Barriers to USMLE Step-1 accommodations: Students with Type 1 Diabetes.

PURPOSE: Students who earn their medical doctorate (MD) in the U.S. must pass the United States Medical Licensing Exam (USMLE) Step-1. The application process for students with disabilities who seek Step-1 accommodations can be arduous, barrier-ridden, and can impose a significant burden that may have long-lasting effects. We sought to understand the experiences of medical students with Type-1 Diabetes (T1D) who applied for Step-1 accommodations. METHODS: A Qualtrics survey was administered to students enrolled in Liaison Committee on Medical Education (LCME)-accredited MD programs who disclosed having a primary diagnosis of T1D. Basic counts and qualitative inductive analyses were conducted. RESULTS: Of the 21 surveys sent, 16 (76.2%) participants responded. Of the 16 respondents, 11 (68.8%) applied for USMLE Step-1 accommodations, whereas 5 (31.2%) did not. Of the 11 who applied for accommodations, 7 (63.6%) received the accommodations requested, while 4 (36.4%) did not. Of those who received the accommodations requested, 5/7 (71.4%) experienced at least one diabetes-related barrier on exam day. Of those who did not apply for Step-1 accommodations, 4/5 (80%) participants reported experiencing at least one diabetes-related barrier on exam day. Overall, 11/16 (68.8%) students experienced barriers on exam day with or without accommodations. Qualitative analysis revealed themes among participants about their experience with the process: frustration, anger, stress, and some areas of general satisfaction. CONCLUSIONS: This study reports the perceptions of students with T1D about barriers and inequities in the Step-1 accommodations application process. Students with and without accommodations encountered T1D-related obstacles on test day.

Engaging Premedical Students in Medical Education Research: Benefits of Clinical Skills Observation Studies.

PURPOSE: Observations requiring evaluation and critical thinking can be powerful learning experiences. Video-recorded standardized patient encounters are underused resources for evaluation and research. The authors engaged premedical students in medical education research reviewing standardized patient encounters. This study aims to explore participant perceptions of the research experience and how they gained clinical skills. METHOD: This mixed-method study was completed between 2019 and 2022. Premedical participants coded medical students' clinical skills in video-recorded standardized patient encounters. Each participant also completed their own new patient history in a standardized patient encounter at both the beginning and end of their research project. Participants then completed an end-of-program debrief to discuss their experiences coding the clinical skills encounters. The authors coded communication skills implemented in the pre/postencounters and completed a thematic analysis of the debrief transcripts. RESULTS: All 21 participants demonstrated significant clinical skills gain after their research project, which included spending more time with the patient (pre-M=5 minutes, post-M=19 minutes, t=13.2, P<.001) and asking more questions (pre-M=13, post-M=40, t=9.3, P<.001). Prior clinical experience did not influence pre- or postoutcomes, but the number of videos coded was associated with asking more questions in the postencounter. Participants described learning actively and reflected that their clinical skills research project gave them greater insight into patient-care aspects of medical school and how medical students learn. CONCLUSIONS: These data demonstrate that observational studies in which premedical students evaluate standardized patient encounters gave the students context to medical education while enabling them to develop and transfer their own clinical skills. Studies observing standardized patient encounters provide rich insight into clinical skills development, and this work generates both research outcomes and actionable program evaluation data for medical educators. Purposefully engaging premedical students in such experiential learning opportunities benefits the students and helps cultivate early medical education pathways for these learners.

Infusing intellectual and Developmental disability training into Medical School curriculum: a Pilot intervention.

PURPOSE: Despite the rising prevalence of developmental disabilities (DD) in the US, there remains insufficient training for healthcare professionals to care for this medically underserved population - particularly adults. The National Inclusive Curriculum for Health Education (NICHE) aims to improve attitudes and knowledge towards people with intellectual and developmental disabilities (PWIDD); herein we describe one such intervention. METHOD: The intervention integrated didactic, panel presentation and clinical skills components into a 2nd year medical school curriculum.  The didactic session, covering  health and assessment of PWIDDs, history of IDD, stigma, etc., was co-taught by a developmental pediatrician, family medicine physician and social worker.  A panel of 3 adult self-advocates (SAs) with DD and a parent of a child with DD spoke about their lived experiences.  One week later, students practiced taking clinical histories of SAs within small group settings with adult PWIDDs, facilitated by medical school faculty. Students completed the NICHE Knowledge(49 items) and Attitudes (60 items) surveys. The evaluation analyzed pre/post intervention differences in a) knowledge and attitude scores overall and b) by student age, gender, intended medical specialty, and prior experiences with PWIDDs. Open-ended comments were analyzed with content analysis. RESULTS: Overall Knowledge scores increased from pre-to posttest (n = 85; 65[19] vs. 73[17], p = 0.00), while Attitudes score improved (i.e., decreased) (n = 88; 0.55 [.06] vs. 0.53 [0.06]); p = 0.00).  Higher pretest knowledge was found among female identified students (vs. others; p = 0.01) and those knowing > = 5 PWIDD (vs < 5; p = 0.02).  Students characterize their IDD training and experience prior to intervention as 'lacking' and described the sessions as effective. CONCLUSIONS: A brief (4 hours total) intervention was associated with modest but significant improved knowledge and attitudes towards PWIDDs. Replication and sustainability of this and other NICHE interventions are needed to fill gaps in PWIDDs' health care.

Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity.

BACKGROUND: Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co-localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits. METHODS: This study included adult subjects with EoE (n = 13) and non-EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co-localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4-food protein interactions were confirmed with co-immunoprecipitation and mass spectrometry. RESULTS: IgG4-CMP co-localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co-localization was also significantly higher in the active EoE group compared to non-EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil-derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain-14 in IgG4-enriched areas. Co-immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens. CONCLUSION: These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression.

Impaired Response to Polysaccharide Vaccine in Selective IgE Deficiency.

PURPOSE: Immunoglobulin E deficiency (IgED) (defined as IgE < 2 IU/mL) is enriched in patients with primary antibody deficiency (PAD). We hypothesized that selective IgED (sIgED) is a more sensitive predictor of the development of PAD than declining IgG, as IgE production typically requires two class switch recombination (CSR) events in contrast to IgG. Thus, the inability of patients with sIgED to mount an appropriate antibody response to a T-cell independent antigen or evidence of aberrant induction of ɛ germ line (ɛGL) or IgE heavy chain (IgEHC) transcripts in vitro would support the concept that sIgED is a biomarker for emerging PAD. METHODS: We compared pre- and post-polysaccharide vaccination titers in healthy patients with sIgED without a history of recurrent infections or autoimmunity (n = 20) and in healthy controls (HCs) (n = 17). Subsequently, we assessed in vitro induction of εGL and IgEHC transcripts in patients with sIgED and HC (n = 6) in response to IL-4 + CD40L stimulation. RESULTS: Thirty percent of patients with sIgED did not have a robust vaccine response compared to 0% of HCs (p = 0.017). Individuals with sIgED with an abnormal vaccine response demonstrated persistent germline mRNA expression in their B-cells at day 5, with lower levels of IgEHC, compared to both HCs and sIgED participants with a normal vaccine response. CONCLUSION: Patients with sIgED are more likely to have abnormal antibody responses to a T cell-independent antigen and may have dysregulated CSR machinery. Following individuals with sIgED longitudinally may be beneficial in the early identification of PAD.

Association between Cystic Fibrosis exacerbations, lung function, T2 inflammation and microbiological colonization.

BACKGROUND: The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients. RESEARCH QUESTION: This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data. STUDY DESIGN AND METHODS: We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL. RESULTS: Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization. INTERPRETATION: This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment.

LGBTQ+ Microaggressions in Health Care: Piloting an Observation Framework in a Standardized Patient Assessment.

Microaggressions are subtle derogatory behaviors that unintentionally communicate hostility toward marginalized social groups. This article describes the preliminarily validation of a framework for observing LGBTQ+ microaggressions in health care, which can lead to distrust and disengagement from the healthcare system. Coders used the framework to observe microaggressions in video-recorded clinical-skills assessments with medical students who elicited health histories from standardized patients. Microaggression classifications were reviewed to determine construct reliability and the presence/absence among eight framework categories. Among 177 encounters with sexual and gender minority standardized patients, heteronormative/cisnormative language and assumptions occurred in the largest proportion of encounters (85.3%). Only identity-based referrals decreased significantly after a clinical skills intervention (20.0% to 4.9%, p = .01). These outcomes show that LGBTQ+ healthcare microaggressions are pervasive and will likely require nuanced training to address them. This groundwork can also be used to develop scales for patients and observers to identify microaggressions and assess perceived impact.

Epistemic Peerhood as a Model To Improve Gender-Affirming Care in Medical Education.

Issue: Inadequate training around gender-affirming care is a critical gap in health care and medical education that causes disparities and leads to injury for transgender, nonbinary, and other gender-diverse patients. In contrast to this widespread provider knowledge gap, gender-diverse patients bring critical knowledge from their own experiences to health care. Embracing varied epistemologies, or sources of knowledge, within medical education has the potential to enhance gender-affirming care by intentionally placing value on the lived experiences and emphasizing the credibility of gender-diverse patients. Evidence: In this article, the authors endorse a model of epistemic peerhood in which the embodied knowledge of gender-diverse patients and the authoritative knowledge of providers are each valued for their contribution to care. The authors reflect on experiences developing gender-affirming healthcare curricula and how medical education has not yet adequately addressed gender-diverse care without embracing community knowledge. Implications: The authors identify three vital areas to integrate epistemic peerhood in medical training to address gaps in gender-affirming care: (1) collaborative student training methods that reflect embodied knowledge in the absence of, or in addition to, clinical expertise on gender-affirming care; (2) sustainable partnerships between academic programs and gender-diverse communities that foster continuous engagement from collaborators with lived experience; and (3) broad community input about best practices for representing gender diversity in patient simulation. Embracing epistemic peerhood in each of these areas would result in broader gender-diverse community representation and leadership in medical education, which would ultimately strengthen gender-affirming healthcare training.

Gender Diverse Representation in Patient Simulation: A Scoping Review.

PURPOSE: Despite recent advocacy for transgender and nonbinary (TGNB) health competencies in medical education, there is little guidance on how to represent diverse gender identities for clinical skills training. Published literature is one of few resources available to inform educators' decisions, so this study aims to summarize how medical education scholarship portrays TGNB identities in patient simulation. METHOD: This scoping review used PRISMA guidelines with search strings encompassing diverse gender identities and patient simulation. This search was completed in July 2021, and all years of publication were included. The authors completed a 3-tiered review to identify relevant studies and then extracted data to summarize how TGNB patients were portrayed and training outcomes. RESULTS: After screening 194 total articles, 44 studies met the criteria for full review. Of these, 22 studies involved TGNB simulated patient cases. Within these, 15 (68%) reported the specific gender identities represented in the patient case, revealing mostly binary transgender identities. Sixteen studies (73%) reported the gender identities of all actors who portrayed the patient. The identities of all patients and actors matched in only 10 articles (45%), indicating that most programs portray TGNB identities with cisgender or unspecified standardized patients. Nearly all studies reported desirable learner outcomes. Several noted the advantage of authenticity in recruiting TGNB actors and the need to achieve more accurate representation of TGNB patients. CONCLUSIONS: Educators are increasingly representing TGNB identities in clinical skills training. These results show a lack of nonbinary representation and discrepancies between TGNB patient cases and standardized patient identities. These data also suggest that simulation programs need and desire better recruitment strategies within TGNB communities. Because TGNB communities are not a monolith, reporting out and analyzing gender identities of simulation cases and people hired to portray TGNB patients helps ensure that TGNB care is taught effectively and respectfully.

Gender-Affirming Care With Transgender and Genderqueer Patients: A Standardized Patient Case.

Introduction: Transgender and gender-diverse (TGD) patients experience health disparities and bias in health care settings. To improve care for TGD patients, medical trainees can practice gender-affirming care skills such as inclusive communication and discussing hormone therapy through patient simulation. Systematically evaluating these simulation outcomes also helps educators improve training on gender-affirming care. Methods: A standardized patient case with a patient establishing primary care was developed for rising third-year medical students. The case featured multiple patient iterations to portray individuals with the same health history but a different gender identity and/or sex assigned at birth. Each student was randomly assigned to one patient encounter. Gender-affirming care skills were assessed through standardized patient checklists, postencounter notes, and preventive care recommendations. Results: Over 2 years, 286 students participated in the simulation. Transgender men and women, cisgender men and women, and genderqueer patients were portrayed. Performance gaps such as misgendering patients and incorrect cancer screening recommendations based on perceived gender identity (rather than sex assigned at birth) were documented. Ninety-eight percent of students agreed that the encounter helped them practice clinical skills needed to see actual patients, and students described the case as challenging but important. Discussion: This case served dual roles for medical training: (1) Students working with TGD patients practiced skills for gender-affirming care, and (2) portraying TGD patients along with cisgender patients allowed educators to identify biased recommendations that necessitated additional training. The outcomes further highlighted the importance of students routinely practicing gender-inclusive communication with all patients during simulation.

Perspectives of Transgender and Genderqueer Standardized Patients.

Phenomenon: Disparities in health and healthcare for gender minorities (GMs) such as transgender people are significant, and medical educators have a responsibility to ensure trainees master the clinical skills required to provide them with quality care. We implemented a standardized patient (SP) scenario designed to measure students' ability to provide gender-affirming care and sought to understand the experiences and perceptions of the GMs who served as SPs in this case. Our key research question was: how do GM SPs describe the experience of serving as an SP on a gender-affirming care clinical case? Approach: Semi-structured focus groups were conducted with GM SPs (n = 10) to understand their experiences and gauge their perceptions of portraying a patient seeking gender-affirming care. The patient they portrayed matched their own gender identity. Focus groups were transcribed verbatim and analyzed using inductive thematic analysis. Findings: We developed three primary themes in our analysis: personal connection, gap identification, and insight into medical education. The SPs reported a personal connection to this case, enabling them to give nuanced feedback, confront bias they encountered, and foster connection to their broader community. They were able to identify specific gaps related to communication skills, assumptions, and knowledge about gender identity and gender-affirming care. They gained valuable insight into medical education such as the complexity of learning clinical skills and roadblocks to inclusive simulation. Insights: By sharing the perspectives of GMs in patient simulation, this study demonstrates that GMs can also benefit from engagement with medical education, as the SPs in our study described hope, empowerment, and engagement as positive aspects of participation. This study also shows that GMs' lived experiences seeking medical care were instrumental in their ability to note gaps, which provides valuable insight for other institutions attempting to improve students' GM clinical skills. Further, GM SPs' perspectives are valuable to provide a rationale and guidance to other schools implementing gender-affirming education. Efforts to create and implement gender-affirming care curriculum should include GMs in order to build partnerships and prioritize the voices and agency of GMs.

Gender Minorities in Simulation: A Mixed Methods Study of Medical School Standardized Patient Programs in the United States and Canada.

PURPOSE: A provider's ability to translate knowledge about transgender health to affirming patient care is key to addressing disparities. However, standardized patient (SP) programs have little published guidance for gender-affirming care or addressing disparities experienced by transgender and nonbinary patients. METHOD: Between 2018 and 2019, we invited all 208 accredited US and Canadian medical schools to participate in a study to determine how gender minorities are represented in SP encounters. Responding programs (n = 59, response rate = 28%) that represented patients with diverse gender identities were invited to complete semistructured interviews about SP case content, impact, and barriers to this work. Discussions were analyzed using a modified grounded theory method. RESULTS: Fifty nine of 208 eligible programs (response rate = 28.3%) completed our survey and 24 completed interviews. More than half of programs used gender minority SPs (n = 35, 59.3%). More than half of the programs also reported portraying gender minority cases (n = 31, 52.5%). Interviewees described how effective SP simulation required purposeful case development, engaging subject matter experts with lived experience, and ensuring psychological safety of gender minority SPs. Barriers included recruitment, fear of disrespecting gender minority communities, and transphobia. Engaging gender minorities throughout case development, training, and implementation of SP encounters was perceived to reduce bias and stereotyping, but respondents unanimously desired guidance on best practices on SP methodology regarding gender identity. CONCLUSIONS: Many programs have established or are developing SP activities that portray gender minority patients. Effective SP simulation hinges on authenticity, but the decisions around case development and casting vary. Specifically, programs lack consensus about who should portray gender minority patients. This research suggests that input from gender minority communities both to inform best practices at the macro level and in an ongoing advisory capacity at the program level will be essential to teach gender-affirming care.

Engaging the Transgender Community to Improve Medical Education and Prioritize Healthcare Initiatives.

Phenomenon: Transgender patients experience discrimination, limited access to care, and inadequate provider knowledge in healthcare settings. Medical education to address transgender-specific disparities is lacking. Research that engages transgender community members may help address health disparities by empowering patients, increasing trust, and informing medical curricula to increase competence. APPROACH: A 2015 Community Forum on Transgender Health Care was hosted at the University of Louisville School of Medicine, which included healthcare professionals and transgender community members to facilitate dialogue among mixed-participant groups using a World Café model. Fifty-nine participants discussed the status of transgender healthcare and made recommendations for local improvements. A follow-up survey was administered to 100 individuals, including forum participants and their referrals. The forum discussion and survey responses were analyzed to determine common perceptions of transgender healthcare, priorities for improvement interventions, and themes to inform curriculum. FINDINGS: The community forum discussion showed that local transgender care is overwhelmingly underdeveloped and unresponsive to the needs of the transgender community. The follow-up survey revealed that priorities to improve transgender care included a multidisciplinary clinic for lesbian, gay, bisexual, and transgender (LGBT) patients, an LGBT-friendly network of physicians, and more training for providers and support staff. This mutually constructive engagement experience influenced reform in undergraduate curricula and continuing education opportunities. Insights: Community engagement in healthcare disparities research can cultivate improbable discussions, yield innovative insight from marginalized populations, and build relationships with community members for future collaborations and interventions. Societal acceptance of transgender identities, which could be promoted through healthcare providers, could stimulate significant progress in transgender healthcare. Supplemental educational interventions for practicing physicians will improve the current conditions of transgender healthcare, but a comprehensive medical school curriculum specifically for transgender health that includes interactions between the transgender community and medical students could be particularly impactful.

SGK1 regulation by miR-466g in cortical collecting duct cells.

Micro-RNAs (miRNAs) are noncoding RNAs that bind target mRNA transcripts and modulate gene expression. In the cortical collecting duct (CCD), aldosterone stimulates the expression of genes that increase activity of the epithelial sodium channel (ENaC); in the early phase of aldosterone induction, one such gene is serum and glucocorticoid regulated kinase 1 (SGK1). We hypothesized that aldosterone regulates the expression of miRNAs in the early phase of induction to control the expression of target genes that stimulate ENaC activity. We treated mpkCCDc14 cells with aldosterone or vehicle for 1 h and used a miRNA microarray to analyze differential miRNA expression. We identified miR-466g as a miRNA that decreased by 57% after 1 h of aldosterone treatment. Moreover, we identified a putative miR-466g binding site in the 3'-untranslated region of SGK1. We constructed an SGK1 3'-untranslated region luciferase reporter and found that cotransfection of miR-466g suppressed luciferase activity in human embryonic kidney-293 cells in a dose-dependent manner. Deletion or introduction of point mutations that disrupt the miR-466g target site attenuated miR-466g-directed suppression of luciferase activity. Finally, we generated stably transduced mpkCCDc14 cell lines overexpressing miR-466g. Cells overexpressing miR-466g demonstrated 12.9-fold lower level of SGK1 mRNA compared with control cells after 6 h of aldosterone induction; moreover, cells overexpressing miR-466g exhibited 25% decrease in amiloride-sensitive current after 6 h of aldosterone induction and complete loss of amiloride-sensitive current after 24 h of aldosterone induction. Our findings implicate miR-466g as a novel early-phase aldosterone responsive miRNA that regulates SGK1 and ENaC in CCD cells.

Vigabatrin can enhance electroretinographic responses in pigmented and albino rats.

PURPOSE: To evaluate the effects of the antiepileptic medication vigabatrin (VGB) on the retina of pigmented rats. METHODS: Scotopic and photopic electroretinograms were recorded from dark- and light-adapted Long-Evans (pigmented) and Sprague Dawley (albino) rats administered, daily, 52-55 injections of 250 mg·kg(-1)·day(-1) VGB or 25-26 injections of 500 mg·kg(-1)·day(-1) VGB, or a corresponding number of sham injections. Sensitivity and saturated amplitude of the rod photoresponse (S, Rm(P3)) and postreceptor response (1/σ, Vm) were derived, as were sensitivity and amplitude of the cone-mediated postreceptor response (1/σ(cone), Vm(cone)). The oscillatory potentials and responses to a series of flickering lights (6.25, 12.5, 25 and 50 Hz) were studied in the time and frequency domains. A subset of rats' eyes was harvested for Western blotting or histology. RESULTS: Of the parameters derived from dark-adapted ERG responses, in both pigmented and albino rats, VGB repeatedly and reliably enhanced electroretinographic parameters; no significant ERG deficits were noted. No significant alterations were observed in ER/oxidative stress or in the Akt cell death/survival pathway. There were migrations of photoreceptor nuclei toward the RPE and outgrowths of bipolar cell dendrites into the outer nuclear layer in VGB-treated rats; these were never observed in sham-treated animals. CONCLUSIONS: Although VGB is associated with retinal dysfunction in patients and VGB toxicity has been demonstrated by other laboratories in the albino rat, in our pigmented and albino rats, VGB did not induce deficits in, but rather enhanced, retinal function. Nonetheless, retinal neuronal dysplasia was observed.

Non-coding RNAs turn up the heat: an emerging layer of novel regulators in the mammalian heat shock response.

The field of non-coding RNA (ncRNA) has expanded over the last decade following the discoveries of several new classes of regulatory ncRNA. A growing amount of evidence now indicates that ncRNAs are involved even in the most fundamental of cellular processes. The heat shock response is no exception as ncRNAs are being identified as integral components of this process. Although this area of research is only in its infancy, this article focuses on several classes of regulatory ncRNA (i.e., miRNA, lncRNA, and circRNA), while summarizing their activities in mammalian heat shock. We also present an updated model integrating the traditional heat shock response with the activities of regulatory ncRNA. Our model expands on the mechanisms for efficient execution of the stress response, while offering a more comprehensive summary of the major regulators and responders in heat shock signaling. It is our hope that much of what is discussed herein may help researchers in integrating the fields of heat shock and ncRNA in mammals.

The rat with oxygen-induced retinopathy is myopic with low retinal dopamine.

PURPOSE: Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small. The eye of the rat with oxygen-induced retinopathy (OIR) is characterized by retinal dysfunction and short axial length. There have been several investigations of the early maturation of DA in rat retina, but little at older ages, and not in the OIR rat. Therefore, DA, retinal function, and refractive state were investigated in the OIR rat. METHODS: In one set of rats, the development of dopaminergic (DAergic) networks was evaluated in retinal cross-sections from rats aged 14 to 120 days using antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA). In another set of rats, retinoscopy was used to evaluate spherical equivalent (SE), electoretinography (ERG) was used to evaluate retinal function, and high-pressure liquid chromatography (HPLC) was used to evaluate retinal contents of DA, its precursor levodopamine (DOPA), and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). RESULTS: The normally rapid postnatal ramification of DAergic neurons was disrupted in OIR rats. Retinoscopy revealed that OIR rats were relatively myopic. In the same eyes, ERG confirmed retinal dysfunction in OIR. HPLC of those eyes' retinae confirmed low DA. Regression analysis indicated that DA metabolism (evaluated by the ratio of DOPAC to DA) was an important additional predictor of myopia beyond OIR. CONCLUSIONS: The OIR rat is the first known animal model of myopia in which the eye is smaller than normal. Dopamine may modulate, or fail to modulate, neural activity in the OIR eye, and thus contribute to this peculiar myopia.