study visits approximately 6 months apart. Half of the women received the Justa after visit 2 and half after visit 4. At each visit, we measured 24-h gravimetric personal and kitchen fine particulate matter (PM2.5) concentrations, qualitative and quantitative cookstove use and adoption metrics, and indicators of cardiometabolic health. The primary health endpoints were blood pressure, C-reactive protein, and glycated hemoglobin. Overall study goals are to explore barriers and enablers of new cookstove adoption and sustained use, compare health endpoints by assigned cookstove type, and explore the exposure-response associations between PM2.5 and indicators of cardiometabolic health. DISCUSSION: This trial, utilizing an economically feasible, community-vetted cookstove and evaluating endpoints relevant for the major causes of morbidity and mortality in LMICs, will provide critical information for household air pollution stakeholders globally. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02658383 , posted January 18, 2016, field work completed May 2018. Official title, "Community-Based Participatory Research: A Tool to Advance Cookstove Interventions." Principal Investigator Maggie L. Clark, Ph.D. Last update posted July 12, 2018.

Otitis Media: Rapid Evidence Review.

Acute otitis media (AOM) is the most common diagnosis in childhood acute sick visits. By three years of age, 50% to 85% of children will have at least one episode of AOM. Symptoms may include ear pain (rubbing, tugging, or holding the ear may be a sign of pain), fever, irritability, otorrhea, anorexia, and sometimes vomiting or lethargy. AOM is diagnosed in symptomatic children with moderate to severe bulging of the tympanic membrane or new-onset otorrhea not caused by acute otitis externa, and in children with mild bulging and either recent-onset ear pain (less than 48 hours) or intense erythema of the tympanic membrane. Treatment includes pain management plus observation or antibiotics, depending on the patient's age, severity of symptoms, and whether the AOM is unilateral or bilateral. When antibiotics are used, high-dose amoxicillin (80 to 90 mg per kg per day in two divided doses) is first-line therapy unless the patient has taken amoxicillin for AOM in the previous 30 days or has concomitant purulent conjunctivitis; amoxicillin/clavulanate is typically used in this case. Cefdinir or azithromycin should be the first-line antibiotic in those with penicillin allergy based on risk of cephalosporin allergy. Tympanostomy tubes should be considered in children with three or more episodes of AOM within six months or four episodes within one year with one episode in the preceding six months. Pneumococcal and influenza vaccines and exclusive breastfeeding until at least six months of age can reduce the risk of AOM.

Risk of Atherosclerotic Cardiovascular Disease Among US Adults: Use of 1999-2014 NHANES Data.

One in four deaths in the US is caused by cardiovascular disease (CVD), and early detection may be a key aspect of prevention. We assessed the probability of a first hard atherosclerotic cardiovascular disease (ASCVD) event within 10 years in US Non-Hispanic White and African American population aged 40-79 years. With data from 16 years of the National Health and Nutrition Examination Survey (NHANES), we utilized the 2013 Pooled Cohort Equations developed by the American College of Cardiology and the American Heart Association to calculate risk scores for a representative sample. NHANES is a repeated, cross-sectional survey aimed at assessing the health and nutritional status of the country. Out of 17,087 eligible participants, a sample of 1876 (11%) remained for the analysis after excluding participants missing data required to compute the scores. Our results showed that 25.2% of the sample had a greater than 10% risk of contracting ASCVD within 10 years, and we also found sex-, race-, and age-based disparities. The ASCVD risk scores can thus be used to evaluate the general cardiac health of the population. Results showed that a quarter of the US adult population was at risk to contract ASCVD in the next 10 years, indicating the need for targeted preventative measures. With the aging population and rise in obesity rates, these results may also indicate trend continuation of high CVD-related morbidity and mortality.

Interactions Between Diet and Exposure to Secondhand Smoke on Glycated Hemoglobin Levels Among US Children: Results From NHANES 2007-2012.

INTRODUCTION: Antioxidant-rich diets may lessen the adverse metabolic responses triggered by exposure to secondhand smoke (SHS), but no studies have investigated these potential interactions. OBJECTIVE: To examine the interaction between diet and exposure to SHS on glycated hemoglobin (HbA1c) levels among 2551 children, ages 12-19 years, who participated in the 2007-2012 National Health and Nutrition Examination Survey (NHANES). METHODS: Exposure to SHS was assessed by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), cotinine, and self-report. Weighted linear regression models evaluated the cross-sectional association between exposure to SHS and HbA1c levels. Additive interaction was assessed by introducing product terms (with SHS) of individual nutrients (dietary fiber, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], vitamin C, and vitamin E) to separate models. RESULTS: Over half of the children had NNAL or cotinine levels above the limit of detection (56% and 71%, respectively). The median HbA1c level was 5.2% (95% confidence interval: 5.17%, 5.23%). The interaction results suggest that the effects of exposure to SHS and certain dietary nutrients (EPA, DHA, vitamin C) on HbA1c levels may not be independent. For example, although there was only a slight difference in adjusted mean HbA1c levels across NNAL categories among children with high EPA intakes, the adjusted mean HbA1c level was 0.09% higher for high NNAL as compared to low NNAL among children with low EPA intakes. CONCLUSIONS: Further research is needed to inform public health strategies for limiting increases in HbA1c levels among children. Messages may need to focus both on reducing exposure to SHS and improving diets to obtain the maximum benefit. IMPLICATIONS: Our results suggest that the effects of exposure to SHS and diet on HbA1c levels may not be independent. For example, although there was little effect of exposure to SHS on HbA1c levels among children with high EPA intakes, high exposure to SHS was associated with an increase in HbA1c levels among children with low EPA intakes. Further research is necessary; however, based on these joint effects, strategies for limiting increases in HbA1c levels that focus both on reducing exposure to SHS and improving diets may achieve the largest public health benefits.

Cognitive decline and the PPAR-γ Pro12Ala genotype: variation by sex and ethnicity.

Objective: We investigated the association between the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12Ala polymorphism and cognitive decline in older adults. Methods: Participants from a population-based cohort of older Hispanic and non-Hispanic white adults (n = 492) were administered the Mini Mental State Examination (MMSE), a multi-domain cognitive screening tool, and the Behavioral Dyscontrol Scale (BDS), a measure of executive cognitive function, at baseline and at follow-up, an average of 22 months later. Multiple linear regression was used to investigate the association between the two cognitive test scores and the Pro12Ala polymorphism. Results: At baseline, presence of the Ala12 allele was not significantly associated with MMSE score (P = 0.62) nor with BDS score (P = 0.85). Heterogeneity was present for cognitive decline as measured by the MMSE among ethnic, sex and Ala12 allele status (P = 0.04 for three-way interaction term). Stratification by the cross-classification of sex and ethnicity revealed significantly greater declines in MMSE score among male Hispanic carriers of the Ala12 allele compared to male Hispanic non-carriers (decline = 4.0 versus 1.6 points; P = 0.02). A significant difference in decline between Ala12 carriers and non-carriers was not present among the other sex/ethnic groups. Conclusions: Carriers of the PPAR-γ Ala12 allele showed greater cognitive decline compared to non-carriers as detected by the MMSE but the risk varied across sex and ethnic groups. Male Ala12 carriers of Hispanic origin may be a high-risk group for cognitive decline.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation.

The coordination of multiple cytokines and transcription factors with their downstream signaling pathways has been shown to be integral to nephron maturation. Here we present a completely novel role for the helix-loop-helix transcription factor Early B-cell factor 1 (Ebf1), originally identified for B-cell maturation, for the proper maturation of glomerular cells from mesenchymal progenitors. The expression of Ebf1 was both spatially and temporally regulated within the developing cortex and glomeruli. Using Ebf1-null mice, we then identified biochemical, metabolic, and histological abnormalities in renal development that arose in the absence of this transcription factor. In the Ebf1 knockout mice, the developed kidneys show thinned cortices and reduced glomerular maturation. The glomeruli showed abnormal vascularization and severely effaced podocytes. The mice exhibited early albuminuria and elevated blood urea nitrogen levels. Moreover, the glomerular filtration rate was reduced >66% and the expression of podocyte-derived vascular endothelial growth factor A was decreased compared with wild-type control mice. Thus, Ebf1 has a significant and novel role in glomerular development, podocyte maturation, and the maintenance of kidney integrity and function.

Deletion of the transcription factor EBF1 in perivascular stroma disrupts skeletal homeostasis and precipitates premature aging of the marrow microenvironment.

Early B cell factor 1 (EBF1) is a transcription factor expressed by multiple lineages of stromal cells within the bone marrow. While cultures of Ebf1-deficient cells have been demonstrated to have impaired differentiation into either the osteoblast or adipogenic lineage in vitro by several groups, in vivo there has been a nominal consequence of the loss of EBF1 on skeletal development. In this study we used Prx-cre driven deletion of Ebf1 to eliminate EBF1 from the entire mesenchymal lineage of the skeleton and resolve this discrepancy. We report here that EBF1 is expressed primarily in the Mesenchymal Stem and Progenitor Cell (MSPC)-Adipo, MSPC-Osteo, and the Early Mesenchymal Progenitors, and that loss of EBF1 has a plethora of consequences to maintenance of the skeleton throughout adulthood. Stroma from the Prx-cre;Ebf1fl/fl bones had impaired osteogenic differentiation, an age-dependent loss of CFU-F, and elevated senescence accompanying Ebf1-deletion. New bone formation was reduced after 3 months, and resulted in a quiescent bone environment with fewer osteoblasts and an accompanied reduction in osteoclast-mediated remodeling. Consequently, bones were less ductile at a younger age, and deletion of EBF1 dramatically impaired fracture repair. Disruption of EBF1 in perivascular populations also rearranged the vascular network within these bones and disrupted cytokine signaling from key hematopoietic niches resulting in anemia, reductions in B cells, and myeloid skewing of marrow hematopoietic lineages. Mechanistically we observed disrupted BMP signaling within Ebf1-deficient progenitors with reduced SMAD1-phosphorylation, and elevated secretion of the soluble BMP-inhibitor Gremlin from the MSPC-Adipo cells. Ebf1-deficient progenitors also exhibited posttranslational suppression of glucocorticoid receptor expression. Together, these results suggest that EBF1 signaling is required for mesenchymal progenitor mobilization to maintain the adult skeleton, and that the primary action of EBF1 in the early mesenchymal lineage is to promote proliferation, and differentiation of these perivascular cells to sustain a healthy tissue.

Maternal Risk of Cardiovascular Disease Is Associated With Higher BMI Among Preschool-Aged Children: A Cross-Sectional Study.

Childhood obesity is an ongoing concern in the United States. Higher weight status in early childhood is associated with higher weight status at older ages. The Maternal Obesity Matters (MOMs) Study investigated associations between maternal risk of cardiovascular disease (CVD) and child BMI z-scores (BMIz) among preschool-aged children. This cross-sectional exploratory study included mothers and their 3- to 5-year-old children in Colorado, United States. Maternal nonfasting blood samples, blood pressure, and maternal and child anthropometrics were collected. Maternal CVD risk was assessed on a scale of 0-5 using five health measures. Multivariate regression tested associations between maternal CVD risk and child BMIz. Each 1-point increase in maternal CVD risk was associated with a 0.18 increase in child BMIz, controlling for maternal employment. Intervening upon maternal health may be an important strategy for addressing childhood obesity.