Calosides A-F, Cardenolides from Calotropis gigantea and Their Cytotoxic Activity.

Phytochemical analysis of the roots of Calotropis gigantea led to the isolation of six new cardenolide glycosides, calosides A-F (1-6), and five known cardenolides (7-11). The structures of 1-6 were elucidated based on NMR and ECD spectroscopic data interpretation. Caloside D (4) is the first naturally occurring example of a cardenolide containing a C-8/C-19 oxygen bridge. In turn, calosides E (5) and F (6) represent the first naturally occurring 3-epi-cannogenol diglycosides having potent cytotoxicity against the PANC-1 cell line (IC50, 0.081 and 0.070 µM, respectively) and HeLa (IC50, both 0.17 µM) cells, under normoglycemic conditions.

Retiform Purpura as a Sign of Necrotizing Cellulitis in an Immunocompetent Boy.

Severe group A streptococcus (GAS) infections, particularly necrotizing soft tissue infections (NSTIs), have been associated with the development of streptococcal toxic-shock syndrome (STSS), a systemic illness caused by GAS-derived toxins. Traditional physical examination findings in NSTIs include skin necrosis, crepitus, and hemorrhagic bullae. However, these findings are limited in sensitivity and additional clinical markers may aid in making an early diagnosis of NSTI. We present a case of a superficial infection, specifically GAS necrotizing cellulitis, complicated by STSS in a healthy boy with an associated skin finding of retiform purpura that aided in early diagnosis of a NSTI.

Violaceous nodules in an HIV-positive man.

Plasmablastic lymphoma (PBL) is a rare and aggressive malignancy associated with immunosuppression and the oncogenic effects of the Epstein-Barr virus (EBV). We present an HIV-positive man with PBL that presented as ulcers and violaceous exophytic nodules on the legs. The clinical features, histologic appearance, and differential diagnosis of this malignancy are briefly reviewed.

Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea.

A new lignan, 9'-methoxypinoresinol (1), and two new glycosylated 5-hydroxymethylfurfurals, calofurfuralside A (2), and calofurfuralside B (3), together with nine known compounds (4-12) have been isolated from the active fractions, CHCl3 (IC50, 0.32µgmL-1) and EtOAc (IC50, 0.55µgmL-1) fractions of the leaves of Calotropis gigantea. Their structures were elucidated based on NMR and MS data. Among the isolated compounds, compounds 1 and 9 exhibited potent cytotoxicity against PANC-1 human pancreatic cancer cell line under the normoglycemic condition with IC50 values of 3.7 and 3.3µM, respectively. 9'-Methoxypinoresinol (1) significantly inhibited the colony formation of PANC-1 cells in a concentration-dependent manner.

Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses.

BACKGROUND: Human polyomavirus (HPyV)6 and HPyV7 are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. OBJECTIVE: We determined whether biopsy specimens showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. METHODS: We screened biopsy specimens showing "peacock plumage" histology by polymerase chain reaction for HPyVs. Cases positive for HPyV6 or HPyV7 were then analyzed by immunohistochemistry, electron microscopy, immunofluorescence, quantitative polymerase chain reaction, and complete sequencing, including unbiased, next-generation sequencing. RESULTS: We identified 3 additional cases of HPyV6 or HPyV7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared with normal-appearing skin and the identification of intact virions by both electron microscopy and next-generation sequencing support a role for active viral infections in these skin diseases. LIMITATION: This was a small case series of archived materials. CONCLUSION: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a distinctive histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses."

Evaluation of sun-protective behaviors in transplant clinic patients: a longitudinal analysis.

Organ transplant recipients (OTRs) are at a significantly elevated risk for developing cutaneous malignancies. In recent years, the advent of dermatology clinics dedicated to this specific patient population has aimed to provide increased access and specialized care, including important sun-protective behavior education. It has been shown that OTRs tend to have poor sun-protective practices, and care at these specialized dermatology clinics has facilitated an improvement in sun-protective behavior. Previously, sun-protective behavior of patients within these specialized clinics has been characterized longitudinally, though only for a short duration of 3 months. We retrospectively analyzed a cohort of 230 OTRs seen at a single academic institution's transplant clinic between 2016-2020 and sought to characterize sun-protective behavior at baseline and longitudinally. 78 patients returned for at least one follow-up visit, and the median follow-up duration was 15.1 months (IQR 8.4-24.3 months). Sun-protective behavior was quantified using the average score of questions addressing sunscreen usage frequency, consistency, circumstance of application, reapplication, and sun avoidance. We utilized paired Wilcoxon signed-rank tests to analyze changes in sun-protective behavior between initial visits and subsequent follow-up visits. Sun-protective behavior was increased at the first follow-up visit (median change in sun-protective score - 0.04, p = 0.017) and second follow-up visit (median change in sun-protective score - 0.25, p = 0.026) compared to the initial visit. Multivariable logistic regression and mixed effects modeling were employed to quantify patient features associated with increased sun-protective behavior. Female sex [OR 3.79, 95% CI (1.83, 8.04)] and personal history of skin cancer [OR 3.06, 95% CI (1.25, 7.76)] were associated with stronger sun-protective behaviors at baseline. Female sex [OR 13.77, 95% CI (2.44, 77.52)] was the only characteristic associated with increased sun-protective behavior over time. Our findings identify patient characteristics that are associated with increased sun-protective behavior after education in a dermatology clinic dedicated to OTRs.

Utilization of teledermatology services for dermatological diagnoses during the COVID-19 pandemic.

Little is known about trends in teledermatology adoption and use for managing dermatologic patients, especially changes in use influenced by the COVID-19 pandemic. In this retrospective cohort study, we analyzed encounter data from the Healthjump dataset (containing electronic health record data from throughout the USA) for visits from November 2019 to July 2021 with a primary dermatology-related diagnosis. There was a striking rise in teledermatology use with the onset of the pandemic in February 2020, peaking in April 2020 with 2178 teledermatology encounters (32.8% of all encounters). Subsequently, teledermatology use waned. Most teledermatology care was delivered via synchronous means with little use of asynchronous or telephone communication. When compared to those with neoplastic skin diseases, patients with inflammatory skin diseases were more likely to be seen via teledermatology (OR 3.30, 95% CI 3.12-3.49). Certain demographic groups were less likely to receive care via teledermatology, such as men (compared with females, OR 0.76, 95% CI 0.74-0.78) and patients 65 and older (compared with those below 65, OR 0.59, 95% CI 0.57-0.62). Our work shows increased adoption of teledermatology at the onset of the COVID-19 pandemic with decreasing use over time. Future efforts are needed to ensure continued and expanded use of a valuable care modality to reach vulnerable populations.

Changes in Use of Radiotherapy Among Dermatologists From 2013 to 2017.

Importance: Concerns have been raised about the use of radiotherapy (RT) by dermatologists. Little is known about temporal trends in payment for RT among dermatologists. Objective: To characterize changes in RT use and payment among dermatologists treating patients enrolled in Medicare. Design, Setting, and Participants: A cross-sectional, population-based retrospective analysis of dermatologists submitting Medicare claims was conducted. Dermatologists identified in the 2013-2017 Medicare Physician and Other Supplier Public Use File, which includes information on fee-for-service payments and service use among physicians caring for Medicare beneficiaries, were included in the analysis. The study was conducted from March 18 to October 22, 2020. Main Outcomes and Measures: Numbers and types of RT, current terminology codes billed by dermatologists, number of dermatologists providing RT services, total payments and median payments per dermatologist for RT services, total services and median services per dermatologist, and number of dermatologists billing for both RT and Mohs micrographic surgery services. Results: From 2013 to 2017, dermatologists billed RT codes, which included RT planning, preparation, delivery, and management services with varying levels of complexity. The number of dermatologists using RT increased from 115 to 198 between 2013 to 2017. Total payments and total services for RT have fluctuated over time. Median payments per dermatologist and median services provided per dermatologist for RT reached their highest level in 2017 ($80 810 and 629 services). In 2013, RT delivery was the highest reimbursed RT service type (total paid, $9 121 505). By 2017, clinical treatment planning and simulation was the highest reimbursed service type (total paid, $20 288 796). Conclusions and Relevance: The findings of this cross-sectional study indicate that dermatologist use of RT continues to increase. A wide variety of RT services are billed by dermatologists. Further research is needed to ensure expanded use is safe, efficacious, and cost-effective.

A new cytotoxic cardenolide from the roots of Calotropis gigantea.

Bioactivity-guided isolation of the CHCl3-soluble fraction of the roots of Calotropis gigantea was carried out to obtain a new cardenolide glycoside, caloside G. Its absolute structure was elucidated based on NMR and ECD spectroscopic data interpretation. Caloside G showed noteworthy cytotoxicity against the PANC-1 human pancreatic and HeLa human cervical carcinoma cell lines, with the submicromolar IC50 values of 0.038 and 0.09 µM, respectively.

The Biology and Clinical Features of Cutaneous Polyomaviruses.

Human polyomaviruses are double-stand DNA viruses with a conserved genomic structure, yet they present with diverse tissue tropisms and disease presentations. Merkel cell polyomavirus, trichodysplasia spinulosa polyomavirus, human polyomavirus 6 and 7, and Malawi polyomavirus are shed from the skin, and Merkel cell polyomavirus, trichodysplasia spinulosa polyomavirus, human polyomavirus 6 and 7 have been linked to specific skin diseases. We present an update on the genomic and clinical features of these cutaneous polyomaviruses.

Invasive cutaneous squamous cell carcinoma incidence in US health care workers.

Little data on cutaneous squamous cell carcinoma (SCC) epidemiology within the United States are currently available. Prior studies have focused on populations outside of the United States or been limited to regions within the US. In this study, prospective data were collected via biennial questionnaires from a total of 261,609 participants, which included women in the Nurses' Health Study (NHS, 1976-2008) and Nurses' Health Study II (NHS II, 1989-2009), and men in the Health Professionals Follow-Up Study (HPFS, 1986-2008). History of physician-diagnosed invasive SCC was confirmed by pathology record review. Over the entire follow-up period for each cohort, there were 1,265 invasive SCC cases per 100,000 persons in the NHS cohort, 389 cases per 100,000 persons in NHS II, and 2,154 cases per 100,000 persons in HPFS. An 18-year follow-up of participants in these cohorts revealed increasing invasive SCC incidence rates over time, with rates for men being consistently higher than those for women. In women, a larger proportion of invasive SCC lesions occurred on the lower extremities as compared to men (21 % in NHS vs. 6 % in HPFS, p < 0.0001; 14 % in NHS II vs. 6 % in HPFS, p < 0.0001), while in men, a larger proportion occurred on the head/neck (43 % in NHS vs. 60 % in HPFS, p < 0.0001; 48 % in NHS II vs. 60 % in HPFS, p < 0.0001). In summary, invasive SCC incidence rates among US men have been greater than those for women with distinct sites of common occurrence between men and women.

Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation.

Pluripotent embryonic stem cells have a shortened cell cycle that enables their rapid proliferation. The embryonic stem cell-specific miR-290 and miR-302 microRNA families promote proliferation whereas let-7 microRNAs inhibit self-renewal, and promote cell differentiation. Lin28 suppresses let-7 expression in embryonic stem cells. Here to gain further insight into mechanisms controlling embryonic stem cell self-renewal, we explore the molecular and cellular role of the let-7 target Trim71 (mLin41). We show that Trim71 associates with Argonaute2 and microRNAs, and represses expression of Cdkn1a, a cyclin-dependent kinase inhibitor that negatively regulates the G1-S transition. We identify protein domains required for Trim71 association with Argonaute2, localization to P-bodies, and for repression of reporter messenger RNAs. Trim71 knockdown prolongs the G1 phase of the cell cycle and slows embryonic stem cell proliferation, a phenotype that was rescued by depletion of Cdkn1a. Thus, we demonstrate that Trim71 is a factor that facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal.