Dermatology's Ethical Obligations to DEI and Antisemitism.

In 2023-2024 a resolution was proposed to "sunset" the American Academy of Dermatology's (AAD) Diversity, Equity, and Inclusion (DEI) initiatives, citing concerns about stifling diversity of thought, and promoting antisemitism. Although this resolution was ultimately withdrawn, there are many ethical issues surrounding this complex issue. Herein we explore ways in which DEI and the fight against antisemitism are not only compatible but synergistic.

In Silico and In Vitro Evaluation of the Antifungal Activity of a New Chromone Derivative against Candida spp.

Candida species are frequently implicated in the development of both superficial and invasive fungal infections, which can impact vital organs. In the quest for novel strategies to combat fungal infections, there has been growing interest in exploring synthetic and semi-synthetic products, particularly chromone derivatives, renowned for their antimicrobial properties. In the analysis of the antifungal activity of the compound (E)-benzylidene-chroman-4-one against Candida, in silico and laboratory tests were performed to predict possible mechanisms of action pathways, and in vitro tests were performed to determine antifungal activity (MIC and MFC), to verify potential modes of action on the fungal cell membrane and wall, and to assess cytotoxicity in human keratinocytes. The tested compound exhibited predicted affinity for all fungal targets, with the highest predicted affinity observed for thymidylate synthase (-102.589 kJ/mol). MIC and CFM values ranged from 264.52 µM (62.5 µg/mL) to 4232.44 µM (1000 µg/mL). The antifungal effect likely occurs due to the action of the compound on the plasma membrane. Therefore, (E)-benzylidene-chroman-4-one showed fungicidal-like activity against Candida spp., possibly targeting the plasma membrane.

Isotretinoin for Acne in Transgender and Gender-Diverse Individuals Receiving Masculinizing Hormone Therapy.

Importance: Masculinizing gender-affirming hormonal therapy is associated with the development of acne. While isotretinoin is a highly effective acne treatment, little is known about its effectiveness and safety among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Objective: To evaluate clinical outcomes of isotretinoin among transgender and gender-diverse individuals receiving gender-affirming hormonal therapy. Design, Setting, and Participants: This multicenter retrospective case series study was conducted at 4 medical centers: Mass General Brigham, University of Pennsylvania, Emory University, and Fenway Health. It included patients aged between 12 and 49 years who were receiving masculinizing gender-affirming hormonal therapy and prescribed isotretinoin for the management of acne between August 14, 2015, and September 20, 2023. Exposure: Isotretinoin therapy for the management of acne. Main Outcomes and Measures: The percentage of patients experiencing improvement or clearance of acne, as well as rates of acne recurrence. Adverse effects and reasons for treatment discontinuation were also evaluated. Results: Among 55 included patients, the mean (SD) age was 25.4 years; 4 (7.3%) were Asian, 2 (3.6%) were Black, 4 (7.2%) were Hispanic, 1 was (1.8%) multiracial, and 36 (65.5%) were White. The median isotretinoin course duration was 6 months (IQR, 4.0-8.0), with a median cumulative dose of 132.7 mg/kg (IQR, 66.4-168.5); the cumulative dose was less than 90 mg/kg for 16 patients (29.1%) and less than 120 mg/kg for 22 patients (40.0%). Isotretinoin was associated with improvement in 48 patients (87.3%) and clearance in 26 patients (47.3%). For the 33 patients treated with a cumulative dose of 120 mg/kg or more, these rates increased to 32 patients (97.0%) and 21 patients (63.6%), respectively. Among the 20 patients who achieved acne clearance and had any subsequent health care encounters, the risk of recurrence was 20.0% (n = 4). The most frequently reported adverse effects were dryness (n = 44; 80.0%), joint pain (n = 8; 14.5%), and eczema (n = 5; 9.1%). Laboratory abnormalities were uncommon. Reasons for premature treatment discontinuation included cost, pharmacy issues, adverse effects, logistical reasons (scheduling), and wound healing concerns for gender-affirming surgery. Conclusion and Relevance: In this case series study of individuals with acne who were receiving masculinizing gender-affirming hormonal therapy and underwent isotretinoin treatment, isotretinoin was often effective and well tolerated. However, premature treatment discontinuation was common and associated with poorer outcomes. Further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving masculinizing gender-affirming hormonal therapy.

Cosmetic Skin Lightening: Contextualizing Biomedical and Ethical Issues.

The skin lightening (SL) industry has a global reach and is projected to continue to grow over the coming decade. While SL treatments may be safely prescribed for treatment of some dermatologic conditions, many over-the-counter SL products contain ingredients that can cause harm to the skin and other organ systems. Given a lack of transparent information to patients and the historical colorist foundation that contextualizes a component of the cosmetic SL industry, dermatologists need to navigate biomedical and ethical concerns when explaining SL products to patients. This commentary briefly outlines the medical ethical issues surrounding this topic and describes avenues by which dermatologists may provide informed patient care that best supports beneficence, justice, autonomy, and nonmaleficence.

Interventions to Mitigate Financial Toxicity in Adult Patients with Cancer in the United States: A Scoping Review.

Financial toxicity adversely affects quality of life and treatment outcomes for patients with cancer. This scoping review examined interventions aimed at mitigating financial toxicity in adult patients with cancer and their effectiveness. We utilized five bibliographical databases to identify studies that met our inclusion criteria. The review included studies conducted among adult patients with cancer in the United States and published in English between January 2011 to March 2023. The review identified eight studies that met the inclusion criteria. Each of the studies discussed the implementation of interventions at the patient/provider and/or health system level. Collectively, the findings from this scoping review highlight both the limited number of published studies that are aimed at mitigating financial toxicity and the need to create and assess interventions that directly impact financial toxicity in demographically diverse populations of adult patients with cancer.

Derivative of 7-hydroxycoumarin has antifungal potential against Candida species and low cytotoxicity against human cells: In silico studies and biological evaluation.

This study investigates the antifungal and cytotoxic properties of 7-(pentyloxy)-2H-chromen-2-one. Through molecular docking and dynamics simulations, we explored the compound's interactions with fungal cell protein targets. Notably, it exhibited strong affinities for 1,3ß-glucan synthase, squalene epoxidase, δ-14-sterol reductase, 14-α-demethylase, and thymidylate synthase, with binding energies ranging from -100.39 to -73.15 kcal/mol. Molecular dynamics simulations confirmed its stable binding at active targets. The MIC and MFC values ranged from 67.16 µM (15.6 µg/mL) to 537.28 µM (125.0 µg/mL). The compound displayed promising antifungal effects, inhibiting fungal growth for at least 24 hours. Fungal plasma membrane function alteration likely contributed to these antifungal mechanisms. Additionally, the combination of the compound with nystatin, fluconazole, and caspofungin showed indifferent effects on antifungal activity. Cytotoxicity assessment in human keratinocyte cells (HaCaT) revealed an IC50 of 100 µM, which was approximately 1.5 times higher than the MIC for C. krusei. Thus, the compound exhibited strongly in silico and in vitro antifungal activity with low cytotoxicity in HaCaT cells. These findings support its potential as a candidate for further development as an antifungal compound.

Reliability and validity of the gait classification system in children with cerebral palsy (GCS-CP).

BACKGROUND: Gait classification systems (GCS) may enable clinicians to differentiate gait patterns into clinically significant categories that assist in clinical decision-making and assessment of outcomes. Davids and Bagley in 2014 [1] described a GCS for children with cerebral palsy (GCS-CP). The purpose of our study was to use the GCS-CP for the first time on a sample of patients with CP and to evaluate the reliability and utility of the classification system. METHODS: The gait of 131 children with CP was retrospectively reviewed and classified according to Davids and Bagley's classification using two-dimensional (2D) video and three-dimensional (3D) lower limb kinematics and kinetics. Gross Motor Function Classification System (GMFCS) levels were determined, and the Gait Profile Scores (GPS) calculated to characterize the sample concerning gait classification. The comparison between the groups was performed using the Kruskal-Wallis test with respect to the non-normal distribution of the data. The intrarater and interrater reliability was determined using the Kappa index (k) statistics with 95% CI. RESULTS: All GCS-CP groups were represented within the evaluated sample. Of the 131 cases evaluated, 127 (96.95%) were able to be classified with respect to sagittal plane stance phase gait deviations. All patients in the sample were able to be classified with respect to sagittal plane swing phase and transverse plane gait deviations. The interrater reliability was 0.596 and 0.485 for the first and second levels of the classification, respectively, according to the Fleiss's Kappa statistics. Intrarater reliability was 0.776 and 0.714 for the raters one and two, respectively, according to the Cohen's Kappa statistics. SIGNIFICANCE: The GCS-CP exhibited clinical utility, successfully classifying almost all subjects with CP in two planes, based upon kinematic and kinetic data. The classification is valid and has moderate interrater and moderate to substantial intrarater reliability.

Synthesis of Coumarin and Homoisoflavonoid Derivatives and Analogs: The Search for New Antifungal Agents.

A set of twenty-four synthetic derivatives, with coumarin and homoisoflavonoid cores and structural analogs, were submitted for evaluation of antifungal activity against various species of Candida. The broth microdilution test was used to determine the Minimum Inhibitory Concentration (MIC) of the compounds and to verify the possible antifungal action mechanisms. The synthetic derivatives were obtained using various reaction methods, and six new compounds were obtained. The structures of the synthesized products were characterized by FTIR spectroscopy: 1H-NMR, 13C-NMR, and HRMS. The coumarin derivative 8 presented the best antifungal profile, suggesting that the pentyloxy substituent at the C-7 position of coumarin ring could potentiate the bioactivity. Compound 8 was then evaluated against the biofilm of C. tropicalis ATCC 13803, which showed a statistically significant reduction in biofilm at concentrations of 0.268 µmol/mL and 0.067 µmol/mL, when compared to the growth control group. For a better understanding of their antifungal activity, compounds 8 and 21 were submitted to a study of the mode of action on the fungal cell wall and plasma membrane. It was observed that neither compound interacted directly with ergosterol present in the fungal plasma membrane or with the fungal cell wall. This suggests that their bioactivity was due to interaction involving other pharmacological targets. Compound 8 was also subjected to a molecular modeling study, which showed that its antifungal action mechanism occurred mainly through interference in the redox balance of the fungal cell, and by compromising the plasma membrane; not by direct interaction, but by interference in ergosterol synthesis. Another important finding was the antifungal capacity of homoisoflavonoids 23 and 24. Derivative 23 presented slightly higher antifungal activity, possibly due to the presence of the methoxyl substituent in the meta position in ring B.

Breakpoints for the Classification of Anti-Candida Compounds in Antifungal Screening.

INTRODUCTION: The absence of a standardized classification scheme for the antifungal potency of compounds screened against Candida species may hinder the study of new drugs. This systematic review proposes a scheme of interpretative breakpoints for the minimum inhibitory concentration (MIC) of bioactive compounds against Candida species in in vitro tests. MATERIALS AND METHODS: A literature search was conducted in the PubMed, Scopus, Web of Science, Lilacs, and SciFinder databases for the period from January 2015 to April 2020. The following inclusion criterion was used: organic compounds tested by the microdilution technique according to the Clinical and Laboratory Standards Institute protocol against reference strains of the genus Candida. A total of 545 articles were retrieved after removing duplicates. Of these, 106 articles were selected after applying the exclusion criteria and were evaluated according to the number of synthesized molecules and their chemical classes, the type of strain (reference or clinical) used in the antifungal test, the Candida species, and the MIC (in µg/mL) used. RESULTS: The analysis was performed based on the median, quartiles (25% and 75%), maximum, and minimum values of four groups: all strains, ATCC strains, C. albicans strains, and C. albicans ATCC strains. The following breakpoints were proposed to define the categories: MIC < 3.515 µg/mL (very strong bioactivity); 3.516-25 µg/mL (strong bioactivity); 26-100 µg/mL (moderate bioactivity); 101-500 µg/mL (weak bioactivity); 500-2000 µg/mL (very weak bioactivity); and >2000 µg/mL (no bioactivity). CONCLUSIONS: A classification scheme of the antifungal potency of compounds against Candida species is proposed that can be used to identify the antifungal potential of new drug candidates.