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Identifying risk factors that contribute to the development of anorexia nervosa (AN) is critical for the implementation of early intervention strategies. Anxiety, obsessive-compulsive behavior, and immune dysfunction may be involved in the development of AN; however, their direct influence on susceptibility to the condition remains unclear. Here, we used the activity-based anorexia (ABA) model to examine whether activity, anxiety-like behavior, compulsive behavior, and circulating immune markers predict the subsequent development of pathological weight loss.Female Sprague-Dawley rats (n = 44) underwent behavioral testing before exposure to ABA conditions after which they were separated into susceptible and resistant subpopulations. Blood was sampled before behavioral testing and after recovery from ABA to screen for proinflammatory cytokines.Rats that were vulnerable to pathological weight loss differed significantly from resistant rats on all key ABA parameters. While the primary measures of anxiety-like or compulsive behavior were not shown to predict vulnerability to ABA, increased locomotion and anxiety-like behavior were both associated with the extent of weight loss in susceptible but not resistant animals. Moreover, the change in expression of proinflammatory markers IL-4 and IL-6 evoked by ABA was associated with discrete vulnerability factors. Intriguingly, behavior related to risk assessment was shown to predict vulnerability to ABA.We did not find undisputable behavioral or immune predictors of susceptibility to pathological weight loss in the ABA rat model. Future research should examine the role of cognition in the development of ABA, dysfunction of which may represent an endophenotype linking anorectic, anxiety-like and compulsive behavior.Anorexia nervosa (AN) has among the highest mortality rates of all psychiatric disorders and treatment options remain limited in their efficacy. Understanding what types of risk factors contribute to the development of AN is essential for implementing early intervention strategies. This study describes how some of the most common psychological features of AN could be used to predict susceptibility to pathological weight loss in a well-established animal model.

Dermatologists diagnose and treat many immune-mediated inflammatory diseases (IMID). Understanding the inherent immune dysregulation of these diseases as well as the additional disruption that comes as a result of IMID treatments has been important during the COVID-19 pandemic. With vaccines becoming widely available, dermatologists need to be familiar with the risks and benefits of vaccination in these patients, particularly those taking biologics, in order to have informed discussions with their patients. In this review, we present the current evidence related to COVID-19 vaccine safety and efficacy in patients with IMID and review existing recommendations for vaccination against SARS-CoV-2. Given the current evidence, there is minimal concern that these patients are at any greater risk of harm from COVID-19 vaccination compared to healthy controls. For most, the benefit of avoiding severe COVID-19 through vaccination will outweigh the theoretical risk of these vaccines. A question that is still outstanding is whether patients on biologics will generate a sufficient immune response to the vaccine, which may be dependent on the specific biologic therapy and indication being treated. This underscores the importance of following patients with IMID after vaccination to determine the safety, efficacy, and duration of the vaccine in this population.

Disseminated mucormycosis is a rare, opportunistic, and aggressive infection typically presenting in immunocompromised patients. Herein, we report a 55-year-old male with a past medical history of Philadelphia-negative B-cell acute lymphoblastic leukemia who presented with a 2-month history of non-painful necrotic ulcers on the nose, knuckles, elbow, foot, and scrotum following 3 months of voriconazole (VRC) exposure in the setting of an unrelated fungal pneumonia. Our case reinforces the virulent and often fatal nature of the disease amongst immunocompromised patients, along with extensive VRC exposure as a possible supplementary risk factor. Disseminated cutaneous mucormycosis should be regarded as a differential diagnosis in all immunocompromised patients, especially those with hematologic malignancies or a history of VRC use, who present with cutaneous ulcerations and eschars.

Anorexia nervosa (AN) has high rates of mortality and low rates of recovery, with outcomes that worsen with illness duration. Improved early intervention strategies are required and identifying risk factors that contribute to the development of AN is critical to their implementation. The development of AN often follows a pre-existing diagnosis of anxiety disorders and obsessive-compulsive disorder and substantial genetic overlap between these conditions suggest common underlying features may predict vulnerability to AN. Moreover, patients with AN have increased levels of circulating proinflammatory cytokines, which may be involved in susceptibility to pathological weight loss considering that children with immune dysfunction have a higher risk of subsequent AN diagnoses.Here, we used the activity-based anorexia (ABA) model to examine whether baseline levels of locomotion, anxiety-like behaviour, compulsive behaviour, and circulating immune markers predict the subsequent development of pathological weight loss in adolescent female rats. While none of these primary features were shown to differentiate rats that went on to be susceptible or resistant to weight loss in ABA, increased locomotion and anxiety-like behaviour were both associated with the extent of weight loss in susceptible but not resistant animals. Intriguingly, behaviour related to poor decision-making in a situation of conflict was shown to predict vulnerability to ABA. Future research using the ABA model to uncover early predictors of AN should focus on translationally relevant assays of decision-making and cognitive behaviour, dysfunction of which may not only predispose animals to ABA but may also represent an endophenotype linking anorectic, anxiety-like and compulsive behaviour.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Transportation investments determine the long-term success or failure of a transportation provider. It is therefore vital for decision makers to have an in-depth understanding of the alternatives available before they choose to invest. However, often, the process of evaluating alternatives is lengthy, costly, and contentious, particularly for transportation infrastructure investment decisions that are large, complex, and interconnected with other economic development and sustainability goals. Furthermore, transportation investments involve many decision makers, each with different priorities and expertise. Therefore, there is a need for transparent, accurate, flexible, and practicable decision-making aids that can handle the complex challenges facing the decision-making bodies of transportation providers and planning organizations. This paper introduces a new decision aid—the CLIOSjre Process—that combines insights from multicriteria decision analysis, multistakeholder negotiation theory, and uncertainty analysis. The CLIOSjre Process helps decision makers compare multiple alternatives across multiple objectives and seek an informed collective transportation investment decision. Unlike other multicriteria decision aids, the CLIOSjre Process accounts for differences of opinion among decision makers and is designed to facilitate constructive negotiation among them. Finally, the CLIOSjre Process formally accounts for sources of uncertainty inherent in these decisions. In this way, the CLIOSjre Process provides a unique and flexible framework for investment analysis that can adapt to changes in transportation alternatives, decision-maker priorities, and emerging real-world conditions. The usefulness of this new decision aid is illustrated for the East Japan Railway Company’s consideration of a transportation investment opportunity in high-speed rail development on the Northeast Corridor of the United States.

Lichen sclerosus (LS) is an inflammatory dermatosis whose pathogenesis is incompletely understood. A retrospective review of patients with biopsy confirmed LS at University of Pittsburgh Medical Center (UPMC) clinical sites between 2009 and 2018 was conducted to study the link between breast cancer and LS. Out of 35 female patients who meet our inclusion criteria, 28.6% had a history of breast cancer, which is significantly higher than breast cancer prevalence (13%) in the United States. Interestingly, we have also observed a high rate of thyroid disease in patients with LS (32.6%), which is consistent with previous studies. Further studies are needed to delineate how breast cancer contributes to the development of LS, and whether screening for breast cancer has any utility in the management of LS.

This medical records review assesses whether dermatologic manifestations of nutrient deficiency are associated with poor outcomes in hospitalized adults.

Methicillin-resistant Staphylococcus aureus (MRSA) presents an increasing threat to public health, with antimicrobial resistance on the rise and infections endemic in the hospital setting. Despite a global research effort to understand and combat antimicrobial resistance, less work has focused on understanding the nuances in the immunopathogenesis of clinical strains. In particular, there is a surprising gap of knowledge in the literature pertaining to how clinical strains are recognized by dendritic cells (DCs). Here, we show that the activation of DCs is compromised in response to MRSA strains resistant to the last-line antibiotic daptomycin. We found a significant reduction in the secretion of proinflammatory cytokines including tumor necrosis factor-α, interleukin-6, regulated upon activation, normal T cell expressed, and secreted and macrophage inflammatory protein-1β, as well as decreased expression of CD80 by DCs responding to daptomycin-resistant MRSA. We further demonstrate that this phenotype is coincident with the acquisition of specific point mutations in the cardiolipin synthase gene cls2, and, partly, in the bifunctional lysylphosphatidylglycerol flippase/synthetase gene mprF, which are genes that are often mutated in clinical daptomycin-resistant strains. Therefore, throughout infection and antibiotic therapy, MRSA has the capacity to not only develop further antibiotic resistance, but also develop resistance to immunological recognition by DCs, because of single amino acid point mutations occurring under the selective pressures of both host immunity and antibiotic therapy. Understanding the diversity of clinical MRSA isolates and the nuances in their immune recognition will have important implications for future therapeutics and the treatment of these infections.

Despite advances in single-cell multi-omics, a single stem or progenitor cell can only be tested once. We developed clonal multi-omics, in which daughters of a clone act as surrogates of the founder, thereby allowing multiple independent assays per clone. With SIS-seq, clonal siblings in parallel "sister" assays are examined either for gene expression by RNA sequencing (RNA-seq) or for fate in culture. We identified, and then validated using CRISPR, genes that controlled fate bias for different dendritic cell (DC) subtypes. This included Bcor as a suppressor of plasmacytoid DC (pDC) and conventional DC type 2 (cDC2) numbers during Flt3 ligand-mediated emergency DC development. We then developed SIS-skew to examine development of wild-type and Bcor-deficient siblings of the same clone in parallel. We found Bcor restricted clonal expansion, especially for cDC2s, and suppressed clonal fate potential, especially for pDCs. Therefore, SIS-seq and SIS-skew can reveal the molecular and cellular mechanisms governing clonal fate.

Background Dysplastic nevi with severe atypia (severely dysplastic nevi [SDN]) are frequently re-excised because of the concern that these lesions may in fact represent early melanoma. Data on long-term follow-up of these patients are limited. Objective We sought to determine the rate of subsequent melanoma development in patients with SDN who underwent re-excision versus those who did not and to determine factors associated with decision to re-excise. Methods A retrospective single institutional study was conducted with 451 adult patients (mean age 41.3 years) with SDN biopsied between November 1994 and November 2004, with clinical follow-up of at least 5 years. Results In 451 patients with SDN, re-excision was performed on 36.6%. Two melanomas were diagnosed in the re-excision specimens. Subsequent metastatic melanoma developed in 7 patients, all of whom had a history of melanoma. Margin comments influenced decision to re-excise. Limitations This was a retrospective study at a single institution. Conclusion Re-excision of all SDN may not be necessary.

Superficial granulomatous pyoderma (SGP) is one of four subtypes of pyoderma gangrenosum (PG), an uncommon neutrophilic dermatosis, that presents as superficial, indolent ulcerative nodules or plaques that arise independently from an associated underlying disease [1]. Granulomatosis and polyangiitis (GPA) is a systemic, cytoplasmic ANCA (cANCA) positive vasculitis of small and medium vessels classically presenting with a triad of vascular, pulmonary, and renal complications [2]. We report a case of a limited variant of GPA presenting as SGP in a 57- year-old male with multiple nonhealing, painful ulcers on the upper extremities, torso, and neck with histologic features of superficial ulcers with predominantly plasma cell infiltrate consistent with atypical SGP. Over the following year, violaceous ulcers appeared, and a larger wedge biopsy demonstrated sinus tract formation with underlying plasmocytosis with histiocytes and giant cells, neutrophilic inflammation, and focal granuloma formation without vasculitis. The patient developed pulmonary symptoms and fever in the setting of markedly elevated cANCA. A chest CT revealed a lung nodule with fine needle aspiration (FNA) demonstrating acute and granulomatous inflammation but no organisms. Based on compatible clinical and histological findings, the diagnosis of GPA presenting as SGP was established. This case of a variant of GPA initially limited to the integument and mistaken for SGP characterizes the clinical and histopathological presentations of two rare diseases and supports the notion that GPA should be included in the differential diagnosis for SGP even before systemic symptoms and elevated cANCA arise to ensure early diagnosis and treatment.

Careful positioning and padding of pressure points during surgery are recommended to prevent pressure ulcers, vascular injury, and nerve damage in an immobilized patient. However, overpadding may have unintended consequences. We report a case of ischemia-induced full-thickness epidermal necrosis secondary to tight foam padding during a cardiac surgery.

Linear porokeratosis is a rare subtype of porokeratosis with a higher rate of malignant transformation than other subtypes of porokeratosis. Identification of cornoid lamellae on histology allows for definitive diagnosis, which makes high clinical suspicion and appropriate biopsy essential in establishing the correct diagnosis and developing an effective management plan. We present a case report of linear porokeratosis and discuss aspects of etiology, diagnosis, and management.

The immunobullous diseases comprise a number of clinically heterogeneous disorders caused by the production of antibodies directed against different proteins present in the skin and/or mucous membranes. Multiple therapies, both topical and systemic, make up the armamentarium for these varied conditions. In terms of the systemic therapies that are available, the appropriate medication in each individual patient must take into account the specific diagnosis, severity of the disease, comorbidities of the patient, potential interactions with other medications, and short and long-term goals of therapy. In this chapter, we review the oral systemic agents that can be used for the different immunobullous diseases and review their efficacy, side effects, and recommendations for patient monitoring for long-term therapy.

Nodular cutaneous amyloidosis (NCA), the least common form of primary cutaneous amyloidosis, is characterized clinically by waxy, purpuric plaques and nodules and histologically by amyloid deposits in the dermis and subcutaneous tissue. We present a patient who developed multiple, non-contiguous NCA lesions over a three year period without evidence of systemic disease. We reviewed the literature and found few other cases of this unusual presentation.

Dendritic cells (DC) are professional antigen presenting cells comprising a variety of subsets, as either resident or migrating cells, in lymphoid and non-lymphoid organs. In the steady state DC continually process and present antigens on MHCI and MHCII, processes that are highly upregulated upon activation. By expressing differential sets of pattern recognition receptors different DC subsets are able to respond to a range of pathogenic and danger stimuli, enabling functional specialisation of the DC. The knowledge of functional specialisation of DC subsets is key to efficient priming of T cells, to the design of effective vaccine adjuvants and to understanding the role of different DC in health and disease. This review outlines mouse and human steady state DC subsets and key attributes that define their distinct functions.

The chronically relapsing nature of alcoholism leads to substantial personal, family, and societal costs. Addiction-Comprehensive Health Enhancement Support System (A-CHESS) is a smartphone application that aims to reduce relapse. To offer targeted support to patients who are at risk of lapses within the coming week, a Bayesian network model to predict such events was constructed using responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol-dependent individuals who recently completed residential treatment. The Weekly Check-in is a self-monitoring service, provided in A-CHESS, to track patients’ recovery progress. The model showed good predictability, with the area under receiver operating characteristic curve of 0.829 in the 10-fold cross-validation and 0.912 in the external validation. The sensitivity/specificity table assists the tradeoff decisions necessary to apply the model in practice. This study moves us closer to the goal of providing lapse prediction so that patients might receive more targeted and timely support.

Ab stract Background Prodromal bullous pemphigoid (PBP) and bullous pemphigoid (BP) demonstrate immunoglobulin G (IgG) and/or C3 deposition at the basement membrane zone (BMZ) on direct immunofluorescence. BP-180-specific IgG1, IgG4, and IgE antibodies have been detected in BP. However, the distribution of IgG subclasses is unknown in PBP. Objectives We will describe the role of anti-BMZ IgG subclasses in PBP and we will correlate these findings to better understand the pathogenesis of PBP. Methods Skin biopsies and serum samples were obtained from 45 patients who had PBP. The skin tissue was processed for direct immunofluorescence studies. Sera were analyzed by indirect immunofluorescence for the presence of circulating anti-BMZ IgG antibodies (by standard IIF) and IgG subclasses antibodies (by sandwich double antibody immunofluorescence [SDAI]). Sera were also analyzed for antibodies against BP-180 and BP-230 antigens by enzyme-linked immunosorbent assay (ELISA). Results Thirty-two patients (71%) had IgG and C3 staining at the BMZ, while 13 patients (29%) had isolated C3 staining at the BMZ on direct immunofluorescence. All patients demonstrated staining on the epidermal side of the salt-split skin. Of the seven skin specimens that were available for C5-9 SDAI testing, all were found to be positive along BMZ area. Standard IIF studies demonstrated the presence of circulating BMZ antibodies in 11 of the 30 patients (36.6%). When SDAI for IgG subclass differentiation was utilized, 17 of 30 (56.6%) patients were found to have circulating anti-BMZ antibodies. All of these 17 patients had IgG4 subclass antibodies. Thirteen patients did not have detectable IgG subclass anti-BMZ antibody on SDAI. Sixteen of 30 patients had detectable anti-BP-180 or anti-BP-230 antibodies, while 12 (40%) did not have detectable antibody against BP antigens on ELISA. Conclusions IgG4 is the initial and predominant anti-BMZ antibody subclass detected in PBP. Demonstration of linear C5-9 at the BMZ enhances the early diagnosis of PBP. Predominance of IgG4 and the initial presence of IgG4 on skin lesions as well as the presence of only IgG4 subclass anti-BMZ antibody suggest that IgG4 subclass antibody could be the initial immunologic event encountered in patients with PBP.

Bullous pemphigoid (BP) is an autoimmune blistering disease that commonly occurs in the elderly. Immunosuppressive medications are effective at controlling the disease in the majority of cases. Mortality can occur as a consequence of severe disease or as a result of the therapies that are frequently employed as treatment. Commonly employed therapies include systemic corticosteroids, azathioprine and mycophenolate mofetil. In a small subset of patients, these first- and second-line therapies do not control disease or are not tolerated by the patients. Optional therapies include nicotinamide (niacinamide), tetracycline, intravenous immunoglobulin, cyclophosphamide, dapsone and methotrexate. The majority of BP patients are elderly, and several considerations need to be taken into account before a specific therapy is chosen. Methotrexate provides several advantages in the elderly population in terms of practicality, cost and tolerability. Several retrospective and prospective studies have evaluated its effectiveness in the treatment of BP in the elderly population. The results of these studies indicate that methotrexate is an effective therapy for BP and is a reasonable option for treatment in the elderly population, although maybe not as a first- or second-line therapy.

Darier's disease (DD) is difficult to treat and has no cure. Although many modalities have been investigated, treatment options to date are largely unsatisfactory. Side-effect profiles have limited the use of many of these therapies, as has their ability to target only limited areas of disease. Furthermore, the effectiveness of most available treatments seems to be highly individualized, varying with disease severity and offering little alteration in the natural course of the disease. The present study reports a case of severe DD that was poorly responsive to known therapeutic modalities but responded to electron beam radiotherapy, and recommends this therapeutic modality for localized areas of severe, recalcitrant symptomatic disease.

Objective To measure the performance of smartphone applications that evaluate photographs of skin lesions and provide the user with feedback about the likelihood of malignancy. Design Case-control diagnostic accuracy study. Setting Academic dermatology department. Participants and Materials Digital clinical images of pigmented cutaneous lesions (60 melanoma and 128 benign control lesions) with a histologic diagnosis rendered by a board-certified dermatopathologist, obtained before biopsy from patients undergoing lesion removal as a part of routine care. Main Outcome Measures Sensitivity, specificity, and positive and negative predictive values of 4 smartphone applications designed to aid nonclinician users in determining whether their skin lesion is benign or malignant. Results Sensitivity of the 4 tested applications ranged from 6.8% to 98.1%; specificity, 30.4% to 93.7%; positive predictive value, 33.3% to 42.1%; and negative predictive value, 65.4% to 97.0%. The highest sensitivity for melanoma diagnosis was observed for an application that sends the image directly to a board-certified dermatologist for analysis; the lowest, for applications that use automated algorithms to analyze images. Conclusions The performance of smartphone applications in assessing melanoma risk is highly variable, and 3 of 4 smartphone applications incorrectly classified 30% or more of melanomas as unconcerning. Reliance on these applications, which are not subject to regulatory oversight, in lieu of medical consultation can delay the diagnosis of melanoma and harm users.

Darier's disease (DD) is difficult to treat and has no cure. Although many modalities have been investigated, treatment options to date are largely unsatisfactory. Side-effect profiles have limited the use of many of these therapies, as has their ability to target only limited areas of disease. Furthermore, the effectiveness of most available treatments seems to be highly individualized, varying with disease severity and offering little alteration in the natural course of the disease. The present study reports a case of severe DD that was poorly responsive to known therapeutic modalities but responded to electron beam radiotherapy, and recommends this therapeutic modality for localized areas of severe, recalcitrant symptomatic disease.