Estrogens regulate numerous physiological and pathological processes, including wide-ranging effects in wound healing. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ER β ), that typically regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), that predominantly mediates rapid "non-genomic" signaling. Estrogen modulates the expression of various genes involved in epidermal function and regeneration, inflammation, matrix production, and protease inhibition, all critical to wound healing. Our previous work demonstrated improved myocutaneous wound healing in female mice compared to male mice. In the current study, we employed male and female GPER knockout mice to investigate the role of this estrogen receptor in wound revascularization and tissue viability. Using a murine myocutaneous flap model of graded ischemia, we measured real-time flap perfusion via laser speckle perfusion imaging. We conducted histologic and immunohistochemical analyses to assess skin and muscle viability, microvascular density and vessel morphology. Our results demonstrate that GPER is crucial in wound healing, mediating effects that are both dependent and independent of sex. Lack of GPER expression is associated with increased skin necrosis, reduced flap perfusion and altered vessel morphology. These findings contribute to understanding GPER signaling in wound healing and suggest possible therapeutic opportunities by targeting GPER.

Background On March 11, 2020, the New Mexico Governor declared a public health emergency in response to the COVID-19 pandemic. The New Mexico medical advisory team contacted University of New Mexico (UNM) faculty to form a team to consolidate growing information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease to facilitate New Mexico’s pandemic management. Thus, faculty, physicians, staff, graduate students, and medical students created the “UNM Global Health COVID-19 Intelligence Briefing.” Objective In this paper, we sought to (1) share how to create an informative briefing to guide public policy and medical practice and manage information overload with rapidly evolving scientific evidence; (2) determine the qualitative usefulness of the briefing to its readers; and (3) determine the qualitative effect this project has had on virtual medical education. Methods Microsoft Teams was used for manual and automated capture of COVID-19 articles and composition of briefings. Multilevel triaging saved impactful articles to be reviewed, and priority was placed on randomized controlled studies, meta-analyses, systematic reviews, practice guidelines, and information on health care and policy response to COVID-19. The finalized briefing was disseminated by email, a listserv, and posted on the UNM digital repository. A survey was sent to readers to determine briefing usefulness and whether it led to policy or medical practice changes. Medical students, unable to partake in direct patient care, proposed to the School of Medicine that involvement in the briefing should count as course credit, which was approved. The maintenance of medical student involvement in the briefings as well as this publication was led by medical students. Results An average of 456 articles were assessed daily. The briefings reached approximately 1000 people by email and listserv directly, with an unknown amount of forwarding. Digital repository tracking showed 5047 downloads across 116 countries as of July 5, 2020. The survey found 108 (95%) of 114 participants gained relevant knowledge, 90 (79%) believed it decreased misinformation, 27 (24%) used the briefing as their primary source of information, and 90 (79%) forwarded it to colleagues. Specific and impactful public policy decisions were informed based on the briefing. Medical students reported that the project allowed them to improve on their scientific literature assessment, stay current on the pandemic, and serve their community. Conclusions The COVID-19 briefings succeeded in informing and guiding New Mexico policy and clinical practice. The project received positive feedback from the community and was shown to decrease information burden and misinformation. The virtual platforms allowed for the continuation of medical education. Variability in subject matter expertise was addressed with training, standardized article selection criteria, and collaborative editing led by faculty.

Psoriasis is an immune-mediated chronic inflammatory skin disease caused by a combination of environmental incentives, polygenic genetic control, and immune regulation. The inflammation-related gene absent in melanoma 2 ( AIM2 ) was identified as a susceptibility gene for psoriasis. AIM2 inflammasome formed from the combination of AIM2, PYD-linked apoptosis-associated speck-like protein (ASC) and Caspase-1 promotes the maturation and release of inflammatory cytokines such as IL-1β and IL-18, and triggers an inflammatory response. Studies showed the genetic and epigenetic associations between AIM2 gene and psoriasis. AIM2 gene has an essential role in the occurrence and development of psoriasis, and the inhibitors of AIM2 inflammasome will be new therapeutic targets for psoriasis. In this review, we summarized the roles of the AIM2 gene and AIM2 inflammasome in pathogenesis and treatment of psoriasis, hopefully providing a better understanding and new insight into the roles of AIM2 gene and AIM2 inflammasome in psoriasis.

To the Editor: Skin cancer is the most common malignancy in the United States, and melanoma remains a public health concern.1 Primary prevention includes the use of sunscreen, protective clothing, shade seeking, and sun avoidance.2 Secondary prevention includes skin self-examinations and total-body skin examinations.2

Reflectance confocal microscopy is an innovative imaging modality, which noninvasively provides an optical image to aid in the diagnosis of skin lesions. While performing a skin biopsy for histopathologic analysis is the gold standard to definitively diagnose skin disease, this may prove to be more difficult in the pediatric population. This will occasionally necessitate sedation or general anesthesia as an approach, which carries a number of different risks. Reflectance confocal microscopy is an exciting new avenue in the support of diagnosing skin pathology, with the goal of improving pediatric patient tolerance and experience when examining epidermal and superficial dermal skin lesions. This review discusses the utility of reflectance confocal microscopy for pediatric dermatology patients pertaining to melanocytic and non-melanocytic skin neoplasms and inflammatory and infectious skin diseases in children.

Psoriasis (PsO) is a chronic inflammatory skin disease that affects approximately 2% of the population all over the world. Comorbidities of PsO have increasingly garnered more interest in the past decades. Compared with the normal population, the incidences of comorbidities are higher among patients with PsO. In the last 20 years, researchers have focused on studying the genetic components of PsO, and genetic associations between PsO and its comorbidities were elucidated. This review provides an in-depth understanding and summarization of the connection between PsO and its comorbidities from the perspectives of epidemiology and genetics. Further understanding of PsO and its comorbidities will promote research on the pathogenesis, drug development, novel therapy methods, and personalized and precision treatment of PsO and its comorbidities.

Objective: Dermoscopic features of cutaneous vascular anomalies have been reported, but the described features currently known are limited and not well-understood. The aim of this study is to comprehensively summarize and compare the dermoscopic features of the four different types of cutaneous vascular anomalies [infantile hemangiomas (IH), cherry angioma (CA), angiokeratomas (AK), and pyogenic granuloma (PG)] in the Chinese Han population. Materials and Methods: Dermoscopic features of 31 IH, 172 CA, 31 AK, and 45 PG were collected based on the contact non-polarized mode of dermoscopy at 20-fold magnification. Dermoscopic features including background, lacunae, vessel morphology and distribution were collected and summarized. Additionally, we compared these features by age stage, gender, and anatomical locations in CA. Results: The dermoscopic features of IH included the red lacunae, red/red-blue/red-white backgrounds, and vessel morphology such as linear curved vessels, serpiginous vessels, coiled vessels. For CA, the lacunae appeared reddish brown to reddish blue or only red. In terms of vascular morphology, serpentine vessels, coiled vessels, looped vessels, and curved vessels could be seen in the lesions. A few lesions were black or presented with a superficial white veil. There were statistical differences in red background ( P = 0.021), unspecific vessel distribution ( P = 0.030), black area ( P = 0.029), and white surface ( P = 0.042) among different age groups. Red-brown lacunae ( P = 0.039), red-blue ( P = 0.013), red-white background ( P = 0.015), black area ( P = 0.016), and white surface ( P = 0.046) were of statistical difference in terms of the locations of lesions. Lacunae were also observed in AK, which presented with red, dark purple, dark blue, black. Global dermoscopic patterns that were characterized by a homogeneous area were obvious in all PG lesions, among which 30 (66.7%) were red-white and 15 (33.3%) were red. As for local features, “white rail” lines were detected in 19 (42.2%) lesions and white collarette was seen in 34 (75.6%) lesions. Conclusions: Dermoscopy is an applicable diagnostic tool for the diagnosis of cutaneous vascular anomalies. It is necessary to take into account the age stage and lesion location when we diagnose CA using dermoscopy.

Background: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. Methods: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. Results: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in “disturbances of pigmentation” and “neurological and psychogenic dermatoses”. The duration of T2DM also significantly associated with the prevalence of “disturbances of pigmentation” and “neurological and psychogenic dermatoses”. Subsequently, the prevalence of “disturbances of pigmentation” was higher in males than females in NGT ( P < 0.01) and T2DM ( P < 0.01) groups. In addition, the difference in the prevalence of “disturbances of pigmentation” was also significant in NGT and T2DM groups ( P < 0.01). Conclusions: There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.

Background: Subungual splinter hemorrhage (SSH) is a common nail disorder and is difficult to differentiate from other nail diseases because of their similar characteristics. The epidemiological study of SSH is lacking and it is unclear whether SSH needs treatment or not. Aims: The aims of this study were to observe the clinical characteristics of SSH of toenails in Chinese adults and to provide a reference for the diagnosis and prognosis of patients with SSH. Materials and Methods: We collected and followed up 63 SSH patients who were diagnosed through dermoscopic examination. The clinical and dermoscopic characteristics, disease course, and recovery results were recorded. Data sets were analyzed through the use of SPSS 16.0. Literature concerning SSH were reviewed and compared with the results in this study. Results: Sixty-three SSH patients were included with an age range of 17-58 years. Nearly 93.7% of SSH patients occurred in the right, left, or right and left first toenails; 66.7% of SSH patients occurred only in one toenail; there were 60.3% of SSH patients with a clear stimulus causing it and 31.8% of SSH patients with five types of comorbidities. The common characteristics of dermoscopy showed a reddish brown or brown stain with a clear boundary visible under the nail in which the color gradually faded outward from the center, with no blue or white structure. After following up for 24 weeks, the disappearance of hemorrhage was observed in 95.2% of SSH patients. For the recovered SSH patients, data analysis showed no significant difference in the course of SSH in males and females (P = 0.645); the statistical analysis showed that there was no significant correlation (r2 = -0.002) between age and course in recovered SSH patients (P = 0.986). Conclusions: It is unnecessary to do any special treatment during the 1st year. Measures ought to be taken for SSH patients if the course of the disease exceeds more than 1 year.

BACKGROUND On March 11, 2020, the New Mexico (NM) Governor declared a Public Health Emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. The NM Medical Advisory Team (MAT) contacted faculty at the University of New Mexico (UNM) to form a team to assist in consolidating available information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 to facilitate NM’s pandemic management. In response, faculty, physicians, staff, graduate students, and medical students created the “UNM Global Health COVID-19 Intelligence Briefing.” OBJECTIVE Based on the growing number of daily scientific publications and news reports and the potential risk of community misinformation, we formed a team of academics to consolidate and disseminate relevant daily briefings with a goal of informing healthcare and public policy decisions for the state of NM. METHODS Microsoft Teams™ was used for manual and automated capture of COVID-19 articles (daily average=456), and composition of briefings. Articles were summarized according to relevant content and statistical findings. Multi-level triaging allowed for the most impactful articles to be reviewed and summarized with priority placed on randomized controlled studies, meta-analyses, systematic reviews, practice guidelines, and other topics informing on healthcare and policy response to COVID-19. Team members met virtually to edit the briefing on clarity and grammar, and to prioritize articles based on scientific merit. The finalized briefing was emailed to a LISTSERV® and posted on the UNM Digital Repository. An IRB-approved survey to assess the impact of the briefing was sent to readers. RESULTS The briefings reached approximately 1,000 people by email alone. This number was likely higher with direct subscribers forwarding to colleagues. Tracking showed 5,047 downloads across 116 countries as of July 5, 2020. The survey received 114 respondents consisting of physicians, academic faculty, administrators, government employees, students, and nurses. Respondent feedback showed 95% gained relevant knowledge of the pandemic, 79% believed it decreased misinformation, 24% used the briefing as their primary source of information, and 79% forwarded to colleagues. CONCLUSIONS Variability in subject matter expertise was addressed with training, standardized article selection criteria, and collaborative editing. The UNM Global Health COVID-19 Intelligence Briefing accomplished the goal of disseminating relevant COVID-19 information to help guide NM government policy and clinical practice. A secondary benefit included advancing medical student education.

Background Artificial intelligence (AI) has become a powerful tool and is attracting more attention in the field of medicine. There are a number of AI studies focusing on skin diseases, and there are many AI products that have been applied in dermatology. However, the attitudes of dermatologists, specifically those from China, towards AI, is not clear as few, if any studies have focused on this issue. Methods A web-based questionnaire was designed by experts from the Chinese Skin Image Database (CSID) and published on the UMER Doctor platform (an online learning platform for dermatologists developed by the Shanghai Wheat Color Intelligent Technology Company, China). A total of 1,228 Chinese dermatologists were recruited and provided answers to the questionnaire online. The differences of dermatologists' attitudes towards AI among the different groups (stratified by age, gender, hospital level, education degree, professional title, and hospital ownership) were compared by using the Mann-Whitney U test and the Kruskal-Wallis H test. The correlations between stratified factors and dermatologists’ attitudes towards AI were calculated by using the Spearman’s rank correlation test. SPSS (version 22.0) was utilized for all analyses. A two-sided P value <0.05 was considered statistically significant in all analyses. Results A total of 1,228 Chinese dermatologists from 30 provinces, autonomous regions, municipalities, and other regions (including Hong Kong, Macau, and Taiwan) participated in this survey. The dermatologists who participated acquired AI-related information mainly through the Internet, meetings or forums, and 70.51% of participated dermatologists acquired AI-related information by two or more approaches. In total, 99.51% of participated dermatologists pay attention (general, passive-active, and active attention) to information pertaining to AI. Stratified analyses revealed statistically significant differences in their attention levels (unconcerned, general, passive-active, and active attention) to AI-related information by gender, hospital level, education degree, and professional title (P values ≤1.79E−02). In total, 95.36% of the participated dermatologists thought the role of AI to be in “assisting the daily diagnosis and treatment activities for dermatologists”. Stratified analyses about the thought of AI roles (unconcerned, useless, assist, and replace) showed that there was no statistically significant difference except for the hospital level (P value =4.09E−03). The correlations between stratified factors with attention levels and the opinions of AI roles showed extremely weak correlations. Furthermore, 64.17% of participated dermatologists thought secondary hospitals in China are in most need of the application AI, and 91.78% of participated dermatologists thought the priority implementation of AI should be in skin tumors. Conclusions The majority of Chinese dermatologists are interested in AI information and acquired information about AI through a variety of approaches. Nearly all dermatologists are attentive to information on AI and think the role of AI is in “assisting the daily diagnosis and treatment activities for dermatologists”. Future AI implementation should be primarily focused on skin tumors and utilized in in secondary hospitals.

Kinesin-driven motility was shown to be adversely affected in a concentration dependent manner by the addition of osmolytes: glycerol, polyethylene glycol, and trimethylamine N-oxide.

Superficial skin erosion wounds are very common in the clinic, and conventional treatments are not always effective; thus, effective and novel therapy is needed. Cold atmospheric plasma (CAP) has been recognised as a promising approach to wound healing. The purpose of this study is to show the potential clinical application of CAP for the healing of different kinds of superficial skin wounds. Seven patients with different kinds of superficial skin wounds (two patients with pyoderma gangrenosum, two patients with trauma would, one patient with giant genital wart, one patient with diabetic foot, and one patient with chronic eczema) were recruited to this study. All patients accepted and received CAP treatment every other day till the wound healed. The expected results were complete wound healing after CAP treatment. All patients achieved complete wound healing after several rounds (range from two to eight) of CAP treatment, and there was no side effect observed. CAP may provide a new and effective choice to solve the problem of the healing of superficial wounds that are not only caused by trauma but also because of eczema. CAP has certain value in the treatment of superficial skin diseases in the future.

Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of DEFB4, IL22, and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset (≥40 years) Ps patients was significantly higher in type I than in types II and III (P = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P = 0.086). The CNVs of DEFB4 and LCE3C showed no significant differences but the CNV of IL22 significantly differed among the three subclassifications (P = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.

Table S2. Five hundred and eighty-eight CpGs significantly associated with age in PN. (XLSX 46Â kb)

Microtubule dynamics play a critical role in the normal physiology of eukaryotic cells as well as a number of cancers and neurodegenerative disorders. The polymerization/depolymerization of microtubules is regulated by a variety of stabilizing and destabilizing factors, including microtubule-associated proteins and therapeutic agents (e.g., paclitaxel, nocodazole). Here we describe the ability of the osmolytes polyethylene glycol (PEG) and trimethylamine- N-oxide (TMAO) to inhibit the depolymerization of individual microtubule filaments for extended periods of time (up to 30 days). We further show that PEG stabilizes microtubules against both temperature- and calcium-induced depolymerization. Our results collectively suggest that the observed inhibition may be related to combination of the kosmotropic behavior and excluded volume/osmotic pressure effects associated with PEG and TMAO. Taken together with prior studies, our data suggest that the physiochemical properties of the local environment can regulate microtubule depolymerization and may potentially play an important role in in vivo microtubule dynamics.

BACKGROUND:Psoriasis (Ps) is a common chronic inflammatory skin disease. The keratinocytes of psoriatic skin defy normal apoptosis and exhibit active cell proliferation. Aberrant DNA methylation (DNAm) has been suggested relevant through regulating the expression of Ps susceptibility genes. However, it is unclear whether the biological age inferred from DNA methylome is affected.RESULTS:To address the above issue, we applied a recently developed methylation clock model to our Chinese Han population dataset, which includes DNAm data of 114 involved psoriatic skin tissues (PP) and 41 uninvolved psoriatic skin tissues (PN) from Ps patients, and 62 normal skin tissues (NN) from health controls. We first confirmed the applicability of the clock in PN and NN. We then showed that PP samples have largely unchanged DNAm age, and that no association was observed between available clinical features and DNAm age acceleration. Examination of genome-wide CpGs yielded age-associated CpGs with concordant age-association coefficients among the three groups, which was also supported by an external dataset. We also interestingly observed two clock CpGs differentially methylated between PP and PN.CONCLUSIONS:Overall, our results suggest no significant alteration in DNAm age in PN and PP. Therefore, the increase in keratinocyte proliferation and alteration in DNAm caused by Ps may not affect the biological age of psoriatic skin tissue.

Table S5. Thirty nine CpGs that are both age-associated in PP and differently methylated between PP and PN. (XLSX 10Â kb)

Microtubule filaments are one the fundamental structural components of the cytoskeleton in eukaryotic cells. They play an important role in many cellular functions, including cellular division, intracellular transport, and motility. Microtubules have been a prime target of anti-cancer drugs because of their essential role in mitosis. From a broader perspective, microtubules are complex biopolymers that displays dynamic instability, in which the microtubules stochastically switch between states of polymerization (growth) and depolymerization (shrinkage). The process of depolymerization is believed to be induced by conformational changes to the tubulin dimers that create mechanical strain within the microtubule lattice. We investigate how macromolecular crowding contributes to the regulation of depolymerization in microtubules through osmotic pressure. The addition of polyethylene glycol (PEG) in vitro mimics the macromolecular crowding that occurs in cells. In addition to increasing the growth rate of microtubules and promoting the formation of microtubule bundles, we find that PEG also stabilizes microtubules against depolymerization in the absence of any other stabilizer; this stabilization effect lasts for more than 30 days. We further show that PEG-related molecular crowding stabilizes microtubules even in antagonistic environments of extreme temperatures (i.e. <15°C) and destabilizing chemical agents (calcium). Collectively, these data provide critical insights towards understanding microtubule dynamics, specifically the role of mechanical strain in the catastrophic depolymerization of microtubules. Further, as the osmotic pressure in vivo is higher than in typical in vitro experiments, these results are salient for translating between microtubule stability experiments in vitro and in vivo and studying proteins and drugs that interact with microtubules. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc. for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525.