Eosinophil-rich linear IgA bullous dermatosis induced by mRNA COVID-19 booster vaccine.

We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis.

The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal-ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci.

Exploring Patient Motivations and Impact of Asian Blepharoplasty.

To date, patient motivations for Asian blepharoplasty and the surgery's impact on quality of life have not been quantified. Here, we employed structured interviews and a web-based survey to better characterize patient motivations for Asian blepharoplasty and the impact of Asian blepharoplasty on self-reported domains of happiness, self-esteem, attractiveness, social life, and professional life. Structured interviews were conducted to inform a web-based survey regarding Asian blepharoplasty. Survey respondents used visual analog scales to rate their satisfaction with their eye shape, motivations for undergoing Asian blepharoplasty, and perceived outcomes after surgery. A total of 315 participants (mean 25.7 [18-58] years) of East or Southeast Asian descent were included. 185 participants expressed no desire for Asian blepharoplasty, 76 expressed some desire, and 54 had already undergone surgery. There were statistically significant differences regarding baseline satisfaction, perceived social limitation, and perceived professional limitations regarding eye shape (p < 0.0001). The Looking Glass Self index (comprised of media exposure, low self-esteem, and negative stereotypes related to eye shape) is negatively associated with preoperative satisfaction with eye shape (rho = -0.29, p < 0.01). The desire for social-professional advancement and the Looking Glass Self index significantly predict self-reported improvements in professional and social life, respectively (both p < 0.01). Asian blepharoplasty may be driven by functional, social, or economic patient motivations. Some patients may see Asian blepharoplasty as a potential solution for sociological concerns. These expectations should be further explored in physician-patient discussions regarding candidacy for surgery and establishing expectations for postoperative outcomes.

Stretched Earlobe Piercings Negatively Impact Casual Observer Perceptions.

Patients with stretched earlobes seek reconstruction to mitigate social stigma. To date, there have been no studies measuring the impact of stretched earlobe piercings on casual observer perceptions. One-hundred seventy-three casual observers were enrolled via public-access web sites. Participants were randomly shown frontal and profile views of six subjects with stretched earlobe piercings and four controls. Participants evaluated photos for first impressions using a survey containing choices regarding personal attributes. Latent class analysis was performed to categorize observer ratings. Analysis of variance (ANOVA), bootstrap analysis, and permutations testing were used to evaluate the relationship between perceived attractiveness, success, and approachability scoring and stretched earlobe status. Latent class analysis categorized responses into three classes: positive, negative, and neutral. Patients with stretched earlobe piercings were significantly less likely to be classified as positive by observers without body modifications (i.e., tattoos and piercings) in comparison to control photos (30.9 and 40.1%, p = 0.007) and more likely to be classified as negative (38.5 and 28.1%, p = 0.002). These changes were abolished when photos were evaluated by observers with body modifications (p > 0.05). ANOVA revealed that stretched earlobe piercings and observer body modification status have a significant effect on rated approachability (F [1,1726] = 4.08, p = 0.04) and successfulness (F[1,1726] = 9.67, p = 0.002; F [1,1726] = 70.33, p < 0.0005). No significance was found for rated attractiveness (p > 0.05). Patients with stretched earlobe piercings were more likely to be classified as having negative affect display and being less approachable and successful compared with controls when evaluated by observers without body modifications. This effect was abolished when photos were evaluated by observers with body modifications. These findings validate patient motivations for seeking stretched earlobe repair.

Duox, Flotillin-2, and Src42A are required to activate or delimit the spread of the transcriptional response to epidermal wounds in Drosophila.

The epidermis is the largest organ of the body for most animals, and the first line of defense against invading pathogens. A breach in the epidermal cell layer triggers a variety of localized responses that in favorable circumstances result in the repair of the wound. Many cellular and genetic responses must be limited to epidermal cells that are close to wounds, but how this is regulated is still poorly understood. The order and hierarchy of epidermal wound signaling factors are also still obscure. The Drosophila embryonic epidermis provides an excellent system to study genes that regulate wound healing processes. We have developed a variety of fluorescent reporters that provide a visible readout of wound-dependent transcriptional activation near epidermal wound sites. A large screen for mutants that alter the activity of these wound reporters has identified seven new genes required to activate or delimit wound-induced transcriptional responses to a narrow zone of cells surrounding wound sites. Among the genes required to delimit the spread of wound responses are Drosophila Flotillin-2 and Src42A, both of which are transcriptionally activated around wound sites. Flotillin-2 and constitutively active Src42A are also sufficient, when overexpressed at high levels, to inhibit wound-induced transcription in epidermal cells. One gene required to activate epidermal wound reporters encodes Dual oxidase, an enzyme that produces hydrogen peroxide. We also find that four biochemical treatments (a serine protease, a Src kinase inhibitor, methyl-ß-cyclodextrin, and hydrogen peroxide) are sufficient to globally activate epidermal wound response genes in Drosophila embryos. We explore the epistatic relationships among the factors that induce or delimit the spread of epidermal wound signals. Our results define new genetic functions that interact to instruct only a limited number of cells around puncture wounds to mount a transcriptional response, mediating local repair and regeneration.

Leukemia Cutis in Relapsed Acute Myeloid Leukemia: A Call for Distinct Classification.

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

Intrinsic limbic and paralimbic networks are associated with criminal psychopathy.

BACKGROUND: Psychopathy is a personality disorder associated with impairments in decision-making, empathy, and impulsivity. Recent brain imaging studies suggest that psychopathy is associated with abnormalities in limbic/paralimbic brain regions. To date, no studies have examined functional brain connectivity measures using independent component analyses (ICA) in adults with psychopathy. Here, we test hypotheses regarding paralimbic connectivity in adult incarcerated individuals stratified by psychopathy scores. METHODS: One hundred and two prison inmates were rated using the Hare Psychopathy Checklist-Revised (PCL-R). FMRI data were collected while subjects performed an auditory target detection "oddball" task. FMRI data were analyzed using group ICA to identify functional networks responding to the oddball task correlating with psychopathy scores. RESULTS: Components demonstrating significant correlations with psychopathy included a default mode network, a frontoparietal component, and a visual/posterior cingulate component. Modulation trends correlated strongly with factor 2 (impulsivity) and total PCL-R scores in the frontoparietal and visual/posterior cingulate networks, and with factor 1 (affective) scores within the default mode network. The posterior cingulate region factored significantly in the modulation trends observed. CONCLUSION: Consistent with the hypothesis of limbic/paralimbic abnormalities associated with psychopathy, modulation trends correlated strongly with PCL-R scores. There is strong evidence to implicate the posterior cingulate in aberrant functional connectivity associated with the manifestation of psychopathic symptoms. Future investigations comparing functional trends associated with the posterior cingulate in psychopathic subjects may provide further insight into the manifestation of this disorder.

Self-supervised artificial intelligence predicts recurrence, metastasis and disease specific death from primary cutaneous squamous cell carcinoma at diagnosis.

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome (PO) including recurrence, metastasis and disease specific death (DSD) at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. In this multi-institutional study, we developed a state-of-the-art self-supervised deep-learning approach with interpretability power and demonstrated its ability to predict poor outcomes of cSCCs at the time of initial biopsy. By highlighting histomorphological phenotypes, our approach demonstrates that poor differentiation and deep invasion correlate with poor prognosis. Our approach is particularly efficient at defining poor outcome risk in Brigham and Women's Hospital (BWH) T2a and American Joint Committee on Cancer (AJCC) T2 cSCCs. This bridges a significant gap in our ability to assess risk among T2a/T2 cSCCs and may be useful in defining patients at highest risk of poor outcome at the time of diagnosis. Early identification of highest-risk patients could signal implementation of more stringent surveillance, rigorous diagnostic work up and identify patients who might best respond to early postoperative adjunctive treatment.

Multiple transcription factor codes activate epidermal wound-response genes in Drosophila.

Wounds in Drosophila and mouse embryos induce similar genetic pathways to repair epidermal barriers. However, the transcription factors that transduce wound signals to repair epidermal barriers are largely unknown. We characterize the transcriptional regulatory enhancers of 4 genes-Ddc, ple, msn, and kkv-that are rapidly activated in epidermal cells surrounding wounds in late Drosophila embryos and early larvae. These epidermal wound enhancers all contain evolutionarily conserved sequences matching binding sites for JUN/FOS and GRH transcription factors, but vary widely in trans- and cis-requirements for these inputs and their binding sites. We propose that the combination of GRH and FOS is part of an ancient wound-response pathway still used in vertebrates and invertebrates, but that other mechanisms have evolved that result in similar transcriptional output. A common, but largely untested assumption of bioinformatic analyses of gene regulatory networks is that transcription units activated in the same spatial and temporal patterns will require the same cis-regulatory codes. Our results indicate that this is an overly simplistic view.

Acute exposure of Nicotine during Drosophila puncture injury activates an epidermal wound response reaction.

Epidermal wound reaction after injury can be visualized in Drosophila melanogaster embryos by transgenic fluorescent wound reporters. A "local" reaction is limited to the epidermal cells surrounding a wound site occurs in wildtype embryos. A "global" reaction extends beyond the wound site to all epidermal cells occurs in immune response mutants (e.g. Flotillin-2 and Toll). The aim of this investigation is to explore the effect of nicotine on the localization of Drosophila wound reaction. Nicotine may have the potential to negatively affect wound repair by inhibiting a local reaction, and ultimately impeding epidermal wound recovery in Drosophila. We find nicotine exposure activates a global reaction after puncture injury of Drosophila embryos. Determining the effect of nicotine exposure on wound reaction in Drosophila may lead to improved understanding of how nicotine use in humans may influence wound healing after tissue damage.

A systematic review of evidence based treatments for lichen simplex chronicus.

Lichen simplex chronicus (LSC) is a disorder characterized by thickened areas of skin from repeated rubbing or scratching. The multifactorial nature of LSC makes management difficult and there are currently no evidence-based guidelines for treatment. We conducted a systematic review of the literature to evaluate treatments for LSC and provide an evidence-based summary of the current treatments as well as highlight novel therapies. A total of 21 studies were included which comprised 682 patients with LSC involving various areas. The most robust evidence was seen with the use of topical corticosteroids (n = 7 RCTs) and limited data suggest benefit with other treatments such as topical immunomodulators, topical antipruritic agents, oral antihistamines, antiepileptics and antidepressants. We also discuss novel treatment approaches using transcutaneous electrical nerve stimulation, focused ultrasound, and phototherapy. Despite emerging evidence there remains a paucity of high-quality studies supporting treatments for LSC and larger controlled trials are needed.

microRNA-mediated repression of rolled leaf1 specifies maize leaf polarity.

In both animals and plants, many developmentally important regulatory genes have complementary microRNAs (miRNAs), which suggests that these miRNAs constitute a class of developmental signalling molecules. Leaves of higher plants exhibit a varying degree of asymmetry along the adaxial/abaxial (upper/lower) axis. This asymmetry is specified through the polarized expression of class III homeodomain/leucine zipper (HD-ZIPIII) genes. In Arabidopsis, three such genes, PHABULOSA (PHB), PHAVOLUTA (PHV) and REVOLUTA (REV), are expressed throughout the incipient leaf, but become adaxially localized after primordium emergence. Downregulation of the HD-ZIPIII genes allows expression of the KANADI and YABBY genes, which specify abaxial fate. PHB, PHV and REV transcripts contain a complementary site for miRNA165 and miRNA166, which can direct their cleavage in vitro. Here we show that miRNA166 constitutes a highly conserved polarizing signal whose expression pattern spatially defines the expression domain of the maize hd-zipIII family member rolled leaf1 (rld1). Moreover, the progressively expanding expression pattern of miRNA166 during leaf development and its accumulation in phloem suggests that miRNA166 may form a movable signal that emanates from a signalling centre below the incipient leaf.

Phototherapy in the Pediatric Population.

Phototherapy has been used successfully to treat a wide range of pediatric skin conditions. It is a viable option in children with severe dermatologic disease or who have failed first-line treatments, and several studies have demonstrated its efficacy and safety in the pediatric population. Despite the growing body of evidence on the use of phototherapy in children, large controlled trials and long-term studies are lacking. Moreover, special considerations must be taken when using phototherapy in children. This review highlights the recent evidence supporting the efficacy and safety of phototherapy in children, with focus on the common light-sensitive pediatric skin conditions.

Transoral neck surgery prevents attentional bias towards the neck compared to open neck surgery.

OBJECTIVE: Measure attentional distraction of neck scars after open neck surgery compared to transoral endoscopic thyroidectomy via a vestibular approach (TOETVA) or transoral endoscopic parathyroidectomy via a vestibular approach (TOEPVA) using eye-tracking technology. METHODS: Casual observers viewed facial images of patients who underwent open neck surgery, TOETVA/TOEPVA, or no surgery (controls). An eye-tracking monitor recorded eye fixations in real time. Multivariate Hotelling's analysis followed by post-hypothesis testing compared fixation durations for predefined regions of interest, including the eyes, nose, mouth, neck, and remaining face between open neck surgery patients, transoral neck surgery patients, and controls. RESULTS: One hundred forty observers completed the experiment. The majority of their attention was directed towards the central triangle (eyes, nose, mouth). On multivariate analysis, distribution of attention was significantly different on the faces of those who underwent open neck surgery versus TOETVA/TOEPVA (T2 = 43.66; F[32,131] = 14.5389, P < .0001). Observers attended significantly more to the neck (0.20 seconds, P < .0001; 95% CI, 0.13, 0.26 s) and less to the peripheral face (-0.24 seconds, P = .0031; 95% CI, -0.39, -0.08 s) of open neck surgery patients. In patients who followed up months after surgery, significant differences persisted (T2 = 13.97; F[3451] = 4.6377, P = .0033). By contrast, fixation patterns for TOETVA/TOEPVA patients were not significantly different from controls (T2 = 5.59, F[31,186] = 1.8602, P = .1345). Observer race and gender did not significantly affect attention to neck scars. CONCLUSION: Scars following open neck surgery draw attention in casual observers. This attentional distraction is prevented in TOETVA/TOEPVA patients due to the absence of a scar, even months after surgery. Moreover, visual processing of TOETVA/TOEPVA patients' faces is similar to that of controls. These data support the effectiveness of transoral neck surgery in giving patients a cosmetic result that does not distract the attention of observers. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1603-1608, 2020.

Normal Gaze Patterns of the Face in Lateral View.

Importance: Current efforts to quantify the attentional distraction of facial deformities have been limited to deformities that are best perceived when the face is in frontal view, and there remains a paucity of knowledge of societal perception of the face in lateral view. To date, no attempts have been made to characterize the fixation patterns of the face in lateral view. Objective: To characterize the fixation patterns and gaze patterns of the face in lateral view. Design, Setting, and Participants: This was a prospective randomized controlled trial at an academic tertiary medical center. Eighty participants (mean age 23.6 ± 1.7 years, 52.5% female) gazed freely at 11 images of faces in lateral view for 10 s each as an infrared eye-tracker recorded eye movements in real time. Main Outcomes and Measures: Recorded eye movements are superimposed on the images to visualize areas of interest (AOIs) that attract the most attention. Fixation duration targeted at each AOI is transformed into relative fixation of the entire face and neck. Hotelling's test of variance followed by post hoc t-testing assessed for the significance of fixation differences between the mouth and cheeks. Results: Participants spent an average of 6.0 (95% CI 5.8-6.2) s gazing at the face and neck areas of each image. Of this attention, 2.8 s or 49.8% (45.4-54.2%) was directed toward the eye, followed distantly by the nose (mean, 95% CI) (16.4%, 14.5-18.3%), cheek (12.0%, 11.4-14.5%), neck (4.6%, 3.8-5.4%), and mouth (4.0%, 3.4-4.6%). These differences were found to be significant by Hotelling's analysis and post hoc testing. A student's t-test also indicated observers directed significantly more attention within the eye-nose-cheek triangle [4.6 s or 79.5% (75.6-83.5)] compared with the eye-nose-mouth triangle [4.1 s or 71.2% (66.9-75.5)] (p < 0.001). Conclusions and Relevance: When perceiving novel faces in lateral view, casual observers preferentially directed attention toward the eye, nose, and cheek. These findings suggest that we draw from a slightly different collection of features to build a schema of the sagittal face, which may serve to complement the central triangle and build upon a three-dimensional model of the "normal" human face. Level of Evidence: NA.

Objectively measuring social attention of thyroid neck scars and transoral surgery using eye tracking.

OBJECTIVE: Measure the social attention of thyroid neck scars and transoral surgery using eye tracking. METHODS: Observers viewed images of patients with thyroid neck scars, control patients with no scars, and patients who underwent transoral thyroidectomy as an eye-tracking monitor recorded their eye movements. Hotelling's multivariate analysis, followed by planned posthypothesis testing, were used to compare fixation times for the central triangle (CT), peripheral face, and neck between the three groups. To assess if these gaze patterns would normalize with transoral surgery, a two-sample t test was done to assess for differences in neck fixations between control and transoral patients and between transoral and traditional thyroidectomy. RESULTS: One hundred and thirty participants completed the eye-tracking experiment (mean age 24.3 years, 65 females). Observers directed the majority of their attention to the CT in both control and scar patients. Observers paid more attention to the neck (103.72 ms, P < .0001, 95% confidence interval [CI] [55, 152] ms) and less to the peripheral face (115.50 ms, P = .01, 95% CI [19, 211] ms) in patients with neck scars than in control patients. Furthermore, transoral surgery eliminated this attentional distraction wherein there was no difference in the fixation time to the neck (-39.198 ms P = .16, 95% CI [-93.978, 15.5816] ms) between controls and those who underwent transoral surgery. CONCLUSION: Observers directed their gaze away from the face and toward the neck in patients with thyroid neck scars. Furthermore, this distraction was eliminated with tranoral surgery. These findings shed light onto the altered observer perceptions of patients with thyroid neck scars. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2789-2794, 2019.