Suicidality Among Black Women: Considering Resiliency Within the Historic and Societal Context of Risk

Suicide is a global health challenge that has been historically understudied among Black women. The interpersonal-psychological theory of suicidality (IPTS) is a primary theory examined in suicidality; however, the three factors within the theory (lack of belongingness, perceived burdensomeness, and capability to die) focus on the individual. The purpose of the current study was to examine these factors in an expanded context of the historical and societal impact of oppression. A mixed methods Qualtrics study was administered to Black women who voluntarily completed the survey anonymously. Quantitatively, the study found significant differences between the impact of the IPTS factors on different ecological systems (self, immediate environment, community, larger culture) within participants’ lives. The study also revealed significant differences between the assessed factors that impacted participants in general, and more specifically contributed to their suicidality. Qualitatively, there were also differences across ecological systems. Themes emerged around financial stressors and trauma related to risk, and family, jobs, and comradery of experience amongst protective factors. Moving forward, prevention and intervention efforts should take the lived experiences of Black women into account

Timing of Childhood Adversities and Self-Injurious Thoughts and Behaviors in Adolescence

Greater childhood adversity predicts a higher likelihood of later self-injurious thoughts and behaviors (SITB). There is little research focused on whether the timing of childhood adversity predicts SITB. The current research examined whether the timing of childhood adversity predicted parent- and youth-reported SITB at age 12 and 16 years in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN) cohort (n = 970). We found that greater adversity at age 11–12 years consistently predicted SITB at age 12 years, while greater adversity at age 13–14 years consistently predicted SITB at age 16 years. These findings suggest there may be sensitive periods during which adversity may be more likely to lead to adolescent SITB, which can inform prevention and treatment

The Effects of a Web-Based Alcohol Prevention Program on Social Norms, Expectancies, and Intentions to Prevent Harm among College Student-Athletes

College athletes are at risk for heavy alcohol use, which jeopardizes their general health, academic standing, and athletic performance. Effective prevention programming reduces these risks by targeting theory-based intermediate factors that predict alcohol use while tailoring content to student-athletes. The purpose of this study was to examine the impact of the myPlaybook online prevention program on student-athletes’ social norms, negative alcohol expectancies, and intentions to use alcohol-related harm prevention strategies. NCAA Division II student-athletes were recruited from 60 institutions across the United States to complete myPlaybook and pretest/posttest surveys measuring demographics and targeted outcome variables. Participants were randomly assigned to the treatment group (pretest-program-posttest; final n=647) or the delayed treatment “control” group (pretest-posttest-program; final n=709). Results revealed significant program effects on social norms (pp=.14). Implications for future research and practice are discussed

Energy availability and sex steroid hormones in physically active females

Sex steroid hormones (i.e., estrogen, progesterone) are major determinants of a women’s health status and play a role in almost every physiological system, including reproductive, endocrine, urinary, nervous, immune, musculoskeletal and cardiovascular. Physically active females have lower estrogen and progesterone when compared to inactive individuals, yet exercise alone does not appear to decrease hormones but alters hormones as a component of energy availability. Energy availability is the amount of energy left after subtracting the energy cost of exercise relative to fat free mass (FFM) from energy intake. When energy availability is inadequate (i.e., low energy availability (LEA)), disruptions to hormonal and metabolic systems occur that can lead to performance decrements and serious psychological and physiological (i.e., menstrual dysfunction) health outcomes. Furthermore, stress can disrupt estrogen and progesterone but how stress affects the relationship between energy availability and sex steroid hormones is unknown. Most research surrounding this topic includes only highly competitive, elite level female athletes and little is known about how energy availability alters hormone levels in physically active females. Since low sex steroid hormone concentrations and LEA are associated with serious health risks, further investigation into the association of energy availability and menstrual cycle hormones in physically active females is warranted. Thus, the purpose of this dissertation was to examine the relationship between energy availability and sex steroid hormones in active females across the menstrual cycle. Healthy, exercising females (n=21; age 21.3 ± 3.1 years) not on oral contraceptives completed measures over two menstrual cycles. Daily saliva measurements were taken across both menstrual cycles to create hormonal profiles of estrogen and progesterone. Energy availability was measured twice within one menstrual cycle, with energy intake recorded for seven days at two timepoints. Participants were all physically active and were asked to continue exercising normally and to record all exercise with a heart rate monitor. The first timepoint (T1) started during menses between day (D) 2-4 and the second timepoint (T2) started between 5-8 days post ovulation. A laboratory visit occurred on the first day of each timepoint, where resting metabolic rate and body composition were measured. Stress was measured with the Acute Recovery and Stress Scale at the beginning and end of each timepoint. Area under the curve (AUC) and range (i.e., difference in minimum and maximum values) for estrogen and progesterone for T1 and T2 was used for analyses. Most of the active females (71%, n = 15) were in a reduced energy state and 23% (n = 6) had subclinical menstrual dysfunction. Energy intake and energy availability remained constant across the two timepoints despite that estrogen and progesterone were significantly different (p = .003, p = .001, respectively). When the components of energy availability and hormones were assessed, progesterone range was positively associated with FFM (T1 p = .015, r=.537; T2 p = .001, r = .674) and RMR (T2 p = .005, r = .605) yet T2 progesterone range, FFM, and RMR were all negatively associated with energy availability (p = .032, r = -.479; p = .001, r = -.672; p = .009, r = -.558). Energy intake was correlated with the progesterone to estrogen ratio (P:E2) (p = .026, r= .321, 95% CI [0.04, 0.55]), but not progesterone or estrogen alone. The results also demonstrated that estrogen, progesterone, and the estrogen progesterone product in T1 exhibited a negative relationship with T2 energy availability ((ß = -.36, p = .009; ß = -.37, p = .008; ß = -.31, p = .029), in active females across a single menstrual cycle. In addition, stress and recovery do not moderate the relationship between hormones and energy availability within a timepoint or across timepoints of one menstrual cycle even though a stress subscale, negative emotional state, was significantly higher post ovulation towards the end of the cycle while recovery and other stress scales remained constant (F (3, 54) = 7.07, p = .000). These data suggest that physically active females are at risk for inadequate energy availability and subclinical menstrual dysfunction. Estrogen and progesterone affect energy intake at the beginning of the cycle and energy availability across timepoints but do not appear to be altered by stress and recovery. A higher progesterone to estrogen ratio was associated with higher energy intake during T1. Furthermore, higher estrogen and progesterone at the beginning of the menstrual cycle are associated with lower energy availability post ovulation. These data highlight the importance of including physically active females in future research on energy availability and emphasizes issues with energy availability are present in physically active females, not just elite athletes. Further investigations are needed to fully elucidate the relationship between energy availability, estrogen and progesterone

‘I know my rights, but am I better off?’: institutions and disability in Uganda

Uganda is internationally recognised for both its legal and constitutional provisions for people with disabilities, and the presence of disabled persons’ organisations that provide informal advocacy and support. Using a unique dataset of 579 Ugandans with physical disabilities, we develop a conceptual framework on social capital to investigate the factors correlated with knowledge of formal institutions that target disability. In examining whether this knowledge results in higher incomes we find that gender matters. A woman’s education and membership of external networks are correlates of knowledge; higher levels of this knowledge are associated with substantially higher levels of income

Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes were evaluated by mining GWAS datasets. eQTL analysis identified 1,971 and 2,078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2, were identified in both tissues. 62.1% of top cis-eSNPs were within ±50kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes, (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu) and identified genetically-regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes

Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a

<p>Abstract</p> <p>Background</p> <p>Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells from local soft tissues may also take on an osteogenic phenotype. Myoblasts are known to adopt a bone gene program upon treatment with the osteogenic bone morphogenetic proteins (BMP-2,-4,-6,-7,-9), but their osteogenic capacity relative to other progenitor types is unclear. We further hypothesized that the sensitivity of cells to BMP-2 would correlate with BMP receptor expression.</p> <p>Methods</p> <p>We directly compared the BMP-2 sensitivity of myoblastic murine cell lines and primary cells with osteoprogenitors from osseous tissues and fibroblasts. Fibroblasts forced to undergo myogenic conversion by transduction with a MyoD-expressing lentiviral vector (LV-MyoD) were also examined. Outcome measures included alkaline phosphatase expression, matrix mineralization, and expression of osteogenic genes <it>(alkaline phosphatase, osteocalcin </it>and <it>bone morphogenetic protein receptor-1A) </it>as measured by quantitative PCR.</p> <p>Results</p> <p>BMP-2 induced a rapid and robust osteogenic response in myoblasts and osteoprogenitors, but not in fibroblasts. Myoblasts and osteoprogenitors grown in osteogenic media rapidly upregulated <it>Bmpr-1a </it>expression. Chronic BMP-2 treatment resulted in peak <it>Bmpr-1a </it>expression at day 6 before declining, suggestive of a negative feedback mechanism. In contrast, fibroblasts expressed low levels of <it>Bmpr-1a </it>that was only weakly up-regulated by BMP-2 treatment. Bioinformatics analysis confirmed the presence of myogenic responsive elements in the proximal promoter region of human and murine <it>BMPR-1A/Bmpr-1a</it>. Forced myogenic gene expression in fibroblasts was associated with a significant increase in <it>Bmpr-1a </it>expression and a synergistic increase in the osteogenic response to BMP-2.</p> <p>Conclusion</p> <p>These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the variable response of different cell lineages to BMP-2.</p

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies

Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.Peer reviewe