CATCH-UP vaccines: protocol for a randomized controlled trial using the multiphase optimization strategy (MOST) framework to evaluate education interventions to increase COVID-19 vaccine uptake in Oklahoma.

BACKGROUND: Oklahoma's cumulative COVID-19 incidence is higher in rural than urban counties and higher than the overall US incidence. Furthermore, fewer Oklahomans have received at least one COVID-19 vaccine compared to the US average. Our goal is to conduct a randomized controlled trial using the multiphase optimization strategy (MOST) to test multiple educational interventions to improve uptake of COVID-19 vaccination among underserved populations in Oklahoma. METHODS: Our study uses the preparation and optimization phases of the MOST framework. We conduct focus groups among community partners and community members previously involved in hosting COVID-19 testing events to inform intervention design (preparation). In a randomized clinical trial, we test three interventions to improve vaccination uptake: (1) process improvement (text messages); (2) barrier elicitation and reduction (electronic survey with tailored questions/prompts); and (2) teachable moment messaging (motivational interviewing) in a three-factor fully crossed factorial design (optimization). DISCUSSION: Because of Oklahoma's higher COVID-19 impact and lower vaccine uptake, identifying community-driven interventions is critical to address vaccine hesitancy. The MOST framework provides an innovative and timely opportunity to efficiently evaluate multiple educational interventions in a single study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05236270, First Posted: February 11, 2022, Last Update Posted: August 31, 2022.

Cutaneous mosaic RASopathies associated with rhabdomyosarcoma.

Variants in RAS are known drivers of certain pediatric blood and solid cancers, including brain tumors. Though most RAS-driven cancers are thought to occur sporadically, genetic syndromes caused by germline RAS variants portend a slightly higher risk of rhabdomyosarcoma (RMS) development. Three new cases and a review of the literature demonstrate that in rare cases, certain somatic RAS variants are associated with an increased risk of RMS and that RMS development may be heralded by the presence of concomitant RAS-driven birthmarks. Further prospective studies are needed to establish incidence and recommend appropriate monitoring guidelines for patients at risk.

Linking the Cherokee Nation Cancer Registry With Electronic Medical Records: A Tribal-Academic Center Partnership.

The Cherokee Nation Cancer Registry (CNCR) is the only tribally operated Surveillance, Epidemiology, and End Results program registry. As registries, including the CNCR, lack detailed data characterizing health behavior or comorbidity, we aimed to enrich the CNCR by linking it with Cherokee Nation's electronic medical record (EMR). We describe the process of a tribal-academic partnership and linking records between the CNCR and the EMR for American Indian people diagnosed with cancer from 2015 to 2020. Prior to data linkage, our team worked with the Cherokee Nation Governance Board and Institutional Review Board to ensure tribal data sovereignty was maintained. While not all persons in the CNCR receive health care at Cherokee Nation, 63% linked with an EMR. We observed differences (P < .001) between cancer site, year at diagnosis, age at diagnosis, and gender by EMR linkage status. Once we further validate linkages and assess data completeness, we will evaluate relationships between behavioral risk factors, comorbidities, and cancer outcomes.

Consensus recommendations for the use of retinoids in ichthyosis and other disorders of cornification in children and adolescents.

Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin.

Basis for the gain and subsequent dilution of epidermal pigmentation during human evolution: The barrier and metabolic conservation hypotheses revisited.

The evolution of human skin pigmentation must address both the initial evolution of intense epidermal pigmentation in hominins, and its subsequent dilution in modern humans. While many authorities believe that epidermal pigmentation evolved to protect against either ultraviolet B (UV-B) irradiation-induced mutagenesis or folic acid photolysis, we hypothesize that pigmentation augmented the epidermal barriers by shifting the UV-B dose-response curve from toxic to beneficial. Whereas erythemogenic UV-B doses produce apoptosis and cell death, suberythemogenic doses benefit permeability and antimicrobial function. Heavily melanized melanocytes acidify the outer epidermis and emit paracrine signals that augment barrier competence. Modern humans, residing in the cooler, wetter climes of south-central Europe and Asia, initially retained substantial pigmentation. While their outdoor lifestyles still permitted sufficient cutaneous vitamin D3 (VD3) synthesis, their marginal nutritional status, coupled with cold-induced caloric needs, selected for moderate pigment reductions that diverted limited nutritional resources towards more urgent priorities (=metabolic conservation). The further pigment-dilution that evolved as humans reached north-central Europe (i.e., northern France, Germany), likely facilitated cutaneous VD3 synthesis, while also supporting ongoing, nutritional requirements. But at still higher European latitudes where little UV-B breaches the atmosphere (i.e., present-day UK, Scandinavia, Baltic States), pigment dilution alone could not suffice. There, other nonpigment-related mutations evolved to facilitate VD3 production; for example, in the epidermal protein, filaggrin, resulting in reduced levels of its distal metabolite, trans-urocanic acid, a potent UV-B chromophore. Thus, changes in human pigmentation reflect a complex interplay between latitude, climate, diet, lifestyle, and shifting metabolic priorities.

Elder mistreatment in underserved populations: Opportunities and challenges to developing a contemporary program of research.

This article provides an overview of the status of research on elder mistreatment among underserved populations in the United States, including gaps in our current knowledge base and scientific and structural barriers to growing research on the exploitation, neglect, and abuse of older people from diverse and disadvantaged ethnic/racial, geographic, sexual identity, and socioeconomic groups. High-priority areas in need of new elder mistreatment research with underserved populations are identified, and suggestions are given for how this research can be facilitated by researchers, university institutional review boards, and funding agencies.

Role of cholesterol sulfate in epidermal structure and function: lessons from X-linked ichthyosis.

X-linked ichthyosis is a relatively common syndromic form of ichthyosis most often due to deletions in the gene encoding the microsomal enzyme, steroid sulfatase, located on the short area of the X chromosome. Syndromic features are mild or unapparent unless contiguous genes are affected. In normal epidermis, cholesterol sulfate is generated by cholesterol sulfotransferase (SULT2B1b), but desulfated in the outer epidermis, together forming a 'cholesterol sulfate cycle' that potently regulates epidermal differentiation, barrier function and desquamation. In XLI, cholesterol sulfate levels my exceed 10% of total lipid mass (≈1% of total weight). Multiple cellular and biochemical processes contribute to the pathogenesis of the barrier abnormality and scaling phenotype in XLI. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Formation and functions of the corneocyte lipid envelope (CLE).

Corneocytes in mammalian stratum corneum are surrounded by a monolayer of covalently bound ω-OH-ceramides that form the corneocyte (-bound) lipid envelope (CLE). We review here the structure, composition, and possible functions of this structure, with insights provided by inherited and acquired disorders of lipid metabolism. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

Development and Initial Validation of a Novel System to Assess Ichthyosis Severity.

IMPORTANCE: A comprehensive, user-friendly system to assess global ichthyosis disease burden is imperative to improving the care of patients with ichthyosis, identifying appropriate participants for clinical trials, and quantifying treatment outcomes. To our knowledge, there is currently no validated scale to objectively and systematically measure ichthyosis severity across the entire body. OBJECTIVE: To create and evaluate a comprehensive and user-friendly instrument to measure total body ichthyosis severity in adults and children. DESIGN, SETTING, PARTICIPANTS: In this qualitative study, ichthyosis experts participated in the content development of the Ichthyosis Scoring System (ISS). The body was divided into 10 regions, and Likert scales (0-4) were created to quantify scale and erythema, with extensive descriptors and photographic standards. An 83-image teaching set was created from photographs of participants with ichthyosis. Two cohorts of dermatologists (11 total) independently scored all test photographs twice to evaluate interrater and intrarater reliabilities. Participants were enrolled worldwide from referral centers and patient advocacy groups. Participants of all ages, races, and ethnicities were included in the creation of ISS, and dermatologists with varying experience and areas of expertise participated as raters to evaluate the ISS. The study was conducted from 2019 to 2021, and the data were analyzed in 2021. MAIN OUTCOMES AND MEASURES: Intraclass correlation coefficients determined overall reliabilities. RESULTS: Across both cohorts of 11 dermatologists in total, the intraclass correlation coefficients for total, scale and erythema scores were greater than 0.90 (95% CI, 0.77-0.97), greater than 0.91 (95% CI, 0.79-0.98), and greater than 0.88 (95% CI, 0.72-0.97), respectively. Most body sites exhibited moderate to good interrater reliabilities for scale and erythema. Intrarater reliabilities were good to excellent. CONCLUSIONS AND RELEVANCE: The results of this qualitative study demonstrate reproducibility and suggest that the ISS is a reliable system to measure global ichthyosis severity in adults and children.

Global warming, heat-related illnesses, and the dermatologist.

Global warming, provoked by the greenhouse effect of high levels of atmospheric gases (most notably carbon dioxide and methane), directly threatens human health and survival. Individuals vary in their capacity to tolerate episodes of extreme heat. Because skin is the organ tasked with heat dissipation, it is important for dermatologists to be versed in the physiology of cutaneous heat dissipation and cognizant of clinical settings in which the skin's thermoregulatory responses may be impaired. When the external temperature is lower than that of the skin, the skin releases internal heat through direct thermal exchange with the environment, a process that is aided by an expansion of cutaneous blood flow and eccrine sweating. Cooling through the evaporation of sweat is effective even when the external temperature exceeds that of skin. Many factors, including environmental and physiological (e.g., age and sex), and pathological (e.g., preexisting illnesses, disorders of eccrine function, and medications) considerations, affect the skin's capacity to thermoregulate. Identification of individuals at increased risk for heat-related morbidity and mortality will become increasingly important in the care of patients.

Nursing student's attitudes toward teams in an undergraduate interprofessional mass casualty simulation.

BACKGROUND: Interprofessional education (IPE) aims to prepare future nurses for collaboration with healthcare professionals. Army style lane training may be an effective pedagogical technique for delivering emergency care and mass casualty training while incorporating IPE. PURPOSE: This study sought to determine attitudes toward IPE and teamwork in pre-licensure, undergraduate nursing students following a lane training simulation. METHOD: Pre- and postsimulation surveys containing sociodemographic, reflection, and KidSIM Attitude Toward Teamwork in Training Undergoing Designed Educational Simulation (KidSIM) items (Sigalet et al., 2012) were conducted. RESULTS: The KidSIM tool was deemed reliable (α = .98). Paired sample t tests resulted in significant increases for the KiDSIM and its subscales, with the exception of communication. However, communication, along with situation assessment and teamwork were reported to be most enhanced by students. CONCLUSION: Results support using the Army lane training model in an IPE environment for teaching emergency care, triage, and mass casualty procedures.

Functional reprogramming of the primary immune response by T cell receptor antagonism.

The T cell receptor must translate modest, quantitative differences in ligand binding kinetics into the qualitatively distinct signals used to determine cell fate. Here, we use mice that express an endogenous T cell receptor (TCR) antagonist and an adoptive transfer system to examine the influence of TCR signal quality on the development of effector function. We show that activation of antigen-specific T cells in the presence of an antagonist results in a functional reprogramming of the primary immune response, marked by altered T cell homing, a failure to develop effector function, and ultimately clonal elimination by apoptosis. Importantly, antagonism does not block cell division, implying that the signals promoting clonal expansion and effector differentiation are distinct.

Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms.

Until quite recently, the pathogenesis of atopic dermatitis (AD) has been attributed to primary abnormalities of the immune system. Intensive study revealed the key roles played by T(H)1/T(H)2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD. Accordingly, current therapy has been largely directed toward ameliorating T(H)2-mediated inflammation and pruritus. In this review we will assess emerging evidence that inflammation in AD results from inherited and acquired insults to the barrier and the therapeutic implications of this paradigm.

Accuracy of smartphone application to monitor heart rate.

BACKGROUND: The use of smartphone applications to monitor heart rate has become increasingly popular. However, there is limited research available on the validity of these applications. The purpose of this study was to examine the accuracy of a free heart rate monitoring application on two smartphone platforms while at rest and during moderate intensity exercise. One heart rate monitor application was chosen for two different technological platforms. METHODS: Twenty-four adults aged 18 and older (six males, 18 females) were randomly assigned a platform. Two groups were formed based on the platform being utilized. Both groups were monitored using an electrocardiograph (ECG) and the smart phone application. Heart rate for each participant was recorded while seated before exercise, and during moderate intensity exercise on an elliptical machine. Measurements were recorded in one-minute intervals. RESULTS: Data was analyzed using correlations and t-tests between platforms. All data was analyzed for both resting and exercise heart rate averages. There was no significant difference in heart rate while seated, t-test (-1.33; P=0.197) nor exercise heart rate, t-test (-1.54; P=0.142) when comparing means of the two platforms to an ECG. CONCLUSIONS: The applications chosen for both platforms to monitor heart rate were found to be fairly accurate, especially at rest. There are small user adaptations for monitoring heart rate, but heart rate applications provide a low-cost and efficient method for non-medical heart rate tracking. Future research should investigate the difference in accuracy for skin tone, ethnicity, race, hand size, and callosity of fingertips.

Comment on: The Vitamin D⁻Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas, Nutrients 2018, 10, 554.

In response to a recent article by Jones et al. (Nutrients 10: 554⁻568, 2018) [1], we agree that three distinctive features evolved in Homo erectus prior to the emergence of modern humans.[...].

Childhood Atopic Dermatitis Impact Scale: reliability, discriminative and concurrent validity, and responsiveness.

OBJECTIVE: To evaluate the test-retest reliability, discriminative and concurrent validity, and responsiveness of the Childhood Atopic Dermatitis Impact Scale (CADIS), a quality-of-life scale with 5 domains. DESIGN: Prospective, longitudinal study. SETTING: Two academic pediatric dermatology practices. PATIENTS: A total of 301 parents of children younger than 6 years with atopic dermatitis. MAIN OUTCOME MEASURES: Participants completed the CADIS, sociodemographic items, and other clinical questions at enrollment and at a 4-week follow-up. In addition, 41 participants completed the CADIS again 48 hours after baseline. Disease severity was measured using the Severity Scoring of Atopic Dermatitis (SCORAD) index for all children. RESULTS: Of 301 enrolled participants, 270 (90%) completed the enrollment materials and 228 (84%) of these completed the 4-week follow-up materials. Thirty-four (83%) of the 41 participants completed the 48-hour materials. Intraclass correlation coefficients of CADIS scores at enrollment and at 48 hours ranged from 0.89 to 0.95. Correlations between CADIS scores and the SCORAD index scores (range, 0.42-0.72) demonstrated that more severe atopic dermatitis is associated with worse quality of life. Scores from all 5 domains of the CADIS significantly differentiated patients at each severity level as measured by the SCORAD index (P<.001). Participants who rated their children as "improved" at the 4-week follow-up had significantly better CADIS scores than those who rated their children as having the "same" or "worse" skin disease (P<.05). CONCLUSIONS: These data confirm the test-retest reliability, concurrent validity, and discriminative validity of the CADIS. In addition, responsiveness evaluation demonstrates that the CADIS accurately measures change in patients whose disease improves.

Dermatology Societies Should Explore Fossil Fuel Divestment.

This Viewpoint describes the importance of dermatology societies and health care organizations divesting from fosile fuel investments to help mitigate the effects of climate change.