Spectroscopic Monitoring and Modeling Drug Dissolution for Undergraduate Chemistry Curriculum.

The pharmaceutical and medicine manufacturing industry has become the largest industrial sector for the employment of chemists, indicating a need for experiments with a pharmaceutical sciences context in the undergraduate chemistry curriculum. In the pharmaceutical industry, testing drug dissolution is a key analytical task for solid oral dosage forms that is performed in different phases of drug development to test the release behavior of new formulations, ensure consistency between manufacturing lots, and help predict the in vivo absorption of the drug substance after administration. However, there are a limited number of laboratory experiments in dissolution testing developed for the undergraduate chemistry curriculum. To help students obtain hands-on experience in dissolution testing, a protocol has been developed for an undergraduate chemistry laboratory course for students to build a dissolution apparatus, monitor dissolution processes, model the dissolution to extract kinetic parameters, and evaluate the consistency between dissolution curves with FDA regulated methods. Students successfully collected dissolution curves and completed the modeling analysis with nonlinear least-squares fitting. The designed dissolution protocol has been evaluated to have consistency and reproducibility to be implemented in the undergraduate chemistry laboratory curriculum.

Multidrug resistant gastrointestinal stromal tumor with multiple metastases to the skin and subcutaneous soft tissue: A case report and review of literature.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms which account for less than 1% of all gastrointestinal malignancies. Of all the extra-abdominal metastases of GIST, superficial soft tissue metastases are the rarest. Previous reports have found success with sunitinib in imatinib-resistant GIST, but we report a certain wild-type KIT mutation GIST with cutaneous and subcutaneous metastasis that was unresponsive to multiple tyrosine kinase inhibitor (TKI) treatments. This case illustrates that knowing the specific type of KIT mutations may uncover resistance of certain GIST's to TKIs, necessitating more targeted and alternative therapy.

The Impact of COVID-19 on the Faces of Frontline Healthcare Workers.

As the coronavirus epidemic continues, a host of new cutaneous complications is seen on the faces of frontline healthcare workers wearing personal protective equipment on a daily basis. To minimize the risk of COVID-19 infection, healthcare workers wear tight-fitting masks that lead to an excessive amount of pressure on the facial skin. Mechanical pressure, mask materials, and perspiration can all lead to various types of cutaneous lesions such as indentations of the face, skin tears, post-inflammatory hyperpigmentation, ulceration, crusting, erythema, and infection. The objective of this article is to provide effective and straightforward recommendations to those health care providers using facial masks in order to prevent skin-related complications. J Drugs Dermatol. 2020;19(9):858-864. doi:10.36849/JDD.2020.5259.

Relationship between human leukocyte antigen alleles and risk of Kaposi's sarcoma in Cameroon.

Several studies published to date report associations between human leukocyte antigen (HLA) alleles and different types of Kaposi's Sarcoma (KS). However, there is little concordance between the HLA alleles identified and the populations studied. To test whether HLA alleles associate with KS in a Cameroonian case-control study, we performed high-resolution HLA typing in KSHV seropositive individuals. Among HIV-positive individuals, carriers of HLA-B*14:01 were at a significantly higher risk of AIDS-KS (p = 0.033). For HIV-negative patients, a gene-wise comparison of allele frequencies identified the HLA-B (p = 0.008) and -DQA1 (p = 0.002) loci as possible risk factors for endemic KS. Our study provides additional understanding of genetic determinants of KS and their implications in disease pathogenesis. Further validation of these findings is needed to define the functional relevance of these associations.

Prevalence of Skin Disease in Urban Haiti: A Cross-Sectional Study.

The prevalence of skin disease varies with geographic location and may be affected by cultural factors. In Haiti, the combination of poor health care access, infrastructure lack, and natural disasters may affect the prevalence of skin conditions. Unfortunately, little epidemiological information has been obtained on the prevalence of skin diseases in Haiti. The objective of this study is to describe data on the prevalence of dermatological conditions in urban areas of Haiti. Univariate, bivariate, and χ2 analyses were used to evaluate associations. During February 2016, we documented 137 patients. The mean age was 27.7 years; most of the subjects were women (61.3%) in a cohort mostly adult (67.1%). The infectious and inflammatory dermatoses were the most prevalent (74.2%). Infectious skin diseases were more prevalent in men and in adults in general (p < 0.01). Inflammatory conditions were also more common in adults (p < 0.05). Additionally, alopecia and dyschromia were limited to women (p < 0.01). Infectious skin diseases, in particular fungal infections, were amongst the most common diagnoses in the urban area of Haiti. Therefore, improved access to antimicrobial and anti-inflammatory medications would likely benefit Haitian patients with dermatological conditions. These findings may help local public health officials and future dermatological expeditions better serve this population.

Reduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells.

BACKGROUND: It has been proposed that cancer establishment, maintenance, and recurrence may be attributed to a unique population of tumor cells termed cancer-initiating cells (CICs) that may include characteristics of putative cancer stem cell-like cells. Studies in lung cancer have shown that such cells can be enriched and propagated in vitro by culturing tumor cells in serum-free suspension as tumorspheres. CICs have been characterized for their phenotype, stem cell-like qualities, and their role in establishing tumor and maintaining tumor growth. Less is known about the interaction of CICs with the immune system. METHODS: We established CIC-enriched tumorspheres from murine TC-1 lung cancer cells, expressing human papillomavirus 16 (HPV-16) E6/E7 antigens, and evaluated their susceptibility to antitumor immune responses both in vitro and in vivo. RESULTS: TC-1 CICs demonstrated reduced expression of surface major histocompatibility complex (MHC)-I molecules compared to non-CICs. We similarly determined decreased MHC-I expression in five of six human lung cancer cell lines cultured under conditions enriching for CICs. In vivo, TC-1 cells enriched for CICs were resistant to human papillomavirus 16 E6/E7 peptide vaccine-mediated killing. We found that vaccinated mice challenged with CIC enriched tumorspheres demonstrated shorter survivals and showed significantly fewer CD8+ tumor infiltrating lymphocytes compared to CIC non-enriched challenged mice. Furthermore, cultured cytotoxic T lymphocytes (CTLs) from vaccinated mice demonstrated reduced capacity to lyse TC-1 cells enriched for CICs compared to non-enriched TC-1 cells. Following treatment with IFN-γ, both CIC enriched and non-enriched TC-1 cells expressed similar levels of MHC-I, and the increased MHC-I expression on CICs resulted in greater CTL-mediated tumor lysis and improved tumor-free survival in mice. CONCLUSIONS: These results suggest that the attenuated expression of MHC-I molecules by CICs represents a potential strategy of CICs to escape immune recognition, and that the development of successful immunotherapy strategies targeting CICs may decrease their resistance to T cell-mediated immune detection by enhancing CIC MHC-I expression.

Influence of sample collection tube method, anticoagulant-containing plasma versus serum, on influenza virus hemagglutination inhibition titer and microneutralization titer serological assays.

BACKGROUND: The hemagglutination-inhibition (HAI) assay is a critical component for measurement of immunogenicity in influenza vaccine development. It is unknown if the results can be influenced by sample type and anticoagulants. The purpose of this study was to evaluate the influence of different sample collection methods, in particular different anticoagulants, and choice of plasma or serum, on influenza virus serological assays. METHODS: Blood samples from thirty donors previously immunized against influenza viruses were collected using six different types of blood collection tubes, two of which collect serum and four of which contain various anticoagulants for collecting plasma. Serum: (1) serum separator tubes (SST); and (2) Plus Plastic serum "red-top serum" tubes. Plasma: (3) spray-coated K2 ethylenediaminetetraacetic acid (EDTA) tubes: (4) Sodium Heparin tubes; (5) Citrate tubes with 3.2% sodium citrate solution; and (6) Glass Blood Collection tubes with acid citrate dextrose. Samples were tested against three different influenza viruses (A/California/07/2009 (H1N1pdm09), A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012) for hemagglutination inhibition titer and virus neutralization titer via a microneutralization (MN) assay, and data compared to that obtained for standard serum sample collected in SST. RESULTS: HAI and MN titers against type A viruses were within two dilutions compared to SST collection method over 96% of the time irrespective of sample type or anticoagulant. However, HAI titers for type B virus were more variable across different collection methods. EDTA plasma samples were greater than two dilutions higher than SST serum samples 70% (21 of 30 samples) of the time. In contrast, MN titers were within two dilutions over 96% of the time, with the highest deviation noted in acid citrate dextrose plasma samples (3 of 30 samples tested, 10%). CONCLUSIONS: These data provide useful guidelines for sample collection and serology testing when screening: (i) influenza vaccine immunogenicity antibody response; (ii) antibody responses to newly emerging viral strains; and (iii) clinical samples for anti-influenza antibody activity.

Worn down nails after acrylic nail removal.

Worn-down nail syndrome is a nail disorder characterized by thinning of the distal nail plate caused by repetitive chemical or mechanical trauma. We present a previously undescribed source of worn-down nail syndrome caused by trauma from nail filing after acrylic nail removal.

Update on Squamous Cell Carcinoma of the Nail Unit: An Human Papillomavirus-Associated Condition.

Background: Squamous cell carcinoma (SCC) and SCC in situ (Bowen's disease) are the most common malignancies of the nail unit. They are frequently seen in men over 50 and most commonly affect the fingers. The role of high-risk human papillomavirus (HPV) infection has been identified as a key contributor to the development of nail unit SCC. Summary: In this review, we aimed to summarize the current state of our understanding of how HPV contributes to nail unit SCC, the role of genitodigital transmission of HPV, and the clinical features of HPV-associated nail unit SCC. We also review current advances in the treatment of nail unit SCC, with a focus on the potential role of HPV vaccination in the treatment and prevention of nail unit SCC. Key Messages: Nail unit SCC should be recognized as an HPV-associated disease. HPV vaccination may represent a non-surgical modality for the management of these challenging malignancies in the appropriate clinical setting.

Natural Treatment Options for Nail Disorders.

The growing demand for natural treatments has raised concerns among clinicians due to limited scientific evidence supporting their use. This review article addresses the issue by assisting dermatologists and general practitioners in recommending natural treatments for the following common nail disorders: nail brittleness, onychomycosis, periungual verrucae, paronychia, chloronychia, nail psoriasis, nail lichen planus, onychocryptosis, onycholysis, and congenital malalignment of the great toenail. One limitation is the scarcity of existing reviews on natural treatment options for nail disorders in the literature. Through a comprehensive review of existing literature, this article consolidates the available evidence on natural treatment options for these conditions. Although some natural treatments for nail disorders are supported by scientific evidence, the indiscriminate use of such remedies may lead to severe poisoning and health problems. Given the widespread and increasing use of natural treatments, clinicians play a pivotal role in educating patients about evidence-based remedies and debunking misleading claims. By doing so, clinicians can enhance patient safety and improve treatment outcomes. It is essential for healthcare professionals to be well-informed and equipped with the knowledge to differentiate between effective natural treatments and unverified claims, ensuring that patients receive appropriate care.

Downregulation of Caveolae-Associated Proteins in Psoriasis: A Case Series Study.

We have previously identified that a structural membrane protein Caveolin-1 (Cav1) is involved in the regulation of aberrant keratinocyte proliferation and differentiation. The aim of this study was to elucidate the role of Cav1, Caveolin-2 (Cav2), and Cavin-1 in the pathogenesis of psoriasis vulgaris and between psoriasis subtypes. We utilized human biopsies from validated cases of psoriasis vulgaris (n = 21) at the University of Miami Hospital and compared the expression of Cav1, Cav2, and Cavin-1 by immunohistochemistry staining with that in normal healthy age-/sex-/location-matched skin (n = 15) and chronic spongiotic dermatitis skin samples (as control inflammatory skin condition) and quantified using QuPath. Distinct subtypes of psoriasis included guttate, inverse, nail, plaque, palmoplantar, and pustular. All biopsy samples exhibited a trend toward downregulation of Cav1, with nail, plaque, and palmoplantar psoriasis exhibiting the most pronounced effects. Only nail and pustular psoriasis samples exhibited significant downregulation of Cav2 and Cavin-1, suggesting Cav1 to be the main caveolar contributor to the pathogenesis of psoriasis. Together, these data support caveolae as pathophysiological targets in nail and pustular psoriasis, whereas Cav1 seems to be a general biomarker of multiple subtypes of psoriasis.

Intramuscular small vessel arteriovenous malformation of the left ventricle in an asymptomatic adolescent: a case report and literature review.

Primary vascular tumours of the heart are rare and heterogeneous in their presentation and classification.We present a primary intramuscular vascular malformation of the left ventricle in an asymptomatic 12-year-old girl. Characteristics on cardiac magnetic resonance imaging, specifically increased signal intensity on T2-weighted images, and marked contrast enhancement with gadolinium were suggestive of increased vascularity. Histologically, the mass was determined to be an intramuscular vascular malformation of the small vessel arteriovenous subtype. This represents one of a select few intramuscular vascular malformations of the left ventricle reported in children. Our patient remains completely asymptomatic and has had no change in the size and appearance of the mass after more than 30 months of follow-up.

Recurrent Fluconazole-Induced Fixed Drug Eruption of the Digit with Nail Matrix Involvement: A Case Report and Review of the Literature.

Introduction: Fixed drug eruptions (FDEs) are cutaneous hypersensitivity reactions due to an offending drug and are rarely associated with nail involvement. Moreover, FDEs associated with fluconazole use are sparsely reported in literature. Case Presentation: We report a case of a recurrent FDE with involvement of one finger and corresponding Beau's lines due to fluconazole use. The diagnosis of FDE secondary to fluconazole use was confirmed histopathologically, with improvement after the application of twice daily 0.05% clobetasol propionate ointment. Conclusion: FDEs are hypersensitivity reactions that occur after exposure to an offending drug. FDEs uncommonly affect the nail matrix and are often not caused by fluconazole. It is important for dermatologists to assess for changes in the nail plate when evaluating a patient with FDE and evaluate all medications a patient is taking.

Monodactylous Longitudinal Melanonychia in Pediatric Skin of Color: A Case Series and Review.

Introduction: Longitudinal melanonychia, a pigmented longitudinal streak on the nail, is a common clinical finding that may be associated with subungual melanoma with varying presentation depending on race and skin tone. It has been long reported that darker skinned ethnicities have a higher prevalence of longitudinal melanonychia in the US population (e.g., African Americans with 77% prevalence) [Indian J Dermatol. 2021;66(4):445], but unfortunately, there are limited studies exclusively looking at longitudinal melanonychia in pediatric patients of color. Case Presentation: In this case series, we review the current literature and report the findings of 8 cases of longitudinal melanonychia in children with skin types IV or greater. Out of the 8 cases identified, only 4 returned to the clinic for monitoring (n = 4), and there was an average of 20.8 months between the initial and final visits. Of the patients that returned for follow-up, 2 showed no relevant changes in the nail pigmentation, 1 showed fading of the band, and 1 patient showed enlargement of the band to involve the whole nail. Conclusion: Although many sources recommend a conservative approach to treatment that involves monitoring and follow-up, our findings indicate that a wait-and-see method cannot be applied to all cases in the pediatric population due to disruptions in continuity of care. An individualized approach considering such factors should be employed for each patient, and certain high-risk features of the ABCDEF nail melanoma model may be relevant in pediatric cases.