Abstract
Women’s health and sex differences research remain understudied. In 2022, to address the topic of sex differences, the Ludeman Family Center for Women’s Health Research (LFCWHR) at the University of Colorado (LudemanCenter.org) held its third National Conference, “Sex Differences Across the Lifespan: A Focus on Metabolism.” The research presentations and discussions from the 2022 conference addressed cardiometabolic sex differences across the lifespan and included sessions focusing on scientific methods with which to study sex differences, effects of estrogen on metabolism, and sex differences in cardiovascular disease—implications for women and policy among others. Over 100 participants, including basic scientists, clinical scientists, policymakers, advocacy group leaders, and federal agency leadership participated. The meeting proceedings reveal that although exciting advances in the area of sex differences have taken place, significant questions and gaps remain about women’s health and sex differences in critical areas of health. Identifying these gaps and the subsequent research that will result may lead to important breakthroughs.
In 2022, the Ludeman Family Center for Women’ s Health Research (LFCWHR) at the University of Colorado (LudemanCenter.org) organized its third National Conference at The Broadmoor Hotel in Colorado Springs, CO. The research presentations and discussions from the 2022 conference addressed sex differences across the lifespan with a focus on cardio-metabolism. Over 100 participants, including basic scientists, clinicians, policy makers, advocacy group leaders, and federal agency representatives participated in the meeting. Immediately before the actual scientific sessions (1-VI), there was an organized community session event/lunch chaired by Dr. Laura Brown (University of Colorado School of Medicine). Four speakers presented inspiring talks for the public: Dr. Anne Libby (University of Colorado Emergency Medicine) spoke about mentoring and educating the next generation of scientists; Dr. Wendy Kohrt (University of Colorado School of Medicine) discussed why exercise is important and the molecular mechanisms of exercise; Dr. Kent Thornburg (Oregon Health & Science University) presented benefits of diet to build a healthier future by reversing the chronic disease epidemic and finally Dr. Cara Tannenbaum (Canadian Institutes of Health Research) discussed planning for impact in women’s health. In this article, we briefly summarize the conference scientific presentations made at the 2022 meeting. We have organized them into six different major themes.
Theme 1: Sex-Omics: A Systems Approach to the Methods of Studying Sex and Gender Differences
Overview
Understanding the differences underlying the concepts of sex and gender is critical to a discussion of women’s health. Sex is considered a biological variable (e.g., chromosomes, gonadal organs, and genetics) while gender refers to socially, psychologically, and culturally constructed factors. These concepts are intertwined and are sometimes difficult to disentangle, but understanding of both is key to a complete understanding of women’s health. For this conference, sex is the major focus, but the concepts associated with gender must be considered. In this thematic session, four speakers presented their research focused on the novel methods/tools that are used to study sex differences. These include the sex chromosome-balancing mechanisms using novel transgenic models, 1,2 sex differences in brain using antidiuretic hormone as an example, 3,4 immune origins of sex differences in the brain 5,6 and sex differences in the heart. 7,8 A variety of cutting-edge multiomics approaches were taken in their studies.
Dr. Geert De Vries (Georgia State University) discussed development and function of sex differences in the brain. In 2020, The Genotype Tissue-Expression Project identified differentially expressed genes in nearly 15,000 RNA-sequencing samples from 49 different nondiseased tissues of 838 postmortem donors (men and women). Before that, in 2017, the landscape of X-chromosome inactivation across human tissues was established. This earlier study identified incomplete X-inactivation results in sex biases in gene expression. One of the X-chromosome-linked candidates identified is the gene that encodes the vasopressin receptor. The ligand arginine vasopressin (AVP) exhibits stronger effects on kidney in females compared with males. Interestingly, the dose of synthetic analog of vasopressin (desmopressin) required is higher for males compared with females for effective biological effect. In case of the prairie voles, sex bias is also observed in AVP fiber density within brain regions with higher density in lateral septa of males compared with females. Similarly, in rats, the AVP-immunoreactive projections of the bed nucleus of the stria terminalis (BNST) and medial amygdaloid nucleus are much denser in males than in females. Ablating or optogenetic inhibition of BNST AVP cells affects males more than females. Further work revealed that transcription factors are not differentially expressed but perhaps other sex-biased mechanisms could be responsible for these effects. Dr. De Vries concluded that sex differences can only be understood from a whole-body physiological perspective.
Dr. Arthur Arnold (University of California, Los Angeles) described sex differences as adaptive sex-balancing mechanisms. One example he focused on was on the Xist regulatory protein that plays critical roles in X-inactivation. Deletion of Xist in epiblast results in the deaths of female, but not male embryos. He further discussed the four core sex chromosome genotypes model in mice. Using transgenesis, his group engineered XX SryTg + and XY SRYΔ mouse models and characterized their hormonal and reproductive phenotypes. This model is widely used in the work of basic scientists to study sex differences. His conclusion was that failure of sex-balancing mechanisms may lead to diseases in mice.
Dr. Margaret McCarthy (University of Maryland School of Medicine) discussed immune origins of sex differences in the brain in particular, focusing on microanatomical, molecular, and transcriptomic sex differences. Her work elucidated that early life steroid exposure during a critical period is a major determinant of brain sex differences in the innate immune system in the brain. For example, size differences exist in sexually dimorphic nuclei (SDN) of the preoptic area (POA) of the brain; SDN are significantly larger in size in males compared with females. Microglia are critical phagocytic cells (macrophages) and represent 1% of brain cell population. In the female rat SDN of POA, 80% of neurons undergo phagocytosis by microglia. Treatment of anti-αCD11B antibody prevents the apoptosis and results in an increase in SDN volume and the size in females. Dr. McCarthy’s work also identified sex differences in hippocampal mast cells during early phases of brain development.
Dr. Leslie Leinwand (University of Colorado, Boulder) focused her presentation on sex differences in the heart. There are more cardiomyocytes in female hearts than male hearts, whereas male hearts contain more endothelial cells. Sex differences also exist in the contractility of the heart reflected in overall cardiac function and strength of the heart, which is greater in males compared with females. Her work identified cellular sex differences specifically in baseline myocyte function and contractility of myofibrils. It is estimated that there are about 14,000 proteins expressed in the heart and 5,200 in cardiomyocytes and about 100 in cardiac myofibrils. Some of the abovementioned cardiac phenotypes were attributed to posttranslational modifications identified by proteomics and phosphoproteomics approaches. In terms of cardiomyocyte gene expression signatures, sex differences were also noted. Approximately 600 genes were sex-specifically expressed in females versus males. Dr. Leinwand also discussed sex differences in exercise-activated phosphoproteins, cardiac responses to exercise, and hypertrophic cardiomyopathy because of myosin mutations.
Gaps identified: Additional development of genetic tools to study sex differences is necessary in both humans and animals. A better understanding of such tools across and within organ systems, such as muscle and brain, is critical. Multiomics data need to be better integrated to discover novel pathways. A better understanding of immune cell function in neurophysiology is needed.
Theme 2: The Placental–Fetal Connection: Programming Adult Metabolic Health
Overview
Placenta is an important mediator of maternal–fetal communication and plays fundamental roles in fetal growth and development. 9 –12 Maternal insults cause fetal reprogramming via several mechanisms and can result in various disorders. 9 –12 Three of the four speakers focused on defense mechanisms at the maternal–fetal interface, placental sex and fetal heart development, and role of the placenta in building the fetal brain. Lastly, it was discussed how fetal influences on life-long body composition can be understood using muscle development as an example.
Dr. Yoel Sadovsky (Magee-Women’s Research Institute, University of Pittsburgh) discussed his recent work on how placental function is regulated by extracellular vesicles, including exosomes and microvesicles. He identified miRNAs in exosomes for antiviral defense that are paternally expressed and imprinted. In particular, his group identified a primate-specific miRNA cluster and further mapped the enhancers using Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC sequencing) sequencing method. Furthermore, his group developed methods to purify exosomes in maternal plasma from women with pregnancy-specific disorders, such as intrauterine growth restriction and preeclampsia. He also discussed an endosomal cargo escape mechanism.
Dr. Kent Thornburg (Oregon Health & Science University) discussed the importance of placenta sex and fetal heart development with an epigenetic lens. The prevalence of diabetes and heart disease was highlighted. He discussed that obesity and diabetes are often associated with DNA methylation patterns. The early effects of environmental stresses during pregnancy can be passed on for generations. He suggested placental efficiency predicts disease vulnerability and highlighted how fetal sex characteristics can influence maternal pregnancy outcomes.
Dr. Theresa Powell (University of Colorado School of Medicine) discussed the key role of placenta in building the fetal brain. It is known that fatty acids are critical for early fetal brain development. Importantly, pregnant women have high circulating lipids and Dr. Powell’s work demonstrated that transplacental transfer of phospholipids is critical for fetal brain development. Her group identified a novel transporter designated Mfsd2a, which transports Lysophosphatidylcholine docosahexaenoic acid (LPC-DHA) lipids to brain from placenta to fetus. Genetically knocking down this transporter by shRNA specifically in placenta reduces the pump activity and results in reduction in phospholipids. Consequently, the knockdown of the transporter affects fetal brain size. Her group is focusing on whether there are structural and functional abnormalities in fetal brain in this novel genetic model.
Dr. Laura Brown (University of Colorado School of Medicine) focused in her presentation on fetal influences on body composition and sarcopenia. She emphasized the importance of the developmental origins of health and disease. Her group has been utilizing the sheep model of placental insufficiency and her findings to date have revealed some key abnormalities. Of note, fetuses/neonates with intrauterine growth retardation reportedly have 25% muscle lean mass compared with non-IUGR fetuses/neonates. In mice, the myofiber number is set at birth. Interestingly, heat stress to pregnant sheep causes placental insufficiency and a subsequent sharp decrease in muscle and number of myofibers. The decrease in myofiber cross-sectional area was noted. Under these conditions, total amino acid (AA) uptake is reduced; particularly branched chain AAs. The uptake of alanine (Ala) and glutamine (Gln) is also reduced. Her group demonstrated that AA supplementation results in net increases in protein synthesis and rescues the muscle phenotype.
Gaps identified: By what pathways does placental efficiency influence and predict lifelong disease vulnerability? How do changes in placental phospholipids impact brain structure and function? Is exosome-mediated, placental–maternal–fetal communication essential for pregnancy health? What physiological adaptations develop in response to placental insufficiency to slow fetal muscle growth, and do these adaptations become permanent or are they reversible?
Theme 3: Sex Differences in Cardiovascular Disease—Implications for Women and Policy
Overview
The study of sex differences in cardiovascular disease (CVD) is an emerging area of medical and basic science research. 13,14 Disparities between women and men have been noted in terms of diagnosis, immediate medical care/services and treatment. 8,15 This session focused on sex differences in heart failure and cardiac transplantation, cardiac rehabilitation (CR), and a new focus on personalized care of heart failure. Finally, CVD in women was discussed from the standpoint of epidemiology, awareness, access and delivery of equitable healthcare perspectives.
Dr. Mary Walsh (St. Vincent Heart Center, Indianapolis, IN) discussed sex differences in cardiac transplantation. She described an important clinical trial known as the Digitalis Investigation Group (DIG trial), a large, placebo-controlled international study, which evaluated the effect of digoxin all-cause mortality in patients with clinical heart failure in sinus rhythm whose ejection fraction is < or = 0.45. The DIG trial demonstrated a decrease in hospitalization for those randomized to digoxin. However, a post hoc analysis of this trial showed an increase in mortality in women. Dr. Walsh explained that men have many more cardiac transplantations than women. Dr. Walsh mentioned that sex differences exist in cardiac transplantation recipients with men receiving transplants more frequently than women and often donors are also men. She noted that the cause of death posttransplantation is mostly due to excess opioid dose because of pain and depression. She concluded her talk by discussing that even for women enrolled in trials, they were less likely to receive guideline-directed therapy than men.
Dr. Linda Peterson (Washington University School of Medicine) focused on sex differences in CR. She noted that despite the significant clinical benefits of CR, women are significantly less likely to receive CR than men whether intensive, traditional, or home based. 16,17 She also pointed out that older women have more comorbidities than men, which may make it harder for women to participate. Sex-related differences in risk factor changes with CR are also a factor. Overall, more barriers exist for women and limit their participation in CR. She described the NAVIGATOR program. This unique program has exercise physiologists see every patient in the hospital who qualifies for CR. The exercise physiologist explains the importance of CR to the patient and family, makes sure there is an order for CR, makes sure the patient has an appointment for CR, and follows up with the patient by phone after discharge to ask if they made their appointment. This program has allowed to double their enrollment in CR.
Dr. David Kao (University of Colorado School of Medicine) described recent advances in personalized care of heart failure. He elaborated upon how artificial intelligence, personalization and data management can be effective in integrating large datasets across multiple institutions. He described his recent work on harmonized clinical trials. He also indicated the efforts that are being carried out integrating the large body of University of Colorado Electronic health records focusing on heart failure. This body of data has the potential to be utilized to answer many key questions about heart failure.
Dr. Nanette Wenger (Emory University School of Medicine) focused her talk on equitable CVD health care for women. She suggested culturally sensitive materials with appropriate translations must be made to promote awareness campaigns because CVD is a major health threat for women. She also suggested emphasizing the benefits of prevention (80–90% of CVD is preventable) as well as benefits of cardiovascular (CV) health optimization for women. She noted that interdisciplinary collaboration between cardiologists, vascular neurologists, primary care clinicians, and Obstetics/Gynecologists (OB-GYN) clinicians must occur to improve prevention and treatment of CVD lifelong in women. Clinical education programs need to be expanded regarding risk factors, which are specific or predominant in women. She concluded by indicating that risk calculators with quantitative measures of risk over the course of life need to be developed.
Gaps identified: Women are less likely to be referred to, enroll in, and complete CR. Women who qualify for CR are more likely than men to have more comorbidities, which may impact their ability to attend CR. Education programs for women (including programs that are culturally sensitive) about CV health have improved, but still a lot of work is needed to ensure that all women are informed of the risks of poor heart health and how to treat CVD. Risk calculators with quantitative measures of risk over the course of life need to be developed.
Theme 4: Sex Differences in Brain, Obesity, and Metabolic Dysregulation across the Lifespan
Overview
This session focused on sex differences in the developmental programming of brain function, neuronal mechanisms that control food intake behavior, 18,19 appetitive function, and how maternal obesity contributes to sex differences in fetal brain and placental programming. 20,21 The topics of prenatal exposure to glucocorticoids and adverse immune exposures due to maternal obesity and their sex-selective impact on the offspring’s autonomic nervous system, CV and metabolic function, 22 and brain development 23 were discussed.
Dr. Taben Hale (University of Arizona College of Medicine) indicated that glucocorticoid exposure impacts CV and autonomic nervous system function in a sex-selective manner. She noted that prenatal dexamethasone exposure caused CV and neurocrine effects. Hydroxy steroid 11β-dehydrogenase (HSD11B) enzyme is responsible for dexamethasone metabolism to cortisol/corticosterone. These metabolites can cross placenta and may lead to preterm labor and reduction in postnatal body weight. Prenatal exposure of dexamethasone in pregnant rats had greater adverse consequences for female versus male offspring on blood pressure and heart rate and thus potential impact on sex-selective development of CVD.
Dr. Kristina Legget (University of Colorado School of Medicine) described eating behaviors and attitudes and pointed out differences between homeostatic versus hedonic eating behaviors. She noted sex-biased differences exist in obesity. She correlated these eating behaviors to functional magnetic resonance imaging (fMRI) and visual cues. She also discussed acute feeding effects and focused on obesity-resistant versus obesity-prone behaviors. Her group continues to decipher neural mechanisms of food intake.
Dr. Andrea Edlow (Harvard Medical School) described maternal obesity and sex differences in placenta and fetal brain. Her group developed mouse models of maternal diet-induced obesity and identified sex-specific fetal brain gene expression signatures. Her group observed sexually dimorphic effects on microglial antigen density in the fetal hippocampus. The hippocampal learning deficits in juvenile life that persist into adulthood occur only in male offspring. Interestingly, ablation of in utero proinflammatory signaling in microglia and Hofbauer cells improves female but not male deficits.
Dr. Laura Holsen (Harvard Medical School) described sex differences in appetitive function in the brain, including impact of stress, mood, and hormones. Sex differences in three major networks that control food intake are leptin, insulin, and ghrelin. She presented data on noninvasive neuroimaging—fMRI. Using this tool, she observed significant differences in basal and secretory dynamics of ghrelin following stress. She noted that chronic stress alters sex differences in appetite hormones and food reward-related brain function. For example, women have higher ghrelin levels than men. She described that healthy men and women differed in their cortisol and ghrelin response to stress.
Gaps identified: The mechanisms by which prenatal glucocorticoid exposure is transmitted through placenta in sex-selective ways are critical and needs to be further investigated. Interventions during pregnancy to manage the conversion of cortisol to cortisone by HSD11B in women who have relatively elevated levels of cortisol due to psychosocial factors or use of life-saving medications need to be explored. As more knowledge is acquired regarding the neural mechanisms that contribute to homeostatic and hedonic eating behaviors, there is a need to translate these findings into intervention development or refinement that address these differences, particularly as they vary by sex. Early interventions, perhaps dietary, could be developed in overweight/obese women that may diminish maternal inflammation and positively impact fetal brain development in a sex-selective way. Further research is needed to develop a better understanding of factors such as timing, dosing, chronicity of psychological interventions that impact both biological and behavioral outcomes associated with sex and gender differences in optimal health.
Theme 5: Female Sex Differences as an Endocrine Disruptor in Diabetes
Overview
This session focused on sex differences in CV risk and type 2 diabetes (T2D) management in women, 24 –26 sex differences in vascular health and, finally, sex differences in comorbidities of youth-onset T2D. 27,28 Several clinical trials and new large-scale studies were discussed. In addition, findings on physical activity and the impact of weight, race, and ethnicity were discussed. 24 –26,29,30
Dr. Jennifer Green (Duke University School of Medicine) focused on sex differences in recent CV outcome trials. The excess CV risk associated with T2D is greater in women than men. She described the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) Trial and the impact of sitagliptin on CV outcomes. Apparently, no heterogeneity of efficacy between sex and effects of sitagliptin treatment was identified. She described the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial, which addresses coronary artery disease and sex effects/interactions. She noted that women had generally worse CV risk factor profiles and less use of cardioprotective medications than men. She found that no heterogeneity of efficacy was observed between sex and effects of exenatide treatment in both sexes.
Dr. Rachel Huxley (Deakin University School of Medicine, Australia) focused on sex differences in vascular health. Overall, she found that women have a lower CVD risk than men at all ages. However, treatment inadequacies exist for women. A common symptom is dementia that can be vascular and/or nonvascular. Vascular dementia is 20% higher risk for women compared with men with T2D. She pointed out that CV-related morbidity is twice as much in women than men with type 1 diabetes.
Dr. Judith Regensteiner (University of Colorado School of Medicine) discussed T2D and exercise influences of sex and gender. She described that peak exercise capacity (measured by peak oxygen capacity) is impaired in men and women with T2D. She observed that the difference in exercise tolerance is greater in women with T2D compared with nondiabetic counterparts than in men with T2D compared with nondiabetic counterparts. She noted that there are sex differences in meeting physical activity guidelines in adolescents, adults, and older adults with T2D with women being less active across all races and ethnicities. She concluded that females consistently engaged in less mid-to-vigorous physical activity and exercise than males across the lifespan.
Dr. Kristen Nadeau (University of Colorado School of Medicine) discussed sex differences in comorbidities of youth-onset T2D. She pointed out the prevalence of type 1 and type 2 diabetes in young children. She described The Restoring Insulin Secretion (RISE) consortium, which is focused on restoring insulin secretion in adults and children. She compared differences in leptin and GH/IGF1 secretion in girls vs. boys. The Treatment Options for Type 2 Diabetes in Adolescents and Youth study (TODAY) generated data on anthropometrics and insulin sensitivity. Dr. Nadeau described sex changes in steroid levels with obesity in kids. Obesity in females may cause early puberty, polycystic ovarian syndrome, elevated dehydroepiandrosterone sulfate (DHEA-S), and testosterone levels. In contrast, obesity in males may cause delayed puberty and suppression of serum hormone binding globulin and testosterone. It is well known that T2D greatly increases the risk of CVD. Premenopausal women have lower CVD risk than similarly aged men but this changes after menopause. She pointed to efforts to identify potential reasons for female T2D predominance in youth and increased CVD risk with diabetes.
Gaps identified: Need better understanding of differences in physiological life course events such as menarche in healthy women and adolescents versus those with T2D. Need better understanding of differences in physiological life course events such as menopause in healthy women versus those with T2D. Research is needed to identify potential reasons for female T2D predominance in youth and increased CVD risk with diabetes. Research is needed to further evaluate the causes of exercise impairment in T2D. Research should assess ways to get women and girls to be more active.
Theme 6: Metabolic Actions of Estrogens
Overview
This session focused on estrogen actions in general and the estrogen-independent actions of the pituitary follicle-stimulating hormone (FSH) in extragonadal tissues. 31 –33 Estrogen regulation of mitochondrial function in brown adipose tissue and thermogenesis was discussed. 34 Estrogen action in skeletal muscle was discussed at length 35,36 and the bioenergetic and metabolic actions of estrogen were presented using physiological suppression of the neuroendocrine axis in women. 37
Dr. T. Rajendra Kumar (University of Colorado School of Medicine) discussed the possibility of estrogen independent actions of FSH in extragonadal tissues in female mice and women. FSH normally acts on ovaries and produces estrogen. It appears that increased FSH levels correlate better than decline in estrogen to osteoporosis in women and elevated FSH or FSHR-mediated signaling is detrimental to bone. Even in the presence of estrogen, loss of FSH alone can result in increase in bone parameters. He described that age-specific FSH glycoforms are produced in pituitaries of women as a function of age. Distinct biological actions of these FSH glycoforms in different ratios may be critical for ovarian aging and bone function. He concluded by pointing to the need for developing genetic models to delineate cell-autonomous roles of FSHR-mediated signaling in extragonadal tissues, such as bone.
Dr. Edward Melanson (University of Colorado School of Medicine) focused on estrogen and energy expenditure. Acutely suppressing ovarian hormones in women decreases resting energy expenditure. Chronic gonadotropin hormone-releasing hormone (GnRH) agonist decreases resting and total energy expenditure by suppressing ovarian function. His group identified functional differences in white adipose tissue and brown adipose tissue (BAT). BAT is associated with cardiometabolic health. Estrogen regulates mitochondrial content in brown adipose tissue. His team developed deoxy glucose uptake and 11C-acetate metabolic labeling studies in women to study mitochondrial and adipose tissue bioenergetics. His team found differences in cold-stimulated BAT metabolic activity is more in premenopausal women.
Dr. Dawn Lowe (University of Minnesota Medical School) described her work on estrogen–estrogen receptor signaling in skeletal muscle. Sarcopenia and dynapenia increase with age. Her team studied muscle fiber–sarcomere and myosin. Her work identified super relaxed myosin has high potential to impact metabolism. Disordered relaxed state-super-relaxed states of myosin (DRX-SRX) are states of myosin that specify ATP turnover rates. Dr. Lowe found that SRX is related to skeletal muscle composition and adiposity and male versus female differences are noted. She also discussed that SRX can be altered by physical activity.
Dr. Wendy Kohrt (University of Colorado School of Medicine) focused on her efforts to understand bioenergetic and metabolic actions of estrogens. Loss of gonadal function impacts other systems besides reproduction and leads to increased disease risk. In preclinical studies using ovariectomized rats, her group found decreases in physical activity, metabolic activity, and increases in absolute fat gain (distribution and composition) leading to metabolic dysfunction, CVD and T2D, and osteoporosis. She found that estradiol improves these deficiencies. Extending these observations to clinical studies her team developed protocols for GnRH agonist treatment and placebo or estrogen add back. Her team tested this protocol in premenopausal and postmenopausal women subjects while combining with and without exercise resistance and endurance exercise.
Gaps identified: Need to develop conditional knockout mouse models to delineate extragonadal actions of FSH and rigorous studies that delineate the actions of estrogens and FSH in humans are needed. Molecular mechanisms of how increased propensity in weight gain during the menopausal transition is, in part, a result of the loss of BAT needs (to be further investigated). The basis for sex differences in DRX-SRX states of myosin need to be further investigated. How estrogens may help to preserve muscle mass and function through anticatabolic or other metabolic actions needs to be investigated in women. How loss of ovarian function affects bone and adiposity and how these effects can be modulated by exercise training needs to be further investigated.
Names of Blitz Presenters in Alphabetical Order (All from CU Anschutz)
Amy Keller, PhD
Ann Caldwell, PhD
Brisa Peña Castellanos, PhD
Christina Metcalf, PhD
Ellen Francis, PhD
Jane Stremming, MD
Kathleen Woulfe, PhD
Layne Dylla, MD, PhD
Matthew Babcock, MS, PhD
Natalie Nokoff, MD
Phoutdavone “Noy” Phimphasone-Brady, PhD
Ramón Lorca, PhD
Rebecca Scalzo, PhD
Stephanie Gilley, MD, PhD
Footnotes
Author Disclosure Statement
None of the authors have any conflicts of interest.
Funding Information
No funding was received for this research.