Puerto Rican physician's recommendations to mitigate medical migration from Puerto Rico to the mainland United States.

Puerto Rico (PR) is a United States (US) territory with a history of colonial violence, poverty, and government corruption. Due to these sociopolitical factors and natural disasters (e.g., hurricanes and earthquakes), there has been a sharp increase in PR residents migrating to the mainland US. Local media and professional health organizations focus on the impact of medical migration on the PR health system (e.g., health personnel shortages and long waiting periods for critical care). According to the PR College of Physicians and Surgeons, 365-500 physicians have left annually since 2014, which represents a crisis of access to health services. However, few studies have focused on ways to mitigate medical migration from PR to the US mainland. This article describes the recommendations provided by migrating and non-migrating Puerto Rican Physicians (PRPs) to mitigate medical migration from PR to the US mainland. We focus on qualitative data from a mixed-methods NIH-funded study (1R01MD014188) to explore factors that motivate or mitigate migration among migrating (n = 26) and non-migrating (n = 24) PRPs. Interviews were analyzed following thematic analysis guidelines. Results show the following themes: 1) strategies to retain early-career medical residents living in PR; 2) recommendations for local government on future health policy; and 3) work environment initiatives for health institutions to mitigate physician migration. Findings suggest multilevel efforts are required to mitigate medical migration in PR.

"They think we wear loincloths": Spatial stigma, coloniality, and physician migration in Puerto Rico.

Puerto Rico (PR) is facing an unprecedented healthcare crisis due to accelerating migration of physicians to the mainland United States (US), leaving residents with diminishing healthcare and excessively long provider wait times. While scholars and journalists have identified economic factors driving physician migration, our study analyzes the effects of spatial stigma within the broader context of coloniality as unexamined dimensions of physician loss. Drawing on 50 semi-structured interviews with physicians throughout PR and the US, we identified how stigmatizing meanings are attached to PR, its people, and its biomedical system, often incorporating colonial notions of the island's presumed backwardness, lagging medical technology, and lack of cutting-edge career opportunities. We conclude that in addition to economically motivated policies, efforts to curb physician migration should also address globally circulating ideas about PR, acknowledge their roots in coloniality, and valorize local responses to the crisis that are in danger of being lost to history.

On leaving: Coloniality and physician migration in Puerto Rico.

Puerto Rico (PR) has a growing physician migration problem. As of 2009, the medical workforce was composed of 14,500 physicians and by 2020 the number had been reduced to 9,000. If this migration pattern continues, the Island will not be able to meet the recommended physicians per capita ratio proposed by the World Health Organization (WHO). Existing research has focused on the personal motivations for movement to, or permanence in, a particular setting, and social variables that encourage physicians to migrate (e.g., economic conditions). Few studies have addressed the role of coloniality in fostering physician migration. In this article we examine the role of coloniality and its impact on PR's physician migration problem. The data presented in this paper stem from an NIH-funded study (1R01MD014188) that aimed to document the factors associated with physician migration from PR to the US mainland and its impact on the Island's healthcare system. The research team used qualitative interviews, surveys, and ethnographic observations. This paper focuses on the data from the qualitative interviews with 26 physicians who had migrated to the USA and ethnographic observations, which were collected and analyzed between September 2020 and December 2022. The results evidence that participants understand physician migration as a consequence of three factors: 1) the historical and multidimensional deterioration of PR, 2) the idea that the current healthcare system is rigged by politicians and insurance companies, and 3) the specific challenges faced by physicians in training on the Island. We discuss the role of coloniality in fostering these factors and how it serves as the backdrop for the problem faced by the Island.

Single-cell dissection of the obesity-exercise axis in adipose-muscle tissues implies a critical role for mesenchymal stem cells.

Exercise training is critical for the prevention and treatment of obesity, but its underlying mechanisms remain incompletely understood given the challenge of profiling heterogeneous effects across multiple tissues and cell types. Here, we address this challenge and opposing effects of exercise and high-fat diet (HFD)-induced obesity at single-cell resolution in subcutaneous and visceral white adipose tissue and skeletal muscle in mice with diet and exercise training interventions. We identify a prominent role of mesenchymal stem cells (MSCs) in obesity and exercise-induced tissue adaptation. Among the pathways regulated by exercise and HFD in MSCs across the three tissues, extracellular matrix remodeling and circadian rhythm are the most prominent. Inferred cell-cell interactions implicate within- and multi-tissue crosstalk centered around MSCs. Overall, our work reveals the intricacies and diversity of multi-tissue molecular responses to exercise and obesity and uncovers a previously underappreciated role of MSCs in tissue-specific and multi-tissue beneficial effects of exercise.

Red tape, slow emergency, and chronic disease management in post-María Puerto Rico.

This paper draws upon the notion of slow emergency as a framework to interpret ethnographic and qualitative findings on the challenges faced by Puerto Ricans with chronic conditions and health sector representatives throughout the island during and after Hurricane María. We conducted participant observation and qualitative interviews with chronic disease patients (n=20) health care providers and administrators (n=42), and policy makers (n=5) from across the island of Puerto Rico in 2018 and 2019. Many Puerto Ricans coping with chronic diseases during and after María experienced bureaucratic red tape as the manifestation of colonial legacies of disaster management and health care. They describe a precarious existence in perpetual "application pending" status, waiting for services that were not forthcoming. Drawing on ethnographically informed case examples, we discuss the effects of these bureaucratic barriers on persons with three chronic conditions: renal disease, opioid dependency, and HIV/AIDS. We argue that while emergency management approaches often presume a citizen-subject with autonomous capacity to prepare for presumably transient disasters and envision a 'post-disaster future' beyond the immediate crisis, Puerto Rican voices draw attention to the longer, sustained, slow emergency of colonial governance.

Sustained inhibition of NPY/AgRP neuronal activity by FGF1.

In rodent models of type 2 diabetes (T2D), central administration of FGF1 normalizes elevated blood glucose levels in a manner that is sustained for weeks or months. Increased activity of NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of hyperglycemia in these animals, and the ARC is a key brain area for the antidiabetic action of FGF1. We therefore sought to determine whether FGF1 inhibits NPY/AgRP neurons and, if so, whether this inhibitory effect is sufficiently durable to offer a feasible explanation for sustained diabetes remission induced by central administration of FGF1. Here, we show that FGF1 inhibited ARC NPY/AgRP neuron activity, both after intracerebroventricular injection in vivo and when applied ex vivo in a slice preparation; we also showed that the underlying mechanism involved increased input from presynaptic GABAergic neurons. Following central administration, the inhibitory effect of FGF1 on NPY/AgRP neurons was also highly durable, lasting for at least 2 weeks. To our knowledge, no precedent for such a prolonged inhibitory effect exists. Future studies are warranted to determine whether NPY/AgRP neuron inhibition contributes to the sustained antidiabetic action elicited by intracerebroventricular FGF1 injection in rodent models of T2D.

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention.

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the ß 3-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

The impact of Hurricane Maria on Puerto Rico's health system: post-disaster perceptions and experiences of health care providers and administrators.

BACKGROUND: After its landfall in Puerto Rico in 2017, Hurricane Maria caused the longest blackout in United States history, producing cascading effects on a health care system that had already been weakened by decades of public sector austerity and neoliberal health reforms. This article addresses how health care professionals and administrators experienced the health care system's collapse and the strategies used by them to meet their communities' health needs. METHODS: Data were collected between September 2018 and February 2020. Ethnographic observations in health care facilities and semi-structured qualitative interviews with representatives of the health care system were conducted. This paper focuses on data from interviews with health care providers (n = 10) and administrators (n = 10), and an ethnographic visit to a pop-up community clinic. The analysis consisted of systematic thematic coding of the interview transcripts and ethnographic field notes. RESULTS: Results provide insight on how participants, who witnessed first-hand the collapse of Puerto Rico's health care system, responded to the crisis after Maria. The prolonged power outage and lack of a disaster management plan were partly responsible for the death of 3,052 individuals who experienced extended interruptions in access to medical care. Participants reported a sense of abandonment by the government and feelings of mistrust. They also described the health sector as chaotic and lacking clear guidelines on how to provide services or cope with personal crises while working under extreme conditions. In such circumstances, they developed resilient responses to meet communities' health needs (e.g., itinerant acupuncture services, re-locating physicians to local pharmacies). CONCLUSIONS: Participants' narratives emphasize that the management of Hurricane Maria was fraught with political and economic constraints affecting Puerto Rico. Ineffective planning and post-Maria responses of the local and federal governments were determinants of the disaster's impact. The findings contribute to a growing scientific literature indicating that Hurricane Maria revealed 'the collapse before the collapse,' alluding to the structural deficiencies that presaged the catastrophic event. In the context of governmental abandonment, the authors argue for the importance of developing alternative strategies in post-disaster health care provision among health professionals and administrators who work at the front lines of recovery.

Evaluation of VGF peptides as potential anti-obesity candidates in pre-clinical animal models.

VGF is a peptide precursor expressed in neuroendocrine cells that is suggested to play a role in the regulation of energy homeostasis. VGF is proteolytically cleaved to yield multiple bioactive peptides. However, the specific actions of VGF-derived peptides on energy homeostasis remain unclear. The aim of the present work was to investigate the role of VGF-derived peptides in energy homeostasis and explore the pharmacological actions of VGF-derived peptides on body weight in preclinical animal models. VGF-derived peptides (NERP-1, NERP-2, PGH-NH2, PGH-OH, NERP-4, TLQP-21, TLQP-30, TLQP-62, HHPD-41, AQEE-30, and LQEQ-19) were synthesized and screened for their ability to affect neuronal activity in vitro on hypothalamic brain slices and modulate food intake and energy expenditure after acute central administration in vivo. In addition, the effects of NERP-1, NERP-2, PGH-NH2, TLQP-21, TLQP-62, and HHPD-41 on energy homeostasis were studied after chronic central infusion. NERP-1, PGH-NH2, HHPD-41, and TLQP-62 increased the functional activity of hypothalamic neuronal networks. However, none of the peptides altered energy homeostasis after either acute or chronic ICV administration. The present data do not support the potential use of the tested VGF-derived peptides as novel anti-obesity drug candidates.

Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission.

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.