73 research outputs found
Trichoscopy for the Hair Transplant Surgeon—Assessing for Mimickers of Androgenetic Alopecia and Preoperative Evaluation of Donor Site Area
No full textPreoperative diagnostic confidence and donor site assessment are important for all hair transplant surgery patients. While the majority of patients seek hair transplantation for male or female pattern hair loss (androgenetic alopecia [AGA]), there are mimickers that must be differentiated from patterned hair loss, as they alter the candidacy of the patient for transplantation. They are termed mimickers as they also can present with patterned hair loss. The use of trichoscopy has become increasingly popular for such use. Patterned hair loss mimickers, which include the underappreciated alopecia areata incognita (AAI) and fibrosing alopecia in patterned distribution (FAPD), can be identified clinically with key trichoscopic findings such as yellow dots and peripilar casts, respectively, that correlate with their histologic diagnosis. Donor hair density and putative hair pathology of the safe donor area can also by assessed via trichoscopy. This article discusses the use of trichoscopy, particularly for diagnosing mimickers of patterned hair loss as well as preoperative donor site assessment
DEVELOPMENT OF NOVEL COMPUTATIONAL METHODS FOR DRUG DISCOVERY AND REPURPOSING IN ONCOLOGIC DISEASES AND OTHER ILLNESSES
No full textPh.D.Targeting disease-related proteins is important for drug discovery, yet target-based method have not been fruitful. Bottlenecks involve: (1) establishing biologically valid drug- protein target associations, and (2) assessing the physiologic effects of those interactions at the systems level. Here we develop novel computational methods for overcoming these challenges. For the accurate prediction of drug-target interactions, we investigate the ability of two independent proteochemometric methods entitled R-TMFS and ES-Screen to prioritize known drug binders over decoys for diverse sets of protein targets. R-TMFS is a docking-based method that incorporates molecule shape and physicochemical properties, whereas ES-Screen is an electrostatics-driven method that accentuates the role of electrostatics in biomolecular recognition and binding kinetics. R-TMFS and ES-Screen are also used to predict previously un-reported kinase targets for the anti-hookworm medication mebendazole. Follow-up in vitro binding assays confirm mebendazole inhibition of multiple kinases such as ABL1, JAK2, JNK3, and RAF1, attesting to the repurposing potential of mebendazole for various cancers. For higher-order physiologic contextualization of drug-target signatures, we devised a computational platform named NET-TMFS that annotates drugs with biological endpoint effects including protein-protein interactions, signaling pathways, molecular functions, and disease effects. NET-TMFS recapitulated over 50 drug-disease, 100 drug-pathway, and drug-PPI associations established in the literature. NET-TMFS also predicted potential carcinogenic effects of the cholesterol-lowering drug ezetimibe, a phenomenon documented in clinical trials. In summary, we have developed novel computational methods for addressing major bottlenecks in the drug discovery process. We hope our methods will aid in finding effective therapeutics for many diseases with greater efficiency and lower costs
Real-World Use of Tapinarof Cream 1% Once Daily in Patients with Seborrheic Dermatitis: A Case Series
No full textSeborrheic dermatitis (SD) is an inflammatory skin disease with multifactorial etiology, involving genetic and environmental factors. Many conventional therapies for SD (ie, topical antifungals, topical corticosteroids) are associated with incomplete efficacy, frequent and sometimes rapid disease recurrence, and restrictions on duration of therapy and anatomic sites of application. This may be because they cannot target multiple disease processes and/or are limited by safety considerations. Topical roflumilast foam was approved for the treatment of SD in 2023, but additional options are needed. The pathophysiology of atopic dermatitis (AD) and psoriasis have similarities with SD, supporting the hypothesis that tapinarof cream 1% once daily (QD) may be beneficial and well tolerated for patients with SD. Tapinarof is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults. Tapinarof downregulates pro-inflammatory cytokines implicated in AD and plaque psoriasis, restores the skin barrier through upregulation of skin barrier components, and reduces oxidative stress. Here, we report that tapinarof cream 1% QD used for the treatment of four adults with mild-to-severe SD affecting the face, neck, back, and chest, demonstrated a rapid onset of efficacy and noticeable improvements in disease activity. Efficacy was maintained after treatment discontinuation, indicating a possible remittive effect as previously described in plaque psoriasis. The efficacy and potential remittive effect may be attributed to the unique mechanism of action and clinical profile of tapinarof cream. Tapinarof is a novel topical therapy that may be beneficial for patients with SD
First Use of Tapinarof Monotherapy for Seborrhoeic Dermatitis: A Case Report
No full textAbstract is missing (Short communication
ES-Screen: A Novel Electrostatics-Driven Method for Drug Discovery Virtual Screening
No full textElectrostatic interactions drive biomolecular interactions and associations. Computational modeling of electrostatics in biomolecular systems, such as protein-ligand, protein–protein, and protein-DNA, has provided atomistic insights into the binding process. In drug discovery, finding biologically plausible ligand-protein target interactions is challenging as current virtual screening and adjuvant techniques such as docking methods do not provide optimal treatment of electrostatic interactions. This study describes a novel electrostatics-driven virtual screening method called ‘ES-Screen’ that performs well across diverse protein target systems. ES-Screen provides a unique treatment of electrostatic interaction energies independent of total electrostatic free energy, typically employed by current software. Importantly, ES-Screen uses initial ligand pose input obtained from a receptor-based pharmacophore, thus independent of molecular docking. ES-Screen integrates individual polar and nonpolar replacement energies, which are the energy costs of replacing the cognate ligand for a target with a query ligand from the screening. This uniquely optimizes thermodynamic stability in electrostatic and nonpolar interactions relative to an experimentally determined stable binding state. ES-Screen also integrates chemometrics through shape and other physicochemical properties to prioritize query ligands with the greatest physicochemical similarities to the cognate ligand. The applicability of ES-Screen is demonstrated with in vitro experiments by identifying novel targets for many drugs. The present version includes a combination of many other descriptor components that, in a future version, will be purely based on electrostatics. Therefore, ES-Screen is a first-in-class unique electrostatics-driven virtual screening method with a unique implementation of replacement electrostatic interaction energies with broad applicability in drug discovery
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Mosaic TP63 variant and associated ectodermal dysplasia features
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Anchored Matching-Adjusted Indirect Comparison of the Long-Term Maintenance of Efficacy of Tralokinumab and Lebrikizumab in Patients with Moderate-to-Severe Atopic Dermatitis
No full textINTRODUCTION: Atopic dermatitis (AD) is a chronic skin disease largely driven by interleukin (IL)-13, which is targeted by tralokinumab and lebrikizumab. Effective, long-term treatments are needed, and head-to-head studies comparing these available therapeutics have yet to be conducted. This analysis indirectly compared the maintenance of efficacy of tralokinumab and lebrikizumab at week 52 in week-16 responders. METHODS: An anchored matching-adjusted indirect comparison was performed using individual patient data (IPD) from the ECZTRA 1 and ECZTRA 2 tralokinumab trials and aggregate data from the ADvocate 1 and ADvocate 2 lebrikizumab trials, with IPD weighted to match ADvocate baseline and week-16 characteristics. Week-16 responders, patients achieving 75% reduction in Eczema Area and Severity Index (EASI-75) or Investigator Global Assessment 0 or 1 (IGA 0/1) with an ≥ 2-point improvement from baseline, were re-randomized to active treatment every 2 weeks (Q2W), every 4 weeks (Q4W), or placebo Q2W for the 36-week maintenance period. Week 52 efficacy outcomes included IGA 0/1, EASI-75, 90% reduction in EASI (EASI-90), EASI percentage improvement, and pruritus numerical rating scale 4-point improvement (pruritus 4pt) from baseline. Response differences relative to placebo for endpoints of interest were calculated between tralokinumab and lebrikizumab for Q2W and Q4W dosing to compare maintenance of efficacy at week 52 among week 16-responders. RESULTS: Differences in efficacy endpoints between tralokinumab and lebrikizumab were not statistically significant; within Q2W dosing, tralokinumab versus lebrikizumab response rate differences at week 52 numerically favored tralokinumab (IGA 0/1: 1.2%, EASI-75: 19.8%, EASI-90: 1.5%, EASI percentage improvement from baseline: 3.3%, pruritus 4pt: 17.6%) while Q4W differences were more variable (IGA 0/1: -20.5%, EASI-75: 15.7%, EASI-90: -8.5%, EASI percentage improvement from baseline: -0.5%, pruritus 4pt: -2.7%). CONCLUSIONS: Comparable maintenance of efficacy was observed between tralokinumab and lebrikizumab after 52 weeks of treatment among patients meeting response criteria at week 16
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