RESUMEN
Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) can be histologically similar. Immunohistochemistry (IHC) for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) are commonly used to differentiate MCC from SCLC; however, these markers have limited sensitivity and specificity. To identify new diagnostic markers, we performed differential gene expression analysis on transcriptome data from MCC and SCLC tumors. Candidate markers included atonal BHLH transcription factor 1 (ATOH1) and transcription factor AP-2ß (TFAP2B) for MCC, as well as carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) for SCLC. Immunostaining for CK20, TTF-1, and new candidate markers was performed on 43 MCC and 59 SCLC samples. All three MCC markers were sensitive and specific, with CK20 and ATOH1 staining 43/43 (100%) MCC and 0/59 (0%) SCLC cases and TFAP2B staining 40/43 (93%) MCC and 0/59 (0%) SCLC cases. TTF-1 stained 47/59 (80%) SCLC and 1/43 (2%) MCC cases. CEACAM6 stained 49/59 (83%) SCLC and 0/43 (0%) MCC cases. Combining CEACAM6 and TTF-1 increased SCLC detection sensitivity to 93% and specificity to 98%. These data suggest that ATOH1, TFAP2B, and CEACAM6 should be explored as markers to differentiate MCC and SCLC.
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Environmental, or exogenous, dermatitis is comprised of irritant and allergic contact dermatitis, which account for 80% and 20% of cases of contact dermatitis, respectively. Contact dermatitis is extremely common, and failure to diagnose this entity may result in overlooking a potentially curable driver of disease. In this review, we describe how clinical features, such as morphology or history, can assist in distinguishing exogenous from endogenous causes of dermatitis, and allergic from irritant contact dermatitis. Additionally, we provide an overview of common contact allergens and how dermatitis distribution can suggest possible culprit allergens. Patch testing is needed to confirm contact allergy.
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Dermatitis Alérgica por Contacto , Dermatitis Irritante , Alérgenos , Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/etiología , Dermatitis Irritante/diagnóstico , Dermatitis Irritante/etiología , Humanos , Pruebas del ParcheAsunto(s)
Carcinoma de Células de Merkel/epidemiología , Neoplasias Cutáneas/epidemiología , Factores de Edad , Anciano , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/patología , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Estado Civil , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Programa de VERF , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Estados Unidos/epidemiologíaRESUMEN
Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. We propose that ARF6 inactivation may occur downstream of PP2A activation since: (1) sphingolipids that fail to activate PP2A did not reduce ARF6-GTP levels; (2) a structurally unrelated PP2A activator disrupted tubular recycling endosome morphology and transporter localization; and (3) overexpression of a phosphomimetic mutant of the ARF6 GEF GRP1 prevented nutrient transporter loss. ARF6 inhibition alone was not toxic; however, the ARF6 inhibitors SecinH3 and NAV2729 dramatically enhanced the killing of cancer cells by SH-BC-893 without increasing toxicity to peripheral blood mononuclear cells, suggesting that ARF6 inactivation contributes to the anti-neoplastic actions of sphingolipids. Taken together, these studies provide mechanistic insight into how ceramide and sphingolipid-like molecules limit nutrient access and suppress tumor cell growth and survival.
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Factores de Ribosilacion-ADP/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Nutrientes/metabolismo , Esfingolípidos/metabolismo , Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Línea Celular Tumoral , Proteínas del Citoesqueleto/metabolismo , Endosomas/efectos de los fármacos , Endosomas/metabolismo , Clorhidrato de Fingolimod/farmacología , Cadena Pesada de la Proteína-1 Reguladora de Fusión/metabolismo , Células HeLa , Humanos , Proteínas con Dominio LIM/metabolismo , Células MCF-7 , Proteínas de Microfilamentos , Oxigenasas de Función Mixta , Esfingolípidos/farmacologíaRESUMEN
Comma and corkscrew hairs are trichoscopic markers of tinea capitis. Although comma hairs have been reported in both black and white patients with tinea capitis, corkscrew hairs were previously hypothesized to manifest exclusively in patients with curly or African hair types. However, we report a significant number of comma and corkscrew hairs in a Hispanic female patient with naturally straight hair and Trichophyton tonsurans tinea capitis. Thus, dermoscopy is a rapid, noninvasive, and cost-effective tool for evaluating tinea capitis and should be used in combination with culture in all patients regardless of hair texture or race.
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Cabello/patología , Tiña del Cuero Cabelludo/patología , Adulto , Dermoscopía , Femenino , Hispánicos o Latinos , Humanos , TrichophytonRESUMEN
GATA2 deficiency is a recently described genetic disorder affecting hematopoietic stem cells and is associated with immunodeficiency, hematologic malignancy, and various cutaneous pathologies including cutaneous tumors. To explore the incidence and clinical course of melanoma in patients with germline GATA2 deficiencies, we conducted a retrospective chart review of 71 such patients and identified two with invasive melanoma. One melanoma was diagnosed early because it was associated with pruritus due to a graft-versus-tumor effect following bone marrow transplantation. The other one, a lentigo maligna melanoma, was locally excised but progressed to widespread metastasis and death several years later. Our observations and published studies of melanoma biology suggest an association between decreased GATA2 expression and melanoma progression. These findings suggest that GATA2 deficient patients may have an increased risk of melanoma and should be observed closely for new or changing skin lesions.
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Factor de Transcripción GATA2/deficiencia , Melanoma/metabolismo , Femenino , Factor de Transcripción GATA2/metabolismo , Humanos , Melanoma/diagnóstico , Melanoma/patología , Modelos Biológicos , Factores de RiesgoRESUMEN
Angiokeratomas can present therapeutic challenges, especially in cases of extensive lesions, where traditional surgical methods carry high risks of scarring and hemorrhage. Argon, pulsed dye (PDL), neodymium-doped yttrium aluminum garnet (Nd:YAG), copper vapor, potassium titanyl phosphate, carbon dioxide, and erbium-doped yttrium aluminum garnet (Er:YAG) lasers have emerged as alternative options. To review the use and efficacy of lasers in treating angiokeratomas. A PubMed search identified randomized clinical trials, cohort studies, case series, and case reports involving laser treatment of cutaneous angiokeratomas. Twenty-five studies were included. Quality ratings were assigned using the Oxford Centre for Evidence-Based Medicine scheme. Several laser modalities are effective in treating multiple variants of angiokeratomas. Vascular lasers like PDL, Nd:YAG, and argon are the most studied and of these, PDL offers the safest side effect profile. Nd:YAG may be more effective for hyperkeratotic angiokeratomas. Combination treatment with multiple laser modalities has also demonstrated some success. Lasers are a promising treatment option for angiokeratomas, but current use is limited by the lack of treatment guidelines. There are limited high quality studies comparing laser treatments to each other and to non-laser options. Additional studies are needed to establish guidelines and to optimize laser parameters.
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Angioqueratoma/cirugía , Terapia por Láser/instrumentación , Láseres de Colorantes/uso terapéutico , Láseres de Gas/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Neoplasias Cutáneas/cirugía , Angioqueratoma/patología , Diseño de Equipo , Humanos , Terapia por Láser/efectos adversos , Láseres de Colorantes/efectos adversos , Láseres de Gas/efectos adversos , Láseres de Estado Sólido/efectos adversos , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
Merkel cell carcinoma is a rare skin cancer associated with Merkel cell polyomavirus in most cases. Prior studies associating Merkel cell carcinoma viral status with prognosis have inconsistent findings. Moshiri et al. used multimodal virus detection to determine that the 81% of patients with virus-positive Merkel cell carcinoma tumors had earlier stage disease and better outcomes relative to virus-negative cases.
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Carcinoma de Células de Merkel/virología , Poliomavirus de Células de Merkel/aislamiento & purificación , Infecciones por Polyomavirus/diagnóstico , Neoplasias Cutáneas/virología , Infecciones Tumorales por Virus/virología , Anciano , Biopsia con Aguja , Carcinoma de Células de Merkel/patología , ADN Viral/análisis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Polyomavirus/patología , Pronóstico , Enfermedades Raras , Medición de Riesgo , Muestreo , Neoplasias Cutáneas/patología , Infecciones Tumorales por Virus/patologíaRESUMEN
Achille Civatte (1877-1956) was one of the most highly regarded dermatologists of the 20th century. We provide a succinct account of Civatte's academic life and contributions to the field of dermatopathology, in addition to briefly discussing his son, Jean Civatte, who himself became a highly regarded dermatologist.
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Dermatología/historia , Microscopía/historia , Francia , Historia del Siglo XIX , Historia del Siglo XX , HumanosRESUMEN
Dermatology departments in the United States face difficulties in recruiting dermatologists to academic positions, raising concerns for the future of dermatology education and research. This preliminary study aimed to explore the impact of student loan burden on career plans in dermatology and to determine if the Public Service Loan Forgiveness (PSLF) program can be used as a recruitment tool for academic positions in dermatology. Results from this electronic survey, which was distributed to dermatology residents and attending physicians, revealed that debt burden may influence career decisions in dermatology. Dermatologists may not be fully educated on loan repayment options. With increased awareness, the PSLF can potentially be used as a recruitment tool for academic positions in dermatology.
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Selección de Profesión , Dermatólogos/educación , Dermatología/educación , Apoyo a la Formación Profesional/economía , Adulto , Dermatólogos/economía , Dermatología/economía , Femenino , Humanos , Internado y Residencia/estadística & datos numéricos , Masculino , Médicos , Encuestas y Cuestionarios , Apoyo a la Formación Profesional/estadística & datos numéricos , Estados UnidosRESUMEN
BACKGROUND: There is growing data on complementary and alternative medicine (CAM) preferences among college students. While several studies have focused on undergraduate students, there is limited data on graduate students. MATERIALS AND METHODS: Cross sectional analysis of undergraduate and graduate students seeking medical care at the University of California Irvine's Student Health Center (SHC). The survey assessed previous CAM use and preferences for future CAM use and education. RESULTS: The majority (67.0%) had used CAM within the last year, 27.0% would use CAM for their current health condition, and 51.9% would consider CAM for their current health condition if they were more knowledgeable. Most respondents desired more CAM education and indicated that they would try CAM modalities if covered under insurance. CONCLUSION: Most college students requested more knowledge to assist in their decisions to use CAM. These findings provide insight for health centers on the preferences of college student patients.
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Terapias Complementarias/estadística & datos numéricos , Aceptación de la Atención de Salud , Estudiantes , Universidades , Adulto , California , Estudios Transversales , Atención a la Salud , Femenino , Instituciones de Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
IMPORTANCE: Although cutaneous warts are common lesions, full remission is not always achieved with conventional therapies. Laser modalities including carbon dioxide (CO2), erbium:yttrium-aluminum-garnet (Er:YAG), pulsed dye (PDL), and Nd:YAG have been investigated as alternative treatments for warts. OBJECTIVE: To review the use and efficacy of lasers for treating nongenital cutaneous warts. EVIDENCE REVIEW: Published randomized clinical trials (RCTs), cohort studies, case series, and case reports involving laser treatment of nongenital warts were retrieved by searching PubMed with no date limits. Quality ratings of studies were based on a modified version of the Oxford Centre for Evidence-Based Medicine scheme for rating individual studies. A higher emphasis was placed on RCTs and prospective cohort studies with large sample sizes and detailed methodology. FINDINGS: There were 35 studies published between 1989 and 2015 that comprised an aggregate of 2149 patients. Simple and recalcitrant nongenital warts treated with lasers show variable response rates (CO2 laser, 50%-100%; Er:YAG laser, 72%-100%; PDL, 47%-100%; and Nd:YAG laser, 46%-100%). Current RCTs suggest that PDL is equivalent to conventional therapies such as cryotherapy and cantharidin. Combination therapies with lasers and other agents including bleomycin, salicylic acid, and light-emitting diode have shown some success. CONCLUSIONS AND RELEVANCE: Lasers can be an effective treatment option for both simple and recalcitrant warts. The lasers most studied for this purpose are CO2, PDL, and Nd:YAG, and of these, PDL has the fewest adverse effects. Currently, use of lasers for wart treatment is limited by lack of established treatment guidelines. Future studies are needed to compare laser modalities with each other and with nonlaser treatment options, and to establish optimal treatment protocols.
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Láseres de Colorantes/uso terapéutico , Láseres de Gas/uso terapéutico , Láseres de Estado Sólido/uso terapéutico , Enfermedades de la Piel/cirugía , Verrugas/cirugía , Humanos , Resultado del TratamientoRESUMEN
INTRODUCTION: We evaluated complementary and alternative medicine (CAM) use among a medically underserved, predominately Hispanic community at the University of California Irvine Family Health Center, a federally qualified health center. METHODS: A cross-sectional, anonymous survey assessed patient use of, interest in, and communication preferences concerning CAM. RESULTS: The 150 respondents primarily self-identified as Hispanic (74%), were born outside the United States (55%), were medically insured (56%), and had a high school education or less (55%). Of these respondents, 63% used at least 1 type of CAM; the most commonly used were: vitamins/supplements (32%), herbal medicine (29%), dietary/nutritional therapy (26%), massage (24%), meditation/relaxation (15%) and chiropractic (11%). Therapies that patients most desired to see provided at the clinic included massage, healthier cooking, guidance on herbs/supplements, and diet/nutrition. Among respondents, 61% were comfortable disclosing CAM use to physicians, 58% agreed physicians should have basic knowledge of CAM, and 47% desired that physicians ask about CAM use. CONCLUSIONS: Results demonstrate that CAM use is common among patients, and a large proportion of patients have interest in accessing CAM through their primary care clinic. Patients recognize the importance of communicating CAM use with their providers and seem receptive to discussing such topics.
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Centros Comunitarios de Salud , Terapias Complementarias/estadística & datos numéricos , Hispánicos o Latinos , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Adulto JovenRESUMEN
Complementary and alternative medicine (CAM) is widely used by adults in the USA. However, most physicians do not inquire about CAM use leading to missed opportunities to dialogue about wellness and detect harmful practices. In 2012, an integrative medicine (IM) consultation clinic alongside an optional IM Residency Track for family medicine residents was established at the University of California, Irvine Family Health Center in Santa Ana, CA. This study evaluated the impact of these programmes on physicians' CAM/IM knowledge and receptiveness. Online surveys assessing self-reported attitudes, knowledge and practices were distributed in 2012 (baseline) and 2014 (follow-up) to family physicians with response rates of 83% (35/42) and 62% (23/37), respectively. At baseline, 91.5% of physicians believed that patient satisfaction would moderately/strongly increase if offered CAM/IM consultations and therapies. At follow- up, physician understanding of clinical applications of massage, acupuncture, meditation/relaxation, yoga and Tai Chi increased. Percentage of physician referrals to a CAM/IM consultation clinic increased (5.7- 69.6%; p < 0.01) as well as physician-initiated CAM/IM discussion (20.0-60.9%; p < 0.01). This study demonstrates the immediate effect of IM education in a primary care training site and the receptiveness of its community-based physicians towards these changes.