Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.

Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.

State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for 'all-optical' electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.

Combined Melanocytic Nevus and Nevus Sebaceus: A Case Series and Review of the Literature.

ABSTRACT: Nevus sebaceus is a rare congenital hamartoma with clinical and histopathological features that change with puberty. It has been associated with a number of secondary neoplasms, most of which are thought to derive from follicular germ cells. In this article, the authors describe a total of 3 cases of combined melanocytic nevus and nevus sebaceus to highlight this rare finding.

Arrhythmogenesis in Fabry Disease.

PURPOSE OF REVIEW: Fabry Disease (FD) is a rare lysosomal storage disorder characterised by multiorgan accumulation of glycosphingolipid due to deficiency in the enzyme α-galactosidase A. Cardiac sphingolipid accumulation triggers various types of arrhythmias, predominantly ventricular arrhythmia, bradyarrhythmia, and atrial fibrillation. Arrhythmia is likely the primary contributor to FD mortality with sudden cardiac death, the most frequent cardiac mode of death. Traditionally FD was seen as a storage cardiomyopathy triggering left ventricular hypertrophy, diastolic dysfunction, and ultimately, systolic dysfunction in advanced disease. The purpose of this review is to outline the current evidence exploring novel mechanisms underlying the arrhythmia substrate. RECENT FINDINGS: There is growing evidence that FD cardiomyopathy is a primary arrhythmic disease with each stage of cardiomyopathy (accumulation, hypertrophy, inflammation, and fibrosis) contributing to the arrhythmia substrate via various intracellular, extracellular, and environmental mechanisms. It is therefore important to understand how these mechanisms contribute to an individual's risk of arrhythmia in FD. In this review, we outline the epidemiology of arrhythmia, pathophysiology of arrhythmogenesis, risk stratification, and cardiac therapy in FD. We explore how advances in conventional cardiac investigations performed in FD patients including 12-lead electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging have enabled early detection of pro-arrhythmic substrate. This has allowed for appropriate risk stratification of FD patients. This paves the way for future work exploring the development of therapeutic initiatives and risk prediction models to reduce the burden of arrhythmia.

Telehealth Use by Pregnancy Stage Among Commercially Insured Patients in the United States, 2016-2019.

Introduction: Relatively little is known about the proportion of maternal health services utilized through telehealth and whether rural-urban disparities in telehealth use exist throughout antenatal, delivery, and postpartum phases of maternal services. In this study, we describe patterns of care, including telehealth utilization, by rurality and racial/ethnic composition of the health service area during the antenatal, labor/delivery, and postpartum stages of pregnancy among commercially insured patients between 2016 and 2019. Methods: We present univariate and comparative descriptive statistics of patient and facility characteristics and site of care by the degree of rurality and racial/ethnic composition of the health service area (defined as geozips). The individual-level utilization data for 238,695 patients were aggregated to the geo-zip level (n = 404). Results: Between 2016 and 2019, 3.5% of pregnancy, delivery, and postpartum-related visits among commercially insured patients were delivered through telehealth. Telehealth use was higher in the antenatal (3.5% of claim lines) and postpartum (4.1% of claim lines) periods, compared with labor and delivery (0.7% of claim lines). We also found that the proportion of telehealth services (of total services billed) increased with the share of Black and Latinx residents at the geozip level. Discussion: Our findings highlight disparities in telehealth use, consistent with findings from studies using different data sources and time periods. Future research is needed to examine whether the relative differences in proportion of telehealth services, even if small, are associated with telehealth capacity in the hospital or community and why the proportion of telehealth services differs across community-level characteristics, specifically rurality and proportion of Black and Latinx residents.

Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

An Asymptomatic Case of Invisible Mycosis Fungoides.

ABSTRACT: Mycosis fungoides has previously been reported in 'invisible' form, when biopsy of normal-appearing skin in the background of undifferentiated chronic pruritus demonstrated histopathologic findings of the malignancy. Asymptomatic cases have been reported more infrequently on biopsies of individual skin lesions. We present a case of invisible and asymptomatic mycosis fungoides, confirmed with immunohistochemical and T-cell receptor gene rearrangement studies, diagnosed on a re-excision specimen of an atypical melanocytic nevus. The case highlights the importance of alert examination of all tissue specimens for evidence of unrelated pathologic findings.

A Rare Case of Hydrophilic Polymer Embolization After Transcatheter Aortic Valve Replacement.

ABSTRACT: Endovascular procedures that use a hydrophilic polymer-coated device carry a risk of embolization and ischemic complications when used intravascularly. Because these coatings are increasingly used worldwide, it is important to identify potential adverse effects early. Cutaneous complications of hydrophilic polymer emboli are rare and not commonly described in the literature. Therefore, we report a case of hydrophilic polymer embolization with cutaneous findings in a patient who underwent a recent transcatheter aortic valve replacement.

Analysis of shared cognitive tasks in the application of non-invasive ventilation to patients with COPD exacerbation.

Interprofessional teamwork plays a key role in the uptake of evidence-based interventions, such as noninvasive ventilation (NIV) for patients with exacerbated Chronic Obstructive Pulmonary Disease (COPD). We aimed to identify the shared cognitive tasks in interprofessional teams using NIV for patients with COPD exacerbation. We used a cognitive task analysis approach (CTA) to engage nurses, rapid response team members, respiratory therapists, and physicians involved in the use of NIV to treat patients with COPD exacerbation. Clinicians participated in a semi-structured interview (n = 21) that elicited cognitions needed to treat COPD exacerbation. Three shared cognitive tasks were identified: Complete a thorough assessment, Formulate a care plan, and Continuously monitor patient status. Findings attest to the importance of having access to up-to-date information and expertise necessary to make accurate clinical inferences for patient assessment. Shared understanding of the formulated care plan among all members of the care team was important to its execution. Continuous monitoring was crucial; however, this cognitive task relied on patient assessment skills and ongoing collaboration within the clinical care team. Application of NIV for patients with COPD exacerbation may require enhancing collaboration through nontechnical skills and interprofessional training.

Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels.

Atrial fibrillation (AF) affects over 1% of the population and is a leading cause of stroke and heart failure in the elderly. A feared side effect of sodium channel blocker therapy, ventricular pro-arrhythmia, appears to be relatively rare in patients with AF. The biophysical reasons for this relative safety of sodium blockers are not known. Our data demonstrates intrinsic differences between atrial and ventricular cardiac voltage-gated sodium currents (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. Reduced atrial INa is only detected at physiological membrane potentials and is driven by alterations in sodium channel biophysical properties and not by NaV1.5 protein expression. Flecainide displayed greater inhibition of atrial INa, greater reduction of maximum upstroke velocity of action potential, and slowed conduction in atrial cells and tissue. Our work highlights differences in biophysical properties of sodium channels in left atria and ventricles and their response to flecainide. These differences can explain the relative safety of sodium channel blocker therapy in patients with atrial fibrillation.

Maturing papillomatous nevoid melanoma in the scalp mimicking recurrent melanocytic nevus: A case report of previously undescribed subtype of nevoid melanoma.

Nevoid melanoma is a subtype of melanoma that histologically resembles a melanocytic nevus. Two subtypes have been proposed for nevoid melanoma, namely papillomatous and maturing. Here, we report the case of a 67-year-old woman who developed two nevoid melanomas on her scalp with composite histological features of papillomatous and maturing subtypes after electrocautery of a nearby solitary scalp papule. The histology of both lesions was very similar, papillary in shape, and both comprised two melanocyte populations, including large atypical melanocytes and small non-atypical melanocytes. Whole-exome sequencing was performed in one of the two lesions, which revealed a high mutation burden (17 mutations/megabase) with co-deletion of CDKN2A. Additional immunohistochemistry revealed that the large and small melanocytes in both lesions were completely negative for p16 and MTAP. A final diagnosis of nevoid melanoma was made. To our knowledge, this is the first report of a nevoid melanoma with both features of papillomatous and maturing subtypes. Pathologists should be aware of this subtype of melanoma to avoid misdiagnosis as a mitotically active melanocytic nevus. In this case, immunohistochemistry for p16 and MTAP, in addition to molecular analysis, helped in the final diagnosis.

Follicular keratosis of the face in pediatric patients of color.

BACKGROUND/OBJECTIVES: Follicular keratosis (FK) is a poorly understood disorder presenting with multiple, grouped hyperkeratotic follicular papules typically affecting the chin or jawline. This study describes the clinical presentation, histopathology, management, and outcomes of a series of pediatric patients of color with FK of the face, thought to be related to rubbing or friction on the skin. METHODS: Retrospective review of 20 pediatric patients with FK of the face who presented to our pediatric dermatology practice between April 2019 and October 2021. RESULTS: Twenty patients (mean age 12.1 years, 13 females), all self-identified as Black/African American, were included. All presented with an initially asymptomatic, hyperpigmented patch containing multiple hyperkeratotic follicular papules, located on the cheek, chin, upper lip, and/or jawline. Five patients endorsed a history of rubbing the site. Nine patients had onset of the lesions during the COVID-19 pandemic. Treatments included topical vitamin D analogs, corticosteroids, and/or retinoids. Topical vitamin D analogs and retinoids improved the texture and hyperpigmentation of the follicular lesions in only four patients, while topical corticosteroids had no effect. Histopathological examination of two patients revealed multiple dilated follicles containing keratinized material and associated with a sparse dermal inflammatory infiltrate in one patient and granulomatous inflammation within the dermis in the other. CONCLUSIONS: In our cohort of pediatric patients with FK, patients of color were preferentially affected, and all cases were associated with hyperpigmentation. Some patients presented during the COVID-19 pandemic suggesting that friction from facial mask wearing may have induced or exacerbated this uncommon condition.

Telestroke Infrastructure, Processes, and Support Needs: A Survey of Hospitals in Five States.

Introduction: Telestroke has been shown to be a cost-effective approach to promoting use and timeliness of evidence-based treatment. However, adoption of telestroke has been relatively low. Several barriers to telestroke implementation have been previously identified in the literature. These barriers, and the strategies needed to overcome them, may vary across hospitals. Our study aimed to examine telestroke programs to identify opportunities for future research and efforts to promote effective implementation and sustainment of telestroke services. Methods: We surveyed hospitals in five states to capture information about the current status of the hospital's telestroke program; the model(s) of delivery being used (e.g., hub-and-spoke and third-party vendor); and telestroke infrastructure, processes, and implementation strategies. The survey included both closed-ended and open-ended response options. Descriptive results are presented, complemented with illustrative examples of open-ended responses. Results: We received 89 responses, each representing a different hospital. Approximately one-third of telestroke programs in our sample began between 2018 and 2020. More than two-thirds reported participating in a collaboration with other organizations to improve telestroke services. The most commonly reported, high-priority topics for additional guidance involved monitoring process measures, using performance indicators for improvement, and sharing data from measures with physicians. Discussion: Results complement prior studies, specifically about impacts of COVID-19 on telestroke programs and capabilities that hospitals most need assistance with. Challenges faced and guidance needed differ across hospitals, suggesting a need for a tailored support. The results also suggest more work is needed to understand factors that threaten sustainability of telestroke programs.

Association of Financial Factors and Telemedicine Adoption for Heart Attack and Stroke Care Among Rural and Urban Hospitals: A Longitudinal Study.

Introduction: To examine trends in telemedicine adoption for stroke and cardiac care among U.S. hospitals, specifically associations between hospital financial indicators and adoption of these telemedicine services. Methods: This is a retrospective analysis of data from the Health Information Management and System Society Dorenfest Database and Healthcare Cost Report Information System from 2012 to 2017. We used a pooled ordinary least squares model and reported results as average marginal effects (AMEs). Results: The number of hospitals with stroke or cardiac telemedicine services in urban and rural areas increased through our study period from 153 (7.30%) to 407 (19.42%) and from 127 (6.31%) to 331 (16.45%), respectively. In rural hospitals, being a for-profit hospital (AME = -10.49, 95% confidence interval [CI] = -14.01 to -6.98) and having an increase in Medicare inpatient mix (AME = -0.31, 95% CI = -0.42 to -0.20) were associated with the probability of telemedicine adoption for heart attack and stroke care. A couple of nonfinancial variables included in the model also were associated with adoption, specifically having one more licensed bed (AME = -0.02, 95% CI = -0.04 to -0.00) and higher number of emergency department visits (AME = 5.64, 95% CI = 2.83 to 7.20). In urban hospitals, being a for-profit hospital (AME = -8.94, 95% CI = -11.76 to -6.11) and having a higher total margin (AME = 0.17, 95% CI = 0.08 to 0.26) were associated with the probability of telemedicine adoption for heart attack and stroke care. Two nonfinancial variables also were statistically significant: having one more licensed bed (AME = 0.01, 95% CI = 0.041 to 0.02) and being closer to another telemedicine hospital (AME = 0.81, 95% CI = -1.62 to 0.01). Discussions: Telemedicine adoption rate for cardiac and stroke care has increased significantly in recent years. Financial status may be a bigger driver of adoption for urban hospitals than rural hospitals.

Strengthening methods for tracking adaptations and modifications to implementation strategies.

BACKGROUND: Developing effective implementation strategies requires adequate tracking and reporting on their application. Guidelines exist for defining and reporting on implementation strategy characteristics, but not for describing how strategies are adapted and modified in practice. We built on existing implementation science methods to provide novel methods for tracking strategy modifications. METHODS: These methods were developed within a stepped-wedge trial of an implementation strategy package designed to help community clinics adopt social determinants of health-related activities: in brief, an 'Implementation Support Team' supports clinics through a multi-step process. These methods involve five components: 1) describe planned strategy; 2) track its use; 3) monitor barriers; 4) describe modifications; and 5) identify / describe new strategies. We used the Expert Recommendations for Implementing Change taxonomy to categorize strategies, Proctor et al.'s reporting framework to describe them, the Consolidated Framework for Implementation Research to code barriers / contextual factors necessitating modifications, and elements of the Framework for Reporting Adaptations and Modifications-Enhanced to describe strategy modifications. RESULTS: We present three examples of the use of these methods: 1) modifications made to a facilitation-focused strategy (clinics reported that certain meetings were too frequent, so their frequency was reduced in subsequent wedges); 2) a clinic-level strategy addition which involved connecting one study clinic seeking help with community health worker-related workflows to another that already had such a workflow in place; 3) a study-level strategy addition which involved providing assistance in overcoming previously encountered (rather than de novo) challenges. CONCLUSIONS: These methods for tracking modifications made to implementation strategies build on existing methods, frameworks, and guidelines; however, as none of these were a perfect fit, we made additions to several frameworks as indicated, and used certain frameworks' components selectively. While these methods are time-intensive, and more work is needed to streamline them, they are among the first such methods presented to implementation science. As such, they may be used in research on assessing effective strategy modifications and for replication and scale-up of effective strategies. We present these methods to guide others seeking to document implementation strategies and modifications to their studies. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03607617 (first posted 31/07/2018).

Effects of genetic background, sex, and age on murine atrial electrophysiology.

AIMS: Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized. METHODS AND RESULTS: We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (-7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (-20% vs. average) and atrial ERP (-25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age. CONCLUSION: This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.

Role of Wnt signaling in dermatofibroma induction phenomenon.

BACKGROUND: Dermatofibroma (DF) is a common benign skin neoplasm. Induction above DF lesions, including follicular unit induction, is a frequently observed phenomenon. Wnt signaling is known to be critical in hair follicle morphogenesis. Our study assesses the role of Wnt signaling in DF induction by evaluating intracellular localization of ß-catenin in various types of DF induction. METHODS: Archived tissue collected between 1 October 1980 and 1 October 2013 was stained per protocol using hematoxylin and eosin and anti-ß-catenin monoclonal antibody. Specimens were grouped into categories based on the presence or absence and type of induction. All specimens were scored for nuclear ß-catenin localization. RESULTS: Of 62 specimens, 42 (68%) showed induction while 20 (32%) showed none. Nuclear ß-catenin staining was detected in 23 (55%) of the induction and in none of the no-induction specimens (P-value < 0.001). Types of induction included: 15 (24%) follicular induction, 31 (50%) acanthosis, and 4 (6%) sebaceous induction. For follicular induction, 13 (87%) showed positive nuclear ß-catenin staining compared to 11 (35%) for acanthosis and 1 (25%) for sebaceous induction (P-value = 0.002). CONCLUSION: Our findings support the hypothesis that DFs promote an ectopic activation of Wnt pathway signaling in follicular induction phenomenon.

Evaluating the association of social needs assessment data with cardiometabolic health status in a federally qualified community health center patient population.

BACKGROUND: Health systems are increasingly using standardized social needs screening and response protocols including the Protocol for Responding to and Assessing Patients' Risks, Assets, and Experiences (PRAPARE) to improve population health and equity; despite established relationships between the social determinants of health and health outcomes, little is known about the associations between standardized social needs assessment information and patients' clinical condition. METHODS: In this cross-sectional study, we examined the relationship between social needs screening assessment data and measures of cardiometabolic clinical health from electronic health records data using two modelling approaches: a backward stepwise logistic regression and a least absolute selection and shrinkage operation (LASSO) logistic regression. Primary outcomes were dichotomized cardiometabolic measures related to obesity, hypertension, and atherosclerotic cardiovascular disease (ASCVD) 10-year risk. Nested models were built to evaluate the utility of social needs assessment data from PRAPARE for risk prediction, stratification, and population health management. RESULTS: Social needs related to lack of housing, unemployment, stress, access to medicine or health care, and inability to afford phone service were consistently associated with cardiometabolic risk across models. Model fit, as measured by the c-statistic, was poor for predicting obesity (logistic = 0.586; LASSO = 0.587), moderate for stage 1 hypertension (logistic = 0.703; LASSO = 0.688), and high for borderline ASCVD risk (logistic = 0.954; LASSO = 0.950). CONCLUSIONS: Associations between social needs assessment data and clinical outcomes vary by cardiometabolic condition. Social needs assessment data may be useful for prospectively identifying patients at heightened cardiometabolic risk; however, there are limits to the utility of social needs data for improving predictive performance.

Immobilized collagen prevents shedding and induces sustained GPVI clustering and signaling in platelets.

Collagen, the most thrombogenic constituent of blood vessel walls, activates platelets through glycoprotein VI (GPVI). In suspension, following platelet activation by collagen, GPVI is cleaved by A Disintegrin And Metalloproteinase (ADAM)10 and ADAM17. In this study, we use single-molecule localization microscopy and a 2-level DBSCAN-based clustering tool to show that GPVI remains clustered along immobilized collagen fibers for at least 3 hours in the absence of significant shedding. Tyrosine phosphorylation of spleen tyrosine kinase (Syk) and Linker of Activated T cells (LAT), and elevation of intracellular Ca2+, are sustained over this period. Syk, but not Src kinase-dependent signaling is required to maintain clustering of the collagen integrin α2ß1, whilst neither is required for GPVI. We propose that clustering of GPVI on immobilized collagen protects GPVI from shedding in order to maintain sustained Src and Syk-kinases dependent signaling, activation of integrin α2ß1, and continued adhesion.

Radiation safety education and diagnostic imaging in pediatric patients with surgically treated hydrocephalus: the patient and family perspective.

PURPOSE: Surgically treated hydrocephalus patients are frequently imaged with head computed tomography (CT), and risk/benefit communication with families is inconsistent and unknown. We aimed to educate patients and caregivers about radiation safety in CT and explore their communication preferences. METHODS: We conducted a pediatric CT radiation safety and diagnostic imaging educational workshop for patients and caregivers at a national conference on hydrocephalus to characterize current practice and desired communication about CT imaging. Our workshop consisted of an interactive educational intervention with pre-/post-session surveys followed by feedback from participants. RESULTS: Our session included 34 participants (100% response rate for surveys) with 28 being parents of individuals with hydrocephalus. A total of 76% (n = 26) participants showed an increase in knowledge after the session (p < 0.01). All participants (N = 34) uniformly desired risk/benefit discussions before CT scans. However, 71% stated that they were not informed of risks/benefits of CT scans by a medical professional. Following the session, the number of participants indicating that informed consent should be obtained before CT scans increased from 30 to 33. Respondents also revealed that 14% of children and young adults had received > 100 CT scans for shunt evaluation with the median being 25 scans (IQR 20). CONCLUSIONS: Caregivers desire and deserve to be empowered through education and social support, and continuously engaged through sharing decisions and co-designing care plans. The neurosurgical community is in an ideal position to collaborate with radiologists, primary care providers, and parents in the development and testing of credible, high-quality online and social media resources.