Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project–imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P < 5 × 10$^{−8}$) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Family and School Connectedness Associated with Lower Depression among Latinx Early Adolescents in an Agricultural County

Depression constitutes one of the greatest sources of morbidity and mortality for U.S. adolescents. Latinx are the fastest growing U.S. adolescent population, particularly in rural communities, and suffer from depression at higher rates than other racial/ethnic groups. Informed by community perspectives on adolescent health, we examined factors associated with depression among Latinx early adolescents in an agricultural community. We surveyed 599 predominantly Latinx 8th graders (12 to 15&nbsp;years old) recruited from middle schools in Salinas, California. Depression was measured cross-sectionally with the Patient Health Questionnaire-8. Exposures included environmental, cultural, and family factors, assessed using validated measures. We used hierarchical logistic regression guided by Garcia Coll's Model for the Study of Developmental Competencies in Minority Children to examine associations between protective factors within each domain and depression. Eighty-six of the 599 youth (14%) scored above the clinical threshold for depression, with higher prevalence among females (19%) than males (10%), p&nbsp;=&nbsp;.001. Environmental (school connectedness and neighborhood social cohesion) and family factors were associated with a lower odds of depression (all p&nbsp;≤&nbsp;.01). Social cohesion in neighborhoods and family communication offered similarly strong protective associations with depression. Increased language assimilation was associated with an increased odds of depression (p&nbsp;=&nbsp;.007)

Disparities in access to eating disorders treatment for publicly-insured youth and youth of color: a retrospective cohort study

BackgroundEating disorders are associated with substantial morbidity and mortality that can be minimized by timely access to evidence-based treatment. However, disparate access to eating disorders treatment may contribute to significant health disparities amongst marginalized groups. This study examined the association between insurance type (public vs. private) and receipt of recommended mental health treatment in a sample of racially/ethnically diverse youth who presented to an adolescent medicine clinic with malnutrition secondary to disordered eating.MethodsA retrospective chart review was conducted for youth ages 11-25&nbsp;years (N = 1060) who presented to an urban adolescent medicine specialty program between June 1, 2012 and December 31, 2019 for malnutrition secondary to disordered eating. Bivariate and logistic regression analyses examined the association between insurance type (public vs. private) and other demographic/clinical factors on receipt of recommended treatment within six months of the initial evaluation.ResultsPatients with public insurance were one third as likely to receive recommended treatment as patients with private insurance (AOR = 3.23; 95% CI = 1.99, 4.52), after adjusting for demographic and clinical factors. Latinx (AOR = 0.49; 95% CI = 0.31, 0.77) and Asian (AOR = 0.55; 95% CI = 0.32, 0.94) patients were half as likely to receive recommended treatment as White patients.ConclusionsAccess to evidence-based mental health treatment is a necessary first step towards health equity for individuals with eating disorders. Additional work is needed to dismantle systemic inequities that contribute to disparities in care for youth of color and those with public insurance

Telemedicine in an adolescent and young adult medicine clinic: a mixed methods study.

BackgroundAdolescents and young adults are a diverse patient population with unique healthcare needs including sensitive and confidential services. Many clinics serving this population began offering telemedicine during the Covid-19 pandemic. Little is known regarding patient and parent experiences accessing these services via telemedicine.MethodsTo assess for trends and disparities in telemedicine utilization in the first year of the pandemic, we used the electronic health record to obtain patient demographic data from an adolescent and young adult medicine clinic in a large urban academic institution. Characteristics of patients who had accessed telemedicine were compared to those who were only seen in person. Mean age was compared using t-test, while other demographic variables were compared using chi-squared test or Fisher's exact test. We performed qualitative semi-structured interviews with patients and parents of patients in order to characterize their experiences and preferences related to accessing adolescent medicine services via telemedicine compared to in-person care.ResultsPatients that identified as female, white race, Hispanic/Latinx ethnicity were more likely to have utilized telemedicine. Telemedicine use was also more prevalent among patients who were privately insured and who live farther from the clinic. Although interview participants acknowledged the convenience of telemedicine and its ability to improve access to care for people with geographic or transportation barriers, many expressed preferences for in-person visits. This was based on desire for face-to-face interactions with their providers, and perception of decreased patient and parent engagement in telemedicine visits compared to in-person visits. Participants also expressed concern that telemedicine does not afford as much confidentiality for patients.ConclusionsMore work is needed to address patient and parent preferences for telemedicine as an adjunct modality to in-person adolescent and young adult medicine services. Optimizing quality and access to telemedicine for this patient population can improve overall healthcare for this patient population

Telemedicine in an adolescent and young adult medicine clinic: a mixed methods study

Abstract Background Adolescents and young adults are a diverse patient population with unique healthcare needs including sensitive and confidential services. Many clinics serving this population began offering telemedicine during the Covid-19 pandemic. Little is known regarding patient and parent experiences accessing these services via telemedicine. Methods To assess for trends and disparities in telemedicine utilization in the first year of the pandemic, we used the electronic health record to obtain patient demographic data from an adolescent and young adult medicine clinic in a large urban academic institution. Characteristics of patients who had accessed telemedicine were compared to those who were only seen in person. Mean age was compared using t-test, while other demographic variables were compared using chi-squared test or Fisher’s exact test. We performed qualitative semi-structured interviews with patients and parents of patients in order to characterize their experiences and preferences related to accessing adolescent medicine services via telemedicine compared to in-person care. Results Patients that identified as female, white race, Hispanic/Latinx ethnicity were more likely to have utilized telemedicine. Telemedicine use was also more prevalent among patients who were privately insured and who live farther from the clinic. Although interview participants acknowledged the convenience of telemedicine and its ability to improve access to care for people with geographic or transportation barriers, many expressed preferences for in-person visits. This was based on desire for face-to-face interactions with their providers, and perception of decreased patient and parent engagement in telemedicine visits compared to in-person visits. Participants also expressed concern that telemedicine does not afford as much confidentiality for patients. Conclusions More work is needed to address patient and parent preferences for telemedicine as an adjunct modality to in-person adolescent and young adult medicine services. Optimizing quality and access to telemedicine for this patient population can improve overall healthcare for this patient population

Early Sexual Debut and Neighborhood Social Environment in Latinx Youth

ObjectivesTo examine whether social aspects of the neighborhood environment are associated with early sexual initiation in a California agricultural community of predominantly Latinx adolescents.MethodsIn a prospective cohort study of 599 eighth graders recruited from middle schools in Salinas, California (2015-2019), participants completed five interviews over 2 years. Social environment measures included neighborhood social dynamics (neighborhood disorder, social cohesion, and social network gang exposure); experiences of discrimination; and school connectedness. We estimated associations between baseline social environment and early sexual initiation (&lt;15 years) using Poisson regression with robust standard errors. We compared contraceptive self-efficacy and attitudes by sexual initiation status using ANOVA.ResultsMost youth were Latinx (94%) and age 13 (70%) at enrollment; 53% were female and 49% had a parent employed in agriculture. Additionally, 14% reported first vaginal sex before age 15. Neighborhood disorder (relative risk [RR], 1.13; 95% confidence interval [CI], 1.05-1.21), social network gang exposure (RR, 2.23; 95% CI, 1.49-3.33), and experiences of discrimination (RR, 1.67 [1-2 events versus none], 95% CI, 1.09-2.55; RR, 2.33 [3+ events versus none], 95% CI, 1.07-4.64) were associated with early sexual initiation. School connectedness was protective (RR, 0.44, 95% CI, 0.29-0.69). Youth who initiated sex before age 15 had more negative birth control attitudes and expressed lower motivation to use contraceptives.ConclusionsFindings underscore opportunities to promote early adolescent sexual health through strengthening supportive and safe neighborhood environments with the promise of addressing disparities in unintended pregnancy and sexually transmitted infection rates in later adolescence

Angiogenic endothelium shows lactadherin-dependent phagocytosis of aged erythrocytes and apoptotic cells

Angiogenic endothelium plays a crucial role in tumor growth. During angiogenesis, complex alterations in the microenvironment occur. In response, the endothelium undergoes phenotypic changes, for example overexpression of alpha(v)-integrins. Here, we show that the overexpression of alpha(v)-integrins on angiogenic endothelial cells is engaged in phagocytic actions involving binding ("tethering") and uptake ("tickling") of lactadherin (also termed MFG-E8)-opsonized particles. Phosphatidylserine (PS)-exposing multilamellar vesicles, "aged" erythrocytes, and apoptotic melanoma cells incubated with lactadherin were all phagocytosed by angiogenic endothelial cells in vitro. Furthermore, we demonstrated lactadherin expression in and around tumor blood vessels making opsonization in situ plausible. By engineering the surface of erythrocytes with covalently coupled cyclic Arg-Gly-Asp (RGD) peptides-mimicking lactadherin opsonization-we could induce phagocytosis by angiogenic endothelial cells both in vitro and in vivo. In vitro, this was confirmed by cytochalasin D preincubation. When RGD-erythrocytes were administered intravenously in tumor-bearing mice, blood vessel congestion followed by tumor core necrosis was seen. Moreover, RGD-erythrocytes could delay tumor growth in a murine melanoma model, possibly through induction of tumor infarctions. These results reveal that angiogenic endothelial cells have phagocytic properties for lactadherin-opsonized large particles and apoptotic cells. Implications of our findings for diagnostic and therapy of angiogenesis-driven diseases are discussed