RESUMEN
Immune cells and epithelium form sophisticated barrier systems in symbiotic relationships with microbiota. Evidence suggests that immune cells can sense microbes through intact barriers, but regulation of microbial commensalism remain largely unexplored. Here, we uncovered spatial compartmentalization of skin-resident innate lymphoid cells (ILCs) and modulation of sebaceous glands by a subset of RORγt+ ILCs residing within hair follicles in close proximity to sebaceous glands. Their persistence in skin required IL-7 and thymic stromal lymphopoietin, and localization was dependent on the chemokine receptor CCR6. ILC subsets expressed TNF receptor ligands, which limited sebocyte growth by repressing Notch signaling pathway. Consequently, loss of ILCs resulted in sebaceous hyperplasia with increased production of antimicrobial lipids and restricted commensalism of Gram-positive bacterial communities. Thus, epithelia-derived signals maintain skin-resident ILCs that regulate microbial commensalism through sebaceous gland-mediated tuning of the barrier surface, highlighting an immune-epithelia circuitry that facilitates host-microbe symbiosis.
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Linfocitos/inmunología , Glándulas Sebáceas/metabolismo , Glándulas Sebáceas/microbiología , Animales , Bacterias/metabolismo , Citocinas/metabolismo , Epitelio/inmunología , Folículo Piloso/metabolismo , Folículo Piloso/microbiología , Inmunidad Innata , Interleucina-7/metabolismo , Linfocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microbiota/inmunología , Receptores CCR6/metabolismo , Receptores Notch/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Glándulas Sebáceas/inmunología , Piel/metabolismo , Fenómenos Fisiológicos de la Piel , Simbiosis , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects 2.5 million people worldwide. Growing evidence suggests that perturbation of the gut microbiota, the dense collection of microorganisms that colonize the gastrointestinal tract, plays a functional role in MS. Indeed, specific gut-resident bacteria are altered in patients with MS compared to healthy individuals, and colonization of gnotobiotic mice with MS-associated microbiota exacerbates preclinical models of MS. However, defining the molecular mechanisms by which gut commensals can remotely affect the neuroinflammatory process remains a critical gap in the field. METHODS: We utilized monophasic experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice and relapse-remitting EAE in SJL/J mice to test the effects of the products from a human gut-derived commensal strain of Lactobacillus paracasei (Lb). RESULTS: We report that Lb can ameliorate preclinical murine models of MS with both prophylactic and therapeutic administrations. Lb ameliorates disease through a Toll-like receptor 2-dependent mechanism via its microbe-associated molecular patterns that can be detected in the systemic circulation, are sufficient to downregulate chemokine production, and can reduce immune cell infiltration into the central nervous system (CNS). In addition, alterations in the gut microbiota mediated by Lb-associated molecular patterns are sufficient to provide partial protection against neuroinflammatory diseases. CONCLUSIONS: Local Lb modulation of the gut microbiota and the shedding of Lb-associated molecular patterns into the circulation may be important physiological signals to prevent aberrant peripheral immune cell infiltration into the CNS and have relevance to the development of new therapeutic strategies for MS.
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Sistema Nervioso Central/inmunología , Microbioma Gastrointestinal/inmunología , Lacticaseibacillus paracasei/inmunología , Leucocitos/inmunología , Animales , Sistema Nervioso Central/patología , Femenino , Humanos , Leucocitos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
Microglia are the only resident myeloid cell in the central nervous system (CNS) parenchyma, but the role of microglia in the context of neurotropic viral infection is poorly understood. Using different amounts of Theiler's murine encephalomyelitis virus (TMEV) in a preclinical model of epilepsy and PLX5622, a colony stimulating factor-1 receptor inhibitor that selectively depletes microglia in the CNS, we report that microglia-depleted, TMEV-infected mice develop seizures, manifest paralysis, and uniformly succumb to fatal encephalitis regardless of viral amount. CNS demyelination correlates with viral amount; however, viral amount does not correlate with axon damage and TMEV antigen in the CNS.
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Infecciones por Cardiovirus/inmunología , Encefalitis Viral/inmunología , Microglía/inmunología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Theilovirus/inmunologíaAsunto(s)
Dermatología , Humanos , Utah , Wyoming , Estudios Retrospectivos , Accesibilidad a los Servicios de SaludRESUMEN
As skin cancer rates continue to rise, targeted efforts to reduce excessive exposure to ultraviolet radiation are crucial. Adolescents are a high-risk population for intentional tanning; thus, we sought to determine whether the novel use of skin age analysis with ultraviolet (UV) photography would be an effective tool for reducing intentions to tan in adolescents with a calculated skin age (measured by complexion analysis software) that exceeds their actual age. Surveying 85 students in this study, skin age difference above zero was associated with reduced intentions to tan (P = 0.006) and high-risk sun exposure behaviors were identified. This provides rationale for skin age analysis as a potentially effective intervention in decreasing intentions to tan in this high-risk young population.
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Conocimientos, Actitudes y Práctica en Salud , Envejecimiento de la Piel/fisiología , Baño de Sol , Rayos Ultravioleta/efectos adversos , Adolescente , Conducta del Adolescente , Femenino , Humanos , Intención , Masculino , Proyectos Piloto , Factores de Riesgo , Piel , Adulto JovenRESUMEN
BACKGROUND: Total body photography (TBP) can facilitate identification of new and changing lesions. By confirming that particular nevi are stable, TBP may reduce nevus biopsies. OBJECTIVES: We sought to determine the number and rate of nevus biopsies before and after TBP, and the factors associated with increased biopsy rate during monitoring by TBP. METHODS: We reviewed records of all patients in 2 pigmented lesion clinics (PLCs) who received TBP and had 2 or more follow-up visits over a period of 2 years or longer. RESULTS: Before PLCs and TBP, the mean number of nevus biopsies per patient was 5.92 (589 patients) at a mean rate of 1.62 per year (160 patients). After TBP in PLCs, the same patients averaged 1.56 biopsies at a mean rate of 0.34 per year (P < 2 × 10(-16)). The entire cohort (926 patients) averaged similarly low post-TBP biopsy rates of less than 0.2 per year and per visit. Biopsy rates after TBP were positively correlated with decreased age, male gender, and family history of melanoma, but not nevus number. LIMITATIONS: Some information was not available for some patients. CONCLUSIONS: Patients at risk for melanoma experienced a 3.8-fold reduction in nevus biopsies after TBP. Younger male patients with family history of melanoma had higher biopsy rates after TBP.
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Biopsia/estadística & datos numéricos , Melanoma/patología , Nevo/patología , Fotograbar , Vigilancia de la Población/métodos , Neoplasias Cutáneas/patología , Adulto , Factores de Edad , Biopsia/tendencias , Femenino , Humanos , Masculino , Melanoma/diagnóstico por imagen , Melanoma/genética , Persona de Mediana Edad , Nevo/diagnóstico por imagen , Nevo/genética , Fotograbar/métodos , Factores Sexuales , Piel/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/genéticaRESUMEN
The criterion standard for diagnosing cutaneous melanoma continues to be histologic examination. However, classifying some melanocytic lesions by conventional microscopy can be problematic if they exhibit some architectural or morphologic characteristics of both nevus and melanoma. Moreover, histologic appearance does not always predict biologic behavior. There is therefore a need and opportunity to develop new technologies that can facilitate the histologic diagnosis of melanoma and potentially help distinguish lesions with a lesser or greater risk of metastasis. In part II of this 2-part continuing medical education article, we will review the molecular technologies currently available for facilitating melanoma diagnosis, including comparative genomic hybridization, fluorescence in situ hybridization, and epidermal genetic retrieval. Our goal is to provide the clinician with an up to date understanding of these molecular approaches so that they can be applied to their management of challenging melanocytic lesions.
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Síndrome del Nevo Displásico/diagnóstico , Melanoma/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Neoplasias Cutáneas/diagnóstico , Hibridación Genómica Comparativa , Diagnóstico Diferencial , Síndrome del Nevo Displásico/genética , Educación Médica Continua , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ/métodos , Masculino , Melanoma/genética , Nevo de Células Epitelioides y Fusiformes/genética , Sensibilidad y Especificidad , Neoplasias Cutáneas/genéticaAsunto(s)
Continuidad de la Atención al Paciente/organización & administración , Dermatología/organización & administración , Personas con Mala Vivienda/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Enfermedades de la Piel/terapia , Adulto , Continuidad de la Atención al Paciente/estadística & datos numéricos , Dermatología/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Humanos , Perdida de Seguimiento , Masculino , Persona de Mediana Edad , Derivación y Consulta/estadística & datos numéricos , Enfermedades de la Piel/diagnósticoRESUMEN
Pharmacological inhibition of KRAS>RAF>MEK1/2>ERK1/2 signaling has provided no clinical benefit to patients with pancreatic ductal adenocarcinoma (PDAC). Interestingly, combined inhibition of MEK1/2 (with trametinib [T]) plus autophagy (with chloroquine [CQ] or hydroxychloroquine [HCQ]) demonstrated striking anti-tumor effects in preclinical models and in a patient (Patient 1). However, not all patients respond to the T/HCQ regimen, and Patient 1 eventually developed resistant disease. Here we report that primary or acquired resistance is associated with focal DNA copy number gains encompassing c-MYC. Furthermore, ectopic expression of c-MYC in PDAC cell lines rendered them T/HCQ resistant. Interestingly, a CDK4/6 inhibitor, palbociclib (P), also induced autophagy and overrode c-MYC-mediated T/HCQ resistance, such that P/HCQ promoted regression of T/HCQ-resistant PDAC tumors with elevated c-MYC expression. Finally, P/HCQ treatment of Patient 1 resulted in a biochemical disease response. These data suggest that elevated c-MYC expression is both a marker and a mediator of T/HCQ resistance, which may be overcome by the use of P/HCQ.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Cloroquina/farmacología , Cloroquina/uso terapéutico , Quinasa 4 Dependiente de la Ciclina/uso terapéutico , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Lisosomas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias PancreáticasRESUMEN
Preventing or effectively treating metastatic uveal melanoma (UM) is critical because it occurs in about half of patients and confers a very poor prognosis. There is emerging evidence that hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1) promote metastasis and contribute to the striking metastatic hepatotropism observed in UM metastasis. However, the molecular mechanisms by which HGF and IGF-1 promote UM liver metastasis have not been elucidated. ASAP1, which acts as an effector for the small GTPase ARF6, is highly expressed in the subset of uveal melanomas most likely to metastasize. Here, we found that HGF and IGF-1 hyperactivate ARF6, leading to its interaction with ASAP1, which then acts as an effector to induce nuclear localization and transcriptional activity of NFAT1. Inhibition of any component of this pathway impairs cellular invasiveness. Additionally, knocking down ASAP1 or inhibiting NFAT signaling reduces metastasis in a xenograft mouse model of UM. The discovery of this signaling pathway represents not only an advancement in our understanding of the biology of uveal melanoma metastasis but also identifies a novel pathway that could be targeted to treat or prevent metastatic uveal melanoma.
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Melanoma , Neoplasias de la Úvea , Humanos , Animales , Ratones , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Melanoma/patología , Neoplasias de la Úvea/metabolismo , Modelos Animales de Enfermedad , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
Viral encephalitis is a major cause of morbidity and mortality, but the manifestation of disease varies greatly between individuals even in response to the same virus. Microglia are professional antigen presenting cells that reside in the central nervous system (CNS) parenchyma that are poised to respond to viral insults. However, the role of microglia in initiating and coordinating the antiviral response is not completely understood. Utilizing Theiler's murine encephalomyelitis virus (TMEV), a neurotropic picornavirus, and PLX5622, a small molecule inhibitor of colony-stimulating factor 1 receptor (CSF1R) signaling that can deplete microglia in the CNS; we investigated the role of the CSF1R-microglia axis in neurotropic picornavirus infection of C57BL/6J and SJL/J mice. These mouse strains differ in their ability to clear TMEV and exhibit different neurological disease in response to TMEV infection. CSF1R antagonism in C57BL/6J mice, which normally clear TMEV in the CNS, led to acute fatal encephalitis. In contrast, CSF1R antagonism in SJL/J mice, which normally develop a chronic CNS TMEV infection, did not result in acute encephalitis, but exacerbated TMEV-induced demyelination. Immunologically, inhibition of CSF1R in C57BL/6J mice reduced major histocompatibility complex II expression in microglia, decreased the proportion of regulatory T cells in the CNS, and upregulated proinflammatory pathways in CNS T cells. Acute CSF1R inhibition in SJL/J mice had no effect on microglial MHC-II expression and upregulated anti-inflammatory pathways in CNS T cells, however chronic CSF1R inhibition resulted in broad immunosuppression. Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.
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Infecciones por Cardiovirus/inmunología , Microglía/inmunología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/metabolismo , Compuestos Orgánicos/farmacología , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Theilovirus/inmunologíaRESUMEN
NTRK1 gene fusions are actionable drivers of numerous human malignancies. Here, we show that expression of the TPR-NTRK1 fusion kinase in immortalized mouse pancreatic ductal epithelial (IMPE) (pancreas) or mouse lung epithelial (MLE-12) cells is sufficient to promote rapidly growing tumors in mice. Both tumor models are exquisitely sensitive to targeted inhibition with entrectinib, a tropomyosin-related kinase A (TRKA) inhibitor. Initial regression of NTRK1-driven tumors is driven by induced expression of BIM, such that BIM silencing leads to a diminished response to entrectinib in vivo. However, the emergence of drug-resistant disease limits the long-term durability of responses. Based on the reactivation of RAF>MEK>ERK signaling observed in entrectinib-treated tumors, we show that the combination of entrectinib plus the MEK1/2 inhibitor cobimetinib dramatically forestalls the onset of drug resistance in vivo. Collectively, these data provide a mechanistic rationale for rapid clinical deployment of combined inhibition of TRKA plus MEK1/2 in NTRK1-driven cancers.
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Benzamidas/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Indazoles/farmacología , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Modelos Biológicos , Neoplasias/enzimología , Neoplasias/patología , Inhibidores de Proteínas Quinasas/farmacología , Receptor trkA/metabolismo , Animales , Apoptosis/efectos de los fármacos , Proteína 11 Similar a Bcl2/metabolismo , Línea Celular Tumoral , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/patología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Femenino , Células HEK293 , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos NOD , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/patologíaRESUMEN
Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluated for recurrence risk. One hundred and fifty-six patients total had an average follow-up of 5.6 years. Twenty-nine (18.6%) patients underwent cartilage-sparing surgery and 99 (63.5%) patients underwent SLNB, 14.1% of whom had micrometastatic disease. Ten (6.4%) patients recurred loco-regionally. Recurrence was associated with Breslow depth, initial stage at diagnosis, and SLNB status. Cartilage-sparing surgery was not associated with increased recurrence. Sentinel lymph node identification rate was 100% based on clinical detection with use of lymphoscintigraphy. In addition to confirming established risk factors for melanoma recurrence, we confirm the feasibility of SLNB in stratifying recurrence risk. Although we did not see an increased recurrence risk with surgical technique and cartilage-sparing approaches, these findings are limited by small sample size.
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Oído Externo/patología , Oído Externo/cirugía , Melanoma/cirugía , Recurrencia Local de Neoplasia/cirugía , Ganglio Linfático Centinela/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo , Neoplasias Cutáneas/patología , Adulto JovenRESUMEN
PURPOSE: Mutational activation of GNAQ or GNA11 (GNAQ/11), detected in >90% of uveal melanomas, leads to constitutive activation of oncogenic pathways, including MAPK and YAP. To date, chemo- or pathway-targeted therapies, either alone or in combination, have proven ineffective in the treatment of patients with metastatic uveal melanoma. EXPERIMENTAL DESIGN: We tested the efficacy of chloroquine or hydroxychloroquine, in combination with MAPK pathway inhibition in GNAQ/11-mutated cells in vitro and in vivo and identified mechanisms of MEK1/2 inhibitor plus chloroquine-induced cytotoxicity. RESULTS: Inhibition of GNAQ/11-mediated activation of MAPK signaling resulted in the induction of autophagy. Combined inhibition of Gα and autophagy or lysosome function resulted in enhanced cell death. Moreover, the combination of MEK1/2 inhibition, using trametinib, with the lysosome inhibitor, chloroquine, also increased cytotoxicity. Treatment of mice bearing GNAQ/11-driven melanomas with trametinib plus hydroxychloroquine resulted in inhibition of tumor growth and significantly prolonged survival. Interestingly, lysosomal- and autophagy-specific inhibition with bafilomycin A1 was not sufficient to promote cytotoxicity in combination with trametinib. However, the addition of YAP inhibition with trametinib plus bafilomycin A1 resulted in cell death at comparable levels to trametinib plus chloroquine (T/CQ) treatment. Furthermore, T/CQ-treated cells displayed decreased YAP nuclear localization and decreased YAP transcriptional activity. Expression of a constitutively active YAP5SA mutant conferred resistance to T/CQ-induced cell death. CONCLUSIONS: These results suggest that YAP, MEK1/2, and lysosome function are necessary and critical targets for the therapy of GNAQ/11-driven melanoma, and identify trametinib plus hydroxychloroquine as a potential treatment strategy for metastatic uveal melanoma.
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Cloroquina/farmacología , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP/genética , MAP Quinasa Quinasa 1/antagonistas & inhibidores , MAP Quinasa Quinasa 2/antagonistas & inhibidores , Melanoma/tratamiento farmacológico , Mutación , Piridonas/farmacología , Pirimidinonas/farmacología , Neoplasias de la Úvea/tratamiento farmacológico , Animales , Antimaláricos/farmacología , Apoptosis , Proliferación Celular , Resistencia a Antineoplásicos , Quimioterapia Combinada , Humanos , Melanoma/genética , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Inhibidores de Proteínas Quinasas/farmacología , Células Tumorales Cultivadas , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Melanoma/patología , Melanoma/cirugía , Cirugía de Mohs/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Adolescente , Adulto , Anciano , Niño , Estudios de Cohortes , Femenino , Humanos , Peca Melanótica de Hutchinson/patología , Peca Melanótica de Hutchinson/cirugía , Masculino , Persona de Mediana Edad , Neoplasia Residual/patología , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
In the version of this article initially published, the label over the bottom schematic in Fig. 1a was "pH > 5.0"; it should have been "pH < 5.0". Further, the original article misspelt the surname of Katrin P. Guillen as "Gullien". These errors have been corrected in the print, PDF and HTML versions of the article.
RESUMEN
Pancreatic ductal adenocarcinoma (PDA) was responsible for ~ 44,000 deaths in the United States in 2018 and is the epitome of a recalcitrant cancer driven by a pharmacologically intractable oncoprotein, KRAS1-4. Downstream of KRAS, the RAFâMEKâERK signaling pathway plays a central role in pancreatic carcinogenesis5. However, paradoxically, inhibition of this pathway has provided no clinical benefit to patients with PDA6. Here we show that inhibition of KRASâRAFâMEKâERK signaling elicits autophagy, a process of cellular recycling that protects PDA cells from the cytotoxic effects of KRAS pathway inhibition. Mechanistically, inhibition of MEK1/2 leads to activation of the LKB1âAMPKâULK1 signaling axis, a key regulator of autophagy. Furthermore, combined inhibition of MEK1/2 plus autophagy displays synergistic anti-proliferative effects against PDA cell lines in vitro and promotes regression of xenografted patient-derived PDA tumors in mice. The observed effect of combination trametinib plus chloroquine was not restricted to PDA as other tumors, including patient-derived xenografts (PDX) of NRAS-mutated melanoma and BRAF-mutated colorectal cancer displayed similar responses. Finally, treatment of a patient with PDA with the combination of trametinib plus hydroxychloroquine resulted in a partial, but nonetheless striking disease response. These data suggest that this combination therapy may represent a novel strategy to target RAS-driven cancers.
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Autofagia/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/patología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas ras/metabolismo , Animales , Antígeno CA-19-9/metabolismo , Línea Celular Tumoral , Cloroquina/farmacología , Humanos , Ratones SCID , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas B-raf/metabolismo , Piridonas/farmacología , Pirimidinonas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias PancreáticasRESUMEN
PURPOSE: To assess the effectiveness of lectures for continuing medical education (CME) in dermatology in a global health setting and to determine provider and patient demographics of physician assistants (PAs) practicing in rural Ghana. METHODS: Physician assistants from Ghana who attended dermatology lectures at the International Seminar for Physician Assistants in 2011 or 2014 were included in this study. Surveys were administered to participants to determine dermatology resource availability, commonly encountered skin diseases, and management practices. Quizzes were administered before and after CME dermatology lectures to assess short-term retention of lecture material. RESULTS: In all, 353 PAs participated in this study. Physician assistants reported seeing an average of 55 patients per day. The most commonly seen skin diseases were infections, with antifungals and antibiotics being the most commonly prescribed medications. Dermatology-related complaints represented 9.5% of total clinic visits. Among practicing PAs, 23.2% reported having internet access. A total of 332 PAs completed the quizzes, and a statistically significant increase in test scores was noted in postlecture quizzes. CONCLUSIONS: This study reinforces the importance of dermatology education for PAs practicing in rural areas of Ghana and lends insight to critical topics for dermatology curriculum development. In addition, the increase in test scores after CME sessions suggests that lectures are an effective tool for short-term retention of dermatology-related topics. Our study indicates that as the need for health workers increases globally and a paradigm shift away from the traditional physician model of care occurs, dermatology training of PAs is not only important but also achievable.