Improving Family Medicine Residents' Provision of Gender-Affirming Care.

BACKGROUND AND OBJECTIVES: Family physicians are uniquely poised to provide gender-affirming care (GAC) to transgender and nonbinary patients, but current undergraduate and graduate medical education in this field is lacking. Little is known about the impact of various GAC curricula on the clinical care provided by resident physicians. We aimed to assess the efficacy of a multimodal educational framework on the quality of GAC provided by residents at a large academic family medicine program. METHODS: This pilot study used chart review to assess the impact of a multifaceted educational intervention around GAC in an academic family medicine practice. Components included faculty-specific didactics, resident feedback and didactics, standardized note templates, and compiled resources. We completed pre- and postintervention analysis of resident-led GAC encounters using a novel rubric based on standards of care and compared these results using descriptive statistics. RESULTS: Following a multimodal educational intervention, residents demonstrated improvement in multiple domains of gender-affirming care, including documenting informed consent, counseling on pregnancy and contraception, and laboratory monitoring for patients initiating gender-affirming hormone therapy. CONCLUSIONS: This widespread improvement suggested that a multimodal approach to resident and faculty education may help enhance the quality of GAC provided by family medicine residents. Chart review offers a feasible and effective method for identifying gaps in resident knowledge and documentation in GAC. Further research should specifically explore faculty development in this area and expanded patient-centered quality metrics and outcomes that encompass GAC.

Looking Back to Move Forward: First-Year Medical Students' Meta-Reflections on Their Narrative Portfolio Writings.

The day-to-day rigors of medical education often preclude learners from gaining a longitudinal perspective on who they are becoming. Furthermore, the current focus on competencies, coupled with concerning rates of trainee burnout and a decline in empathy, have fueled the search for pedagogic tools to foster students' reflective capacity. In response, many scholars have looked to the tradition of narrative medicine to foster "reflective spaces" wherein holistic professional identity construction can be supported. This article focuses on the rationale, content, and early analysis of the reflective space created by the narrative medicine-centered portfolio at the Columbia University Vagelos College of Physicians and Surgeons. In January 2015, the authors investigated learning outcomes derived from students' "Signature Reflections," end-of-semester meta-reflections on their previous portfolio work. The authors analyzed the Signature Reflections of 97 (of 132) first-year medical students using a constant comparative process. This iterative approach allowed researchers to identify themes within students' writings and interpret the data. The authors identified two overarching interpretive themes-recognition and grappling-and six subthemes. Recognition included comments about self-awareness and empathy. Grappling encompassed the subthemes of internal change, dichotomies, wonder and questioning, and anxiety. Based on the authors' analyses, the Signature Reflection seems to provide a structured framework that encourages students' reflective capacity and the construction of holistic professional identity. Other medical educators may adopt meta-reflection, within the reflective space of a writing portfolio, to encourage students' acquisition of a longitudinal perspective on who they are becoming and how they are constructing their professional identity.

A Culture of Understanding: Reflections and Suggestions from a Genomics Research Community Board.

There has been limited community engagement in the burgeoning field of genomics research. In the wake of a new discovery of genetic variants that increase the risk of kidney failure and are almost unique to people of African ancestry, community and clinical leaders in Harlem, New York, formed a community board to inform the direction of related research. The board advised all aspects of a study to assess the impact of testing for these genetic variants at primary care sites that serve diverse populations, including explaining genetic risk to participants. By reflecting on the board's experiences, we found that community voices can have tangible impact on research that navigates the controversial intersection of race, ancestry, and genomics by heightening vigilance, fostering clear communication between researchers and the community, and encouraging researchers to cede some control. Our reflections and work provide a strong justification for longitudinal community partnerships in genomics research.

Life after Stroke in an Urban Minority Population: A Photovoice Project.

Stroke is a leading cause of disability in the United States and disproportionately affects minority populations. We sought to explore the quality of life in urban, minority stroke survivors through their own photos and narratives. Using the Photovoice method, seventeen stroke survivors were instructed to take pictures reflecting their experience living with and recovering from stroke. Key photographs were discussed in detail; participants brainstormed ways to improve their lives and presented their work in clinical and community sites. Group discussions were recorded, transcribed, and coded transcripts were reviewed with written narratives to identify themes. Participants conveyed recovery from stroke in three stages: learning to navigate the initial physical and emotional impact of the stroke; coping with newfound physical and emotional barriers; and long-term adaptation to physical impairment and/or chronic disease. Participants navigated this stage-based model to varying degrees of success and identified barriers and facilitators to this process. Barriers included limited access for disabled and limited healthy food choices unique to the urban setting; facilitators included presence of social support and community engagement. Using Photovoice, diverse stroke survivors were able to identify common challenges in adapting to life after stroke and important factors for recovery of quality of life.

Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice.

The etiology of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder characterized by progressive muscle weakness and spasticity, remains largely unknown. Approximately 5-10% of cases are familial, and of those, 15-20% are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Mutations of the SOD1 gene interrupt cellular homeostasis and contribute to cellular toxicity evoked by the presence of altered SOD1, along with other toxic species, such as advanced glycation end products (AGEs). AGEs trigger activation of their chief cell surface receptor, RAGE (receptor for advanced glycation end products), and induce RAGE-dependent cellular stress and inflammation in neurons, thereby affecting their function and leading to apoptosis. Here, we show for the first time that the expression of RAGE is higher in the SOD1 transgenic mouse model of ALS vs. wild-type mouse spinal cord. We tested whether pharmacological blockade of RAGE may delay the onset and progression of disease in this mouse model. Our findings reveal that treatment of SOD1 transgenic mice with soluble RAGE (sRAGE), a natural competitor of RAGE that sequesters RAGE ligands and blocks their interaction with cell surface RAGE, significantly delays the progression of ALS and prolongs life span compared to vehicle treatment. We demonstrate that in sRAGE-treated SOD1 transgenic animals at the final stage of the disease, a significantly higher number of neurons and lower number of astrocytes is detectable in the spinal cord. We conclude that RAGE antagonism may provide a novel therapeutic strategy for ALS intervention.

C-Arm Fluoroscope Angle Settings for Fluoroscopically Guided Lumbar Transforaminal Epidural Injections.

BACKGROUND DATA: Minimizing fluoroscopy time in spine interventions is critical for time of procedure as well as radiation safety of the patient and medical personnel. Specific fluoroscopy angle settings for fluoroscopically guided L4-S1 transforaminal epidural injections (TFEIs) have not been described. OBJECTIVES: To describe the most common encountered settings for the C-arm fluoroscope angles for fluoroscopically guided L4-S1 (TFEI). METHODS: Each subject was placed in prone position on a flat fluoroscopy table without utilizing any device to alter innate lumbar spine curvature. The data from 246 consecutive patients at their first encounter in the fluoroscopy suite for a single level subpedicular lumbosacral TFEI was retrospectively analyzed. Most procedures occurred at the L4-5, L5-S1, and S1 levels (227 subjects). The C-arm angles including the oblique, cephalad/caudal were recorded for each subject upon observing final needle positioning for successful completion of the procedure according to ISIS Guidelines. RESULTS: For the L4-5 level, 71% of cases had oblique angle of 30°±5° and 94% of cases had neutral cephalad/caudal tilt (0°±5°) observed. For the L5-S1, 72% of cases had oblique angle of 30°±5° and 62% of cases had cephalad tilt angle of 15°±5° observed. For the S1 level, 73% of cases had oblique angle of 5°±5° and 69% of cases had cephalad tilt angle of 15°±5° observed. DISCUSSION/CONCLUSION: This retrospective descriptive study suggests fluoroscope angles for L4-S1 TFEI as a starting point before fine tuning views accounting for individual anatomy. Angles suggested for each level (oblique/cephalad tilt angles) are as follows: L4-5 (30/0°), L5-S1 (30/15°), and S1 (5/15°). Prospective studies using these guidelines would need to be undertaken to prove reproducibility between interventionalists, time efficiency, and radiation exposure reduction.

Enhancing a geriatric emergency department care coordination intervention using automated health information exchange-based clinical event notifications.

PURPOSE: In a health care system where patients often have numerous providers and multiple chronic medical conditions, interoperability of health information technology (HIT) is of paramount importance. Regional health information organizations (RHIO) often provide a health information exchange (HIE) as a solution, which gives stakeholders access to clinical data that they otherwise would not otherwise have. A secondary use of preexisting HIE infrastructure is clinical event notification (CEN) services, which send automated notifications to stakeholders. This paper describes the development and implementation of a CEN service enabled by a RHIO in the New York metropolitan area to improve care coordination for patients enrolled in a geriatric emergency department care coordination program. INNOVATION: This operational CEN system incorporates several innovations that to our knowledge have not been implemented previously. They include the near real-time notifications and the delivery of notifications via multiple pathways: electronic health record (EHR) "in-baskets," email, text message to internet protocol-based "zone" phones, and automated encounter entry into the EHR. Based on these alerts the geriatric care coordination team contacts the facility where the patient is being seen and offers additional information or assistance with disposition planning with the goal of decreasing potentially avoidable admissions and duplicate testing. FINDINGS: During the nearly one-year study period, the CEN program enrolled 5722 patients and sent 497 unique notifications regarding 206 patients. Of these notifications, 219 (44%) were for emergency department (ED) visits; 121 (55%) of those notifications were received during normal business hours when the care coordination team was available to contact the ED where the patient was receiving care. Hospital admissions resulted from 45% of ED visits 17.8% of these admissions lasted 48 hours or less, suggesting some might potentially be avoidable. CONCLUSIONS AND DISCUSSION: This study demonstrates the potential of CEN systems to improve care coordination by notifying providers of the occurrence of specific events. Although it could not directly be demonstrated here, we believe that widespread use of CEN systems have potential to reduce potentially avoidable admissions and duplicate testing, likely leading to decreased costs.

Active zone protein expression changes at the key stages of cerebellar cortex neurogenesis in the rat.

Signal transduction and neurotransmitter release in the vertebrate central nervous system are confined to the structurally complex presynaptic electron dense projections called "active zones." Although the nature of these projections remains a mystery, genetic and biochemical work has provided evidence for the active zone (AZ) associated proteins i.e. Piccolo/Aczonin, Bassoon, RIM1/Unc10, Munc13/Unc13, Liprin-α/SYD2/Dliprin and ELKS/CAST/BRP and their specific molecular functions. It still remains unclear, however, what their precise contribution is to the AZ assembly. In our project, we studied in Wistar rats the temporal and spatial distribution of AZ proteins and their colocalization with Synaptophysin in the developing cerebellar cortex at key stages of cerebellum neurogenesis. Our study demonstrated that AZ proteins were already present at the very early stages of cerebellar neurogenesis and exhibited distinct spatial and temporal variations in immunoexpression throughout the course of the study. Colocalization analysis revealed that the colocalization pattern was time-dependent and different for each studied protein. The highest collective mean percentage of colocalization (>85%) was observed at postnatal day (PD) 5, followed by PD10 (>83%) and PD15 (>80%). The findings of our study shed light on AZ protein immunoexpression changes during cerebellar cortex neurogenesis and help frame a hypothetical model of AZ assembly.

ERp29 restricts Connexin43 oligomerization in the endoplasmic reticulum.

Connexin43 (Cx43) is a gap junction protein that forms multimeric channels that enable intercellular communication through the direct transfer of signals and metabolites. Although most multimeric protein complexes form in the endoplasmic reticulum (ER), Cx43 seems to exit from the ER as monomers and subsequently oligomerizes in the Golgi complex. This suggests that one or more protein chaperones inhibit premature Cx43 oligomerization in the ER. Here, we provide evidence that an ER-localized, 29-kDa thioredoxin-family protein (ERp29) regulates Cx43 trafficking and function. Interfering with ERp29 function destabilized monomeric Cx43 oligomerization in the ER, caused increased Cx43 accumulation in the Golgi apparatus, reduced transport of Cx43 to the plasma membrane, and inhibited gap junctional communication. ERp29 also formed a specific complex with monomeric Cx43. Together, this supports a new role for ERp29 as a chaperone that helps stabilize monomeric Cx43 to enable oligomerization to occur in the Golgi apparatus.

Identification of rab20 as a potential regulator of connexin 43 trafficking.

Connexin oligomerization and trafficking are regulated processes. To identify proteins that control connexin 43 (Cx43), a screen was designed using HeLa cells expressing a Cx43 construct with di-lysine endoplasmic reticulum (ER)-retention/retrieval motif, Cx43-HKKSL. At moderate levels of expression, Cx43-HKKSL is retained in the ER as monomers; however, Cx43-HKKSL stably overexpressed by HeLa cells localizes to the perinuclear region and oligomerizes. HeLa/Cx43-HKKSL overexpressors were transiently transfected with pooled clones from a human kidney cDNA library and used immunofluorescence microscopy to identify cDNAs that enabled overexpressed Cx43-HKKSL to convert from a perinuclear to ER localization pattern. Using this approach, a small molecular weight GTPase, rab20, was identified as a candidate protein with the ability to regulate Cx43 trafficking. Enhanced green fluorescent protein (EGFP)-tagged rab20 showed a predominantly perinuclear and ER localization pattern and caused wild-type Cx43 to be retained inside the cell. By contrast, mutant EGFP-rab20T19N, which lacks the ability to bind GTP, had no effect on Cx43. These results suggest Cx43 is transported through an intracellular compartment regulated by rab20 along the secretory pathway.

The concerted contribution of the S4-S5 linker and the S6 segment to the modulation of a Kv channel by 1-alkanols.

Gating of voltage-gated K(+) channels (K(v) channels) depends on the electromechanical coupling between the voltage sensor and activation gate. The main activation gate of K(v) channels involves the COOH-terminal section of the S6 segment (S6-b) and the S4-S5 linker at the intracellular mouth of the pore. In this study, we have expanded our earlier work to probe the concerted contribution of these regions to the putative amphipathic 1-alkanol site in the Shaw2 K(+) channel. In the S4-S5 linker, we found a direct energetic correlation between alpha-helical propensity and the inhibition of the Shaw2 channel by 1-butanol. Spectroscopic structural analyses of the S4-S5 linker supported this correlation. Furthermore, the analysis of chimeric Shaw2 and K(v)3.4 channels that exchanged their corresponding S4-S5 linkers showed that the potentiation induced by 1-butanol depends on the combination of a single mutation in the S6 PVPV motif (PVAV) and the presence of the Shaw2 S4-S5 linker. Then, using tandem-heterodimer subunits, we determined that this potentiation also depends on the number of S4-S5 linkers and PVAV mutations in the K(v) channel tetramer. Consistent with the critical contribution of the Shaw2 S4-S5 linker, the equivalent PVAV mutation in certain mammalian K(v) channels with divergent S4-S5 linkers conferred weak potentiation by 1-butanol. Overall, these results suggest that 1-alkanol action in Shaw2 channels depends on interactions involving the S4-S5 linker and the S6-b segment. Therefore, we propose that amphiphilic general anesthetic agents such as 1-alkanols may modulate gating of the Shaw2 K(+) channel by an interaction with its activation gate.

Physiological and molecular genetic evaluation of the dechlorination agent, pyridine-2,6-bis(monothiocarboxylic acid) (PDTC) as a secondary siderophore of Pseudomonas.

The bacterial metabolite and transition metal chelator pyridine-2,6-dithiocarboxylic acid (PDTC), promotes a novel and effective means of dechlorination of the toxic and carcinogenic pollutant, carbon tetrachloride. Pyridine-2,6-dithiocarboxylic acid has been presumed to act as a siderophore in the Pseudomonas strains known to produce it. To explore further the physiological function of PDTC production, we have examined its regulation, the phenotype of PDTC-negative (pdt) mutants, and envelope proteins associated with PDTC in P. putida strain DSM 3601. Aspects of the regulation of PDTC production and outer membrane protein composition were consistent with siderophore function. Pyridine-2,6-dithiocarboxylic acid production was coordinated with production of the well-characterized siderophore pyoverdine; exogenously added pyoverdine led to decreased PDTC production, and added PDTC led to decreased pyoverdine production. Positive regulation of a chromosomal pdtI-xylE transcriptional fusion, and of a 66 kDa outer membrane protein (IROMP), was seen in response to exogenous PDTC. Tests with transition metal chelators indicated that PDTC could provide a benefit under conditions of metal limitation; the loss of PDTC biosynthetic capacity caused by a pdtI transposon insertion resulted in increased sensitivity to 1,10-phenanthroline, a chelator that has high affinity for a range of divalent transition metals (e.g. Fe(2+), Cu(2+), Zn(2+)). Exogenously added PDTC could also suppress a phenotype of pyoverdine-negative (Pvd-) mutants, that of sensitivity to EDDHA, a chelator with higher affinity and specificity for Fe(3+). Measurement of 59Fe incorporation showed uptake from 59Fe:PDTC by DSM 3601 grown in low-iron medium, but not by cells grown in high iron medium, or by the pdtI mutant, which did not show expression of the 66 kDa envelope protein. These data verified a siderophore function for PDTC, and have implicated it in the uptake of transition metals in addition to iron.

José Ducci Kallens M.D. 1884-1931: un homenaje / José Ducci Kallens M.D. 1884-1931: a tribute

Porque recordamos a Ducci, fue un hombre Universal, de gan cultura, sobervia mentalidad, valor moral inquebrantable y, podríamos decir, el padre la Radiología Chilena. Con sus descubrimientos la hizo más práctica: con sus diagnósticos, más precisa; con sus conferencias, artículos y trabajo diario, atrajo una multitud de discípulos que, como él, atravesaron las fronteras de la envoltura humana para penetrar en su ser. Y eso basta para que su memoria se perpetúe.