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Aims Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. Methods and results In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. Conclusion Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Telomere length is often used in studies of adults as a biomarker of cellular aging and an indicator of stress exposure. However, we know little about how telomeres change over time, particularly over the course of the important developmental period of adolescence. We use data on telomere length collected at two points in time spanning adolescence (Years 9 and 15) from the Fragile Families and Child Wellbeing Study to examine longitudinal patterns (n = 1,654) in telomere length. We find a quantitatively small but significant average lengthening in telomere length across adolescence and little evidence of associations between telomere length and pubertal development. [ABSTRACT FROM AUTHOR]

Background and Objectives Although individual age and preexisting health conditions are well-documented risk factors for coronavirus disease 2019 (COVID-19) mortality, it is unclear whether these 2 factors capture unique dimensions of risk for epidemic severity at the national level. In addition, no studies have examined whether national distributions of these factors are associated with epidemic experiences to date. Research Design and Methods Drawing on surveys of older adults from 42 countries and estimated case fatality ratios by age and preexisting health conditions, we document and compare national profiles of COVID-19 mortality risks among older adults. We develop 2 measures of national risk profiles: one based on age structures and another based on distributions of preexisting health conditions. Our analysis compares these constructs and documents their associations with national COVID-19 mortality rates. Results National profiles of COVID-19 mortality risk based on age structure and preexisting health conditions are moderately uncorrelated, capturing different aspects of risk. Both types of national risk profiles correlate meaningfully with countries' COVID-19 mortality experiences to date. Discussion and Implications Measures of population age structure are readily available for every country in the world, while cross-national measures of older adult population health are more limited. In the COVID-19 crisis, these factors give different pictures of the countries with high and low risks of COVID-19 mortality. Moreover, our results suggest that both types of national risk profiles based on population health reflect current COVID-19 mortality severity in several countries, highlighting the need for more cross-national comparative data on older adult population health. [ABSTRACT FROM AUTHOR]

Emergency contraceptive (EC) pills may be less effective for women with higher body mass index (BMI), but little is known about public response to the fact that EC may lose efficacy as weight increases. In November 2013, European authorities changed the label for a levonorgestrel EC product to warn of a reduction in effectiveness for women with higher BMI, garnering significant media coverage in the United States. Ulipristal acetate (UPA) EC may be more effective than levonorgestrel for women with BMI levels designated as obese. Among 8,019 women who received UPA from the online pharmacy KwikMed from 2011 to 2015 and self-reported their height, weight and reasons for seeking UPA online, we analyzed changes in the proportion of women in different BMI categories before and after the label change. For the 25 month-period after the label change, the proportion of women in the obese category rose by 26.7 percentage points relative to the 35 months before (B = 0.2665, p <.01). Mean BMI (25.5 versus 29.4, p <.001) and average weight (148.6 pounds versus 175.5 pounds, p <.001) of users were higher after the label change. Some women appear to have acted on the information that EC efficacy may be associated with body weight. [ABSTRACT FROM AUTHOR]

Introduction: Upper-limb amputations make up 10% to 20% of the total amputations in the United States. Of the two million individuals currently living with limb loss, 30% to 50% do not wear their prosthesis regularly. This is a result of lack of education, lack of training, discomfort, poor cosmetics, and cost. Three-dimensional (3D) printing may provide a cost-effective alternative for upper-limb prostheses. The purpose of this pilot study was to test and compare efficiency and functional capabilities of a 3D-printed and commercially available manufactured myoelectric hand. Materials and Methods: The research team designed a quasi-experimental, static group comparison trial. A box and blocks test was used to assess the efficiency of the i-limb and Limbitless Arm. The two prosthetic hands were tested over two visits with a 2-week crossover period. Two custom devices, to which the two hands attach distally, were created to accommodate the ablebodied subjects. Results: Twenty-four able-bodied (mean age, 26.1 ± 4.2 yrs), healthy, right-hand--dominant participants were recruited for this study. There were 14men and 10 women. Themean number of blocks using the Limbitless Armwas significantly lower than the i-limb. For trial 1, the mean was 8.4 ± 3.6 versus 12.9 ± 3.3 (P < 0.001). For trial 2, the mean was 8.3 ± 3.6 versus 13.8 ± 4.1 (P < 0.001). Furthermore, the mean number of blocks improved when using the i-limb versus the 3D-printed hand by 53.6% in trial 1 and 66.3% in trial 2. Similar findings were obtained when we ran the analyses separately for men (trial 1, the mean was 9.1 ± 3.3 vs. 12.9 ± 3.7, P = 0.01 and trial 2, the mean was 9.6 ± 3.2 vs. 14.1 ± 4.7, P = 0.02) and women (trial 1, the mean 7.5 ± 3.9 vs. 12.8 ± 2.9, P = 0.00 and trial 2, the mean 6.3 ± 3.4 vs. 13.4 ± 3.2, P = 0.00). Conclusions: The results and observations made by the researchers suggested the i-limb was more efficient than the Limbitless Arm. There is a potential for 3D-printed prostheses to be a viable option for prosthetic care in the future with better development and technological advancements. However, at this point,myoelectric prostheses such as the i-limb aremore practical and effective. [ABSTRACT FROM AUTHOR]

The present study explores how genital self-image may be related to considerations of surgically altering one's genitals and documents the wanted genital changes among young adults. Evidence of a nontrivial proportion of respondents (98 of 1,110) had seriously considered elective genital surgery. Regression models indicate that, for both men and women, identifying as heterosexual and reporting lower composite genital self-image scores results in higher odds of considering genital surgery. Additionally for men, feeling unsatisfied with penis size increased the odds. Clinical and educational efforts to normalize and celebrate genital variation may influence considerations for genital modification in young adults. [ABSTRACT FROM AUTHOR]

Atrial natriuretic peptide (NP) and BNP increase cGMP, which reduces blood pressure and cardiac hypertrophy by activating guanylyl cyclase (GC)-A, also known as NPR-A or Npr1. Although GC-A is highly phosphorylated, and dephosphorylation inactivates the enzyme, the significance of GC-A phosphorylation to heart structure and function remains unknown. To identify in vivo processes that are regulated by GC-A phosphorylation, we substituted glutamates for known phosphorylation sites to make GC-A8E/8E mice that express an enzyme that cannot be inactivated by dephosphorylation. GC-A activity, but not protein, was increased in heart and kidney membranes from GC-A8E/8E mice. Activities were threefold higher in female compared to male cardiac ventricles. Plasma cGMP and testosterone were elevated in male and female GC-A8E/8E mice, but aldosterone was only increased in mutant male mice. Plasma and urinary creatinine concentrations were decreased and increased, respectively, but blood pressure and heart rate were unchanged in male GC-A8E/8E mice. Heart weight to body weight ratios for GC-A8E/8E male, but not female, mice were 12% lower with a 14% reduction in cardiomyocyte cross-sectional area. Subcutaneous injection of fsANP, a long-lived ANP analog, increased plasma cGMP and decreased aldosterone in male GC-AWT/WT and GC-A8E/8E mice at 15 min, but only GC-A8E/8E mice had elevated levels of plasma cGMP and aldosterone at 60 min. fsANP reduced ventricular ERK1/2 phosphorylation to a greater extent and for a longer time in the male mutant compared to WT mice. Finally, ejection fractions were increased in male but not female hearts from GC-A8E/8E mice. We conclude that increased phosphorylation-dependent GC-A activity decreases cardiac ERK activity, which results in smaller male hearts with improved systolic function. [ABSTRACT FROM AUTHOR]

A portable, handheld electrospinning apparatus is designed and constructed using off-the-shelf components and 3D-printed parts. The portable electrospinner is used to generate nanofibers with diameters ranging from 85 to 600 nm; examination of these fibers is achieved with scanning electron microscopy. This portable electrospinner has similar capabilities to standard stationary benchtop electrospinners in terms of the diversity of polymers the device is able to spin into nanofibers and their resulting size and morphology. However, it provides much more ambulatory flexibility, employs current-limiting measures that allow for safer operation and is cost effective. As a demonstration of the device's unique application space afforded by its portability, the device is applied in direct-to-skin electrospinning to improve the aesthetics of simulated hair loss in a mouse model by electrospinning dyed polyacrylonitrile nanofibers that mimic hair. The superficial nanofiber treatment for thinning hair is able to achieve an improvement in appearance similar to that of a commercially available powder product but outperforms the powder in the nanofiber's superior adherence to the affected area. The portable electrospinning apparatus overcomes many limitations of immobile benchtop electrospinners and holds promise for applications in consumer end-use scenarios such as the treatment of alopecia via cosmetic hair thickening. [ABSTRACT FROM AUTHOR]

Objectives. To identify factors that influence when people who use drugs (PWUDs) call 911 for an overdose. Methods. We conducted 45 qualitative interviews and 180 surveys with PWUDs who had recently witnessed overdoses in Southern California from 2017 to 2019. We used conditional inference tree and random forest models to generate and validate a model to predict whether 911 would be called. Results. Our model had good in- (83%) and out-of-sample (84%) predictive accuracy. Three aspects of the social and policy environment influenced calling 911 for an overdose: the effectiveness of response strategies employed, the behavior of other bystanders, and whether the responder believes it is their responsibility to call. Conclusions. Even in the presence of policies that provide some protections, PWUDs are faced with difficult decisions about calling 911 and must weigh their own safety against that of an overdose victim. Potential interventions include strengthening training and safety planning for PWUDs, bolstering protections for PWUDs when they call 911, and separating law enforcement response from emergency medical response to overdoses.

In the social upheaval arising from the coronavirus disease 2019 (COVID-19) pandemic, we do not yet know how union formation, particularly marriage, has been affected. Using administration records-marriage certificates and applications-gathered from settings representing a variety of COVID-19 experiences in the United States, the authors compare counts of recorded marriages in 2020 against those from the same period in 2019. There is a dramatic decrease in year-to-date cumulative marriages in 2020 compared with 2019 in each case. Similar patterns are observed for the Seattle metropolitan area when analyzing the cumulative number of marriage applications, a leading indicator of marriages in the near future. Year-to-date declines in marriage are unlikely to be due solely to closure of government agencies that administer marriage certification or reporting delays. Together, these findings suggest that marriage has declined during the COVID-19 outbreak and may continue to do so, at least in the short term., (© The Author(s) 2020.)

Telomeres are repetitive nucleotide sequences located at the ends of chromosomes that protect genetic material. We use data from the Fragile Families and Child Wellbeing Study to analyze the relationship between exposure to spatially concentrated disadvantage and telomere length for white and black mothers. We find that neighborhood disadvantage is associated with shorter telomere length for mothers of both races. This finding highlights a potential mechanism through which the unique spatially concentrated disadvantage faced by African Americans contributes to racial health disparities. We conclude that equalizing the health and socioeconomic status of black and white Americans will be very difficult without reducing levels of residential segregation in the United States.