The Associations Between Health-Related Knowledge and Health Beliefs Regarding Risk for Gestational Diabetes in American Indian and Alaska Native Female Adolescents and Young Adults at Risk for Gestational Diabetes and Their Female Caregivers: A Cross-Sectional Dyadic Analysis.

INTRODUCTION: Research on associations between knowledge and health beliefs for women at risk for gestational diabetes mellitus (GDM) has focused on adults at risk for or having GDM. Gaps also exist in examining interpersonal associations with family members or peers. We examined dyadic associations between knowledge and health beliefs about the risk for GDM between and within American Indian and Alaska Native (AIAN) female adolescents and young adults (FAYAs) at risk for GDM and their mothers or adult female caregivers (FCs). METHODS: Grounded in the Expanded Health Belief Model, we employed a cross-sectional design using baseline data from 147 dyads of AIAN FAYAs at risk for GDM and their FCs who participated in the Stopping GDM in Daughters and Mothers trial. FAYAs were 12.0 to 24.5 years of age, and 89.1% were students. FCs had a mean (SD) age of 44.0 (9.3) years, 87.0% were AIAN, 44.9% were college educated, 19.7% had ever had GDM, and 81.0% were the FAYA's mother. FAYAs and FCs completed surveys about knowledge and health beliefs (benefits, barriers, severity, susceptibility) regarding GDM risk and prevention. Bivariate correlational analyses were performed to examine associations between and within dyad members. Dyadic associations were investigated using actor-partner interdependence modeling (APIM) assuming distinguishable dyad members. RESULTS: Compared with their FCs, FAYAs had lower health-related knowledge and perceived benefits of GDM prevention and susceptibility regarding GDM risk. APIM revealed actor and partner effects of health-related knowledge on health beliefs for dyads. In particular, positive actor effects were found for FAYAs and FCs for GDM-related knowledge with perceived benefits (P < .001), and positive partner effects of GDM-related knowledge for FCs were related to perceived susceptibility and severity for FAYAs (P < .05). DISCUSSION: As shown in these AIAN dyads, FAYAs and their FCs, as members of one another's social network, may influence each other's health beliefs regarding GDM risk and prevention.

Comparing American Indian/Alaska Native Adolescent Daughters' and Their Mothers' Awareness, Knowledge, Attitudes, and Behaviors Regarding Risk for Gestational Diabetes: Implications for Mother-Daughter Communication on Reproductive Health.

PURPOSE: The purpose of the study was to describe, compare, and examine associations at baseline of reproductive health awareness, knowledge, health beliefs, communication and behaviors related to gestational diabetes (GDM) and GDM risk reduction in a vulnerable population of both American Indian/Alaska Native (AIAN) adolescent girls and their mothers. METHODS: Descriptive/comparative/correlational analyses examined multitribal baseline data on 149 mother-daughter (M-D) dyads (N = 298; daughter age = 12-24 years) enrolled in a longitudinal study to adapt and evaluate a culturally relevant diabetes preconception counseling (PC) program (Stopping-GDM). The associations between GDM risk reduction awareness, knowledge, health beliefs, and behaviors (eg, daughters' eating, physical activity, reproductive-health [RH] choices/planning, M-D communication, daughters' discussions on PC) were examined. Data collected online from 5 national sites. RESULTS: Many M-D lacked awareness/knowledge of GDM and risk reduction. Both M-D were unaware of the girl's risk for GDM. Mothers' knowledge and beliefs on GDM prevention/RH were significantly higher than daughters. Younger daughters had greater self-efficacy healthy living. Overall sample reported low to moderate scores for both M-D communication and daughters' GDM and RH risk-reduction behaviors. CONCLUSIONS: Knowledge, communication, and behaviors to prevent GDM were low in AIAN M-D, especially daughters. More than daughters, mothers perceive greater risk of GDM for daughters. Early culturally responsive dyadic PC programs could help decrease risk of developing GDM. Implications for M-D communication is compelling.

The Experiences of American Indian Participants and Site Coordinators in a Gestational Diabetes Risk Reduction Trial.

Gestational diabetes mellitus is the most common complication of pregnancy and contributes to increased risk for type 2 diabetes in both the mother and offspring. We developed and evaluated a gestational diabetes risk reduction and preconception counseling program, Stopping GDM (SGDM), for American Indian females. The purpose of this study is to examine the experiences of American Indian mother-daughter dyad participants and the site coordinators who facilitated the SGDM randomized controlled trial to inform program revisions. We engaged mother-daughter dyads (n = 22 dyads) and site coordinators (n = 6) in focus group interviews. Four themes emerged: (1) SGDM sparked valuable quality conversation for dyads; (2) gestational diabetes risk factors and risk reduction was new information for most dyads; (3) all trial sites experienced challenges to recruitment and engagement; and (4) study-improvement recommendations. These findings will be used to enhance SGDM to decrease adverse intergenerational health impacts of gestational diabetes in American Indian communities.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

CONTEXT: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. OBJECTIVE: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. METHODS: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. RESULTS: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. CONCLUSIONS: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

Values-based interprofessional education: how interprofessional education and values- based practice interrelate and are vehicles for the benefit of patients and health and social care professionals.

The 2016 All Together Better Health VIII Oxford conference brought together interprofessional education (IPE) and values-based practice (VBP) communities. As there is a paucity of research and publications in the area, following the event a working party consisting of representatives from both communities continued to meet and has developed a joint community of practice. This report describes the work achieved by the group so far and is intended for those involved in the planning and implementation of IPE and collaborative working. The authors consider that incorporating principles of VBP within a framework of IPE can provide a different perspective and understanding of the complexities involved in delivering realistic, student centered learning for collaborative practice, relevant in the 21st century workplace. In particular the authors suggest that using the principles of values and VBP in this way can inform the transition between IPE and collaborative practice facilitating effective person centered collaborative care. This process will require not only the incorporation of these principles within IPE sessions, but also incorporation within the training and support of new and established teachers involved in IPE.

Technology for Augmenting Type 1 Diabetes Mellitus Management.

Type 1 diabetes mellitus has witnessed significant progress in its management over the past several decades. This review highlights technologic advancements in type 1 diabetes management. Continuous glucose monitoring systems are now available at various functionality and cost levels, addressing diverse patient needs, including a recently US Food and Drug Administration (FDA)-approved implantable continuous glucose monitoring system (CGMS). Another dimension to these state-of-the-art technologies is CGMS and insulin pump integration. These integrations have allowed for CGMS-based adjustments to basal insulin delivery rates and suspension of insulin delivery when a low blood glucose event is predicted. This review also includes a brief discussion of upcoming technologies such as patch-based CGMS and insulin-glucagon dual-hormonal delivery.

Evolving Pharmacotherapeutic Strategies for Type 1 Diabetes Mellitus.

Despite pharmacotherapeutic advancements in the management of type 1 diabetes mellitus during the past several decades, patients struggle to achieve glycemic goals. Additionally, hypoglycemia, especially in extremes of age, decreases quality of life. The lack of optimal glycemic control and risk for hypoglycemia are multifactorial. Nevertheless, endeavors aiming to develop pharmacotherapeutic options with enhanced pharmacokinetic, pharmacodynamic, and clinical profiles continue. This review article discusses recent ventures in 3 categories of insulin, non-insulin, and glucagon products.

Neonatal Diabetes: Case Report of a 9-Week-Old Presenting Diabetic Ketoacidosis Due to an Activating ABCC8 Gene Mutation.

Context: Neonatal diabetes mellitus, a rare condition occurring in approximately 1 in 500 000 live births, is defined as insulin-requiring hyperglycemia presenting in the first months of life. Neonatal diabetes can be transient or permanent, with studies characterizing the condition as a monogenic disorder. Case Report: We describe a case of a 9-week-old infant with neonatal diabetes who presented in diabetic ketoacidosis due to a mutation affecting the ABCC8 gene that encodes the SUR1 subunit of the potassium ATP channel. Conclusion: This genetic diagnosis has therapeutic implications regarding the initiation of sulfonylurea administration as 85% of patients with neonatal diabetes due to ABCC8 gene mutations can be successfully treated with oral sulfonylurea treatment.

Epidermal stem cells: an update on their potential in regenerative medicine.

INTRODUCTION: Adult epidermal stem cells are crucial for skin tissue regeneration during homeostasis and disease. Recent updates relating to the function, cellular role and properties of these cells have been published. Notably, a recent study showed that keratinocytes may possess a transcriptional profile that is more amenable to reprogramming and this may open new avenues for exploring novel strategies to create patient-specific cell therapies. AREAS COVERED: In this paper, an overview of recent research pertaining to epidermal stem cells' properties and location, and their capacity for differentiation and transdifferentiation, as well as potential for tumorigenesis are presented. EXPERT OPINION: More efforts should be made to develop effective approaches to induce lineage conversion between different cell types and tailor the treatment to specific patient, while minimizing cancer risk.

Metabolic syndrome and daily ambulation in children, adolescents, and young adults.

PURPOSES: To compare daily ambulatory measures in children, adolescents, and young adults with and without metabolic syndrome and to assess which metabolic syndrome components, demographic measures, and body composition measures are associated with daily ambulatory measures. METHODS: Two-hundred fifty subjects between the ages of 10 and 30 yr were assessed on metabolic syndrome components, demographic and clinical measures, body fat percentage, and daily ambulatory strides, durations, and cadences during seven consecutive days. Of the 250 subjects, 45 had metabolic syndrome, as defined by the International Diabetes Federation. RESULTS: Subjects with metabolic syndrome ambulated at a slower daily average cadence than those without metabolic syndrome (13.6 ± 2.2 vs 14.9 ± 3.2 strides per minute; P = 0.012), and they had slower cadences for continuous durations of 60 min (P = 0.006), 30 min (P = 0.005), 20 min (P = 0.003), 5 min (P = 0.002), and 1 min (P = 0.001). However, the total amount of time spent ambulating each day was not different (P = 0.077). After adjustment for metabolic syndrome status, average cadence is linearly associated with body fat percentage (P < 0.001) and fat mass (P < 0.01). Group difference in average cadence was no longer significant after adjusting for body fat percentage (P = 0.683) and fat mass (P = 0.973). CONCLUSIONS: Children, adolescents, and young adults with metabolic syndrome ambulate more slowly and take fewer strides throughout the day than those without metabolic syndrome, although the total amount of time spent ambulating is not different. Furthermore, the detrimental influence of metabolic syndrome on ambulatory cadence is primarily a function of body fatness.

Metabolic syndrome and arterial elasticity in youth.

OBJECTIVE: To compare arterial elasticity in children, adolescents, and young adults with and without metabolic syndrome (MetS), and to assess which MetS components, demographic measures, and body composition measures are associated with arterial elasticity. MATERIALS/METHODS: Two-hundred six subjects (107 females and 99 males) between the ages of 10 and 20years were recruited by local newspaper advertisements, university email advertisements, and informational flyers. Subjects were assessed on MetS components, demographic measures, body composition measures, and arterial elasticity via radial tonometry. Forty-five subjects (22%) had MetS, as defined by the International Diabetes Federation, and 161 subjects (78%) did not. RESULTS: The primary novel finding was that group differences were not observed for large artery elasticity index (LAEI) (MetS=16.1±4.4 (ml×mmHg(-1))×10 (mean±SD), control=15.4±4.9, (ml×mmHg(-1))×10, p=0.349), and small artery elasticity index (SAEI) (MetS=9.2±2.7 (ml×mmHg(-1))×100, control=8.4±2.9, (ml×mmHg(-1))×100, p=0.063). In the MetS group, fat free mass was positively associated with arterial elasticity, and was the strongest multivariate predictor of LAEI (partial R(2)=0.41) and SAEI (partial R(2)=0.29). CONCLUSIONS: Youth with MetS did not exhibit differences in LAEI and SAEI compared to controls. Furthermore, fat free mass of youth with MetS was positively associated with arterial elasticity, and was the strongest predictor of both LAEI and SAEI. The clinical implication is that exercise intervention designed to increase fat free mass might increase arterial elasticity in youth, particularly in youth with MetS.

Electric fields guide migration of epidermal stem cells and promote skin wound healing.

Migration of epidermal stem cells (EpSCs) into wounds may play an important role in wound healing. Endogenous electric fields (EFs) arise naturally at wounds. Consistent with previous reports, we measured outward electric currents at rat skin wounds using vibrating probes. Topical use of prostaglandin E2 significantly promoted wound healing. However, it is not known whether EpSCs respond to EFs. We first isolated and characterized EpSCs from rat skin. We then demonstrated that EpSCs isolated from the epidermis migrated directionally toward the cathode in EFs of 50-400 mV/mm. The directedness values increased in a dose- and time-dependent fashion. The migration speed of EpSCs was significantly increased in EFs. EFs induced asymmetric polymerization of intracellular F-actin and activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathways. Inhibition of epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, or PI3K significantly inhibited the cathodal distribution of F-actin and the electrotactic response of EpSCs. These data for the first time show that EpSCs possess obvious electrotaxis, in which the epidermal growth factor receptor-mitogen activated protein kinase-PI3K pathways are involved. These data thus suggest a novel aspect of electric signaling in wound healing-to stimulate and guide migration of EpSCs and to regulate wound healing.

Transition from pediatric to adult care for adolescents and young adults with a disorder of sex development.

Over the past twenty years, there has been an increasing awareness of the transition to adult-oriented health care in adolescents and young adults with a chronic illness. While general guidelines for health care transition have been established, some have called for illness-specific guidelines which are tailored to the needs of specific illness populations. The current paper sought to outline illness-specific guidelines for health care transition in adolescents and young adults with disorders of sex development based upon the recent American Academy of Pediatrics guidelines. We also suggest indicators of successful transition for adolescents and young adults with disorders of sex development as well as areas for future research.

Electric field-controlled directed migration of neural progenitor cells in 2D and 3D environments.

Endogenous electric fields (EFs) occur naturally in vivo and play a critical role during tissue/organ development and regeneration, including that of the central nervous system(1,2). These endogenous EFs are generated by cellular regulation of ionic transport combined with the electrical resistance of cells and tissues. It has been reported that applied EF treatment can promote functional repair of spinal cord injuries in animals and humans(3,4). In particular, EF-directed cell migration has been demonstrated in a wide variety of cell types(5,6), including neural progenitor cells (NPCs)(7,8). Application of direct current (DC) EFs is not a commonly available technique in most laboratories. We have described detailed protocols for the application of DC EFs to cell and tissue cultures previously(5,11). Here we present a video demonstration of standard methods based on a calculated field strength to set up 2D and 3D environments for NPCs, and to investigate cellular responses to EF stimulation in both single cell growth conditions in 2D, and the organotypic spinal cord slice in 3D. The spinal cordslice is an ideal recipient tissue for studying NPC ex vivo behaviours, post-transplantation, because the cytoarchitectonic tissue organization is well preserved within these cultures(9,10). Additionally, this ex vivo model also allows procedures that are not technically feasible to track cells in vivo using time-lapse recording at the single cell level. It is critically essential to evaluate cell behaviours in not only a 2D environment, but also in a 3D organotypic condition which mimicks the in vivo environment. This system will allow high-resolution imaging using cover glass-based dishes in tissue or organ culture with 3D tracking of single cell migration in vitro and ex vivo and can be an intermediate step before moving onto in vivo paradigms.

Electrical signaling in control of ocular cell behaviors.

Epithelia of the cornea, lens and retina contain a vast array of ion channels and pumps. Together they produce a polarized flow of ions in and out of cells, as well as across the epithelia. These naturally occurring ion fluxes are essential to the hydration and metabolism of the ocular tissues, especially for the avascular cornea and lens. The directional transport of ions generates electric fields and currents in those tissues. Applied electric fields affect migration, division and proliferation of ocular cells which are important in homeostasis and healing of the ocular tissues. Abnormalities in any of those aspects may underlie many ocular diseases, for example chronic corneal ulcers, posterior capsule opacity after cataract surgery, and retinopathies. Electric field-inducing cellular responses, termed electrical signaling here, therefore may be an unexpected yet powerful mechanism in regulating ocular cell behavior. Both endogenous electric fields and applied electric fields could be exploited to regulate ocular cells. We aim to briefly describe the physiology of the naturally occurring electrical activities in the corneal, lens, and retinal epithelia, to provide experimental evidence of the effects of electric fields on ocular cell behaviors, and to suggest possible clinical implications.

A Molecular Link Between Interleukin 22 and Intestinal Mucosal Wound Healing.

BACKGROUND: Interleukin 22 (IL-22) and signal transducer and activator of transcription 3 (STAT3) are two important regulators of inflammation. Crohn's disease and ulcerative colitis are considered inflammatory bowel diseases (IBDs), due to the belief that these diseases result from dysregulated responses of the intestinal immune system to bacteria present in the commensal flora. THE PROBLEM: It is debated whether a breakdown of immune tolerance is the primary cause of these diseases or occurs downstream of an initial defect of the intestinal barrier and intestinal epithelial cells (IECs). BASIC/CLINICAL SCIENCE ADVANCES: Recent reports suggest a crucial role for IL-22 in the regulation of gut inflammation as well as epithelial barrier integrity. Local IL-22 gene delivery enhances expression of its downstream effector, STAT3, within colonic epithelial cells and induces both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. IEC-specific deletion of STAT3 results in significant susceptibility to experimental colitis with a striking defect in epithelial restitution. STAT3 activation, thus, may regulate immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing. CLINICAL CARE RELEVANCE: The importance of IL-22/STAT3 signaling in IEC wound healing suggests a critical role for epithelial homeostasis in IBDs. CONCLUSION: Effective healing of the IECs could be considered a primary target in the development of treatments for IBDs. IL-22/STAT3 signaling exerts a protective role in the process of intestinal mucosal wound healing and may thereby provide a promising therapeutic approach to the treatment of IBDs.

A model of delivering multi-disciplinary care to people with 46 XY DSD.

In 2006, a consensus statement was jointly produced by the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society of Paediatric Endocrinology (ESPE) concerning the management of disorders of sex development (DSD) [1]. A recommendation provided by this consensus was that evaluation and long-term care for people affected by DSD should be performed at medical centers with multi-disciplinary teams experienced in such conditions. Here we provide our team's interpretation of the 2006 consensus statement recommendations and its translation into a clinical protocol for individuals affected by 46 XY DSD with either female, or ambiguous, genitalia at birth. Options for medical and surgical management, transitioning of care, and the use of mental health services and peer support groups are discussed. Finally, we provide preliminary data to support the application of our model for delivering multi-disciplinary care and support to patients and their families.

Normal sex differences in prenatal growth and abnormal prenatal growth retardation associated with 46,XY disorders of sex development are absent in newborns with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD) in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences. METHODS: In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained. Mid-parental height was considered in the analyses. RESULTS: Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (P > 0.05). The expected sex difference in favor of heavier males was not seen (P > 0.05). Of the 105 subjects, 44 (27%; 34 females, 10 males) had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile), which differed from the expected standard population median of 50th percentile (P = 0.0082). The expected sex difference in favor of longer males was also not seen (P > 0.05). CONCLUSION: The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who participated in this study. We speculate that these differences were ameliorated in this study because of increased levels of prenatal androgens experienced by the females infants.