Single Residue Variation in Skeletal Muscle Myosin Enables Direct and Selective Drug Targeting for Spasticity and Muscle Stiffness.

Muscle spasticity after nervous system injuries and painful low back spasm affect more than 10% of global population. Current medications are of limited efficacy and cause neurological and cardiovascular side effects because they target upstream regulators of muscle contraction. Direct myosin inhibition could provide optimal muscle relaxation; however, targeting skeletal myosin is particularly challenging because of its similarity to the cardiac isoform. We identified a key residue difference between these myosin isoforms, located in the communication center of the functional regions, which allowed us to design a selective inhibitor, MPH-220. Mutagenic analysis and the atomic structure of MPH-220-bound skeletal muscle myosin confirmed the mechanism of specificity. Targeting skeletal muscle myosin by MPH-220 enabled muscle relaxation, in human and model systems, without cardiovascular side effects and improved spastic gait disorders after brain injury in a disease model. MPH-220 provides a potential nervous-system-independent option to treat spasticity and muscle stiffness.

Titin activates myosin filaments in skeletal muscle by switching from an extensible spring to a mechanical rectifier.

Titin is a molecular spring in parallel with myosin motors in each muscle half-sarcomere, responsible for passive force development at sarcomere length (SL) above the physiological range (>2.7 µm). The role of titin at physiological SL is unclear and is investigated here in single intact muscle cells of the frog (Rana esculenta), by combining half-sarcomere mechanics and synchrotron X-ray diffraction in the presence of 20 µM para-nitro-blebbistatin, which abolishes the activity of myosin motors and maintains them in the resting state even during activation of the cell by electrical stimulation. We show that, during cell activation at physiological SL, titin in the I-band switches from an SL-dependent extensible spring (OFF-state) to an SL-independent rectifier (ON-state) that allows free shortening while resisting stretch with an effective stiffness of ~3 pN nm-1 per half-thick filament. In this way, I-band titin efficiently transmits any load increase to the myosin filament in the A-band. Small-angle X-ray diffraction signals reveal that, with I-band titin ON, the periodic interactions of A-band titin with myosin motors alter their resting disposition in a load-dependent manner, biasing the azimuthal orientation of the motors toward actin. This work sets the stage for future investigations on scaffold and mechanosensing-based signaling functions of titin in health and disease.

Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice.

Post-traumatic stress disorder (PTSD) is a hypermnesic condition that develops in a subset of individuals following exposure to severe trauma. PTSD symptoms are debilitating, and include increased anxiety, abnormal threat generalization, and impaired extinction. In developing treatment strategies for PTSD, preclinical studies in rodents have largely focused on interventions that target post-encoding memory processes such as reconsolidation and extinction. Instead, here we focus on forgetting, another post-encoding process that regulates memory expression. Using a double trauma murine model for PTSD, we asked whether promoting neurogenesis-mediated forgetting can weaken trauma memories and associated PTSD-relevant behavioral phenotypes. In the double trauma paradigm, consecutive aversive experiences lead to a constellation of behavioral phenotypes associated with PTSD including increases in anxiety-like behavior, abnormal threat generalization, and deficient extinction. We found that post-training interventions that elevate hippocampal neurogenesis weakened the original trauma memory and decreased these PTSD-relevant phenotypes. These effects were observed using multiple methods to manipulate hippocampal neurogenesis, including interventions restricted to neural progenitor cells that selectively promoted integration of adult-generated granule cells into hippocampal circuits. The same interventions also weakened cocaine place preference memories, suggesting that promoting hippocampal neurogenesis may represent a broadly useful approach in hypermnesic conditions such as PTSD and substance abuse disorders.

How effective are exercises delivered digitally (requiring internet), amongst patients with hip or knee osteoarthritis? A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis is to describe the effect of digitally delivered exercise on pain, physical function and quality of life (QoL) for people with knee or hip osteoarthritis (OA). METHODS: Articles were eligible for inclusion if they were of a randomized control trial that evaluated the prescription of digitally delivered exercise (requiring the internet) in people with symptomatic primary hip and/or knee OA. Risk of bias was assessed using the Physiotherapy Evidence Database scale, and levels of evidence were assessed according to Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Digitally delivered exercise was delivered via synchronous and asynchronous methods (or a combination of both). Digitally delivered exercise was superior to education only for pain and physical function, with high-quality evidence for quality-of-life outcomes in the long-term (standardized mean difference -0.35, 95% confidence interval -0.59 to -0.12, P = 0.003) in people with knee OA. Furthermore, there was very low to low-quality evidence that digitally delivered exercise was comparable to face-to-face delivery in the short and long-term for people with hip or knee OA and comparable in the medium-term for people with knee OA only. DISCUSSION: The review demonstrated very low to low-quality evidence that digitally delivered exercise was comparable to face-to-face delivery for pain, function and QoL. In the absence of higher-level evidence, we would provisionally recommend that healthcare providers offer the choice of face-to-face or digitally delivered exercise intervention for people with hip or knee OA. Further work is required to understand these programs' reach, access, uptake and implementation across diverse population groups.

TAPBPR employs a ligand-independent docking mechanism to chaperone MR1 molecules.

Chaperones tapasin and transporter associated with antigen processing (TAP)-binding protein related (TAPBPR) associate with the major histocompatibility complex (MHC)-related protein 1 (MR1) to promote trafficking and cell surface expression. However, the binding mechanism and ligand dependency of MR1/chaperone interactions remain incompletely characterized. Here in vitro, biochemical and computational studies reveal that, unlike MHC-I, TAPBPR recognizes MR1 in a ligand-independent manner owing to the absence of major structural changes in the MR1 α2-1 helix between empty and ligand-loaded molecules. Structural characterization using paramagnetic nuclear magnetic resonance experiments combined with restrained molecular dynamics simulations reveals that TAPBPR engages conserved surfaces on MR1 to induce similar adaptations to those seen in MHC-I/TAPBPR co-crystal structures. Finally, nuclear magnetic resonance relaxation dispersion experiments using 19F-labeled diclofenac show that TAPBPR can affect the exchange kinetics of noncovalent metabolites with the MR1 groove, serving as a catalyst. Our results support a role of chaperones in stabilizing nascent MR1 molecules to enable loading of endogenous or exogenous cargo.

Diagnosis and management of longitudinal erythronychia: A clinical review by an expert panel.

Longitudinal erythronychia (LE) is defined as a longitudinal red band of the nail(s) and is classified as localized (involvement of 1 nail) or polydactylous (involvement of more than 1 nail). The differential diagnosis is distinct for these classifications. The etiologies of localized longitudinal erythronychia are most frequently benign subungual neoplasms and less often malignancies. Polydactylous longitudinal erythronychia is typically secondary to regional or systemic diseases, including lichen planus and Darier disease. LE is a common but underrecognized clinical finding. Increased dermatologist awareness of the clinical characteristics and differential diagnosis for LE is necessary given the possibility for malignancy and associated systemic disease. In this clinical review, the clinical features, differential diagnosis, evaluation, and management of LE are described.

Non-classical measurement error in instrumental variables estimation: An application to the medical care costs of obesity.

Estimates of the impact of body mass index and obesity on health and labor market outcomes often use instrumental variables estimation (IV) to mitigate bias due to endogeneity. When these studies rely on survey data that include self- or proxy-reported height and weight, there is non-classical measurement error due to the tendency of individuals to under-report their own weight. Mean reverting errors in weight do not cause IV to be asymptotically biased per se, but may result in bias if instruments are correlated with additive error in weight. We demonstrate the conditions under which IV is biased when there is non-classical measurement error and derive bounds for this bias conditional on instrument strength and the severity of mean-reverting error. We show that improvements in instrument relevance alone cannot eliminate IV bias, but reducing the correlation between weight and reporting error mitigates the bias. A solution we consider is regression calibration (RC) of endogenous variables with external validation data. In simulations, we find IV estimation paired with RC can produce consistent estimates when correctly specified. Even when RC fails to match the covariance structure of reporting error, there is still a reduction in asymptotic bias.

Clinical, onychoscopic, nail clipping, and histopathological findings of malignant onychopapilloma.

This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma.

A Mixed-Methods Cohort Study Evaluating the Impact of a One-Day Well-Being Course for Anesthesia Providers Working in Low-Resource Settings.

BACKGROUND: Burnout, depression, and anxiety are increasingly recognized as common among health care providers. Risks for these conditions are exacerbated in low-resource settings by excessive workload, high disease burden, resource shortage, and stigma against mental health issues. Based on discussions and requests to learn more about burnout during the Vital Anaesthesia Simulation Training (VAST), our team developed VAST Wellbeing, a 1-day course for health care providers in low-resource settings to recognize and mitigate burnout and to promote personal and professional well-being. METHODS: This mixed-methods study used quantitative pre- and postcourse surveys using validated mental health measures and qualitative semistructured interviews to explore participants' experience of VAST Wellbeing during and after the course. Quantitative outcomes included burnout and professional fulfillment as measured by the Professional Fulfillment Index and general well-being as measured by the Warwick-Edinburgh Mental Wellbeing Scale. RESULTS: Twenty-six participants from 9 countries completed the study. In the immediate postcourse survey, study participants rated the course overall as "very good" (60.7%) and "excellent" (28.6%). Quantitative analysis showed no statistical differences in levels of work exhaustion, interpersonal disengagement, burnout, professional fulfillment, or general mental well-being 2 months after the course. Five themes on the impact of VAST Wellbeing were identified during qualitative analysis: (1) raising awareness, breaking taboos; (2) not feeling alone; (3) permission and capacity for personal well-being; (4) workplace empowerment; and (5) VAST Wellbeing was relevant, authentic, and needed. CONCLUSIONS: Causes of burnout are complex and multidimensional. VAST Wellbeing did not change measures of burnout and fulfillment 2 months postcourse but did have a meaningful impact by raising awareness, reducing stigma, fostering connection, providing skills to prioritize personal well-being, and empowering people to seek workplace change.

Patient and Staff Insights on Digital Care Pathways for Patients With Low Back Pain in the Emergency Department: A Qualitative Study.

BACKGROUND: Back pain is a huge global problem. For some people, the pain is so severe that they feel the need to present to an emergency department (ED). Our aim was to explore patient and staff perspectives for the development of a digital care pathway (DCP) for people with back pain who have presented to ED, including acceptability, barriers and facilitators. METHODS: We used a descriptive phenomenology approach using semi-structured interviews with patient and staff participants at a tertiary hospital. Interviews were transcribed and data codes were developed using inductive thematic analysis. Themes were discussed between researchers until consensus was achieved. RESULTS: A total of 16 interviews were carried out, half of which involved patient participants. We identified three major themes: (i) expectations and experiences of staff and patients with low back pain in ED; (ii) a digital care pathway can empower patients and support clinicians in providing care; and (iii) acceptability, barriers, facilitators and recommendations of engaging with a DCP to track the trajectory of back pain. Each theme was further categorised into subthemes. CONCLUSION: Introducing a DCP was perceived as acceptable and beneficial by patients and staff. Both groups were aware of the potential participant burden if surveys were too long. Introducing a DCP could be a valuable adjunct to current management care models, providing a standardised source of education with the potential for individualised tracking and monitoring. The design and development of a DCP will need to consider reported facilitators and address perceived barriers for engagement. PATIENT OR PUBLIC CONTRIBUTION: This project sought insights from patients and staff about a digital care pathway. This forms the first step of patient and consumer consultation before implementing a digital care pathway. All consumers were offered the opportunity to review their responses and our interpretation.

Prevalence of subungual melanoma in patients with cutaneous malignant melanoma: A systematic review and meta-analysis.

BACKGROUND: Subungual melanoma (SUM) is a rare type of cutaneous malignant melanoma (CMM) associated with poor prognosis, while data regarding its prevalence are scarce. OBJECTIVES: We sought to provide a comprehensive systematic review and meta-analysis of the prevalence rates of SUM among all types of CMM, considering certain demographic and clinical characteristics. METHODS: The MEDLINE electronic database was searched systematically to identify eligible studies providing prevalence rate estimates of SUM in patients with CMM. Included studies were further analysed to estimate the relative prevalences of SUM according to study design, study years, geographical region and sex distribution. RESULTS: Twenty-eight studies met the inclusion criteria. The overall SUM prevalence was 1.9% (95% CI [1.5%-2.3%]). The prevalence of SUM did not differ significantly between population- and hospital-based studies and remained stable over time. However, it was found to be significantly higher in Asians compared to patients of other geographical regions as well as in studies with more men than women compared to those with female preponderance (p < 0.001). CONCLUSIONS: In all, the overall SUM prevalence among all subtypes of CMM was estimated at 1.9%, without significant changes over time, and was found to exhibit significant variability between subgroups of different geographical regions.

Racial and Ethnic Minorities Underrepresented in Pain Management Guidelines for Total Joint Arthroplasty: A Meta-analysis.

BACKGROUND: Total joint arthroplasty aims to improve quality of life and functional outcomes for all patients, primarily by reducing their pain. This goal requires clinical practice guidelines (CPGs) that equitably represent and enroll patients from all racial/ethnic groups. To our knowledge, there has been no formal evaluation of the racial/ethnic composition of the patient population in the studies that informed the leading CPGs on the topic of pain management after arthroplasty surgery. QUESTIONS/PURPOSES: Using papers included in the 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines and comparing them with US National census data, we asked: (1) What is the representation of racial/ethnic groups in randomized controlled trials compared with their representation in the US national population? (2) Is there a relationship between the reporting of racial/ethnic groups and year of data collection/publication, location of study, funding source, or guideline section? METHODS: Participant demographic data (study year published, study type, guideline section, year of data collection, study site, study funding, study size, gender, age, and race/ethnicity) were collected from articles cited by this guideline. Studies were included if they were full text, were primary research articles conducted primarily within the United States, and if they reported racial and ethnic characteristics of the participants. The exclusion criteria included duplicate articles, articles that included the same participant population (only the latest dated article was included), and the following article types: systematic reviews, nonsystematic reviews, terminology reports, professional guidelines, expert opinions, population-based studies, surgical trials, retrospective cohort observational studies, prospective cohort observational studies, cost-effectiveness studies, and meta-analyses. Eighty-two percent (223 of 271) of articles met inclusion criteria. Our original literature search yielded 27 papers reporting the race/ethnicity of participants, including 24 US-based studies and three studies conducted in other countries; only US-based studies were utilized as the focus of this study. We defined race/ethnicity reporting as the listing of participants' race or ethnicity in the body, tables, figures, or supplemental data of a study. National census information from 2000 to 2019 was then used to generate a representation quotient (RQ), which compared the representation of racial/ethnic groups within study populations to their respective demographic representation in the national population. An RQ value greater than 1 indicates an overrepresented group and an RQ value less than 1 indicates an underrepresented group, relative to the US population. Primary outcome measures of RQ value versus time of publication for each racial/ethnic group were evaluated with linear regression analysis, and race reporting and manuscript parameters were analyzed with chi-square analyses. RESULTS: Two US-based studies reported race and ethnicity independently. Among the 24 US-based studies reporting race/ethnicity, the overall RQ was 0.70 for Black participants, 0.09 for Hispanic participants, 0.1 for American Indian/Alaska Natives, 0 for Native Hawaiian/Pacific Islanders, 0.08 for Asian participants, and 1.37 for White participants, meaning White participants were overrepresented by 37%, Black participants were underrepresented by 30%, Hispanic participants were underrepresented by 91%, Asian participants were underrepresented by 92%, American Indian/Alaska Natives were 90% underrepresented, and Native Hawaiian Pacific Islanders were virtually not represented compared with the US national population. On chi-square analysis, there were differences between race/ethnicity reporting among studies with academic, industry, and dual-supported funding sources (χ2 = 7.449; p = 0.02). Differences were also found between race/ethnicity reporting among US-based and non-US-based studies (χ2 = 36.506; p < 0.001), with 93% (25 of 27) of US-based studies reporting race as opposed to only 7% (2 of 27) of non-US-based studies. Finally, there was no relationship between race/ethnicity reporting and the year of data collection or guideline section referenced. CONCLUSION: The 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines provide evidence-based recommendations that reflect the current standards in orthopaedic surgery, but the studies upon which they are based overwhelmingly underenroll and underreport racial/ethnic minorities relative to their proportions in the US population. As these factors impact analgesic administration, their continued neglect may perpetuate inequities in outcomes after TJA. CLINICAL RELEVANCE: Our study demonstrates that all non-White racial/ethnic groups were underrepresented relative to their proportion of the US population in the 2021 Anesthesia and Analgesia in Total Joint Arthroplasty Clinical Practice Guidelines, underscoring a weakness in the orthopaedic surgery evidence base and questioning the overall external validity and generalizability of these combined CPGs. An effort should be made to equitably enroll and report outcomes for all racial/ethnic groups in any updated CPGs.

Quantifying Patient Expectations for Total Knee Arthroplasty: Expectations for Improvement Are Greater Than Minimal Clinically Important Difference.

BACKGROUND: Achieving a minimal clinically important difference (MCID) in patient-reported outcomes following total knee arthroplasty (TKA) is common, yet up to 20% patient dissatisfaction persists. Unmet expectations may explain post-TKA dissatisfaction. No prior studies have quantified patient expectations using the same patient-reported outcome metric as used for MCID to allow direct comparison. METHODS: This was a prospective study of patients undergoing TKA with 5 fellowship-trained arthroplasty surgeons at one academic center. Baseline Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) domains were assessed. Expected PROMIS scores were determined by asking patients to indicate the outcomes they were expecting at 12 months postoperatively. Predicted scores were generated from a predictive model validated in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) dataset. T-tests were used to compare baseline, expected, and predicted PROMIS scores. Expected scores were compared to PROMIS MCID values obtained from the literature. Regression models were used to identify patient characteristics associated with high expectations. RESULTS: There were 93 patients included. Mean age was 67 years (range, 30 to 85) and 55% were women. Mean baseline PROMIS PF and PI was 34.4 ± 6.7 and 62.2 ± 6.4, respectively. Patients expected significant improvement for PF of 1.9 times the MCID (MCID = 11.3; mean expected improvement = 21.6, 95% confidence interval [CI] 19.6 to 23.5, P < .001) and for PI of 2.3 times the MCID (MCID = 8.9; mean expected improvement = 20.6, 95% CI 19.1-22.2, P < .001). Predicted scores were significantly lower than expected scores (mean difference = 9.5, 95% CI 7.7 to 11.3, P < .001). No unique patient characteristics were associated with high expectations (P > .05). CONCLUSIONS: To our knowledge, this study is the first to quantify preoperative patient expectations using the same metric as MCID to allow for direct comparison. Patient expectations for improvement following TKA are ∼2× greater than MCID and are significantly greater than predicted outcome scores. This discrepancy challenges currently accepted standards of success after TKA and indicates a need for improved expectation setting prior to surgery.

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock after valve replacement.

BACKGROUND: Limited data evaluated the outcomes of extracorporeal membrane oxygenation (ECMO) in patients with prosthetic valves. This study aimed to compare the outcomes of ECMO support for postcardiotomy cardiogenic shock in patients with mechanical versus bioprosthetic valves. METHODS: This retrospective study included patients with ECMO support for postcardiotomy cardiogenic shock after valve replacement. Patients were grouped into bioprosthetic (n = 49) and mechanical valve (n = 22) groups. RESULTS: There were no differences in ECMO duration, inotropic support, intra-aortic balloon pump (IABP), stroke, duration of ICU, and hospital stay between groups. Postoperative thrombosis occurred in 2 patients with bioprosthetic valves (5.41%) and 2 with mechanical valves (14.29%), p = .30. All patients with thrombosis had central ECMO cannulation, concomitant IABP, and inotropic support during ECMO. All thrombi were related to the mitral valve. Three patients with thrombi had hospital mortality.Survival at 6, 12, and 36 months for bioprosthetic valve patients was 30.88%, 28.55%, and 25.34% and for mechanical valves was 36.36% for all time intervals (Log-rank p = .93). One patient had bioprosthetic aortic valve endocarditis after 1 year. Three patients with bioprosthetic valves had structural valve degeneration after 1, 2, and 5 years. CONCLUSIONS: Outcomes of ECMO in patients with prosthetic valves are comparable between bioprosthetic and mechanical valves. Thrombosis might occur in both valve types and was associated with high mortality. ECMO could affect the long-term durability of the bioprosthetic valves.

BackTrAC: A Digital Care Pathway for People Presenting to Emergency with Lower Back Pain. A Development and Feasibility Study Protocol.

OBJECTIVES: Back pain is a prevalent condition that affects 1 in 6 Australians at any time, with high associated health care costs. To date, there is limited information relating to symptom severity and recovery trajectory in people with back pain who present to the emergency department for care. A digital care pathway (DCP) can track patient outcomes following presentation with back pain. The primary aim of this protocol is to outline the co-development, implementation, and evaluation of a DCP for back pain patients who present to the emergency department. METHODS: The primary aim will be addressed in 3 overlapping phases: Phase 1 (co-design) will include interviews with back pain patients and health care professionals from the Northern Hospital Emergency Department. Interview findings will inform education resources featured on the DCP and establish questionnaire content and frequency acceptability. Phase 2 (implementation) will include the rollout of the DCP and tracking of patient-reported outcome measures, which will be collected over 12 weeks. Phase 3 (evaluation) will include interviews with a subset of back pain patients who have participated in Phase 2 to evaluate the acceptability of the DCP and the barriers and facilitators of using the DCP. ETHICS AND DISSEMINATION: This project has been approved via the National Health and Medical Research Council of Australia's National Mutual Acceptance Scheme by St Vincent's Hospital Human Ethics Committee (2022/PID06476), La Trobe University Research Governance (HEC#206/22), and Northern Health Research Governance (NH-2023-372687). We plan to publish the findings in a peer-reviewed journal and present them at conferences.

A call for nail clipping histopathology to become an essential component of the routine evaluation of melanonychia: Benefitting patients as a triage and surgical planning maneuver.

We call on dermatologists and dermatopathologists to include nail clipping histopathology as an essential component of the routine evaluation of melanonychia. This manuscript demonstrates a case where an adult woman with broad melanonychia of the right thumbnail declined a nail matrix biopsy, but was amenable to a nail clipping.The nail clipping showed pigmentation, melanocyte remnants, and small cavities in the nail plate. These features have been published previously by our group as a clue to nail unit melanoma within nail clippings.This patient was rapidly triaged for nail matrix biopsy, which demonstrated nail unit melanoma in situ. Every patient with melanonychia can benefit from a nail clipping by examination of the location of the pigmentation within the nail plate for surgical planning, and if melanocyte remnants are detected, the nail clipping also serves as a rapid triage mechanism for nail matrix biopsy to evaluate for nail unit melanoma. Fontana-stained sections will highlight the pigmentation in the nail plate, and its location in the nail plate can easily be described by the dermatopathologist. Nail clippings performed in the setting of clinically apparent melanonychia may show helpful histopathologic findings of pigmented fungi, hemorrhage, external pigmentation, features of other pigmented nail unit tumors, as well as other entities. Nail clipping histopathology can provide extensive information in the evaluation of melanonychia with minimal discomfort for a patient, and little disruption to a physician's clinic flow. With this additional case of a nail unit melanoma diagnosed after initial concern found in a nail clipping, as well as other information in the literature, it is clear that melanocyte remnants found in nail clippings are reliable concerning features related to nail unit melanoma in adults. With knowledge of these histopathologic features in nail clippings and the significance of melanocyte remnants, the dermatopathologist can play a crucial role in the use of a nail clipping as a life-saving diagnostic maneuver. Accordingly, given the potential benefit to patients in this setting, as well as other uses of a nail clipping in the evaluation of melanonychia, we call on dermatologists and dermatopathologists to innovate the routine evaluation of melanonychia through the routine employment of nail clippings for histopathologic evaluation.

Pleomorphic acquired digital fibrokeratoma: A novel clinicopathologic entity.

A 26-year-old male presented with a 2-year history of a hyperkeratotic growth from the left index finger. Histopathology was consistent with an acquired digital fibrokeratoma with changes of a pleomorphic fibroma. Lesional cells were negative for CD34, Rb, and p53, and were positive for FXIIIa. We introduce the pleomorphic acquired digital fibrokeratoma as a novel clinicopathologic entity.

Clinicohistopathologic challenges and traps in the diagnosis of nail unit melanoma.

Melanoma of the nail apparatus is challenging to diagnose for both dermatologists and dermatopathologists. Misdiagnosis or delayed diagnosis of nail unit melanoma can have fatal consequences and legal ramifications. This review educates dermatopathologists on challenges and traps they should be aware of to avoid misdiagnosis of nail unit melanoma. We present illustrative difficult cases that introduce several themes regarding challenges in the diagnosis of nail unit melanoma: specimens with subtle histopathologic findings, challenges in immunoperoxidase interpretation, and how clinical knowledge and surgical procedural knowledge are mandatory to make the diagnosis. Dermatopathologists will be aware of when and how to suspect nail unit melanoma in unusual circumstances.

Skill Translation Following the Vital Anesthesia Simulation Training Facilitator Course: A Qualitative Study.

BACKGROUND: Simulation-based education (SBE) is common in resource-rich locations, but barriers exist to widespread implementation in low-resource settings (LRSs). Vital Anesthesia Simulation Training (VAST) was developed to offer low-cost, immersive simulation to teach core clinical practices and nontechnical skills to perioperative health care teams. To promote sustainability, courses in new locations are preceded by the VAST Facilitator Course (VAST FC) to train local faculty. The purpose of this study was to explore the experiences of VAST FC graduates in translating postcourse knowledge and skills into their workplaces. METHODS: This qualitative study used focus group interviews with 24 VAST FC graduates (from 12 low- and middle-income and 12 high-income countries) to explore how they had applied new learning in the workplace. Focus groups were conducted by videoconferencing with data transcribed verbatim. Data were analyzed using inductive thematic analysis. RESULTS: Enabler themes for knowledge and skill translation following facilitator training were (1) the structured debriefing framework, (2) the ability to create a supportive learning environment, and (3) being able to meaningfully discuss nontechnical skills. Two subthemes within the debriefing framework were (1.1) knowledge of conversational techniques and (1.2) having relevance to clinical debriefing. Barrier themes limiting skill application were (1) added time and effort required for comprehensive debriefing, (2) unsupportive workplaces, and (3) lack of opportunities for mentorship and practice postcourse. CONCLUSIONS: Participants found parallels between SBE debriefing conversations, clinical event debriefing, and feedback conversations and were able to apply knowledge and skills in a variety of settings post course. This study supports the relevance of simulation facilitator training for SBE in LRSs.

Frequent hospital presenters' use of health information during COVID-19: results of a cross-sectional survey.

BACKGROUND: High-frequency hospital users often present with chronic and complex health conditions and are at increased risk of serious morbidity and mortality if they contract COVID-19. Understanding where high-frequency hospital users are sourcing their information, whether they understand what they find, and how they apply the information to prevent the spread of COVID-19 is essential for health authorities to be able to target communication approaches. METHODS: Cross-sectional survey of 200 frequent hospital users (115 with limited English proficiency) informed by the WHO's "Rapid, simple, flexible behavioral insights on COVID-19". Outcome measures were source of, and trust in information, and knowledge of symptoms, preventive strategies, restrictions, and identification of misinformation. RESULTS: The most frequently cited source of information was television (n = 144, 72%) followed by the internet (n = 84, 42%). One in four television users sought their information from overseas news outlets from their country of origin, while for those using the internet, 56% relied on Facebook and other forms of social media including YouTube and WeChat. Overall, 41.2% of those surveyed had inadequate knowledge about symptoms, 35.8% had inadequate knowledge about preventative strategies, 30.2% had inadequate knowledge about government-imposed restrictions, and 69% believed in misinformation. Half of the respondents (50%) trusted all information, and only one in five (20%) were uncertain or untrusting. English-speaking participants were almost three times more likely to have adequate knowledge about symptoms (OR 2.69, 95%CI 1.47;4.91) and imposed restrictions (OR 2.10 95%CI 1.06; 4.19), and 11 times more likely to recognize misinformation (OR 11.52 95%CI 5.39; 24.60) than those with limited English. CONCLUSION: Within this population of high-frequency hospital users with complex and chronic conditions, many were sourcing their information from less trustworthy or locally relevant sources, including social media and overseas news outlets. Despite this, at least half were trusting all the information that they found. Speaking a language other than English was a much greater risk factor for having inadequate knowledge about COVID-19 and believing in misinformation. Health authorities must look for methods to engage diverse communities, and tailor health messaging and education in order to reduce disparities in health outcomes.