Growing Up Can Be Hard to Do: Reimagining 1 Structurally Supportive Pediatric-to-Adult Transitions of Care from a Rights-Based Perspective.

Extended life expectancies and shifting dynamics in chronic disease have changed the landscape of public health interventions worldwide, with an increasing emphasis on chronic care. As a result, transition from pediatric to adult care for medically complex adolescents and young adults is a growing area of intervention. Transition medicine is a nascent field whose current emphasis is on middle- and high-income countries, and thus far its methods and discourse have reflected those origins. Through several case-based examples, this paper aims to highlight the possibilities of an analytic approach grounded in structural competency for transforming transition medicine through a human rights-based framework, with an emphasis on imagining a more global framework for transition medicine. Our cases highlight the disparities between patients navigating pediatric to adult-based care, illuminating social stigma, stratification between public and private insurances, engagement in risk-taking behaviors, family conflict, and challenges with transition readiness. To reimagine transition medicine so that it is based on human rights, we must prioritize structural solutions that embrace multisectoral integration and holistic mental health support rather than oppress and marginalize these critical systemic adaptations. We aim to reconfigure this scaffolding to center structures that integrate holistic well-being and imagine alternate realities to healing. Our work contributes to the literature bringing structural competency to new spaces of clinical practice, contextualizing new frontiers for the exploration of chronic diseases across diverse clinical contexts worldwide.

MY COVID-19 DIARY.

Written in weekly instalments, Michelle Munyikwa's Covid-19 diary reflects upon the experience of an unfolding pandemic from her dual role as a medical trainee and anthropologist living in the United States. Her observations centre on everyday encounters with scenes or objects that reflect the growing crisis, from the absence of masks outside patient rooms to emergent forms of care through telemedicine. The diary follows the author as she experiences grief, ambivalence and disorientation in the first weeks of the pandemic.

Barriers to Accessing Acute Care for Newly Arrived Refugees.

INTRODUCTION: Over the past decade, the number of refugees arriving in the United States (U.S.) has increased dramatically. Refugees arrive with unmet health needs and may face barriers when seeking care. However, little is known about how refugees perceive and access care when acutely ill. The goal of this study was to understand barriers to access of acute care by newly arrived refugees, and identify potential improvements from refugees and resettlement agencies. METHODS: This was an in-depth, qualitative interview study of refugees and employees from refugee resettlement and post-resettlement agencies in a city in the Northeast U.S. Interviews were audiotaped, transcribed, and coded independently by two investigators. Interviews were conducted until thematic saturation was reached. We analyzed transcripts using a modified grounded theory approach. RESULTS: Interviews were completed with 16 refugees and 12 employees from refugee resettlement/post-resettlement agencies. Participants reported several barriers to accessing acute care including challenges understanding the U.S. healthcare system, difficulty scheduling timely outpatient acute care visits, significant language barriers in all acute care settings, and confusion over the intricacies of health insurance. The novelty and complexity of the U.S. healthcare system drives refugees to resettlement agencies for assistance. Resettlement agency employees express concern with directing refugees to appropriate levels of care and report challenges obtaining timely access to sick visits. While receiving emergency department (ED) care, refugees experience communication barriers due to limitations in consistent interpretation services. CONCLUSION: Refugees face multiple barriers when accessing acute care. Interventions in the ED, outpatient settings, and in resettlement agencies, have the potential to reduce barriers to care. Examples could include interpretation services that allow for clinic phone scheduling and easier access to interpreter services within the ED. Additionally, extending the Refugee Medical Assistance program may limit gaps in insurance coverage and avoid insurance-related barriers to seeking care.

Integrating Theory, Content, and Method to Foster Critical Consciousness in Medical Students: A Comprehensive Model for Cultural Competence Training.

Many efforts to design introductory "cultural competence" courses for medical students rely on an information delivery (competence) paradigm, which can exoticize patients while obscuring social context, medical culture, and power structures. Other approaches foster a general open-minded orientation, which can remain nebulous without clear grounding principles. Medical educators are increasingly recognizing the limitations of both approaches and calling for strategies that reenvision cultural competence training. Successfully realizing such alternative strategies requires the development of comprehensive models that specify and integrate theoretical frameworks, content, and teaching principles.In this article, the authors present one such model: Introduction to Medicine and Society (IMS), a required cultural competence course launched in 2013 for first-year medical students at the Perelman School of Medicine at the University of Pennsylvania. Building on critical pedagogy, IMS is centered on a novel specification of "critical consciousness" in clinical practice as an orientation to understanding and pragmatic action in three relational domains: internal, interpersonal, and structural. Instead of transmitting discrete "facts" about patient "types," IMS content provokes students to engage with complex questions bridging the three domains. Learning takes place in a small-group space specifically designed to spur transformation toward critical consciousness. After discussing the three key components of the course design and describing a representative session, the authors discuss the IMS model's implications, reception by students and faculty, and potential for expansion. Their early experience suggests the IMS model successfully engages students and prepares future physicians to critically examine experiences, manage interpersonal dynamics, and structurally contextualize patient encounters.

The pseudophosphatase MK-STYX induces neurite-like outgrowths in PC12 cells.

The rat pheochromocytoma PC12 cell line is a widely used system to study neuronal differentiation for which sustained activation of the extracellular signaling related kinase (ERK) pathway is required. Here, we investigate the function of MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] in neuronal differentiation. MK-STYX is a member of the MAPK phosphatase (MKP) family, which is generally responsible for dephosphorylating the ERKs. However, MK-STYX lacks catalytic activity due to the absence of the nucleophilic cysteine in the active site signature motif HC(X5)R that is essential for phosphatase activity. Despite being catalytically inactive, MK-STYX has been shown to play a role in important cellular pathways, including stress responses. Here we show that PC12 cells endogenously express MK-STYX. In addition, MK-STYX, but not its catalytically active mutant, induced neurite-like outgrowths in PC12 cells. Furthermore, MK-STYX dramatically increased the number of cells with neurite extensions in response to nerve growth factor (NGF), whereas the catalytically active mutant did not. MK-STYX continued to induce neurites in the presence of a MEK (MAP kinase kinase) inhibitor suggesting that MK-STYX does not act through the Ras-ERK/MAPK pathway but is involved in another pathway whose inactivation leads to neuronal differentiation. RhoA activity assays indicated that MK-STYX induced extensions through the Rho signaling pathway. MK-STYX decreased RhoA activation, whereas RhoA activation increased when MK-STYX was down-regulated. Furthermore, MK-STYX affected downstream players of RhoA such as the actin binding protein cofilin. The presence of MK-STYX decreased the phosphorylation of cofilin in non NGF stimulated cells, but increased its phosphorylation in NGF stimulated cells, whereas knocking down MK-STYX caused an opposite effect. Taken together our data suggest that MK-STYX may be a regulator of RhoA signaling, and implicate this pseudophosphatase as a regulator of neuronal differentiation.

The pseudophosphatase MK-STYX inhibits stress granule assembly independently of Ser149 phosphorylation of G3BP-1.

The pseudophosphatase MK-STYX (mitogen-activated protein kinase phosphoserine/threonine/tyrosine-binding protein) has been implicated in the stress response pathway. The expression of MK-STYX inhibits the assembly of stress granules, which are cytoplasmic storage sites for mRNA that form as a protective mechanism against stressors such as heat shock, UV irradiation and hypoxia. Furthermore, MK-STYX interacts with a key component of stress granules: G3BP-1 (Ras-GTPase activating protein SH3 domain binding protein-1). Because G3BP-1 dephosphorylation at Ser149 induces stress granule assembly, we initially hypothesized that the inhibition of stress granules by MK-STYX was G3BP-1 phosphorylation-dependent. However, in the present study, using MK-STYX constructs and G3BP-1 phosphomimetic or nonphosphorylatable mutants, we show that MK-STYX inhibits stress granule formation independently of G3BP-1 phosphorylation at Ser149. The introduction of point mutations at the 'active site' of MK-STYX that convert serine and phenylalanine to histidine and cysteine, respectively, is sufficient to generate an active enzyme. In separate experiments, we show that this active mutant, MK-STYX(active), has opposite effects to wild-type MK-STYK. Not only does MK-STYX(active) induce stress granules, but also it has the capacity to dephosphorylate G3BP-1. Taken together, these results provide evidence that the pseudophosphatase MK-STYX plays a key role in the cellular response to stress.

Recruitment of the oncoprotein v-ErbA to aggresomes.

Aggresome formation, a cellular response to misfolded protein aggregates, is linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v-ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRα1), accumulates in and sequesters TRα1 into cytoplasmic foci. Here, we show that foci represent v-ErbA targeting to aggresomes. v-ErbA colocalizes with aggresomal markers, proteasomes, hsp70, HDAC6, and mitochondria. Foci have hallmark characteristics of aggresomes: formation is microtubule-dependent, accelerated by proteasome inhibitors, and they disrupt intermediate filaments. Proteasome-mediated degradation is critical for clearance of v-ErbA and T(3)-dependent TRα1 clearance. Our studies highlight v-ErbA's complex mode of action: the oncoprotein is highly mobile and trafficks between the nucleus, cytoplasm, and aggresome, carrying out distinct activities within each compartment. Dynamic trafficking to aggresomes contributes to the dominant negative activity of v-ErbA and may be enhanced by the viral Gag sequence. These studies provide insight into novel modes of oncogenesis across multiple cellular compartments.