Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2 To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension.

An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

A Randomized Controlled Trial of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children referred to specialist outpatient clinics by primary care providers often have long waiting times before being seen. We assessed whether an individualized, web-based, evidence-informed management support for children with urinary incontinence while waiting reduced requests for specialist appointments. MATERIALS AND METHODS: A multicenter, waitlisted randomized controlled trial was conducted for children (5-18 years) with urinary incontinence referred to tertiary pediatric continence clinics. Participants were randomized to the web-based eHealth program electronic Advice and Diagnosis Via the Internet following Computerized Evaluation (eADVICE), which used an embodied conversational agent to engage with the child at the time of referral (intervention) or 6 months later (control). The primary outcome was the proportion of participants requesting a clinic appointment at 6 months. Secondary outcomes included persistent incontinence, and the Paediatric incontinence Questionnaire (PinQ) score. RESULTS: From 2018 to 2020, 239 children enrolled, with 120 randomized to eADVICE and 119 to the control arm. At baseline, participants' mean age was 8.8 years (SD 2.2), 62% were males, mean PinQ score was 5.3 (SD 2.2), 36% had daytime incontinence, and 97% had nocturnal enuresis. At 6 months, 78% of eADVICE participants vs 84% of controls requested a clinic visit (relative risk 0.92, 95% CI 0.79, 1.06, P = .3), and 23% eADVICE participants vs 10% controls were completely dry (relative risk 2.23, 95% CI 1.10, 4.50, P = .03). The adjusted mean PinQ score was 3.5 for eADVICE and 3.9 for controls (MD -0.37, 95% CI -0.71, -0.03, P = .03). CONCLUSIONS: The eADVICE eHealth program for children awaiting specialist appointments doubled the proportion who were dry at 6 months and improved quality of life but did not reduce clinic appointment requests.

Volunteering as prosocial behaviour by medical students following a flooding disaster and impacts on their mental health: A mixed-methods study.

BACKGROUND: Volunteering is a form of prosocial behaviour that has a been recognised as having positive benefits for medical students. However, there is a lack of research on what influences students to volunteer during and after weather-related disasters. Our study (1) explores factors related to medical students' willingness and readiness to volunteer, and (2) describes mental health impacts of the flood events on students. METHODS: We conducted a mixed-methods study of medical students on rural clinical placements in a regional area of Australia, 2 to 6 weeks after two major flooding events in 2022. Data were collected through survey and focus groups. Summary statistics were generated from the survey data, and Fisher's exact test was used to determine associations between student experience of the flood and self-rated well-being. Qualitative data were deductively analysed using Byrne and colleagues' theory of prosocial behaviour during an emergency. RESULTS: The 36 students who participated in focus groups (including the 34 who completed the survey) (response rates 84% and 79%, respectively) demonstrated high levels of prosocial behaviours and were willing to volunteer. A sense of moral obligation was the primary reason for volunteering, whereas concerns for their physical and psychological safety, and missing key aspects of their training, were the strongest reasons for not continuing to volunteer. Students reported personal stress, anxiety and trauma during this period, with significant associations between self-rated impacts on their well-being and feelings of being terrified, helpless and hopeless during the flooding events and of still being distressed weeks later (p < .05). CONCLUSIONS: This study expands on prosocial behaviour theory by applying Byrne and colleagues elaborated model in the context of medical student volunteering during the 2022 major flooding events in Australia. Modifiable barriers to prosocial behaviour are identified along with proposed strategies to address these barriers.

Learning outcomes from a systematic review workshop series for junior doctors.

BACKGROUND: Systematic reviews provide the highest level of evidence about a topic. Ten-week workshops in conducting systematic reviews were held with hospital doctors in 2019 and 2020. AIM: This study analysed participants' feedback about the systematic review workshops to improve how we teach clinicians about conducting systematic reviews. METHODS: Attendees completed a post-workshop survey (with multiple-choice and free-text items) to assess knowledge and skills gained. We compared the responses of senior and junior doctors. We used descriptive statistics for the quantitative data and compared groups using Χ2 testing. Qualitative data were analysed using conceptual content analysis. RESULTS: Of 81 attendees, 52% completed the survey. Of those, 69% had no prior experience with systematic reviews, 93% reported increased knowledge and ability to conduct research and 69% reported increased ability to conduct systematic reviews. More senior than junior clinicians reported gaining knowledge about writing and publishing (37% vs 11%, P = 0.047) and making greater use of skills gained to conduct research (56% vs 23%, P = 0.029). Five themes were identified: learning through course structure; learning through course organisation; teaching style; flexible learning; and suggestions for progression and improvement. Respondents suggested running the workshops during protected teaching time, more time for some sessions, conducting the workshop series more often and making clinicians aware of the workshop series at hospital orientation. CONCLUSION: The skills learnt from the systematic review workshop series impacted not only participants' research knowledge and skills, and plans to conduct future research, but also facilitated looking up medical literature in daily clinical work, supporting evidence-based clinical practice.

Grace Under Pressure: a mixed methods impact assessment of a verbatim theatre intervention to improve healthcare workplace culture.

BACKGROUND: Healthcare workplace mistreatment has been documented globally. Poor workplace behaviour, ranging from incivility to bullying and harassment, is common in healthcare, and contributes significantly to adverse events in healthcare, poor mental health among healthcare workers, and to attrition in the healthcare workforce, particularly in junior years. Poor workplace behaviour is often normalised, and is difficult to address. Verbatim theatre, a form of research informed theatre in which plays are created from informants' exact words only, is particularly suited to facilitating workplace culture change by raising awareness about issues that are difficult to discuss. The objective of this study was to assess the impact of the verbatim theatre play 'Grace Under Pressure' on workplace culture in NSW hospitals. METHODS: The intervention was conducted in 13 hospitals from 8 Local Health Districts (LHDs) in NSW, Australia, in October and November 2019, with aggregated impact across all sites measured by a bespoke survey ('Pam McLean Centre (PMC) survey') at the conclusion of the intervention. This study was conducted in 3 Local Health Districts (one urban, one regional, one remote), with data collection conducted in November-December 2019 and December 2020. The study design was a mixed methods assessment of the play's impact using (1) validated baseline measures of psychosocial risk, analysed descriptively, (2) overall findings from the PMC survey above, analysed descriptively, (3) interviews conducted within a month of the intervention, analysed thematically and (4) interviews conducted one year later, analysed thematically. RESULTS: Half (51.5%) of the respondents (n = 149) to the baseline survey had scores indicating high risk of job strain and depressive symptoms. Of 478 respondents to the PMC survey (response rate 57%), 93% found the play important, 92% recommended others see the play, 89% considered that it stimulated thinking about workplace behaviour, and 85% that it made discussing these issues easier. Thematic analysis of interviews within one month (n = 21) showed that the play raised awareness about poor workplace behaviour and motivated behaviour change. Interviews conducted one year later (n = 6) attributed improved workplace culture to the intervention due to improved awareness, discussion and capacity to respond to challenging issues. CONCLUSIONS: Verbatim theatre is effective in raising awareness about difficult workplace behaviour in ways that motivate behaviour change, and hence can be effective in catalysing real improvements in healthcare workplace culture. Creative approaches are recommended for addressing similarly complex challenges in healthcare workforce retention.

Xylazine co-occurrence with illicit fentanyl is a growing threat in the Deep South: a retrospective study of decedent data.

BACKGROUND: Xylazine is a dangerous veterinary sedative found mainly in illicit fentanyl in the Northeast and Midwest. Its role in the Deep South overdose crisis is not well-characterized. METHODS: We conducted a retrospective review of autopsy data in Jefferson County, Alabama to identify trends in xylazine prevalence among people who fatally overdosed from June 2019 through June 2023. RESULTS: 165 decedents met inclusion criteria. While the first identified xylazine-associated overdose was in June 2019, xylazine has become consistently prevalent since January 2021. All cases of xylazine-associated fatal overdoses were accompanied by fentanyl, and most (75.4%) involved poly-drug stimulant use. The average age was 42.2, and most decedents were white (58.8%) and male (68.5%). Overall, 18.2% of people were unhoused at the time of death. DISCUSSION: Xylazine is prevalent in the Deep South. Efforts to promote harm reduction, publicly viewable drug supply trends, and legalization of drug checking and syringe service programs should be prioritized.

Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment.

BACKGROUND: Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. METHODS: Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA-negative infants in whom RNA was not detectable until after 6 weeks. RESULTS: Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1-18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0-76.9), 39.7% (CrI, 17.9-65.9), and 20.9% (CrI, 4.6-44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. CONCLUSIONS: Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment.

Overall Vertical Transmission of Hepatitis C Virus, Transmission Net of Clearance, and Timing of Transmission.

BACKGROUND: It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%-6% in monoinfected women, and that 25%-40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates "net" of clearance. METHODS: We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries. RESULTS: Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%-8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%-16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%-4.1%), and 4.1% (95% CrI, 1.7%-7.3%). We estimated that 24.8% (95% CrI, 12.1%-40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%-83.3%) later in utero, and 9.3% (95% CrI, 0.5%-30.6%) during delivery. CONCLUSIONS: Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.

Copper induces neuron-sparing, ferredoxin 1-independent astrocyte toxicity mediated by oxidative stress.

Copper is an essential enzyme cofactor in oxidative metabolism, anti-oxidant defenses, and neurotransmitter synthesis. However, intracellular copper, when improperly buffered, can also lead to cell death. Given the growing interest in the use of copper in the presence of the ionophore elesclomol (CuES) for the treatment of gliomas, we investigated the effect of this compound on the surround parenchyma-namely neurons and astrocytes in vitro. Here, we show that astrocytes were highly sensitive to CuES toxicity while neurons were surprisingly resistant, a vulnerability profile that is opposite of what has been described for zinc and other toxins. Bolstering these findings, a human astrocytic cell line was similarly sensitive to CuES. Modifications of cellular metabolic pathways implicated in cuproptosis, a form of copper-regulated cell death, such as inhibition of mitochondrial respiration or knock-down of ferredoxin 1 (FDX1), did not block CuES toxicity to astrocytes. CuES toxicity was also unaffected by inhibitors of apoptosis, necrosis or ferroptosis. However, we did detect the presence of lipid peroxidation products in CuES-treated astrocytes, indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Indeed, treatment with anti-oxidants mitigated CuES-induced cell death in astrocytes indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Lastly, prior induction of metallothioneins 1 and 2 in astrocytes with zinc plus pyrithione was strikingly protective against CuES toxicity. As neurons express high levels of metallothioneins basally, these results may partially account for their resistance to CuES toxicity. These results demonstrate a unique toxic response to copper in glial cells which contrasts with the cell selectivity profile of zinc, another biologically relevant metal.

Modelling the potential effectiveness of hepatitis C screening and treatment strategies during pregnancy in Egypt and Ukraine.

BACKGROUND & AIMS: HCV test and treat campaigns currently exclude pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine. METHODS: Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, World Health Organization (WHO) risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission [VT]); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected. RESULTS: S0 resulted in the highest proportion of women undiagnosed: 59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatment during pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70%, respectively), and lower levels of VT (3.4% and 3.6%, respectively). CONCLUSIONS: This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes. IMPACT AND IMPLICATIONS: In the context of two lower middle-income countries with high HCV burdens (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy. Assuming direct-acting antiviral treatment during pregnancy would reduce vertical transmission, our findings indicate that the provision of universal (rather than risk-based targeted) screening and treatment would provide the greatest maternal and infant benefits. While future trials are needed to assess the safety and efficacy of direct-acting antivirals in pregnancy and their impact on vertical transmission, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical for policymakers when developing improved screening and treatment recommendations for pregnant women.

Community Support Persons and Mitigating Obstetric Racism During Childbirth.

PURPOSE: We undertook a study to assess whether presence of community support persons (CSPs), with no hospital affiliation or alignment, mitigates acts of obstetric racism during hospitalization for labor, birth, and immediate postpartum care. METHODS: We conducted a cross-sectional cohort study, measuring 3 domains of obstetric racism as defined for, by, and with Black birthing people: humanity (violation of safety and accountability, autonomy, communication and information exchange, and empathy); kinship (denial or disruption of community and familial bonds that support Black birthing people); and racism in the form of anti-Black racism and misogynoir (weaponization of societal stereotypes and scripts in service provision that reproduce gendered anti-Black racism in the hospital). We used a novel, validated instrument, the Patient-Reported Experience Measure of Obstetric Racism (the PREM-OB Scale suite), and linear regression analysis to determine the association between CSP presence during hospital births and obstetric racism. RESULTS: Analyses were based on 806 Black birthing people, 720 (89.3%) of whom had at least 1 CSP present throughout their labor, birth, and immediate postpartum care. The presence of CSPs was associated with fewer acts of obstetric racism across all 3 domains, with statistically significant reductions in scores in the CSP group of one-third to two-third SD units relative to the no-CSP group. CONCLUSIONS: Our findings suggest that CSPs may be an effective way to reduce obstetric racism as part of quality improvement initiatives, emphasizing the need for democratizing the birthing experience and birth space, and incorporating community members as a way to promote the safety of Black birthing people in hospital settings.Annals "Online First" article.

Impact of parental health literacy on the health outcomes of children with chronic disease globally: A systematic review.

AIM: Health literacy is the ability to understand and interpret health information and navigate the health-care system. Low health literacy is associated with poorer health knowledge and disease management, increased chronic illness, underutilisation of preventative health services and increased hospitalisations. The aim of the study is to review the available literature on the relationship between parental health literacy and health outcomes for children with chronic disease in high-income countries (HIC) and low- and middle-income countries (LMIC). METHODS: We systematically searched Medline, EMBASE and Web of Science, and assessed study quality using the Newcastle Ottawa Scale. We reviewed all relevant studies, and identified themes using thematic analysis. RESULTS: Of 1167 studies assessed, 49 were included in the review. All studies were of adequate quality. Twenty-two were from LMIC and 27 from HIC. Six themes were identified: Parental health literacy, parental education, socio-economic conditions, identity and culture, family factors, and health behaviours. In both HIC and LMIC, lower parental health literacy was associated with poorer child health outcomes. Disease-specific knowledge was found in a number of papers to directly impact parent health behaviour and child health outcomes, and may mitigate the effects of low parental health literacy. CONCLUSION: There is a clear link between parental health literacy, health behaviour and health outcomes for children with chronic disease. Disease-specific knowledge as a target for health-care interventions holds promise for application in low-resourced settings with parents (particularly mothers) who have lower health literacy, where disease-specific education may improve child health outcomes, although more research is required to determine how we can best facilitate these programmes.

Patterns of parental online health information-seeking behaviour.

AIM: This study aimed to understand parents' online health information-seeking behaviour and the potential influence of this on their relationship with their child's physician. METHODS: A survey regarding parental online health information-seeking behaviour was administered to parents of children aged under 18 years admitted to an Australian tertiary paediatric hospital, paediatric hospital ward and paediatric clinic, and in their social media networks. Responses were presented as frequencies and percentages. Associations between parents' trust in their child's doctor and survey responses were analysed using χ2 tests. RESULTS: In all, 300 surveys were completed. Most parents (89%) reported searching for online health information when their child was sick. Some (31%) followed online health information instead of going to the doctor. Parents who trusted their child's doctor were more likely to follow the doctor instead of online health information when it contained conflicting advice. Most parents (91%) wanted health-care professionals' help in searching for online health information. CONCLUSION: Almost all parents search for online health information, but most do not act on it. Parents' trust in their child's doctor influences how parents use online health information. Thus, clinicians could recommend trustworthy websites with information that complements their advice to ensure parents access reliable online health information.

COVID-19 and Dr. Google: Parents' changing experience using online health information about their children's health during the pandemic.

AIMS: To identify how the COVID-19 pandemic influences parents' use of the internet, including social media, when seeking health-related information about the pandemic relevant to their children. METHODS: This study employed semi-structured interviews to explore the factors affecting parents of young children when information-seeking online about their children's health related to the COVID-19 pandemic. Parents of children with and without chronic health conditions were interviewed in July and August 2020. Interviews were audio-recorded and transcribed verbatim, then analysed using theoretical thematic analysis, based on Social Cognitive Theory. RESULTS: Through interviews with 13 parents, we identified a myriad of factors that affected parents' internet searching. The decision to access online health information and the regulation of its usage was multifaceted and relied upon the interactions between environmental triggers and parents' information needs, personal attitudes, and circumstances. Overall, parents felt supported by online health information during the COVID-19 pandemic, and the majority were confident in their ability to navigate the plethora of online health information. However, parents of children with chronic conditions had unmet information needs in relation to COVID-19 and their children's condition. CONCLUSIONS: Understanding parents' attitudes and behaviours when seeking online health information that is relevant to their children during a global pandemic can inform the optimisation of online health content delivery to parents.

Reducing Fear to Help Build Healthy Families: Investing in Non-Punitive Approaches to Helping People with Substance Use Disorder.

BACKGROUND: Many pregnant and parenting people with substance use disorders (SUD) refrain from seeking perinatal care or treatment for their SUD for fear of being treated poorly by health care providers and/or triggering a child welfare investigation. For those who do seek treatment, there are relatively few clinicians willing and able to prescribe medications for opioid use disorder (MOUD) to pregnant people. Both stigma and lack of access to treatment put many pregnant and parenting people at risk. Drug-related deaths contribute significantly to U.S. maternal mortality rates, with people at especially high risk of drug overdose in the months following delivery. METHODS: The Foundation for Opioid Response Efforts (FORE) is a national philanthropy focused on finding and fostering solutions to the opioid crisis. We draw lessons from our grantees' efforts to expand access to substance use treatment and recovery supports for pregnant and parenting people. RESULTS: To build systems of care that ensure more pregnant people get timely perinatal care, we need to expand training for perinatal providers on how to provide OUD treatment, clarify child welfare reporting rules, and engage and support trusted organizations and community-based services. CONCLUSIONS: In addition to changes to our systems of SUD treatment and recovery, we need greater philanthropic investment in efforts to combat the public health crisis of substance use and overdose among pregnant and parenting people. Private funders have the leeway to act quickly, take risks, and demonstrate the effectiveness of new approaches, building the case for investment of public resources in such initiatives.

'Every Human Interaction Requires a Bit of Give and Take': Medical Students' Approaches to Pursuing Feedback in the Clinical Setting.

PhenomenonStudents, alongside teachers, play a key role in feedback. Student behavior in feedback processes may impact feedback outcomes. Student feedback behavior includes recognizing, seeking, evaluating, and utilizing feedback. Student feedback behavior is influenced by numerous student attributes and environmental factors. ApproachWe aimed to explore influences on medical student feedback behavior during clinical attachments. We adopted a subjective inductive qualitative approach. We conducted 7 focus groups with 46 medical students undertaking pediatric hospital-based attachments. We based our discussion framework on existing characterizations of student feedback behavior and the educational alliance model with its focus on the relationship between learners and teachers, and the active role played by both. During initial data analysis, we identified that our results exhibited aspects of Bandura's model of Triadic Reciprocal Causation within Social Cognitive Theory. In line with our subjective inductive approach, we adopted Triadic Reciprocal Causation at this point for further analysis and interpretation. This allowed us to conceptualize the emerging interactions between influences on feedback behavior. Findings We identified three key determinants of student feedback behavior: Environmental influences, Student attributes and Relationships between teachers and students. Environmental influences encompassed factors external to the student, including Teacher attributes and behaviors and The clinical learning context. Through the lens of Triadic Reciprocal Causation, the interrelationships between the determinants of feedback behavior gave rise to five key themes: Interactions between student feedback behavior and environmental influences of the clinical learning context, Interactions between student feedback behavior and environmental influences of teacher attributes and behaviors, Interactions between student attributes and student feedback behavior, Interactions between student attributes and environmental influences of teacher attributes and behaviors, and Relationships and the determinants of student feedback behavior. Insights: We apply the Triadic Reciprocal Causation model of Social Cognitive Theory to understand the influences on student feedback behavior and the interactions between them. We extend the model by situating relationships between students and teachers as a central factor. Future interventions to facilitate students' role in feedback will need to address student attributes, environmental factors, and student-teacher relationships, appreciating the codependent nature of these influences.

Impact of Engaging Students in Health Survey Data Analysis and as Full Partners in School Change: Results From a Mixed Methods Study.

Young people demand and deserve participation in shaping the health and well-being of their community. Getting to Y: Youth Bring Meaning to the Youth Risk Behavior Survey (GTY) is a positive youth development initiative, whereby students analyze local youth health data and create change. This article adds definitive evidence to support the theoretical foundations of GTY expounded by Garnett et al. (2019). A mixed methods convergent study design, collecting quantitative data from pre- and postintervention surveys and qualitative data from focus groups, was enacted during the 2018-2019 school year. Survey participants were 256 students attending 20 Vermont middle/high schools. Surveys measured self-efficacy, health literacy, civic engagement, resiliency, and knowledge. Focus groups with 50 students solicited open-ended feedback. Wilcoxon signed-rank tests determined student-level change over time. Focus group transcripts were coded using grounded theory and a priori codes from the survey. Statistically significant improvements were seen in average scores from pre- to postintervention surveys in all five domains and differences in effect by gender. Results from the focus group complement the quantitative findings. Participation in GTY positively affected youth participant's understanding of their own health and well-being and increased agency to take action on behalf of themselves and their community. As the Youth Risk Behavior Survey is available nationwide, GTY is poised for replication to critically engage youth with relevant data to inform social change.

An Angiotensin-Responsive Connection from the Lamina Terminalis to the Paraventricular Nucleus of the Hypothalamus Evokes Vasopressin Secretion to Increase Blood Pressure in Mice.

Blood pressure is controlled by endocrine, autonomic, and behavioral responses that maintain blood volume and perfusion pressure at levels optimal for survival. Although it is clear that central angiotensin type 1a receptors (AT1aR; encoded by the Agtr1a gene) influence these processes, the neuronal circuits mediating these effects are incompletely understood. The present studies characterize the structure and function of AT1aR neurons in the lamina terminalis (containing the median preoptic nucleus and organum vasculosum of the lamina terminalis), thereby evaluating their roles in blood pressure control. Using male Agtr1a-Cre mice, neuroanatomical studies reveal that AT1aR neurons in the area are largely glutamatergic and send projections to the paraventricular nucleus of the hypothalamus (PVN) that appear to synapse onto vasopressin-synthesizing neurons. To evaluate the functionality of these lamina terminalis AT1aR neurons, we virally delivered light-sensitive opsins and then optogenetically excited or inhibited the neurons while evaluating cardiovascular parameters or fluid intake. Optogenetic excitation robustly elevated blood pressure, water intake, and sodium intake, while optogenetic inhibition produced the opposite effects. Intriguingly, optogenetic excitation of these AT1aR neurons of the lamina terminalis also resulted in Fos induction in vasopressin neurons within the PVN and supraoptic nucleus. Further, within the PVN, selective optogenetic stimulation of afferents that arise from these lamina terminalis AT1aR neurons induced glutamate release onto magnocellular neurons and was sufficient to increase blood pressure. These cardiovascular effects were attenuated by systemic pretreatment with a vasopressin-1a-receptor antagonist. Collectively, these data indicate that excitation of lamina terminalis AT1aR neurons induces neuroendocrine and behavioral responses that increase blood pressure.SIGNIFICANCE STATEMENT Hypertension is a widespread health problem and risk factor for cardiovascular disease. Although treatments exist, a substantial percentage of patients suffer from "drug-resistant" hypertension, a condition associated with increased activation of brain angiotensin receptors, enhanced sympathetic nervous system activity, and elevated vasopressin levels. The present study highlights a role for angiotensin Type 1a receptor expressing neurons located within the lamina terminalis in regulating endocrine and behavioral responses that are involved in maintaining cardiovascular homeostasis. More specifically, data presented here reveal functional excitatory connections between angiotensin-sensitive neurons in the lamina terminals and vasopressin neurons in the paraventricular nucleus of the hypothalamus, and further indicate that activation of this circuit raises blood pressure. These neurons may be a promising target for antihypertensive therapeutics.

Identification of Novel Cross-Talk between the Neuroendocrine and Autonomic Stress Axes Controlling Blood Pressure.

The hypothalamic paraventricular nucleus (PVN) controls neuroendocrine axes and the autonomic nervous system to mount responses that cope with the energetic burdens of psychological or physiological stress. Neurons in the PVN that express the angiotensin Type 1a receptor (PVNAgtr1a) are implicated in neuroendocrine and autonomic stress responses; however, the mechanism by which these neurons coordinate activation of neuroendocrine axes with sympathetic outflow remains unknown. Here, we use a multidisciplinary approach to investigate intra-PVN signaling mechanisms that couple the activity of neurons synthesizing corticotropin-releasing-hormone (CRH) to blood pressure. We used the Cre-Lox system in male mice with in vivo optogenetics and cardiovascular recordings to demonstrate that excitation of PVNAgtr1a promotes elevated blood pressure that is dependent on the sympathetic nervous system. Next, neuroanatomical experiments found that PVNAgtr1a synthesize CRH, and intriguingly, fibers originating from PVNAgtr1a make appositions onto neighboring neurons that send projections to the rostral ventrolateral medulla and express CRH type 1 receptor (CRHR1) mRNA. We then used an ex vivo preparation that combined optogenetics, patch-clamp electrophysiology, and Ca2+ imaging to discover that excitation of PVNAgtr1a drives the local, intra-PVN release of CRH, which activates rostral ventrolateral medulla-projecting neurons via stimulation of CRHR1(s). Finally, we returned to our in vivo preparation and found that CRH receptor antagonism specifically within the PVN lowered blood pressure basally and during optogenetic activation of PVNAgtr1a Collectively, these results demonstrate that angiotensin II acts on PVNAgtr1a to conjoin hypothalamic-pituitary-adrenal axis activity with sympathetically mediated vasoconstriction in male mice.SIGNIFICANCE STATEMENT The survival of an organism is dependent on meeting the energetic demands imposed by stressors. This critical function is accomplished by the CNS's ability to orchestrate simultaneous activities of neurosecretory and autonomic axes. Here, we unveil a novel signaling mechanism within the paraventricular nucleus of the hypothalamus that links excitation of neurons producing corticotropin-releasing-hormone with excitation of neurons controlling sympathetic nervous system activity and blood pressure. The implication is that chronic stress exposure may promote cardiometabolic disease by dysregulating the interneuronal cross-talk revealed by our experiments.