Using Photovoice to Understand Survivors' Healthcare Experiences and Strategies.

The unique, individual nature of traumatic experiences and trauma symptoms and the limited healthcare resources typically allocated for individual patients pose barriers to implementing trauma-informed care. Developing knowledge on how survivors of violence engage in healthcare and self-advocate can lead to more empowering and efficient implementation of trauma-informed care. However, survivor perspectives on trauma-informed care are underrepresented in current literature and survivors' strategies for navigating healthcare are understudied. The aims of this participatory Photovoice study were to describe the healthcare experiences of female survivors of violence and their strategies for dealing with difficult healthcare experiences, healthcare providers, and the healthcare system. A sample of community-based women participated in an iterative series of five Photovoice meetings. Participants discussed multifaceted vulnerability in healthcare settings with regard to past traumatic violence, triggering or retraumatizing health care experiences, medical knowledge, and provider-patient relationships. They agreed that providers believing their symptoms, health concerns, and trauma disclosures was essential for positive provider-patient relationships and healthcare experiences. Findings on the importance of perceived belief with regard to trauma disclosure and health concerns and survivors' healthcare strategies are unique contributions to the literature. Providers should be accountable for integrating survivors' self-knowledge in collaborative healthcare decision-making, for making medical records and information easily accessible, and for expressing belief in trauma disclosures and health concerns. Future research should continue using participatory methods to assess evolving trauma-informed practices and patient engagement among survivors and to hasten progress toward trauma-informed care that effectively meets the needs of survivors.

Recognising and responding to intimate partner violence using telehealth: Practical guidance for nurses and midwives.

AIMS: To synthesise the current, global evidence-informed guidance that supports nurses and midwives to recognise and respond to intimate partner violence (IPV), and how these practices can be translated from face-to-face encounters to care that is delivered through telehealth. BACKGROUND: COVID-19-related social and physical distancing measures increase the risk for individuals who are socially isolated with partners who perpetuate violence. Providing support through telehealth is one strategy that can mitigate the pandemic of IPV, while helping patients and providers stay safe from COVID-19. DESIGN AND METHODS: In this discursive paper, we describe how practical guidance for safely recognising and responding to IPV in telehealth encounters was developed. The ADAPT-ITT (Assessment, Decisions, Administration, Production, Topical Experts, Integration, Testing, Training) framework was used to guide the novel identification and adaptation of evidence-informed guidance. We focused on the first six stages of the ADAPT-ITT framework. CONCLUSIONS: This paper fills a gap in available guidance, specifically for IPV recognition and response via telehealth. We present strategies for prioritising safety and promoting privacy while initiating, managing or terminating a telehealth encounter with patients who may be at risk for or experiencing IPV. Strategies for assessment, planning and intervention are also summarised. System-level responses, such as increasing equitable access to telecommunication technology, are also discussed. RELEVANCE TO CLINICAL PRACTICE: Integrating innovative IPV-focused practices into telehealth care is an important opportunity for nurses and midwives during the current global COVID-19 pandemic. There are also implications for future secondary outbreaks, natural disasters or other physically isolating events, for improving healthcare efficiency, and for addressing the needs of vulnerable populations with limited access to health care.

Adolescents' Use of Digital Technologies and Preferences for Mobile Health Coaching in Public Mental Health Settings.

Objective: Youth with mental illnesses often engage in unhealthy behaviors associated with early mortality from physical diseases in adulthood, but interventions to support positive health behaviors are rarely offered as part of routine mental health care for this group. Digital health technology that is desirable, accessible, and affordable has the potential to address health behaviors in public mental health settings where many adolescents with severe mental health problems receive care. The aims of this study were to examine how adolescents receiving public mental health services use digital technology and social media and to explore their preferences using technology to support health and wellness. Methods: Using a convergent parallel mixed methods design, we surveyed adolescents ages 13-18 from four community mental health centers in one state and conducted focus group interviews to explore their perspectives on using digital technology and social media to receive health coaching and connect with peers to support healthy behaviors. The survey and focus group data were merged to inform the future development of a digital health intervention for adolescents receiving public mental health services. Results: Of 121 survey respondents (mean age 15.2, SD = 1.5), 92% had a cell phone, 79% had a smartphone, 90% used text messaging, and 98% used social media. Focus group interviews revealed that adolescents were interested in receiving strengths-based mobile health coaching, and they preferred structured online peer-to-peer interactions in which a professional moderator promotes positive connections and adherence to privacy guidelines. Conclusions: Adolescents receiving public mental health services in this study had access to smartphones and were frequent social media users. These data suggest that digital health interventions to promote health and wellness among adolescents may be scalable in community mental health settings. Adolescent participants suggested that digital health interventions for this group should focus on strengths and online peer support for health promotion should include a professional moderator to foster and manage peer-to-peer interactions.

Discovery of a small molecule RXFP3/4 agonist that increases food intake in rats upon acute central administration.

The relaxin family peptide receptors have been implicated in numerous physiological processes including energy homeostasis, cardiac function, wound healing, and reproductive function. Two family members, RXFP3 and RXFP4, are class A GPCRs with endogenous peptide ligands (relaxin-3 and insulin-like peptide 5 (INSL5), respectively). Polymorphisms in relaxin-3 and RXFP3 have been associated with obesity, diabetes, and hypercholesterolemia. Moreover, central administration of relaxin-3 in rats has been shown to increase food intake, leading to body weight gain. Reported RXFP3 and RXFP4 ligands have been restricted to peptides (both endogenous and synthetic) as well as a low molecular weight positive allosteric modulator requiring a non-endogenous orthosteric ligand. Described here is the discovery of the first potent low molecular weight dual agonists of RXFP3/4. The scaffold identified is competitive with a chimeric relaxin-3/INSL5 peptide for RXFP3 binding, elicits similar downstream signaling as relaxin-3, and increases food intake in rats following acute central administration. This is the first report of small molecule RXFP3/4 agonism.

Discovery and evaluation of spirocyclic derivatives as antagonists of the neuropeptide Y5 receptor.

A novel series of spirocyclic derivatives was synthesized and evaluated as NPY Y5R antagonists for the treatment of obesity. Cis and trans analogs 7a and 8a were equipotent in a Y5R binding assay (K(i)'s ≤ 1 nM) and displayed good stability in human and rat liver microsome preparations. Compound 7a failed to demonstrate weight loss activity in a diet-induced obese (DIO) rat model at unbound drug levels in the brain that exceeded the Y5R K(i) value by 25-fold over a 24-h time-period.

Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity.

Brain-penetrable proline amides were developed as 5HT2c agonists with more than 1000-fold binding selectivity against 5HT2b receptor. After medicinal chemistry optimization and SAR studies, orally active proline amides with robust efficacy in a rodent food intake inhibition model were uncovered.

Design and synthesis of orally-active and selective azaindane 5HT2c agonist for the treatment of obesity.

Based on our original pyrazine hit, CP-0809101, novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the selectivity against 5HT2a and 5HT2b receptors with excellent 2c potency. Orally-active and selective compounds were identified with dose-responsive in vivo efficacy in our pre-clinical food intake model.

Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes.

Hormonal control of metabolic rate can be important in regulating the imbalance between energy intake and expenditure that underlies the development of obesity. In mice fed a high-fat diet, human fibroblast growth factor 19 (FGF19) increased metabolic rate [1.53 +/- 0.06 liters O(2)/h.kg(0.75) (vehicle) vs. 1.93 +/- 0.05 liters O(2)/h.kg(0.75) (FGF19); P < 0.001] and decreased respiratory quotient [0.82 +/- 0.01 (vehicle) vs. 0.80 +/- 0.01 (FGF19); P < 0.05]. In contrast to the vehicle-treated mice that gained weight (0.14 +/- 0.05 g/mouse.d), FGF19-treated mice lost weight (-0.13 +/- 0.03 g/mouse.d; P < 0.001) without a significant change in food intake. Furthermore, in addition to a reduction in weight gain, treatment with FGF19 prevented or reversed the diabetes that develops in mice made obese by genetic ablation of brown adipose tissue or genetic absence of leptin. To explore the mechanisms underlying the FGF19-mediated increase in metabolic rate, we profiled the FGF19-induced gene expression changes in the liver and brown fat. In brown adipose tissue, chronic exposure to FGF19 led to a gene expression profile that is consistent with activation of this tissue. We also found that FGF19 acutely increased liver expression of the leptin receptor (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A carboxylase 2 (0.6-fold; P < 0.05). The gene expression changes were consistent with the experimentally determined increase in fat oxidation and decrease in liver triglycerides. Thus, FGF19 is able to increase metabolic rate concurrently with an increase in fatty acid oxidation.

A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice.

Most mouse models of hepatocellular carcinoma have expressed growth factors and oncogenes under the control of a liver-specific promoter. In contrast, we describe here the formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic mice had elevated hepatic alpha-fetoprotein mRNA as early as 2 months of age, and hepatocellular carcinomas were evident by 10 months of age. Increased proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'-deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear staining for beta-catenin. Sequencing of the tumor DNA encoding beta-catenin revealed point mutations that resulted in amino acid substitutions. These findings suggest a previously unknown role for FGF19 in hepatocellular carcinomas.

Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.

The fibroblast growth factors (FGFs), and the corresponding receptors, are implicated in more than just the regulation of epithelial cell proliferation and differentiation. Specifically, FGF23 is a regulator of serum inorganic phosphate levels, and mice deficient in FGF receptor-4 have altered cholesterol metabolism. The recently described FGF19 is unusual in that it is nonmitogenic and appears to interact only with FGF receptor-4. Here, we report that FGF19 transgenic mice had a significant and specific reduction in fat mass that resulted from an increase in energy expenditure. Further, the FGF19 transgenic mice did not become obese or diabetic on a high fat diet. The FGF19 transgenic mice had increased brown adipose tissue mass and decreased liver expression of acetyl coenzyme A carboxylase 2, providing two mechanisms by which FGF19 may increase energy expenditure. Consistent with the reduction in expression of acetyl CoA carboxylase 2, liver triglyceride levels were reduced.