The histone methyltransferase SETD2 regulates HIV expression and latency.

Understanding the mechanisms that drive HIV expression and latency is a key goal for achieving an HIV cure. Here we investigate the role of the SETD2 histone methyltransferase, which deposits H3K36 trimethylation (H3K36me3), in HIV infection. We show that prevention of H3K36me3 by a potent and selective inhibitor of SETD2 (EPZ-719) leads to reduced post-integration viral gene expression and accelerated emergence of latently infected cells. CRISPR/Cas9-mediated knockout of SETD2 in primary CD4 T cells confirmed the role of SETD2 in HIV expression. Transcriptomic profiling of EPZ-719-exposed HIV-infected cells identified numerous pathways impacted by EPZ-719. Notably, depletion of H3K36me3 prior to infection did not prevent HIV integration but resulted in a shift of integration sites from highly transcribed genes to quiescent chromatin regions and to polycomb repressed regions. We also observed that SETD2 inhibition did not apparently affect HIV RNA levels, indicating a post-transcriptional mechanism affecting HIV expression. Viral RNA splicing was modestly reduced in the presence of EPZ-719. Intriguingly, EPZ-719 exposure enhanced responsiveness of latent HIV to the HDAC inhibitor vorinostat, suggesting that H3K36me3 can contribute to a repressive chromatin state at the HIV locus. These results identify SETD2 and H3K36me3 as novel regulators of HIV integration, expression and latency.

Water Quenched and Acceptor-Doped Textured Piezoelectric Ceramics for Off-Resonance and On-Resonance Devices.

Piezoelectric materials should simultaneously possess the soft properties (high piezoelectric coefficient, d33 ; high voltage coefficient, g33 ; high electromechanical coupling factor, k) and hard properties (high mechanical quality factor, Qm ; low dielectric loss, tan δ) along with wide operation temperature (e.g., high rhombohedral-tetragonal phase transition temperature Tr-t ) for covering off-resonance (figure of merit (FOM), d33  × g33 ) and on-resonance (FOM, Qm  × k2 ) applications. However, achieving hard and soft piezoelectric properties simultaneously along with high transition temperature is quite challenging since these properties are inversely related to each other. Here, through a synergistic design strategy of combining composition/phase selection, crystallographic texturing, defect engineering, and water quenching technique, <001> textured 2 mol% MnO2 doped 0.19PIN-0.445PSN-0.365PT ceramics exhibiting giant FOM values of Qm  × k 31 2 $k_{31}^2$ (227-261) along with high d33  × g33 (28-35 × 10-12 m2 N-1 ), low tan δ (0.3-0.39%) and high Tr-t of 140-190 °C, which is far beyond the performance of the state-of-the-art piezoelectric materials, are fabricated. Further, a novel water quenching (WQ) room temperature poling technique, which results in enhanced piezoelectricity of textured MnO2 doped PIN-PSN-PT ceramics, is reported. Based upon the experiments and phase-field modeling, the enhanced piezoelectricity is explained in terms of the quenching-induced rhombohedral phase formation. These findings will have tremendous impact on development of high performance off-resonance and on-resonance piezoelectric devices with high stability.

Growth Kinetics and Atomistic Mechanisms of Native Oxidation of ZrSxSe2-x and MoS2 Crystals.

A thorough understanding of native oxides is essential for designing semiconductor devices. Here, we report a study of the rate and mechanisms of spontaneous oxidation of bulk single crystals of ZrSxSe2-x alloys and MoS2. ZrSxSe2-x alloys oxidize rapidly, and the oxidation rate increases with Se content. Oxidation of basal surfaces is initiated by favorable O2 adsorption and proceeds by a mechanism of Zr-O bond switching, that collapses the van der Waals gaps, and is facilitated by progressive redox transitions of the chalcogen. The rate-limiting process is the formation and out-diffusion of SO2. In contrast, MoS2 basal surfaces are stable due to unfavorable oxygen adsorption. Our results provide insight and quantitative guidance for designing and processing semiconductor devices based on ZrSxSe2-x and MoS2 and identify the atomistic-scale mechanisms of bonding and phase transformations in layered materials with competing anions.

Evidence-based best practice advice for patients treated with systemic immunosuppressants in relation to COVID-19.

The emergence of the COVID-19 pandemic has led to significant uncertainty among physicians and patients about the safety of immunosuppressive medications used for the management of dermatologic conditions. We review available data on commonly used immunosuppressants and their effect on viral infections beyond COVID-19. Notably, the effect of some immunosuppressants on viruses related to SARS-CoV2, including SARS and MERS, has been previously investigated. In the absence of data on the effect of immunosuppressants on COVID-19, these data could be used to make clinical decisions on initiation and continuation of immunosuppressive medications during this pandemic. In summary, we recommend considering the discontinuation of oral Janus kinase (JAK) inhibitors and prednisone; considering the delay of rituximab infusion; and suggesting the careful continuation of cyclosporine, mycophenolate, azathioprine, methotrexate, and biologics in patients currently benefitting from such treatments.

The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond.

Caveolae are flask-shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin-1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age-related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology.

Denial of Illness in a Patient with Infiltrative Basal Cell Carcinoma.

A 73-year-old Caucasian man presented with a pink, pearly papule anterior to his right ear. He was a well-educated, retired stockbroker. Biopsy revealed an infiltrating basal cell carcinoma (BCC). The dermatologist repeatedly attempted to contact the patient encouraging treatment. After ignoring calls and letters, he was lost to contact with dermatology for 10 years. In the interim, the patient presented to the emergency room after discovering maggots in his ear. He subsequently consulted a head and neck surgeon but refused the recommended surgical excision. Although still operable, by this time the patient had developed significant erosion (Figure 1), nerve damage with loss of taste, facial muscle control, and hearing loss. One year after surgical consultation, he returned to dermatology due to ear discharge and pain while chewing. Multiple clinicians urged him to reconsider surgery. The patient stated that he had avoided treatment for the previous 10 years, because he had felt "stronger than the cancer." He had been convinced that cancer "can't hurt me." Despite this, he conceded that denying treatments earlier was "probably the worst decision of my life." By then the cancer was inoperable and required chemotherapy. The patient again refused treatment and later expired.

Cervical lymphadenopathy from PRP treatment with microneedling therapy.

BACKGROUND: Platelet-rich plasma is highly enriched plasma that contains a large concentration of platelets that secrete various growth factors and is used in a wide variety of surgical and cosmetic procedures, including hair regrowth and skin rejuvenation. METHODS: Microneedling therapy is being combined with platelet-rich plasma to potentiate patient's cosmetic effects. While microneedling therapy and platelet-rich plasma therapy have been around for years and are growing in popularity internationally, there are limited data regarding complications when they are used in conjunction. RESULTS: We present a case in which a patient presented with acute, painful lymphadenopathy shortly after undergoing the combination treatment of a microneedling pen with platelet-rich plasma therapy. CONCLUSION: Individuals should know of the potential adverse effect of microneedling pen therapy used in conjunction with platelet-rich plasma therapy, and it should be included in patient consent forms and doctor-patient education.

Patients' prediction of their wound healing time.

Understanding and managing patients' expectations can help improve their adherence to treatment for chronic wounds; however, little is known concerning about their expectations regarding healing time. Recruited subjects were asked to predict how long their wounds would take to heal and their charts were reviewed to retrieve real time of healing. We recruited 100 subjects from which 77% have healed. Fifty-three subjects (68.8%) had a longer healing time than they predicted (underestimated), and 17 (22.1%) had a shorter healing time than they predicted (overestimated). Subjects with shorter wound duration history tended to predict shorter healing time than subjects with longer wound duration (p < 0.01). However, wound duration did not affect prediction accuracy (p = 0.65). Subjects with chronic wounds seem more often to underestimate their time of healing. Wound duration significantly influenced patients' prediction time, although it did not make their prediction more accurate. Patient education about expectations may be important as patients often expect their wounds to heal faster than they actually do.

Widespread Skin Necrosis Secondary to Gemcitabine Therapy.

Gemcitabine, a pyrimidine nucleoside analogue, is an oncologic agent used in the treatment of cutaneous T-cell lymphoma (CTCL). Common dermatologic reactions associated with gemcitabine include alopecia, mild skin rash, and mucositis but skin necrosis is exceptional. Herein we present an unusual case of widespread skin necrosis mimicking toxic epidermal necrolysis in a 45-year-old woman receiving gemcitabine therapy for stage IIIA cutaneous T-cell lymphoma. This is the first reported case of a TEN-like reaction subsequent to gemcitabine treatment. J Drugs Dermatol. 2018;17(5):582-585.

Development of a Flipped Medical School Dermatology Module.

OBJECTIVES: The flipped classroom module incorporates independent study in advance of in-class instructional sessions. It is unproven whether this methodology is effective within a medical school second-year organ system module. We report the development, implementation, and effectiveness of the flipped classroom methodology in a second-year medical student dermatology module at the University of Miami Leonard M. Miller School of Medicine. METHODS: In a retrospective cohort analysis, we compared attitudinal survey data and mean scores for a 50-item multiple-choice final examination of the second-year medical students who participated in this 1-week flipped course with those of the previous year's traditional, lecture-based course. RESULTS: Each group comprised nearly 200 students. Students' age, sex, Medical College Admission Test scores, and undergraduate grade point averages were comparable between the flipped and traditional classroom students. The flipped module students' mean final examination score of 92.71% ± 5.03% was greater than that of the traditional module students' 90.92% ± 5.51% (P < 0.001) score. Three of the five most commonly missed questions were identical between the two cohorts. The majority of students preferred the flipped methodology to attending live lectures or watching previously recorded lectures. CONCLUSIONS: The flipped classroom can be an effective instructional methodology for a medical school second-year organ system module.

Primary Cribriform Carcinoma of the Eyelid With Neuroendocrine Features: A Case Report.

A variety of tumors may involve the eyelid, most of which are primary, but rarely can be metastatic. Previously reported eyelid primary carcinomas with neuroendocrine features include Merkel cell carcinoma, apocrine and eccrine gland carcinoma, sebaceous gland carcinoma, and one report of primary "well-differentiated neuroendocrine tumor." Herein we report the first case of primary cribriform carcinoma of the eyelid with neuroendocrine features. The patient is a 75-year-old black man who presented to the clinic with a 5-year history of a slowly growing, non-painful, non-exudative lesion of his left lower eyelid. Examination disclosed a non-tender 8 mm by 9 mm ovoid, firm, euchromic subdermal non-adherent nodule involving the left lower eyelid with no madarosis or loss of lid margin architecture, but with overlying induration. An incisional biopsy demonstrated nodules and aggregates of tumor composed of cuboidal hyperchromatic basoloid cells with occasional mitotic figures within sheets in a mostly cribriform and occasionally papillary pattern. The tumor was diffusely positive for cytokeratin, Epithelial Membrane Antigen, and p40 and focally positive for synaptophysin. The tumor was negative with antibodies for Cytokeratin 20 (CK20), p63, CD10, Thyroid Transcription Factor-1, Cytokeratin 7, Prostate Specific Antigen, and Epithelial Specific Antigen. Oncologic evaluation was negative for metastases. The patient underwent a complete excision of his eyelid tumor with 5 mm margins using Mohs surgery, with subsequent reconstruction using a Hughes tarsoconjunctival flap, myocutaneous advancement flap, and lateral canthal tendon plication.

J Drugs Dermatol. 2017;16(2):173-174.

Transsacral-Transiliac Screw Stabilization: Effective for Recalcitrant Pain Due to Sacral Insufficiency Fracture.

OBJECTIVES: To evaluate the effectiveness of transsacral-transiliac screw fixation for the treatment of sacral insufficiency fractures that fail nonoperative treatment. DESIGN: A pilot study series of consecutive patients identified over 5 years were treated and followed prospectively. SETTING: Academic-affiliated, tertiary referral, level 1 trauma center in Dallas, TX. PATIENTS/PARTICIPANTS: Patients were selected on the basis of presenting diagnosis, and failure of nonoperative treatment of their sacral insufficiency fracture. Eleven patients entered to the study, and 10 completed follow-up. INTERVENTION: Placement of transsacral-transiliac screws for sacral insufficiency fracture. MAIN OUTCOME MEASUREMENTS: Comparison of preoperative and postoperative Visual Analog Scale scores and Oswestry Low Back Disability Index scores. RESULTS: Patients experienced statistically significant improvement in both outcome measures after intervention. No complications encountered. CONCLUSIONS: Transsacral-transiliac screw fixation seems to be a safe and effective treatment for sacral insufficiency fractures recalcitrant to nonoperative management. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A Review of Cellular and Acellular Matrix Products: Indications, Techniques, and Outcomes.

BACKGROUND: Wound healing is a dynamic process whereby cells, growth factors (GFs), and the extracellular matrix (ECM) interact to restore the architecture of damaged tissue. Chronic wounds can be difficult to treat due to the increased presence of inflammatory cells that degrade the ECM, GF, and cells necessary for wound healing to occur. Cellular and acellular matrix products can be used in the management of a variety of chronic wounds including venous, diabetic, and pressure ulcers and other conditions such as burns, epidermolysis bullosa, pyoderma gangrenosum, and surgical wounds. These matrices provide cells, GF, and other key elements that act as a scaffold and promote reepithelialization and revascularization of the wound bed. METHODS: This article focuses on cellular and acellular matrix products that have been well-studied clinically with positive results in randomized clinical trials and widely available matrices for chronic nonhealing wounds. We present trial results as well as their indications, techniques, and outcomes. RESULTS: There are a variety of matrix products available on the market. Some of these products are used to treat chronic wounds, for example, diabetic foot ulcers, venous leg ulcers, pyoderma gangrenosum, and pressure ulcers. In this review, we found that wounds of different etiologies have been treated with a variety of matrices, with successful outcomes compared with standard wound care. CONCLUSIONS: Both cellular and acellular matrix products are useful in the management of a variety of chronic wounds. These matrices provide cells, GF, and other key elements that promote reepithelialization and revascularization of the wound bed while preventing degradation of the ECM. The treatment of chronic wounds with matrix products in combination with standard wound care has been proven to aid in wound healing when added to standard of care.

Patient Preference in Dermatologist Attire in the Medical, Surgical, and Wound Care Settings.

IMPORTANCE: Patients' perceptions of their physician can affect subjective and objective outcomes. Physician attire influences patients' perceptions of their physician and consequently may affect patient outcomes. OBJECTIVE: To determine patient preferences for different types of dermatologist attire in dermatology medical, surgical, and wound care clinics. We hypothesized that patients in the dermatology medical setting would prefer professional attire, while patients in the dermatology surgical and wound care setting would prefer surgical scrubs. DESIGN, SETTING, AND PARTICIPANTS: This study analyzed responses to a cross-sectional, anonymous survey by English-speaking dermatology patients (aged 18 years or older) at general, surgical, and wound care clinics in an academic center in Miami, Florida. Patients who could not read and understand the survey were excluded. Participants received pictures of a physician wearing business attire, professional attire, surgical attire, and casual attire, and responded by indicating which physician they preferred for each of 19 questions. Frequencies of responses were recorded, and χ2 and regression tests were performed. MAIN OUTCOMES AND MEASURES: Response frequencies. RESULTS: Surveys were administered to 261 persons, and 255 participated and completed enough of the questions to be included in the outcome analyses (118 men, 121 women, 22 unknown [did not answer sex question]), mean (SD) age, 56.3 (18.6) years; about 49% of those who reported their sex were men; 56% were Hispanic; and 85% were white. Approximately 72% of respondents held a college degree or higher. About 63%, 24%, and 13% of respondents were medical, surgical, and wound care dermatology patients, respectively. Roughly 73%, 19%, 6%, and 2% of cumulative responses were for professional, surgical, business, and casual attire, respectively. Respondents who received a picture of a black male or black female physician were more likely to exclusively prefer professional attire: unadjusted odds ratios (ORs) 3.21 (95% CI, 1.39-7.42) and 2.78 (95% CI, 1.18-6.51), respectively, compared with respondents who received a picture of a white male physician. Nonwhite and unemployed respondents were less likely to prefer professional attire exclusively: ORs, 0.28 (95% CI, 0.1-0.83) and 0.28 (95% CI, 0.08-0.99), respectively. Respondents preferred professional attire in all clinic settings, though respondents in the dermatology surgery clinic were less likely to prefer professional attire compared with respondents in the medical dermatology clinic: race-adjusted OR, 0.74 (95% CI, 0.56-0.98). Wound care and medical dermatology respondents preferred professional attire comparably. CONCLUSIONS AND RELEVANCE: In this study, most patients preferred professional attire for their dermatologists in most settings. It is possible that patients' perceptions of their physicians' knowledge and skill is influenced by the physicians' appearance, and these perceptions may affect outcomes.