Hidradenitis suppurativa in sexual and gender minorities: A review and considerations for providers.

The literature on hidradenitis suppurativa in sexual and gender minorities remains sparse. This review article aims to discuss critical factors for providers to consider in lesbian, gay, bisexual, transgender, queer, intersex, and asexual patients with hidradenitis suppurativa, including associated comorbidities, gender-affirming hormonal therapy, squamous cell carcinoma, infections in HIV-positive patients, and creating a welcoming clinic for sexual and gender minority patients.

Untargeted Large Volume Hyperthermia Reduces Tumor Drug Uptake From Thermosensitive Liposomes.

GOAL: The impact of hyperthermia (HT) method on tumor drug uptake with thermosensitive liposomes (TSL) is not well understood. METHODS: We created realistic three-dimensional (3-D) computer models that simulate TSL-encapsulated doxorubicin (TSL-DOX) delivery in mouse tumors with three HT methods (thermistor probe (T), laser (L) and water bath (WB), at 15 min and 60 min HT duration), with corroborating in vivo studies. RESULTS: Average computer model-predicted tumor drug concentrations (µg/g) were 8.8(T, 15 min), 21.0(T, 60 min), 14.1(L, 15 min), 25.2(L, 60 min), 9.4(WB, 15 min), and 8.7(WB, 60 min). Tumor fluorescence was increased by 2.6 × (T) and 1.6 × (L) when HT duration was extended from 15 to 60 min (p < 0.05), with no increase for WB HT. Pharmacokinetic analysis confirmed that water bath HT causes rapid depletion of encapsulated TSL-DOX in systemic circulation due to the large heated tissue volume. CONCLUSIONS: Untargeted large volume HT causes poor tumor drug uptake from TSL.

Special Forces Medical Sergeant/Special Operations Independent Duty Corpsman Candidates: Large Animal Module.

BACKGROUND: Medical care provided by Special Operations Forces (SOF) combat medics is vital for establishing communication with local populations. In many of these communities, livestock hold a valuable position within the social, political, and cultural structure. The West Virginia University (WVU) Special Forces Medical Sergeant/Special Operations Independent Duty Corpsman (SFMS/SOIDC) Large Animal Module is designed to provide a foundational experience in livestock husbandry and veterinary procedures to SOF combat medic candidates. This study was conducted to determine the participants' base knowledge of food animal production and to evaluate if the program content was sufficient for increasing their knowledge of the subject matter. METHODS: A quasi-experimental design utilizing pre-test and post-test instruments was used. The validity of the testing instruments was established by a panel of subject matter experts and the instruments' reliability was determined by a split-half analysis using SPSS® statistical software. The difference between the pre-test and post-test examinations were compared for 66 candidates who were assigned to WVU Health Sciences Center for the applied medical experience program and 46 counterparts assigned to other institutions by a match pair analysis. RESULTS: Seventy-five percent of the subjects had no previous livestock exposure, and only 7% had previously participated in the 4-H program or Future Farmers of America (FFA). The average improvement in scores, pre-test versus post-test, was significantly greater for those that attended the module (18.5 versus 0.9). CONCLUSION: Few SFMS/SOIDC candidates have prior knowledge of livestock husbandry practices. The large animal module successfully provides education on livestock husbandry practice to participants. Knowledge of livestock production can assist SOF medics in establishing rapport with indigenous populations while on mission.

A Simple Method to Test Mechanical Strain on Epithelial Cell Monolayers Using a 3D-Printed Stretcher.

With the realization that mechanical forces mediate many biological processes and contribute to disease progression, researchers are focusing on developing new methods to understand the role of mechanotransduction in biological systems. Despite recent advances in stretching devices that analyze the effects of mechanical strain in vitro, there are still possibilities to develop new equipment. For example, many of these devices tend be expensive, whereas few have been designed to assess the effects of mechanical strain driven by the extracellular matrix (ECM) to epithelial cell monolayers and to cell-cell adhesion. In this chapter, we introduce a cost-efficient, user-friendly, 3D-printed stretching device that can be used to test the effects of mechanical strain on cultured epithelial cells. Evaluation of the device using speckle-tracking shows homogeneous strain distribution along the horizontal plane of membranes at 2.5% and 5% strains, supporting the reliability of the device. Since cell-cell junctions are mechanosensitive protein complexes, we hereby used this device to examine effects on cell-cell adhesion. For this, we used colon epithelial Caco2 cell monolayers that well-differentiate in culture and form mature adherens junctions. Subjecting Caco2 cells to 2.5% and 5% strain using our device resulted in significant reduction in the localization of the core adherens junction component E-cadherin at areas of cell-cell contact and its increased translocation to the cytoplasm, which in agreement with other methodologies showing that increased ECM-driven strain negatively affects cell-cell adhesion. In summary, we here present a new, cost-effective, homemade device that can be reliably used to examine effects of mechanical strain on epithelial cell monolayers and cell-cell adhesion, in vitro.

Computer Modeling of Drug Delivery with Thermosensitive Liposomes in a Realistic Three-Dimensional Geometry.

Thermosensitive liposomes (TSL) are nanoparticles that can encapsulate therapeutic drugs, and release those drugs when exposed to hyperthermic temperatures (>40 °C). Combined with localized hyperthermia, TSL enable focused drug delivery. In this study, we created a three-dimensional (3D) computer model for simulating delivery with TSL-encapsulated doxorubicin (TSL-Dox) to mouse tumors. A mouse hind limb was scanned by a 3D scanner and the resulting geometry was imported into finite element modeling software, with a virtual tumor added. Then, heating by a surface probe was simulated. Further, a drug delivery model was coupled to the heat transfer model to simulate drug delivery kinetics. For comparison, experimental studies in gel phantoms and in vivo fluorescence imaging studies in mice carrying lung tumor xenografts were performed. We report the tissue temperature profile, drug concentration profile and compare the experimental studies with the computer model. The thermistor produced very localized heating that resulted in highest drug delivery to regions near the probe. The average tumor temperature was 38.2˚C (range 34.4-43.4˚C), and produced an average tumor drug concentration of 11.8 µg/g (0.3-28.1 µg/g) after 15 min heating, and 25.6 µg/g (0.3-52 µg/g), after 60 min heating. The computer model reproduced the temperature profile compared to phantom experiments (mean error 0.71 °C, range 0.59-1.25 °C), as well as drug delivery profile as compared to in vivo studies. Our results suggest feasibility of using this approach to model drug delivery in preclinical studies with accurate model geometry.

The Stockman's Scorecard: quantitative evaluation of beef cattle stockmanship.

An animal's action, or inaction, is the direct result of a stockman's action or inaction. The Stockman's Scorecard is a novel observation instrument that has been proven to be a valid and reliable tool to measure the quality of beef cattle stockmanship. Specific handler actions have been weighted based on their perceived negative relationship to cattle stress from handling. The purpose of this article is to 1) document the initial use of the scorecard in a beef cattle feedlot setting and 2) provide further support to its validity by establishing an association with other quantitative and qualitative means of evaluating stockmanship. The Scorecard was used at 39 beef feedlots in Texas between March 2018 and April 2019. Eighty-four stockman were observed, and the average score received was 84.5 (SD = 14.73, range = 20 to 100). The most frequent mistakes observed were as follows: fills crowd pen/tub over half full (n = 39), slow to remove pressure (n = 29), uses unnecessary noise (n = 25), stands in front and taps rear (n = 24), and fails to regulate animal flow through a pinch point (n = 22). A strong negative association (ρ = -0.51) was found between the points deducted from the Noise and Physical Contact theme of the Scorecard and the number of animals touched with an electric prod from the BQA Feedyard Assessment. Moderate negative associations were found between the Scorecard final score and the number of animals that vocalize in the chute prior to procedures (ρ = -0.31). Those stockmen that scored above average on the Scorecard were qualitatively observed to be calm and quiet while working with the cattle (Kappa = 0.44). The qualitative disposition of cattle had little effect on the final score of stockmen using the Scorecard (Kappa = 0.17). The use of the Scorecard in a feedlot setting has demonstrated that as stockman scores decrease, there is an increase in the number of negative actions toward cattle and a negative behavioral response of the cattle themselves. Establishment of an association between a stockman's score using the Stockman's Scorecard and the animal-based observations from the BQA Feedyard Assessment further strengthens the validity of the Stockman's Scorecard as a tool to measure the quality of beef cattle stockmanship. The Scorecard has application as a tool to identify specific stockmanship deficiencies in order to target stockmanship training.

Linear lipoatrophy following intra-articular triamcinolone acetonide injection mimicking linear scleroderma.

A 12-year-old female with oligoarticular juvenile inflammatory arthritis developed an atrophic linear plaque involving the left medial forearm and proximal arm 7 months after intra-articular triamcinolone injection for arthritis. The plaque spontaneously resolved without treatment over approximately one year. It is important to recognize this rare complication of intra-articular steroid injection in order to avoid potential misdiagnosis as linear scleroderma and subsequent immunosuppressive treatment.

Planimetric Post-hoc Analysis of Women With Onychomycosis from Tavaborole 5% Phase III Studies: Evidence of Greater Improvements in Patients With >50% Baseline Infection.

Women with onychomycosis may suffer more effects on their quality of life than men. There is limited female-specific data on the treatment of onychomycosis. Tavaborole is a topical treatment option for onychomycosis. This post-hoc study evaluated the nail plates of women using data from the tavaborole 5% Phase III studies at baseline and end of study for the areas of healthy nail and infected nail. Over 52 weeks (48-week treatment, 4-week follow up), women treated with tavaborole had an average 32% increase in healthy nail and 21% decrease in infected nail. Patients with baseline infection involving >50% of the nail plate had an average increase in percentage of unaffected nail surface area of 81% and a corresponding 51% decrease in infected nail. These analyses suggest that patients with the greatest toenail involvement at baseline had greater overall improvements than those who were less affected. This evaluation provides additional clinical guidance for treating women with onychomycosis using tavaborole. J Drugs Dermatol. 2018;17(2):168-172.

The Role of Alpha-MSH as a Modulator of Ocular Immunobiology Exemplifies Mechanistic Differences between Melanocortins and Steroids.

Melanocortins are a highly conserved family of peptides and receptors that includes multiple proopiomelanocortin-derived peptides and five defined melanocortin receptors. The melanocortins have an important role in maintaining immune homeostasis and in suppressing inflammation. Within the healthy eye, the melanocortins have a central role in preventing inflammation and maintaining immune privilege. A central mediator of the anti-inflammatory activity is the non-steroidogenic melanocortin peptide alpha-melanocyte stimulating hormone. In this review we summarize the major findings of melanocortin regulation of ocular immunobiology with particular interest in the ability of melanocortin to induce immune tolerance and cytoprotection. The melanocortins have therapeutic potential because their mechanisms of action in regulating immunity are distinctly different from the actions of steroids.

A case and review of congenital leukonychia.

Leukonychia refers to a white discoloration of the nails. Although several conditions may cause white nails, a rare, isolated, congenital form of the disease is hypothesized to stem from disordered keratinization of the nail plate. Herein, we report a case of a 41-year-old woman with congenital leukonychia and review prior cases.

Nail lichen planus in a patient with alopecia totalis.

A 67-year-old man with a three-year history of non-scarring alopecia that progressed to alopecia totalis despite intralesional glucocorticoid injections is presented. He developed 20-nail dystrophy that was recalcitrant to antifungal and anti-inflammatory treatments. Biopsy of the nail matrix showed histopathologic features of lichen planus. Alopecia totalis and isolated lichen planus of the nails are uncommon subtypes of common dermatologic disorders. Rarely reported concurrently, we provide a review of the literature of their association, which is most likely attributed to their autoimmune pathogeneses.

Dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is an autoimmune bullous disease, which represents the cutaneous manifestation of gluten sensitivity, in the setting of celiac disease. Although classical DH is characterized clinically by grouped, vesicles on an erythematous base, primary lesions often are absent owing to the intense, associated pruritus. Instead, many cases present only with erythematous erosions with numerous overlying excoriations. As in celiac disease, the core pathogenic mechanisms of DH are likely mediated by immunoglobulin A class autoantibodies against one of several transglutaminase enzymes. As the production of these autoantibodies is directly correlated with gastrointestinal exposure to gliadin, which is an alcohol-soluble fraction of gluten, a gluten-free diet represents the cornerstone of a DH management regimen. In cases refractory to dietary management alone, dapsone is the first-line agent for the treatment of DH, although many other agents have been anecdotally reported as effective.

Necrolytic acral erythema.

Necrolytic acral erythema is a rare, cutaneous manifestation of hepatitis C virus infection that is characterized by erythematous, violaceous or dusky papules, blisters, and/or erosions in the early stages and by well-demarcated, hyperkeratotic, targetoid plaques with a peripheral rim of macular erythema, secondary lichenification and hyperpigmentation, and overlying fine micaceous or necrotic-appearing scale in the later stages. Because most topical modalities prove ineffective, treatment of the underlying viral infection or therapeutic zinc supplementation are required for clinical improvement.

Serratia marcescens folliculitis and concomitant acne vulgaris.

We present a unique case of S. marcescens folliculitis of the trunk in a 46-year-old woman with a history of facial acne vulgaris during her teen years. Her eruption occurred at the time of elective ambulatory surgery when she was treated with pre and post-operative antibiotics. The diagnosis of S. marcescens folliculitis was made on the basis of histopathologic features and tissue culture of a skin biopsy specimen of a pustule after her eruption was unresponsive to conventional treatment for inflammatory acne vulgaris. The history and pathophysiology of gram-negative folliculitis in the setting of acne vulgaris is reviewed.

Fox-Fordyce disease.

Fox-Fordyce disease (FFD) is a rare inflammatory disorder that affects the apocrine sweat glands. Clinically, lesions are equidistant, smooth, uniform, firm, folliculocentric papules, which can range in color from flesh-colored to red-brown to slightly yellow. Whereas the axillae are most commonly involved, FFD also can involve the anogenital and periareolar areas, lips, umbilicus, sternum, perineum, and upper medial aspects of the thighs. The underlying etiology of FFD remains unclear although epidemiologic data support a hormonal component because women are more commonly affected than men. Moreover, symptoms initially present after the onset of puberty, flare perimenstrually, and often resolve during pregnancy and after menopause. Histopathologic findings include the obstruction of the apocrine duct by a hyperkeratotic plug in the follicular infundibulum, which is believed to represent the primary pathophysiologic process; subsequent ductal rupture and resulting inflammatory response produce the typical clinical picture. Treatment of FFD is difficult because no one agent has proven particularly effective. Topical and interlesional glucocorticoids are often considered the first-line pharmacologic agents, although use is often limited by concerns for atrophy. Other agents that have shown some success include topical and systemic retinoids, topical clindamycin, topical pimecrolimus cream, benzoyl peroxide, and oral contraceptives. For medication-refractory cases, mechanical destruction or removal of the apocrine glands has been efficacious in small case series.

Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone methylation.

The development of disease-modifying pharmacologic therapy for osteoarthritis (OA) currently faces major obstacles largely because the regulatory mechanisms for the function of adult articular chondrocytes remain unclear. We previously demonstrated that lack of Nfat1, one of the nuclear factor of activated T cells (NFAT) transcription factors, causes OA-like changes in adult mice. This study aimed to identify whether Nfat1 specifically regulates adult articular chondrocyte function and its age-dependent regulatory mechanism using both Nfat1-deficient and wild-type mice. Deletion of Nfat1 did not induce OA-like articular chondrocyte dysfunction (e.g., overexpression of proinflammatory cytokines and matrix-degrading proteinases) until the adult stage. RNAi-mediated Nfat1 knockdown caused dysfunction of wild-type adult articular chondrocytes. Nfat1 expression in wild-type articular chondrocytes was low in the embryonic but high in the adult stage. Chromatin immunoprecipitation assays demonstrated that an increase in Nfat1 expression in articular chondrocytes was associated with increased H3K4me2 (a histone modification linked to transcriptional activation), whereas a decrease in Nfat1 expression in articular chondrocytes was correlated with increased H3K9me2 (a histone modification linked to transcriptional repression). Knockdown of lysine-specific demethylase-1 (Lsd1) in embryonic articular chondrocytes upregulated Nfat1 expression concomitant with increased H3K4me2 at the Nfat1 promoter. Knockdown of Jmjc-containing histone demethylase-2a (Jhdm2a) in 6-month articular chondrocytes downregulated Nfat1 expression concomitant with increased H3K9me2 at the Nfat1 promoter. These results suggest that Nfat1 is an essential transcriptional regulator of chondrocyte homeostasis in adult articular cartilage. Age-dependent Nfat1 expression in articular chondrocytes is regulated by dynamic histone methylation, one of the epigenetic mechanisms that regulate gene transcription.

Transcription factor Nfat1 deficiency causes osteoarthritis through dysfunction of adult articular chondrocytes.

Osteoarthritis (OA) is the most common form of joint disease in middle-aged and older individuals. Previous studies have shown that over-expression of matrix-degrading proteinases and proinflammatory cytokines is associated with osteoarthritic cartilage degradation. However, it remains unclear which transcription factors regulate the expression of these cartilage-degrading molecules in articular chondrocytes. This study demonstrated that mice lacking Nfat1, a member of the nuclear factor of activated T cells (NFAT) transcription factors, exhibited normal skeletal development but displayed loss of type II collagen (collagen-2) and aggrecan with over-expression of specific matrix-degrading proteinases and proinflammatory cytokines in young adult articular cartilage of load-bearing joints. These initial changes are followed by articular chondrocyte proliferation/clustering, progressive articular surface destruction, periarticular chondro-osteophyte formation and exposure of thickened subchondral bone, all of which resemble human OA. Forced expression of Nfat1 delivered with lentiviral vectors in cultured 3 month-old primary Nfat1 knockout (Nfat1(-/-)) articular chondrocytes partially or completely rescued the abnormal catabolic and anabolic activities of Nfat1(-/-) articular chondrocytes. These new findings revealed a previously unrecognized critical role of Nfat1 in maintaining the physiological function of differentiated adult articular chondrocytes through regulating the expression of specific matrix-degrading proteinases and proinflammatory cytokines. Nfat1 deficiency causes OA due to an imbalance between the catabolic and anabolic activities of adult articular chondrocytes, leading to articular cartilage degradation and failed repair activities in and around articular cartilage. These results may provide new insights into the aetiology, pathogenesis and potential therapeutic strategies for osteoarthritis.

Two cases of syringotropic cutaneous T-cell lymphoma and review of the literature.

Syringotropic cutaneous T-cell lymphoma (CTCL) is a rare form of CTCL characterized histologically by infiltrates of atypical lymphocytes located primarily in and around hyperplastic eccrine glands and ducts. Currently, syringotropic CTCL is classified as a histopathologic variant of folliculotropic mycosis fungoides (MF); however, the relationship between these two entities remains tenuous. We report two additional cases of syringotropic CTCL and review the differences between these two subtypes of MF with regard to epidemiology, clinical features, prognosis, and treatment. Based on these data, we conclude that syringotropic CTCL should be classified as a distinct variant of MF separate from folliculotropic MF.