Intermittent access to alcohol in rats produces a pattern similar to alcohol binge drinking which has been shown to be associated with of alcohol dependence in humans, however direct causal evidence is missing. Moreover, the neuronal ensemble responsible for the excessive drinking behavior is currently unknown. The corticotropin-releasing factor (CRF) system in the central nucleus of the amygdala (CeA), an anti-reward stress brain system, has been speculated in playing a critical role during alcohol withdrawal. The aims of this set of studies were to test the causal effect of alcohol binge-drinking on the transition to alcohol dependence, and to test the causal role of recruitment of CeA neurons during withdrawal on alcohol drinking. To this end, we first measured the effect of a history of intermittent vs. continuous access to alcohol using a two-bottle choice paradigm on the motivation to drink in a model of alcohol dependence (chronic intermittent ethanol vapor exposure). We found that a history of intermittent access to alcohol accelerated the progression to alcohol dependence. We then tested whether withdrawal-dependent activation of Fos+ neurons in the CeA produces alcohol binge drinking behavior using the Daun02 inactivation method. Results showed that inactivation of Fos+ neurons decreased alcohol drinking both in binge-drinking rats and in dependent rats. These results demonstrate that a history of alcohol binge-drinking facilitates the transition to alcohol dependence and that recruitment of CeA neurons during withdrawal mediates excessive alcohol drinking

Background

Alcohol binge drinking in humans is thought to increase the risk for alcohol use disorder (AUD). Unclear is whether drinking patterns (e.g., bingelike or stable drinking) differentially affect the transition to compulsive-like drinking in dependent individuals. We examined whether chronic bingelike drinking facilitates the transition to compulsive-like drinking in rats.

Methods

Male Wistar rats were given 5 months of intermittent access to ethanol (EtOH) (IAE) or continuous access to EtOH (CAE) in a 2-bottle choice paradigm. Then, rats were given chronic intermittent EtOH (CIE) vapor exposure. Escalation of EtOH intake and compulsive-like responding for EtOH, using a progressive-ratio schedule of reinforcement and quinine-adulterated EtOH, were measured.

Results

IAE rats escalated EtOH drinking after 2 weeks of 2-bottle choice, whereas CAE rats exhibited stable EtOH drinking for 5 months. After 8 weeks of CIE, both IAE + CIE and CAE + CIE rats escalated their EtOH intake. However, IAE rats escalated their EtOH intake weeks sooner than CAE rats and exhibited greater EtOH intake. No differences in compulsive-like responding were found between IAE + CIE and CAE + CIE rats. However, both IAE + CIE and CAE + CIE rats showed strong compulsive-like responding compared with rats without prior IAE or CAE.

Conclusions

Chronic EtOH drinking at stable or escalated levels for several months is associated with more compulsive-like responding for EtOH in rats that are exposed to CIE compared with rats without a prior history of EtOH drinking. Moreover, IAE facilitated the transition to compulsive-like responding for EtOH after CIE exposure, reflected by the escalation of EtOH intake. These results suggest that IAE may facilitate the transition to AUD. This study indicates that despite a moderate level of EtOH drinking, the IAE animal model is highly relevant to early stages of alcohol abuse and suggests that it may be associated with neuroadaptations that produce a faster transition to alcohol dependence.

Aims/hypothesis

Islet amyloid polypeptide (IAPP) misfolding and toxic oligomers contribute to beta cell loss and stress in type 2 diabetes. Pregnancy-related diabetes predicts subsequent risk for type 2 diabetes but little is known about the impact of pregnancy on beta cell mass, turnover and stress. Availability of human pancreas tissue in pregnancy is limited and most widely used mouse models of type 2 diabetes do not develop pregnancy-related diabetes, possibly because rodent IAPP is not prone to form toxic oligomers. We hypothesised that mice transgenic for human IAPP (hIAPP) are prone to pregnancy-related diabetes with beta cell responses reflective of those in type 2 diabetes.

Methods

We evaluated the impact of a first and second pregnancy on glucose homeostasis, beta cell mass and turnover and markers of beta cell stress in hIAPP transgenic (hTG) mice.

Results

Pregnancy induced both endoplasmic reticulum stress and oxidative stress and compromised autophagy in beta cells in hTG mice, which are characteristic of beta cells in type 2 diabetes. Beta cell stress persisted after pregnancy, resulting in subsequent diabetes before or during a second pregnancy.

Conclusions/interpretation

High expression of hIAPP in response to pregnancy recapitulates mechanisms contributing to beta cell stress in type 2 diabetes. We hypothesise that, in individuals prone to type 2 diabetes, pregnancy-induced increased expression of IAPP inflicts beta cell damage that persists and is compounded by subsequent additive stress such as further pregnancy. The hTG mouse model is a novel model for pregnancy-related diabetes.

Hypercalcemia in HIV patients has been previously reported, but 1,25-(OH)₂ vitamin D-mediated hypercalcemia, due to increased activity of extrarenal 1-alpha hydroxylase, is rarely described with HIV-related infections or malignancies. We describe a case of 1,25-(OH)₂ vitamin D-mediated hypercalcemia in a patient presenting with progressive cognitive decline and weakness. Initial evaluation revealed a new diagnosis of HIV, for which he was started on antiretroviral therapy (ART). He was also noted to have mild asymptomatic hypocalcemia, likely from his acute illness and malnutrition, which was not further investigated at the time. While the patient's mental status initially improved with ART, he became progressively delirious and was found to be hypercalcemic approximately 4 weeks after the initiation of ART. Possible etiologies for hypercalcemia were vigorously evaluated, including granulomatous disease, infection, and malignancy, in the setting of suspected immune reconstitution inflammatory syndrome (IRIS), due to recent initiation of ART. Infectious workup was unrevealing, but computed tomography (CT) of the chest, abdomen, and pelvis revealed new extensive diffuse lymphadenopathy and hepatomegaly, not present on admission studies. Cytology and flow cytometry of a liver biopsy specimen revealed CD10 positive high-grade B-cell lymphoma. Chemotherapy was not pursued due to poor performance status. Over the next week, spontaneous tumor lysis developed, and the patient expired. Postmortem, his 1,25-(OH)₂ vitamin D level returned as markedly elevated. Immunohistochemical staining of his liver biopsy tissue showed strong expression of CYP27B1. 1,25-(OH)₂ vitamin D-mediated hypercalcemia is uncommon in a patient with newly diagnosed HIV and, in this case, was likely due to IRIS unmasking an underlying high-grade lymphoma and restoration of immune function (including T-cells and cytokine production). This case emphasizes the importance of including aggressive lymphomas, capable of progressing over days to weeks, in the evaluation of hypercalcemia in HIV patients at risk for developing IRIS and the rapid dynamic changes in mineral homeostasis that can occur with such an aggressive tumor in an immunocompromised host.

Background

Public health research frequently relies on collaborations with community-based organizations, and these partnerships can be essential to the success of a project. However, while public health ethics and oversight policies have historically focused on ensuring that individual subjects are protected from unethical or unfair practices, there are few guidelines to protect the organizations which facilitate relationships with - and are frequently composed of - these same vulnerable populations. As universities, governments, and donors place a renewed emphasis on the need for community engaged research to address systematic drivers of health inequity, it is vital that the ways in which research is conducted does not uphold the same intersecting systems of gender, race, and class oppression which led to the very same health inequities of interest.

Methods

To understand how traditional notions of public health research ethics might be expanded to encompass partnerships with organizations as well as individuals, we conducted qualitative interviews with 39 staff members (executive directors and frontline) at community-based organizations that primarily serve people who use drugs, Black men who have sex with men, and sex workers across the United States from January 2016 - August 2017. We also conducted 11 in-depth interviews with professional academic researchers with experience partnering with CBOs that serve similar populations. Transcripts were analyzed thematically using emergent codes and a priori codes derived from the Belmont Report.

Results

The concepts of respect, beneficence, and justice are a starting point for collaboration with CBOs, but participants deepened them beyond traditional regulatory concepts to consider the ethics of relationships, care, and solidarity. These concepts could and should apply to the treatment of organizations that participate in research just as they apply to individual human subjects, although their implementation will differ when applied to CBOs vs individual human subjects.

Conclusions

Academic-CBO partnerships are likely to be more successful for both academics and CBOs if academic researchers work to center individual-level relationship building that is mutually respectful and grounded in cultural humility. More support from academic institutions and ethical oversight entities can enable more ethically grounded relationships between academic researchers, academic institutions, and community based organizations.

OBJECTIVE: To evaluate the effect of common weight loss pharmacotherapies among low-income, racially diverse adult patients at an urban safety-net weight management clinic. METHODS: Our retrospective review from 2015 to 2019 examined patients who took either GLP-1 analog (GL) or phentermine/topiramate (PT) for ≥90 days and patients who exclusively pursued non-pharmacologic treatment for comparison. Changes in weight, blood pressure, and hemoglobin A1c at 1-year follow-up were reported. RESULTS: We analyzed 22 GL and 26 PT patients and included 40 patients who pursued only lifestyle modifications (LM). All three groups achieved significant weight loss at one year: GL -3.69 (interquartile range (IQR): -11.0, -1.77) kg (p=0.0004), PT -7.01 (IQR: -13.4, -1.45) kg (p<0.001), and LM -3.01 (IQR: -6.81, 1.13) kg (p=0.005). There was no significant difference in the median weight loss (p=0.11) between the three groups. We observed no significant changes in systolic blood pressure but saw a significant change of -0.75 in hemoglobin A1c (IQR: -1.35, -0.25) (p=0.01) among patients with diabetes in the GL group. CONCLUSIONS: Our real-world applications of GLP-1 and phentermine/topiramate suggest that both are effective weight loss medication regimens in low-socioeconomic status patients.

Purpose

We present a case of bilateral extensive peripapillary myelinated retinal nerve fibers (MRNF) in an individual with Crouzon syndrome, an inherited form of craniosynostosis caused by overactivation of fibroblast growth factor receptor 2. As a secondary aim, we examine the utility of optical coherence tomography (OCT) angiography for visualization of peripapillary vasculature obscured by myelination on other imaging modalities.

Methods

A 24-year-old woman with Crouzon syndrome was evaluated for suspected optic neuritis in the right eye.

Results

Funduscopic examination and photography revealed the incidental finding of bilateral extensive peripapillary MRNF. OCT angiography provided excellent visualization of peripapillary retinal vessels, which were partially obscured by myelination on other imaging modalities.

Conclusions

This association of Crouzon syndrome with bilateral peripapillary MRNF may lend insight into the developmental control of optic nerve myelination, the pathogenesis of MRNF, and the potential role of growth factors in these processes. Further, OCT angiography allowed for excellent blood vessel visualization in this case of MRNF.

Objective

The objective of this study was to explore barriers and facilitators to healthy eating among low-income Latino adolescents using an intervention development framework.

Methods

Semi-structured interviews (n = 30) were conducted with Latino youth ages 13-17 who had overweight or obesity at a safety-net clinic in San Francisco, CA. Adolescent beliefs and attitudes regarding healthy eating and individual, family, and community level barriers and facilitators were elicited. Interviews were analyzed using an inductive approach and the Capability-Opportunity-Motivation (COM-B) model.

Results

Participants had capability gaps; while they demonstrated basic nutrition knowledge, they also held significant misconceptions about healthy eating, equating "organic" with healthy and failing to recognize sugar in a number of beverages and foods. Families were a source of support through role modeling and purchasing fresh produce, yet in many cases also undermined adolescents' healthy eating goals through purchases of high calorie low nutrient food, an opportunity facilitator and challenge. By contrast, peers were mostly a negative influence due to frequent consumption of high calorie low nutrient food. The school environment posed opportunity challenges as participants found school lunch unpalatable and had ready access to unhealthy options nearby. Participants were motivated to improve their eating habits but often not resilient in the face of obstacles.

Conclusions

Interventions to promote healthy eating among low-income Latino adolescents should address common nutritional misconceptions, target families as well as teens, consider peer influences, and advocate for policy approaches that improve the school food environment.

Introduction

Latino adolescents experience high rates of obesity and physical activity can protect against obesity and obesity comorbidities. Health interventions to promote physical activity are more likely to be successful if they take into account the experiences and perspectives of their target population. Our study objective was to explore barriers and facilitators to physical activity among Latino adolescents with the goal of informing future interventions for this population.

Method

Semistructured interviews were conducted with (n = 30) low-income, Latino adolescents. The interviews were analyzed using inductive methods and the Capability-Opportunity-Motivation model of behavior.

Results

Adolescents described capability gaps including lacking skills for preferred activities. School physical education and parks provided opportunities for adolescents to be physically active. Adolescents also described opportunity challenges, including age limits, not being able to afford preferred classes, and safety concerns. Families provided role modeling but rarely engaged in activities with adolescents. Adolescents were motivated to engage in physical activity but often lacked the necessary resources.

Conclusions

Interventions to increase physical activity among urban Latino adolescents should offer tailored programming, incorporate families, enhance physical education, and improve the safety and appeal of recreational facilities.