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Early identification of atrial fibrillation (AF) can reduce the risk of stroke, heart failure, and other serious cardiovascular outcomes. However, paroxysmal AF may not be detected even after a two-week continuous monitoring period. We developed a model to quantify the risk of near-term AF in a two-week period, based on AF-free ECG intervals of up to 24 h from 459,889 patch-based ambulatory single-lead ECG (modified lead II) recordings of up to 14 days. A deep learning model was used to integrate ECG morphology data with demographic and heart rhythm features toward AF prediction. Observing a 1-day AF-free ECG recording, the model with deep learning features produced the most accurate prediction of near-term AF with an area under the curve AUC = 0.80 (95% confidence interval, CI = 0.79-0.81), significantly improving discrimination compared to demographic metrics alone (AUC 0.67; CI = 0.66-0.68). Our model was able to predict incident AF over a two-week time frame with high discrimination, based on AF-free single-lead ECG recordings of various lengths. Application of the model may enable a digital strategy for improving diagnostic capture of AF by risk stratifying individuals with AF-negative ambulatory monitoring for prolonged or recurrent monitoring, potentially leading to more rapid initiation of treatment.

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1-4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.

Neurodegenerative diseases are a major cause of disability in the world, but their etiologies largely remain elusive. Genetic factors can only account for a minority of risk for most of these disorders, suggesting environmental factors play a significant role in the development of these diseases. Prolonged exposure to air pollution has recently been identified to increase the risk of Alzheimer's and Parkinson's diseases, but the molecular mechanisms by which it acts are not well understood. Zebrafish embryos exposed to diesel exhaust particle extract (DEPe) lead to dysfunctional autophagy and neuronal loss. Here, we exposed zebrafish embryos to DEPe and performed high throughput proteomic and transcriptomic expression analyses from their brains to identify pathogenic pathways induced by air pollution. DEPe treatment altered several biological processes and signaling pathways relevant to neurodegenerative processes, including xenobiotic metabolism, phagosome maturation, and amyloid processing. The biggest induction of gene expression in brains was in Cyp1A (over 30-fold). The relevance of this expression change was confirmed by blocking induction using CRISPR/Cas9, which resulted in a dramatic increase in sensitivity to DEPe toxicity, confirming that Cyp1A induction was a compensatory protective mechanism. These studies identified disrupted molecular pathways that may contribute to the pathogenesis of neurodegenerative disorders. Ultimately, determining the molecular basis of how air pollution increases the risk of neurodegeneration will help in the development of disease-modifying therapies.

BackgroundA standardized pathology management tool for melanocytic skin lesions may improve patient care by simplifying interpretation and categorization of the diverse terminology currently extant.ObjectiveTo assess an online educational intervention that teaches dermatopathologists to use the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), a schema collapsing multiple diagnostic terms into 5 classes ranging from benign to invasive melanoma.MethodsPracticing dermatopathologists (N = 149) from 40 US states participated in a 2-year educational intervention study (71% response rate). The intervention involved a brief tutorial followed by practice on 28 melanocytic lesions, with the goal of teaching pathologists how to correctly use the MPATH-Dx schema; competence using the MPATH-Dx tool 12-24 months postintervention was assessed. Participants' self-reported confidence using the MPATH-Dx tool was assessed preintervention and postintervention.ResultsAt preintervention, confidence using the MPATH-Dx tool was already high, despite 68% lacking prior familiarity with it, and confidence increased postintervention (P = .0003). During the intervention, participants used the MPATH-Dx tool correctly for 90% of their interpretations; postintervention, participants used the MPATH-Dx tool correctly for 88% of their interpretations.LimitationsFuture research should examine implementing a standardized pathology assessment schema in actual clinical practice.ConclusionDermatopathologists can be taught to confidently and competently use the MPATH-Dx schema with a simple educational tutorial followed by practice.

Background:. Common peroneal nerve (CPN) disruption is the most common lower extremity nerve injury and results in gait disturbances and sensory paresthesias. The goal of this study is to describe branching patterns and the intraneural topography of the CPN to facilitate operative planning in CPN reconstruction. Methods:. The CPN and its distal motor and sensory branches were dissected in 6 lower leg cadavers. Branching patterns and distances were recorded with the fibular head as the landmark. Histological review of the nerve cross sections helped characterize the intraneural topography within the fibular tunnel. Results:. The CPN distal branching patterns were highly variable. The tibialis anterior motor branch was found on average 9.6 cm distal to the fibular head. Despite the variable branching patterns, the fascicular topography of the CPN within the fibular tunnel was consistent. Proximal to the tunnel, the nerve has 3 major fascicles, which include the superficial peroneal motor, common sensory, and deep peroneal motor (DPN) fascicles from lateral to medial. Within the tunnel, the topography consolidates into the superficial peroneal motor and DPN major divisions—motor axons anteriorly and sensory axons posteriorly. Conclusions:. The data presented provide clinically relevant information for the peripheral nerve surgeon where fascicular reconstruction of the nerve and neurolysis should focus on the anterior half of the nerve to restore ankle dorsiflexion. The nerve proximally is divided into 3 major fascicles compared with 2 distally. Surgeons may consider distal nerve transfers from the tibial nerve motor branches to the DPN or tibialis anterior motor branch.

Diagnostic error can be defined as deviation from a gold standard diagnosis, typically defined in terms of expert opinion, although sometimes in terms of unexpected events that might occur in follow-up (such as progression and death from disease). Although diagnostic error does exist for melanoma, deviations from gold standard diagnosis, certainly among appropriately trained and experienced practitioners, are likely to be the result of uncertainty and lack of specific criteria, and differences of opinion, rather than lack of diagnostic skills. In this review, the concept of diagnostic error will be considered in relation to diagnostic uncertainty, and the concept of overdiagnosis in melanoma will be presented and discussed.

Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich pure variants have been distinguished from mixed variants with areas of higher cell density and/or less desmoplastic stroma. This distinction is relevant because patients whose tumours display a pure phenotype have a lower risk for regional lymph node metastasis and distant recurrence. However, little is known about interobserver agreement among pathologists in the subclassification of desmoplastic melanoma. To address this issue, we conducted a study in which eleven dermatopathologists independently evaluated whole slide scanned images of excisions from 30 desmoplastic melanomas. The participating pathologists were asked to classify the tumours as pure or mixed. They were also asked to record the presence or absence of neurotropism and angiotropism. We found substantial interobserver agreement between the 11 dermatopathologists in the classification of tumours as pure versus mixed desmoplastic melanoma (kappa=0.64; p

ImportanceA standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.ObjectiveTo revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).Evidence reviewPracticing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0.FindingsThe new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma.Conclusions and relevanceThe implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients.

BACKGROUND: Evidence exists that escalating melanoma incidence is due in part to overdiagnosis, the diagnosis of lesions that will not lead to symptoms or death. The authors aimed to characterize subsets of melanoma patients with very-low risk of death that may be contributing to overdiagnosis. METHODS: Melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.0 mm thick and negative clinical lymph nodes from the Surveillance, Epidemiology, and End Results database were selected. Classification and regression tree and logistic regression models were developed and validated to identify patients with very-low risk of death from melanoma within 7 years. Logistic models were also used to identify patients at higher risk of death among this group of stage I patients. RESULTS: Compared to an overall 7-year mortality from melanoma of 2.5% in these patients, a subset comprising 25% had a risk below 1%. Younger age at diagnosis and Clark level II were associated with low risk of death in all models. Breslow thickness below 0.4 mm, absence of mitogenicity, absence of ulceration, and female sex were also associated with lower mortality. A small subset of high-risk patients with >20% risk of death was also identified. CONCLUSION: Patients with very-low risk of dying from melanoma within 7 years of diagnosis were identified. Such cases warrant further study and consensus discussion to develop classification criteria, with the potential to be categorized using an alternative term such as melanocytic neoplasms of low malignant potential. LAY SUMMARY: Although melanoma is the most serious skin cancer, most melanoma patients have high chances of survival. There is evidence that some lesions diagnosed as melanoma would never have caused symptoms or death, a phenomenon known as overdiagnosis. In this study, we used cancer registry data to identify a subset of early-stage melanoma patients with almost no melanoma deaths. Using two statistical approaches, we identified patients with

BACKGROUND: Previous studies of second opinions in the diagnosis of melanocytic skin lesions have examined blinded second opinions, which do not reflect usual clinical practice. The current study, conducted in the USA, investigated both blinded and nonblinded second opinions for their impact on diagnostic accuracy. METHODS: In total, 100 melanocytic skin biopsy cases, ranging from benign to invasive melanoma, were interpreted by 74 dermatopathologists. Subsequently, 151 dermatopathologists performed nonblinded second and third reviews. We compared the accuracy of single reviewers, second opinions obtained from independent, blinded reviewers and second opinions obtained from sequential, nonblinded reviewers. Accuracy was defined with respect to a consensus reference diagnosis. RESULTS: The mean case-level diagnostic accuracy of single reviewers was 65.3% (95% CI 63.4-67.2%). Second opinions arising from sequential, nonblinded reviewers significantly improved accuracy to 69.9% (95% CI 68.0-71.7%; P

Abstract Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists’ decisions has not yet been evaluated. Building upon previous research, we introduce an XAI system that provides precise and domain-specific explanations alongside its differential diagnoses of melanomas and nevi. Through a three-phase study, we assess its impact on dermatologists’ diagnostic accuracy, diagnostic confidence, and trust in the XAI-support. Our results show strong alignment between XAI and dermatologist explanations. We also show that dermatologists’ confidence in their diagnoses, and their trust in the support system significantly increase with XAI compared to conventional AI. This study highlights dermatologists’ willingness to adopt such XAI systems, promoting future use in the clinic.

Abstract Early identification of atrial fibrillation (AF) can reduce the risk of stroke, heart failure, and other serious cardiovascular outcomes. However, paroxysmal AF may not be detected even after a two-week continuous monitoring period. We developed a model to quantify the risk of near-term AF in a two-week period, based on AF-free ECG intervals of up to 24 h from 459,889 patch-based ambulatory single-lead ECG (modified lead II) recordings of up to 14 days. A deep learning model was used to integrate ECG morphology data with demographic and heart rhythm features toward AF prediction. Observing a 1-day AF-free ECG recording, the model with deep learning features produced the most accurate prediction of near-term AF with an area under the curve AUC = 0.80 (95% confidence interval, CI = 0.79–0.81), significantly improving discrimination compared to demographic metrics alone (AUC 0.67; CI = 0.66–0.68). Our model was able to predict incident AF over a two-week time frame with high discrimination, based on AF-free single-lead ECG recordings of various lengths. Application of the model may enable a digital strategy for improving diagnostic capture of AF by risk stratifying individuals with AF-negative ambulatory monitoring for prolonged or recurrent monitoring, potentially leading to more rapid initiation of treatment.

Parkinson's disease, as well as other neurodegenerative disorders, are primarily characterized by pathological accumulation of proteins, inflammation, and neuron loss. Although there are some known genetic risk factors, most cases cannot be explained by genetics alone. Therefore, it is important to determine the environmental factors that confer risk and the mechanisms by which they act. Recent epidemiological studies have found that exposure to air pollution is associated with an increased risk for development of Parkinson's disease, although not all results are uniform. The variability between these studies is likely due to differences in what components of air pollution are measured, timing and methods used to determine exposures, and correction for other variables. There are several potential mechanisms by which air pollution could act to increase the risk for development of Parkinson's disease, including direct neuronal toxicity, induction of systemic inflammation leading to central nervous system inflammation, and alterations in gut physiology and the microbiome. Taken together, air pollution is an emerging risk factor in the development of Parkinson's disease. A number of potential mechanisms have been implicated by which it promotes neuropathology providing biological plausibility, and these mechanisms are likely relevant to the development of other neurodegenerative disorders such as Alzheimer's disease. This field is in its early stages, but a better understanding of how environmental exposures influence the pathogenesis of neurodegeneration is essential for reducing the incidence of disease and finding disease-modifying therapies. © 2022 International Parkinson and Movement Disorder Society.

BACKGROUND: Histopathologically ambiguous melanocytic lesions lead some pathologists to list multiple diagnostic considerations in the pathology report. The frequency and circumstance of multiple diagnostic considerations remain poorly characterized. METHODS: Two hundred and forty skin biopsy samples were interpreted by 187 pathologists (8976 independent diagnoses) and classified according to a diagnostic/treatment stratification (MPATH-Dx). RESULTS: Multiple diagnoses in different MPATH-Dx classes were used in n = 1320 (14.7%) interpretations, with 97% of pathologists and 91% of cases having at least one such interpretation. Multiple diagnoses were more common for intermediate risk lesions and are associated with greater subjective difficulty and lower confidence. We estimate that 6% of pathology reports for melanocytic lesions in the United States contain two diagnoses of different MPATH-Dx prognostic classes, and 2% of cases are given two diagnoses with significant treatment implications. CONCLUSIONS: Difficult melanocytic diagnoses in skin may necessitate multiple diagnostic considerations; however, as patients increasingly access their health records and retrieve pathology reports (as mandated by US law), uncertainty should be expressed unambiguously.

Long-term air pollution (AP) exposure, including diesel exhaust exposure, is increasingly being recognized as a major contributor to the development of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. How AP increases the risk of neurodegeneration is not well understood but might include direct neurotoxicity and CNS inflammation. We investigated the impact of diesel exhaust particulate extract (DEPe) exposure on the brain and the mechanisms by which microglia and astroglia might mediate neuronal changes. Zebrafish (ZF) were utilized to determine neuronal toxicity of and microglial response to DEPe and single cell RNA sequencing was employed to study cell type-specific transcriptomic responses within the ZF brain. DEPe exposure induced neuronal injury and microglial activation in vivo. However, preventing the development of microglia did not attenuate DEPe-induced neuron loss, leading us to investigate microglial, astroglial, and neuronal response to DEPe exposure at single-cell resolution. Differentially expressed genes and disease-relevant pathways were identified within glial and neuronal clusters after DEPe exposure. Microglia and astroglia existed in multiple states, some of which appear toxic and others protective to neurons. Neuronal transcriptomic analysis revealed that DEPe exposure reduced expression of autophagy-related genes consistent with direct neurotoxicity. In summary, DEPe exposure was neurotoxic in developing ZF larvae and induced neuroinflammation. The microglial inflammatory response did not contribute to neurotoxicity of DEPe and in fact, some glial clusters upregulated transcriptional pathways that are likely protective. Furthermore, DEPe exposure led to reduced expression of autophagy-related genes in neurons that likely contribute to its toxicity.

The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge.

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone. Herein, we report that i) subjects with MDD and shorter leukocyte telomere length (LTL) show decreased levels of LAC, increased BMI, and a history of specific types of childhood trauma; and that ii) these multidimensional factors spanning mitochondrial metabolism, cellular aging, metabolic function, and childhood trauma provide more detailed signatures to predict longitudinal changes in depression severity in response to pioglitazone than individual factors. The findings of multidimensional signatures involved in the pathophysiology of depression and their role in predicting treatment outcomes provide a starting point for the development of a mechanistic framework linking biological networks and environmental factors to clinical outcomes in pursuit of personalized medicine strategies to effectively treat MDD.

BackgroundSynoptic reporting is recommended by many guideline committees to encourage the thorough histologic documentation necessary for optimal management of patients with melanoma.MethodsOne hundred fifty-one pathologists from 40 US states interpreted 41 invasive melanoma cases. For each synoptic reporting factor, the authors identified cases with "complete agreement" (all participants recorded the same value) versus any disagreement. Pairwise agreement was calculated for each case as the proportion of pairs of responses that agreed, where paired responses were generated by the comparison of each reviewer's response with all others.ResultsThere was complete agreement among all reviewers for 22 of the 41 cases (54%) on Breslow thickness dichotomized at 0.8 mm, with pairwise agreement ranging from 49% to 100% across the 41 cases. There was complete agreement for "no ulceration" in 24 of the 41 cases (59%), with pairwise agreement ranging from 42% to 100%. Tumor transected at base had complete agreement for 26 of the 41 cases (63%), with pairwise agreement ranging from 31% to 100%. Mitotic rate, categorized as 0/mm2 , 1/mm2 , or 2/mm2 , had complete agreement for 17 of the 41 cases (41%), with pairwise agreement ranging from 36% to 100%. Regression saw complete agreement for 14 of 41 cases (34%), with pairwise agreement ranging from 40% to 100%. Lymphovascular invasion, perineural invasion, and microscopic satellites were rarely reported as present. Respectively, these prognostic factors had complete agreement for 32 (78%), 37 (90%), and 18 (44%) of the 41 cases, and the ranges of pairwise agreement were 47% to 100%, 70% to 100%, and 53% to 100%, respectively.ConclusionsThese findings alert pathologists and clinicians to the problem of interobserver variability in recording critical prognostic factors.Lay summaryThis study addresses variability in the assessment and reporting of critical characteristics of invasive melanomas that are used by clinicians to guide patient care. The authors characterize the diagnostic variability among pathologists and their reporting methods in light of recently updated national guidelines. Results demonstrate considerable variability in the diagnostic reporting of melanoma with regard to the following: Breslow thickness, mitotic rate, ulceration, regression, and microscopic satellites. This work serves to alert pathologists and clinicians to the existence of variability in reporting these prognostic factors.

Abstract Acoustic identification of vocalizing individuals opens up new and deeper insights into animal communications, such as individual-/group-specific dialects, turn-taking events, and dialogs. However, establishing an association between an individual animal and its emitted signal is usually non-trivial, especially for animals underwater. Consequently, a collection of marine species-, array-, and position-specific ground truth localization data is extremely challenging, which strongly limits possibilities to evaluate localization methods beforehand or at all. This study presents ORCA-SPY, a fully-automated sound source simulation, classification and localization framework for passive killer whale (Orcinus orca) acoustic monitoring that is embedded into PAMGuard, a widely used bioacoustic software toolkit. ORCA-SPY enables array- and position-specific multichannel audio stream generation to simulate real-world ground truth killer whale localization data and provides a hybrid sound source identification approach integrating ANIMAL-SPOT, a state-of-the-art deep learning-based orca detection network, followed by downstream Time-Difference-Of-Arrival localization. ORCA-SPY was evaluated on simulated multichannel underwater audio streams including various killer whale vocalization events within a large-scale experimental setup benefiting from previous real-world fieldwork experience. Across all 58,320 embedded vocalizing killer whale events, subject to various hydrophone array geometries, call types, distances, and noise conditions responsible for a signal-to-noise ratio varying from $$-14.2$$ - 14.2 dB to 3 dB, a detection rate of 94.0 % was achieved with an average localization error of 7.01 $$^\circ$$ ∘ . ORCA-SPY was field-tested on Lake Stechlin in Brandenburg Germany under laboratory conditions with a focus on localization. During the field test, 3889 localization events were observed with an average error of 29.19 $$^\circ$$ ∘ and a median error of 17.54 $$^\circ$$ ∘ . ORCA-SPY was deployed successfully during the DeepAL fieldwork 2022 expedition (DLFW22) in Northern British Columbia, with a mean average error of 20.01 $$^\circ$$ ∘ and a median error of 11.01 $$^\circ$$ ∘ across 503 localization events. ORCA-SPY is an open-source and publicly available software framework, which can be adapted to various recording conditions as well as animal species.

Abstract Background In the 1990s, transjugular intrahepatic portosystemic shunts (TIPS) were performed using bare metal stents, and stent-induced hemolysis was a complication noted in 10% of patients. This was due to the mechanical stress created by turbulent flow from the uncovered interstices. Polytetrafluoroethylene (PTFE) stents came into regular use in the early 2000s becoming the standard equipment for TIPS placements, which are predominately covered. Due to this, stent-induced hemolysis has become a rare phenomenon. Case presentation We describe a case of TIPS-induced hemolysis in a 53-years-old Caucasian female patient without cirrhosis. The patient had a history of heterozygous factor 5 Leiden mutation and abnormal lupus anticoagulant profile with development of a portal vein thrombus. She had undergone previous TIPS placement complicated by a TIPS thrombosis 3 years after initial placement requiring venoplasty and extension of the stent. Within one month, the patient developed hemolytic anemia with extensive evaluation that did not yield an alternative cause. Due to temporal association and clinical symptoms, the hemolytic anemia was attributed to the recent TIPS revision. Conclusion This particular case of TIPS-induced hemolysis in a patient who does not have cirrhosis has not been previously described in the literature. Our case highlights that TIPS-induced hemolysis should be considered in anyone who could have potential underlying red blood cell dysfunction, not just those with cirrhosis. Further, the case demonstrates an important point that mild hemolysis (i.e., not requiring blood transfusion) can likely be managed conservatively, without stent removal.

Background: A standardized pathology management tool for melanocytic skin lesions may improve patient care by simplifying interpretation and categorization of the diverse terminology currently extant. Objective: To assess an online educational intervention that teaches dermatopathologists to use the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), a schema collapsing multiple diagnostic terms into 5 classes ranging from benign to invasive melanoma. Methods: Practicing dermatopathologists (N = 149) from 40 US states participated in a 2-year educational intervention study (71% response rate). The intervention involved a brief tutorial followed by practice on 28 melanocytic lesions, with the goal of teaching pathologists how to correctly use the MPATH-Dx schema; competence using the MPATH-Dx tool 12-24 months postintervention was assessed. Participants’ self-reported confidence using the MPATH-Dx tool was assessed preintervention and postintervention. Results: At preintervention, confidence using the MPATH-Dx tool was already high, despite 68% lacking prior familiarity with it, and confidence increased postintervention (P = .0003). During the intervention, participants used the MPATH-Dx tool correctly for 90% of their interpretations; postintervention, participants used the MPATH-Dx tool correctly for 88% of their interpretations. Limitations: Future research should examine implementing a standardized pathology assessment schema in actual clinical practice. Conclusion: Dermatopathologists can be taught to confidently and competently use the MPATH-Dx schema with a simple educational tutorial followed by practice.

Long coronavirus disease 2019 (COVID-19) is poorly understood, widespread and debilitating. Integrative medical group visits (IMGVs) provide group medical care virtually or in person and are reimbursed by insurance payors. IMGV introduces integrative modalities such as mindfulness, nutrition, and acupressure in a person-centered, supportive, and educational environment. To evaluate a telehealth IMGV program called Nourish to Flourish (N2F) for patients with long COVID, three researchers conducted a qualitative analysis of pre- and post-group individual interviews. Twenty-five patients provided interviews, of which fifteen included pre- and post-group individual interviews. Main themes were unpredictable symptom patterns, a common range of emotions associated with long COVID experience, reconceptualizing self-identity, multiple barriers to care in conventional settings, and connections formed in N2F. Although symptoms varied, N2F participants found commonalities in their experiences of living with long COVID. They empathized with one another regarding changing symptoms, inconsistent social support, shifting identities, and barriers to effective medical care.

BackgroundDiagnostic terms used in histopathology reports of cutaneous melanocytic lesions are not standardized. We describe dermatopathologists' views regarding diverse diagnostic terminology and the utility of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) for categorizing melanocytic lesions.MethodsJuly 2018-2019 survey of board-certified and/or fellowship-trained dermatopathologists with experience interpreting melanocytic lesions.ResultsAmong 160 participants, 99% reported witnessing different terminology being used for the same melanocytic lesion. Most viewed diverse terminology as confusing to primary care physicians (98%), frustrating to pathologists (83%), requiring more of their time as a consultant (64%), and providing necessary clinical information (52%). Most perceived that adoption of the MPATH-Dx would: improve communication with other pathologists and treating physicians (87%), generally be a change for the better (80%), improve patient care (79%), be acceptable to clinical colleagues (68%), save time in pathology report documentation (53%), and protect from malpractice (51%).ConclusionsMost dermatopathologists view diverse terminology as contributing to miscommunication with clinicians and patients, adversely impacting patient care. They view the MPATH-Dx as a promising tool to standardize terminology and improve communication. The MPATH-Dx may be a useful supplement to conventional pathology reports. Further revision and refinement are necessary for widespread clinical use.

Background: Mental health conditions are common among individuals with intellectual disability. Under recognition of mental health disorders leading to unmet treatment needs is common in this population. This article addresses one major contributing factor, the lack of cognitively accessible self-report measures for individuals with intellectual disability. Method: In this literature-informed overview of the state of the field, we discuss the need for, and complexities of, including individuals with intellectual disability in mental health assessments. Results: With appropriate supports, many individuals with intellectual disability can respond to mental health questions. We discuss evidence-based strategies to make mental health assessments more accessible. Conclusion: We highlight the need to engage individuals with intellectual disability to provide first-hand information about their health and well-being. New instruments and research procedures should be developed in partnership with individuals with intellectual disability. Self-report may be essential to advancing the science of mental health research. [This article was co-authored by the Nisonger Center RRTC on Health and Function.]

We propose the core collaborative community science framework, an original conceptual framework that integrates and modifies best practices from community science and collective impact groups to support investigations of environmental health and justice. The core collaborative community science framework differs from more typical frameworks for community science, which often frame projects as static and either scientist or community led; these framings can limit the potential for co-production and action-oriented models of science. Frameworks are lacking to help community science collaborators determine the contributions and leadership needed to initiate, sustain, and link together multiple projects that jointly support local learning and action, as well as contribute to broader scientific knowledge of complex social-ecological systems. The core collaborative community science framework offers three main innovations and contributions: (1) It invests in a core collaborative group structure, designed to increase community capacity and resilience through an expanded network of partners dedicated to the reduction of systematic inequities and injustices; (2) It seeds and supports multiple, diverse research projects implemented across complex social-ecological systems, focusing first on community-identified needs, and then on the questions community science can help answer; and (3) It facilitates dynamic shared responsibilities and leadership for partners from community, research, and government institutions, recognizing the need for shared contributions at all project phases. We offer examples from the Green Duwamish Learning Landscape in Washington, USA to show how project partners have coordinated their work focused on social, ecological, and human health and navigated challenges related to funding, staffing, and governance. We share insights on how to help integrate community science within the social fabric of communities, especially those faced with environmental health and justice challenges.

BackgroundApproximately 20% of adults in the United States experience chronic pain. Integrative Medical Group Visit (IMGV) offers an innovative approach to chronic pain management through training in mindfulness, nutrition, and other mind-body techniques combined with peer support. To date, there are no studies on IMGV implementation, despite its promise as a feasible non-pharmacological intervention for chronic pain management. In this study, we assessed the feasibility of implementing IMGV and assessing its effectiveness for chronic pain.MethodsImplementation Mapping was used to develop and evaluate implementation strategies for IMGV. Strategies included disseminating educational materials, conducting ongoing training, and conducting educational meetings. IMGV was delivered by three healthcare providers: an allopathic physician, registered yoga teacher, and naturopathic physician. The effectiveness of IMGV on patient health outcomes was assessed through qualitative interviews and a Patient-Reported Outcomes Scale (PROMIS-29). Provider perspectives of acceptability, appropriateness, and feasibility were assessed through periodic reflections (group interviews reflecting on the process of implementation) and field notes. Paired t-tests were used to assess changes between scores at baseline and post intervention. Qualitative data were coded by three experienced qualitative researchers using thematic content analysis.ResultsOf the initial 16 patients enrolled in research, 12 completed at least two sessions of the IMGV. Other than fatigue, there was no statistically significant difference between the pre- and post-scores. Patients reported high satisfaction with IMGV, noting the development of new skills for self-care and the supportive community of peers. Themes from patient interviews and periodic reflections included the feasibility of virtual delivery, patient perspectives on acceptability, provider perspectives of feasibility and acceptability, ease of recruitment, complexity of referral and scheduling process, balancing medical check-in with group engagement, and nursing staff availability.ConclusionsIMGV was feasible, acceptable, and effective from the perspectives of patients and providers. Although statistically significant differences were not observed for most PROMIS measures, qualitative results suggested that participants experienced increased social support and increased pain coping skills. Providers found implementation strategies effective, except for engaging nurses, due to staff being overwhelmed from the pandemic. Lessons learned from this pilot study can inform future research on implementation of IMGV.

Abstract Golden‐winged warblers (Vermivora chrysoptera) are facing population declines in the southern Appalachian Mountains. Breeding habitat loss is considered one of the primary reasons for golden‐winged warbler declines in the region. Expanding breeding habitat availability in a manner that promotes population expansion across an interconnected network of habitat patches is particularly problematic in a landscape dominated by private land ownership. We assessed the connectivity of golden‐winged warbler breeding habitat in a 29,680‐ha landscape with 5,664 ownership parcels between 2 state‐owned game lands in northwestern North Carolina, USA, in fall 2021. We created a connectivity map and provided examples of 3 means of prioritizing parcels for golden‐winged warbler habitat maintenance and management based on dispersal distances of fledglings that could return the following spring with prior familiarity of potential nesting areas. Prioritized parcels can guide land acquisition and conservation easement development as well as active management. Despite being highly parcelized, the area has both well‐connected and disjointed clusters of core habitat patches, but habitat management on privately owned parcels would be needed to connect core habitat patches to enable dispersing golden‐winged warbler fledglings to encounter potential breeding habitat that they could use the following spring.

Objectives"Assurance behaviors," a type of defensive medicine, involve physicians' utilization of additional patient services to avoid adverse legal outcomes. We aim to compare the use of clinical behaviors (such as ordering additional tests, services, and consultations) due to malpractice concerns with the same behaviors due to patient safety concerns.MethodsA national sample of dermatopathologists (n = 160) completed an online survey.ResultsParticipants reported using one or more of five clinical behaviors due to concerns about medical malpractice (95%) and patient safety (99%). Self-reported use of clinical behaviors due to malpractice concerns and patient safety concerns was compared, including ordering additional immunohistochemistry/molecular tests (71% vs 90%, respectively, P < .0001), recommending additional surgical sampling (78% vs 91%, P < .0001), requesting additional slides (81% vs 95%, P < .0001), obtaining second reviews (78% vs 91%, P < .0001), and adding caveats into reports regarding lesion difficulty (85% vs 89%, P > .05).ConclusionsDermatopathologists use many clinical behaviors both as assurance behaviors and due to patient safety concerns, with a higher proportion reporting patient safety concerns as a motivation for specific behaviors.

BackgroundMelanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized.MethodsA test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions.ResultsOf 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1 to 6 cases, and 81 (43%) requested testing for ≥6 cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board-certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH-Dx classes 2 to 4. The median intraobserver concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%-90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39).ConclusionSubstantial variability exists among pathologists in utilizing IHC.