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Anjali Bhagra,1 Husnain Syed,1 Darcy A Reed,1 Thomas H Poterucha,1 Stephen S Cha,2 Tammy J Baumgartner,1 Paul Y Takahashi1 1Department of Internal Medicine, 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA Background: Musculoskeletal joint pain of varied etiology can be diagnosed and treated with joint and soft-tissue corticosteroid injections. Purpose: The purpose of our study was to compare patients’ bodily pain and quality of life (QOL), in addition to the procedural benefit and patient satisfaction, before and after musculoskeletal injections in the office setting. Patients and methods: Patients were eligible for recruitment if they were over age 18 and had an injection for musculoskeletal pain from a primary care provider in an office procedural practice. Included in our analysis were knee joint/bursa, trochanteric bursa, and shoulder joint/bursa injection sites. The variables measured were pain, benefit from the injection, QOL physical and mental components, and patient satisfaction. This was a retrospective cohort study approved by the institutional review board. Results: Patients’ pain was assessed by the patients using a six-point Likert scale (none, very mild, mild, moderate, severe, and very severe). We noted that self-perception of pain decreased from 3.10 (± standard deviation at baseline 0.96) before to 2.36 (± standard deviation after the infection 1.21) (P = 0.0001) after the injection. In terms of the impact on QOL, our patients had a pre-injection physical score of 37.25 ± 8.39 and a mental score at 52.81 ± 8.98. After the injections, the physical score improved to 42.35 ± 9.07 (P = 0.0001) and the mental to 53.54 ± 8.20 (P = 0.0001) for the overall group. Ninety-six percent of the patients reported they were satisfied or extremely satisfied in the procedure clinic. Conclusion: In this study, we found significant pain relief and improved physical QOL in patients undergoing an injection in the knee joint/bursa, shoulder joint/bursa, or trochanteric bursa by primary care providers in the office setting. Keywords: injections, musculoskeletal, quality of life, joints, efficacy

Background: Medical knowledge and clinical performance ratings are major criteria for assessing the competence of resident physicians. However, these assessments may be influenced by residents' mental health. The relationship between residents' well-being and empathy and assessments of their global performance remains unclear.Objective: To determine whether resident well-being and empathy are associated with assessments of their medical knowledge and clinical performance.Design, Setting, and Participants: We studied 730 clinical performance assessments completed by peers, supervising residents, and allied health professionals; 193 mini-clinical evaluation exercise (mini-CEX) evaluations; and 260 in-training examinations (ITE) of Mayo Clinic internal medicine residents between January 2009 and August 2010. Multivariate generalized estimating equations were used to evaluate associations between residents' well-being and empathy and assessments of their knowledge and clinical performance.Measurements: Independent variables were empathy using the Interpersonal Reactivity Index (IRI), burnout using the Maslach Burnout Inventory, depression using a standardized two-question screening instrument, and quality of life using a Linear Analog Self-Assessment item and the Medical Outcomes Study Short Form (SF-8). Dependent variables were mini-CEX, ITE, and the validated six-item Mayo clinical performance assessment.Results: 202 residents (64.7%) provided both well-being and at least one category of assessment data. In multivariate models, residents' scores on the IRI empathy measure of "the tendency to adopt the psychological view of others" were associated with higher peer ratings on "desirability as a physician for a family member" (beta = 0.023, 95% CI = 0.007-0.039, p = 0.004). Additionally, burnout was associated with higher supervisor ratings of communication (beta = 0.309, 95% CI = 0.100-0.517, p = 0.004). There were no observed associations between ITE or mini-CEX scores and resident quality of life, burnout, fatigue, depression, or empathy.Conclusions: Most dimensions of resident well-being were not associated with residents' knowledge scores and assessments of their clinical performance by other members of the health care team, which supports the trustworthiness of these measures. Nonetheless, correlations of resident empathy and burnout with assessments completed by peers and supervising residents suggest that some ratings of residents may be influenced by interpersonal factors. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Accreditation Council for Graduate Medical Education's new duty-hour standards limit interns' shifts to 16 hours and night float to 6 consecutive nights. Protected sleep time (that is, 'nap') is strongly encouraged. As duty-hour reforms are implemented, examination of the quality and outcomes of the relevant literature is important. PURPOSE: To systematically review the literature examining shift length, protected sleep time, and night float. DATA SOURCES: MEDLINE, PREMEDLINE, and EMBASE from January 1989 through May 2010. STUDY SELECTION: Studies examined the associations of shift length, protected sleep time, or night float with patient care, resident health, and education outcomes among residents in practice settings. DATA EXTRACTION: Study quality was measured by using the validated Medical Education Research Study Quality Instrument and the U.S. Preventive Services Task Force criteria. Two investigators independently rated study quality, and interrater agreement was calculated. DATA SYNTHESIS: Sixty-four studies met inclusion criteria. Most studies used single-group cross-sectional (19 studies [29.7%]) or pre-post (41 studies [64.1%]) designs, and 4 (6.3%) were randomized, controlled trials. Five studies (7.8%) were multi-institutional. Twenty-four of 33 (72.7%) studies examining shift length reported that shorter shifts were associated with decreased medical errors, motor vehicle crashes, and percutaneous injuries. Only 2 studies assessed protected sleep time and reported that residents' adherence to naps was poor. Night floats described in 33 studies involved 5 to 7 consecutive nights. LIMITATIONS: Most studies used single-institution, observational designs. Publication bias is likely but difficult to assess in this methodologically weak and heterogeneous body of evidence. CONCLUSION: For the limited outcomes measured, most studies supported reducing shift length but did not adequately address the optimal shift duration. Studies had numerous methodological limitations and unclear generalizability for most outcomes. Specific recommendations about shift length, protected sleep time, and night float should acknowledge the limitations of this evidence. PRIMARY FUNDING SOURCE: Accreditation Council for Graduate Medical Education. [ABSTRACT FROM AUTHOR]

Medical Education 2010: 44 : 248-255 Objectives Resident reflection on the clinical learning environment is prerequisite to identifying quality improvement (QI) opportunities and demonstrating competence in practice-based learning. However, residents' abilities to reflect on QI opportunities are unknown. Therefore, we developed and determined the validity of the Mayo Evaluation of Reflection on Improvement Tool (MERIT) for assessing resident reflection on QI opportunities. Methods The content of MERIT, which consists of 18 items structured on 4-point scales, was based on existing literature and input from national experts. Using MERIT, six faculty members rated 50 resident reflections. Factor analysis was used to examine the dimensionality of MERIT instrument scores. Inter-rater and internal consistency reliabilities were calculated. Results Factor analysis revealed three factors (eigenvalue; number of items): Reflection on Personal Characteristics of QI (8.5; 7); Reflection on System Characteristics of QI (1.9; 6), and Problem of Merit (1.5; 5). Inter-rater reliability was very good (intraclass correlation coefficient range: 0.73-0.89). Internal consistency reliability was excellent (Cronbach's [alpha] 0.93 overall and 0.83-0.91 for factors). Item mean scores were highest for Problem of Merit (3.29) and lowest for Reflection on System Characteristics of QI (1.99). Conclusions Validity evidence supports MERIT as a meaningful measure of resident reflection on QI opportunities. Our findings suggest that dimensions of resident reflection on QI opportunities may include personal, system and Problem of Merit factors. Additionally, residents may be more effective at reflecting on 'problems of merit' than personal and systems factors. [ABSTRACT FROM AUTHOR]

Background: Medical malpractice is prominently positioned in the consciousness of American physicians, and the perceived threat of malpractice litigation may push physicians to practice defensively and alter their teaching behaviors. Purpose: The purposes of this study were to characterize the attitudes of academic medical faculty toward malpractice litigation and to identify teaching behaviors associated with fear of malpractice litigation. Methods: We surveyed 270 full-time clinically active physicians in the Department of Medicine at a large academic medical center. The survey assessed physicians' attitudes toward malpractice issues, fear of malpractice litigation, and self-reported teaching behaviors associated with concerns about litigation. Results: Two hundred and fifteen physicians responded (80%). Faculty scored an average of 25.5 +/- 6.9 (range = 6-42, higher scores indicate greater fear) on a reliable malpractice fear scale. Younger age (Spearman's [rho] = 0.19, p = .02) and greater time spent in clinical activities ([rho] = 0.26, p < .001) were correlated with higher scores on the Malpractice Fear Scale. Faculty reported that because of the perceived prevalence of lawsuits and claims made against physicians, they spend more time writing clinical notes for patients seen by learners (74%), give learners less autonomy in patient care (44%), and limit opportunities for learners to perform clinical procedures (32%) and deliver bad news to patients (33%). Faculty with higher levels of fear on the Malpractice Fear Scale were more likely to report changing their teaching behaviors because of this perceived threat ([rho] = 0.38, p < .001). Conclusions: Physicians report changes in teaching behaviors because of concerns about malpractice litigation. Although concerns about malpractice may promote increased supervision and positive role modeling, they may also limit important educational opportunities for learners. These results may serve to heighten awareness to the fact that teaching behaviors and decisions may be influenced by the malpractice climate. [ABSTRACT FROM AUTHOR]

While explicit conceptual models help to inform research, they are left out of much of the health professions education (HPE) literature. One reason may be the limited understanding about how to develop conceptual models with intention and rigor. Group concept mapping (GCM) is a mixed methods conceptualization approach that has been used to develop frameworks for planning and evaluation, but GCM has not been common in HPE. The purpose of this article is to describe GCM in order to make it more accessible for HPE scholars. We recount the origins and evolution of GCM and summarize its core features: GCM can combine multiple stakeholder perspectives in a systematic and inclusive manner to generate explicit conceptual models. Based on the literature and prior experience using GCM, we detail seven steps in GCM: (1) brainstorming ideas to a specific "focus prompt," (2) preparing ideas by removing duplicates and editing for consistency, (3) sorting ideas according to conceptual similarity, (4) generating the point map through quantitative analysis, (5) interpreting cluster map options, (6) summarizing the final concept map, and (7) reporting and using the map. We provide illustrative examples from HPE studies and compare GCM to other conceptualization methods. GCM has great potential to add to the myriad of methodologies open to HPE researchers. Its alignment with principles of diversity and inclusivity, as well as the need to be systematic in applying theoretical and conceptual frameworks to practice, make it a method well suited for the complexities of contemporary HPE scholarship., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

We report the use of porous organic layers in two-dimensional hybrid organic-inorganic perovskites (HOIPs) to facilitate permanent small molecule intercalation and new post-synthetic modifications. While HOIPs are well-studied for a variety of optoelectronic applications, the ability to manipulate their structure after synthesis is another handle for control of physical properties and could even enable use in future applications. If designed properly, a porous interlayer could facilitate these post-synthetic transformations. We show that for a series of copper-halide perovskites, a crystalline arrangement of designer ammonium groups allows for permanently porous interlayer space to be accessed at room temperature. Intercalation of the electroactive molecules ferrocene and tetracyanoethylene into this void space can be performed with tunable loadings, and these intercalated perovskites are stable for months. The porosity also enables reactivity at the copper-halide layer, allowing for facile halide replacement. Through this, we access previously unobserved reactivity with halogens to perform halide substitution, and even replace halides with pseudohalides. In the latter case, the porous structure allows for stabilization of new phases, specifically a novel copper-thiocyanate perovskite phase, only accessible through post-synthetic modification. We envision that this broad design strategy can be expanded to other industrially relevant HOIPs to create a new class of highly adjustable perovskites., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC ( Pdx1-Cre , LSL-Kras G12D/+ , LSL-Trp53 R172H/+ ) and poorly metastatic KP fl C ( Pdx1-Cre , LSL-Kras G12D/+ , Trp53 fl/+ ) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KP fl C, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

Background: All individuals and groups have blind spots that can create problems if unaddressed. The goal of this study was to examine blind spots in medical education from international perspectives., Methods: From December 2022 to March 2023, we distributed an electronic survey through international networks of medical students, postgraduate trainees, and medical educators. Respondents named blind spots affecting their medical education system and then rated nine blind spot domains from a study of U.S. medical education along five-point Likert-type scales (1 = much less attention needed; 5 = much more attention needed). We tested for differences between blind spot ratings by respondent groups. We also analyzed the blind spots that respondents identified to determine those not previously described and performed content analysis on open-ended responses about blind spot domains., Results: There were 356 respondents from 88 countries, including 127 (44%) educators, 80 (28%) medical students, and 33 (11%) postgraduate trainees. At least 80% of respondents rated each blind spot domain as needing 'more' or 'much more' attention; the highest was 88% for 'Patient perspectives and voices that are not heard, valued, or understood.' In analyses by gender, role in medical education, World Bank country income level, and region, a mean difference of 0.5 was seen in only five of the possible 279 statistical comparisons. Of 885 blind spots documented, new blind spot areas related to issues that crossed national boundaries (e.g. international standards) and the sufficiency of resources to support medical education. Comments about the nine blind spot domains illustrated that cultural, health system, and governmental elements influenced how blind spots are manifested across different settings., Discussion: There may be general agreement throughout the world about blind spots in medical education that deserve more attention. This could establish a basis for coordinated international effort to allocate resources and tailor interventions that advance medical education.

Background: Although medical education is affected by numerous blind spots, there is limited evidence to determine which blind spots to prioritize., Methods: In summer 2022, we surveyed stakeholders from U.S. medical education who had identified 9 domains and 72 subdomains of blind spots. Respondents used 4-point Likert-type scales to rate the extent and magnitude of problems caused for each domain and subdomain. Respondents also provided comments for which we did content analysis., Results: A total of 23/27 (85%) stakeholders responded. The majority of respondents rated each blind spot domain as moderate-major in both extent and problems they cause. Patient perspectives and voices that are not heard, valued, or understood was the domain with the most stakeholders rating extent ( n  = 20, 87%) and problems caused ( n  = 23, 100%) as moderate or major. Admitting and selecting learners likely to practice in settings of highest need was the subdomain with the most stakeholders rating extent ( n  = 21, 91%) and problems caused ( n  = 22, 96%) as moderate or major. Respondents' comments suggested blind spots may depend on context and persist because of hierarchies and tradition., Discussion: We found blind spots differed in relative importance. These data may inform further research and direct interventions to improve medical education.

The spheroidal shape of the eye lens is crucial for precise light focusing onto the retina. This shape is determined by concentrically aligned, convexly elongated lens fiber cells along the anterior and posterior axis of the lens. Upon differentiation at the lens equator, the fiber cells increase in height as their apical and basal tips migrate towards the anterior and posterior poles, respectively. The forces driving this elongation and migration remain unclear. We found that, in the mouse lens, membrane protrusions or lamellipodia are observed only in the maturing fibers undergoing cell curve conversion, indicating that lamellipodium formation is not the primary driver of earlier fiber migration. We demonstrated that elevated levels of fibroblast growth factor (FGF) suppressed the extension of Rac-dependent protrusions, suggesting changes in the activity of FGF controlling Rac activity, switching to lamellipodium-driven migration. Inhibitors of ROCK, myosin and actin reduced the height of both early and later fibers, indicating that elongation of these fibers relies on actomyosin contractility. Consistent with this, active RhoA was detected throughout these fibers. Given that FGF promotes fiber elongation, we propose that it does so through regulation of Rho activity., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The migration of mandibular fibrochondrocytes is important for the development of the mandible, the homeostasis of the mandibular cartilage, and for the capacity of the tissue to respond to injury. Mandibular fibrochondrocytes have to overcome formidable obstacles during migration including a dense and heterogeneous three-dimensional matrix. Guiding the direction of cell migration and commitment to a migratory phenotype in this microenvironment necessitates a multivalent response to chemotactic and extracellular matrix-mediated stimuli. One of the key matrix components in the cartilage of the temporomandibular joint is type VI collagen. Neuron/glial antigen 2 (NG2/CSPG4) is a transmembrane proteoglycan that binds with collagen VI and has been implicated in a wide range of cell behaviors including cell migration, motility, adhesion, and proliferation. While NG2/CSPG4 has been shown to be a key regulator of mandibular cartilage homeostasis, its role in the migration of mandibular fibrochondrocytes during normal and cell stress conditions has yet to be resolved. Here, we address this gap in knowledge by characterizing NG2/CSPG4-dependent migration in mandibular fibrochondrocytes using primary mandibular fibrochondrocytes isolated from control and full length NG2/CSPG4 knockout mice, in primary mandibular fibrochondrocytes isolated from NG2|DsRed reporter mice and in an immortalized mandibular fibrochondrocyte cell line with a mutated NG2/CSPG4 ectodomain. All three cells demonstrate similar results, with loss of the full length or truncated NG2/CSPG4 increasing the rate of cell migration in serum starvation/cell stress conditions. These findings clearly implicate NG2/CSPG4 as a key molecule in the regulation of cell migration in mandibular fibrochondrocytes in normal and cell stress conditions, underscoring the role of NG2/CSPG4 as a mechanosensitive signaling hub in the mandibular cartilage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahn, Bagheri Varzaneh, Zhao, Rozynek, Ravindran, Banks, Chaudhry and Reed.)

Phenomenon: All individuals and groups have blind spots that can lead to mistakes, perpetuate biases, and limit innovations. The goal of this study was to better understand how blind spots manifest in medical education by seeking them out in the U.S., Approach: We conducted group concept mapping (GCM), a research method that involves brainstorming ideas, sorting them according to conceptual similarity, generating a point map that represents consensus among sorters, and interpreting the cluster maps to arrive at a final concept map. Participants in this study were stakeholders from the U.S. medical education system (i.e., learners, educators, administrators, regulators, researchers, and commercial resource producers) and those from the broader U.S. health system (i.e., patients, nurses, public health professionals, and health system administrators). All participants brainstormed ideas to the focus prompt: "To educate physicians who can meet the health needs of patients in the U.S. health system, medical education should become less blind to (or pay more attention to) …" Responses to this prompt were reviewed and synthesized by our study team to prepare them for sorting, which was done by a subset of participants from the medical education system. GCM software combined sorting solutions using a multidimensional scaling analysis to produce a point map and performed cluster analyses to generate cluster solution options. Our study team reviewed and interpreted all cluster solutions from five to 25 clusters to decide upon the final concept map., Findings: Twenty-seven stakeholders shared 298 blind spots during brainstorming. To decrease redundancy, we reduced these to 208 in preparation for sorting. Ten stakeholders independently sorted the blind spots, and the final concept map included 9 domains and 72 subdomains of blind spots that related to (1) admissions processes; (2) teaching practices; (3) assessment and curricular designs; (4) inequities in education and health; (5) professional growth and identity formation; (6) patient perspectives; (7) teamwork and leadership; (8) health systems care models and financial practices; and (9) government and business policies., Insights: Soliciting perspectives from diverse stakeholders to identify blind spots in medical education uncovered a wide array of issues that deserve more attention. The concept map may also be used to help prioritize resources and direct interventions that can stimulate change and bring medical education into better alignment with the health needs of patients and communities.

Purpose: Populations most affected by obesity are not reflected in the patients who undergo bariatric surgery. Gaps in the referral system have been studied, but there is a lack of literature investigating obstacles patients encounter after first contact with bariatric surgery clinics. We aim to identify patient populations at risk for attrition during bariatric surgery evaluation and determine patient reported barriers to bariatric surgical care., Materials and Methods: This study was a single institution, retrospective, mixed methods study from 2012 to 2021 comparing patients who underwent bariatric surgery to those that withdrew. Surveys were performed of patients who withdrew, collecting information on patient knowledge, expectations, and barriers., Results: This study included 5982 patients evaluated in bariatric surgery clinic. Those who attained bariatric surgery (38.8%) were more likely to be White (81.2 vs. 75.6%, p<0.001), married (48.5 vs. 44.1%, p=0.004), and employed full time (48.2 vs. 43.8%, p=0.01). They were less likely to live in an area with low income (37.1 vs. 40.7%, p=0.01) or poverty (poverty rate 15.8 vs. 17.4, p<0.001). Of the 280 survey respondents, fear of complications, length of insurance approval process, and wait time between evaluation and surgery were the most reported barriers., Conclusion: Patients who undergo bariatric surgery were more likely to be White, married, employed full time, and reside in more resourced environments which is not reflective of communities most affected by obesity. The complexity of insurance coverage requirements was a major barrier to bariatric surgery and should be a focus of future healthcare reform., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma., (© 2023. The Author(s).)

Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.