Epidemiology of Geriatric-Dermatology virtual clinic: Teledermatology-Based care for elderly patients with skin diseases in Qatar.

Background: The 'GeriDerm' (geriatric dermatology) clinic, is a new dermatology-based service at Hamad Medical Corporation (HMC), accommodating the needs of our elderly population living in the State of Qatar. Due to the global demographic transition towards an elderly population (≥65 years of age), incidences of chronic diseases, including dermatologic conditions, rise in parallel. Patients of older age are at higher risk of using multiple medications, seeing multiple care providers, often receiving multiple diverging pieces of information, and feeling lost within the system. Taking into consideration the elderly unique characteristics, the Geriatric Dermatology telemedicine clinic is a novel approach to meeting the many challenges our elderly patients face via providing quick, accurate assessments of cognition, functional status, frailty screening, and assessment for polypharmacy. Methods: Data of 1080 elderly patients with various skin disorders from June 2020 to July 2021 was received from the Dermatology Geriatric clinic, and then reviewed. Results: There were 521(48.2%) new cases and 559(51.8%) follow-up cases who attended the clinic either virtually or face to face consultation. A total of 587(54.4%) female and 493(45.6%) male elderly patients attended the clinic. The mean age was 74.6, with a minimum age of 60 and a maximum age of 106 years. 57.9%(625) of GeriDerm patients were Qatari, followed by Palestinian 75(6.9%), Syrian 51(4.7%), Egyptian 46(4.3%), and Indian 44(4.1%); while other nationalities constituted 239(22.1%). The majority of the cases were Contact Dermatitis 146(13%), Bullous Pemphigoid 107 (10%), and Pruritis 101(9.4%). Conclusion: The 'GeriDerm' service at HMC aimed to achieve the best healthcare standards for the elderly population of Qatar during COVID-19 pandemic, and is now established as a continuous advanced technology-based framework facilitating caring for older patients with skin disease via providing a clear pathway for adequate triaging, identification of severe conditions (red flag) requiring in-person clinic visits, while managing non-life threatening dermatoses via a teledermatology based approach.

Macropinocytosis dependent entry of Chikungunya virus into human muscle cells.

Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity. CHIKV is now considered endemic in many countries across Asia and Africa. In this study, the susceptibility of various human, mammalian and mosquito cell lines to CHIKV infection was evaluated. CHIKV infection was found to be cell-type dependent and virus strain-specific. Furthermore, SJCRH30 (human rhabdomyosarcoma cell line) was showed to be highly permissive to CHIKV infection, with maximum production of infectious virions observed at 12 h.p.i. Pre-infection treatment of SJCRH30 with various inhibitors of endocytosis, including monodansylcadaverine (receptor-mediated endocytic inhibitor), dynasore (clathrin-mediated endocytic inhibitor), as well as filipin (caveolin-mediated endocytosis inhibitor), resulted in minimal inhibition of CHIKV infection. In contrast, dose-dependent inhibition of CHIKV infection was observed with the treatment of macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Furthermore, siRNA-mediated knockdown of sortin nexin 9 (SNX9) a protein involved in macropinosome formation, also resulted in a significant dose-dependent reduction in viral titre. By performing a virus entry assay, CHIKV particles were also observed to colocalize with FITC-dextran, a macropinosome marker. This study shows for the first time, that the infectious entry of CHIKV into human muscle cells is mediated by macropinocytosis. Together, the data from this study may pave the way for the development of specific inhibitors that target the entry process of CHIKV into cells.

Fatal metastatic cutaneous squamous cell carcinoma evolving from a localized verrucous epidermal nevus.

A malignant transformation is known to occur in many nevi such as a sebaceous nevus or a basal cell nevus, but a verrucous epidermal nevus has only rarely been associated with neoplastic changes. Keratoacanthoma, multifocal papillary apocrine adenoma, multiple malignant eccrine poroma, basal cell carcinoma and cutaneous squamous cell carcinoma (CSCC) have all been reported to develop from a verrucous epidermal nevus. CSCC has also been reported to arise from other nevoid lesions like a nevus comedonicus, porokeratosis, a sebaceous nevus, an oral sponge nevus and an ichthyosiform nevus with CHILD syndrome. Here we report a case of progressive poorly differentiated CSCC arising from a localized verrucous epidermal nevus, which caused both spinal cord and brain metastasis.

The essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71.

Little is currently known about the infectious entry process of human enterovirus 71 (HEV71) into host cells, which may represent potential anti-viral targeting sites. In this study a targeted small-interfering RNA (siRNA) screening platform assay was established and validated to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics, and endosomal trafficking essential for HEV71 infection. Screen evaluation was conducted via the expression of well characterized dominant-negative mutants, bioimaging studies (double-labeled immunofluorescence assays, transmission electron microscopy analysis), secondary siRNA-based dosage dependence studies, and drug inhibition assays. The infectious entry of HEV71 into rhabdomyosarcoma cells was shown to be significantly inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis (CME) that include AP2A1, ARRB1, CLTC, CLTCL1, SYNJ1, ARPC5, PAK1, ROCK1, and WASF1. The functional role of CME was verified by the observation of strong co-localization between HEV71 particles and clathrin as well as dose-dependent inhibition of HEV71 infection upon siRNA knockdown of CME-associated genes. HEV71 entry by CME was further confirmed via inhibition by dominant-negative EPS15 mutants and treatment of CME drug inhibitors, with more than 80% inhibition observed at 20 µm chlorpromazine. Furthermore, HEV71 infection was shown to be sensitive to the disruption of human genes in regulating early to late endosomal trafficking as well as endosomal acidic pH. The identification of clathrin-mediated endocytosis as the entry pathway for HEV71 infection of susceptible host cells contributes to a better understanding of HEV71 pathogenesis and enables future development of anti-viral strategies against HEV71 infection.