RESUMEN
Drug resistant cancers like pancreatic ductal adenocarcinoma (PDAC) are difficult to treat, and nanoparticle drug delivery systems can overcome some of the limitations of conventional systemic chemotherapy. In this study, we demonstrate that FdUMP and dFdCMP, the bioactive, phosphorylated metabolites of the chemotherapy drugs 5-FU and gemcitabine, can be encapsulated into calcium phosphosilicate nanoparticles (CPSNPs). The non-phosphorylated drug analogs were not well encapsulated by CPSNPs, suggesting the phosphate modification is essential for effective encapsulation. In vitro proliferation assays, cell cycle analyses and/or thymidylate synthase inhibition assays verified that CPSNP-encapsulated phospho-drugs retained biological activity. Analysis of orthotopic tumors from mice treated systemically with tumor-targeted FdUMP-CPSNPs confirmed the in vivo up take of these particles by PDAC tumor cells and release of active drug cargos intracellularly. These findings demonstrate a novel methodology to efficiently encapsulate chemotherapeutic agents into the CPSNPs and to effectively deliver them to pancreatic tumor cells.
Asunto(s)
Antineoplásicos/administración & dosificación , Compuestos de Calcio/química , Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/administración & dosificación , Nanopartículas/química , Neoplasias Pancreáticas/tratamiento farmacológico , Silicatos/química , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/administración & dosificación , Desoxicitidina/química , Desoxicitidina/uso terapéutico , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Humanos , Masculino , Ratones , Ratones Desnudos , Nanopartículas/ultraestructura , Fosforilación , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
BACKGROUND: Tristimulus colorimetry, which uses the Commission Internationale de l'Eclairage L*a*b* model to quantify color, has previously been used to analyze pigmentation and erythema in human skin; however, colorimetry of African American skin is not well characterized. OBJECTIVE: We sought to analyze skin color patterns in African Americans and compare them with those of Caucasians. METHODS: Colorimetry readings of the sun-protected buttock and sun-exposed back of forearm were taken from 40 Caucasian and 43 African American participants from March 2011 through August 2015. African American participants also completed a lifestyle questionnaire. Correlation coefficients, paired t tests, and multivariable linear regression analyses were used for statistical comparisons. RESULTS: Forearm skin was lighter in African Americans ages 65 years and older versus 18 to 30 years (P = .02) but darker in Caucasians ages 65 years or older versus 18 to 30 years (P = .03). In African Americans ages 18 to 30 years, the buttock was darker than the forearm (P < .001), whereas in Caucasians the buttock was lighter than the forearm (P < .001). A lighter forearm than buttock was correlated with supplement use, smoking (ages 18-30 years), and less recreational sun exposure (ages ≥65 years) in African Americans. LIMITATIONS: Our study was limited by the sample size and focal geographic source. CONCLUSIONS: Pigmentation patterns regarding sun-protected and sun-exposed areas in African Americans may differ from that of Caucasians, suggesting that other factors may contribute to skin pigmentation in African Americans.
Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Hipopigmentación/fisiopatología , Pigmentación/fisiología , Envejecimiento de la Piel/fisiología , Población Blanca/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Envejecimiento/fisiología , Estudios de Cohortes , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
Background: A model employing entry to practice nursing students as health assistants in nursing (HANs) was developed to support the nursing workforce.Objective: This research examines the perceived benefits of being employed as a HAN to graduate entry to practice nursing students.Design: Cross-sectional studyMethods: A web-based 33-item questionnaire was open to entry to practice nursing students employed as a HAN. Categorical measures were summarised using descriptive statistics. Qualitative comments were analysed thematically.Results: Of the 39 enrolled participants, 38 (97.4%) completed the study. Fifteen students (39.5%) commenced a graduate year in 2019, 12 (31.6%) commenced a graduate year in 2020 and 11 (28.9%) will commence a graduate year in 2021. The participants viewed HAN employment as an opportunity to further develop as nurses and suggested that the HAN scope of practice expand to include their existing nursing scope of practice, thereby optimising their learning experience.Conclusion: The HAN model is viewed as a valuable model of employment by entry to practice nursing students; however, the HAN scope of practice is viewed as too limited and not conducive to self-development. This may impact on the retention of HAN employees as they transition to registered graduate nurse employment.Impact statement: Graduate entry to practice nursing students offer direction on how to improve the Health Assistants in Nursing employment model.
Asunto(s)
Bachillerato en Enfermería , Estudiantes de Enfermería , Estudios Transversales , Empleo , Humanos , Modelos de EnfermeríaRESUMEN
Historical reviews suggest that tanning first became fashionable in the 1920s or 1930s. To quantitatively and qualitatively examine changes in tanning attitudes portrayed in the popular women's press during the early 20th century, we reviewed summer issues of Vogue and Harper's Bazaar for the years 1920, 1927, 1928, and 1929. We examined these issues for articles and advertisements promoting skin tanning or skin bleaching and protection. We found that articles and advertisements promoting the fashionable aspects of tanned skin were more numerous in 1928 and 1929 than in 1927 and 1920, whereas those promoting pale skin (by bleaching or protection) were less numerous. These findings demonstrate a clear shift in attitudes toward tanned skin during this period.
Asunto(s)
Publicidad/historia , Actitud , Bronceado , Femenino , Historia del Siglo XX , Humanos , Publicaciones Periódicas como Asunto/historia , Estados UnidosAsunto(s)
Servicios de Diagnóstico/organización & administración , Disparidades en Atención de Salud/organización & administración , Disparidades en Atención de Salud/estadística & datos numéricos , Medicina Estatal/organización & administración , Eficiencia Organizacional , Inglaterra , Geografía , Humanos , Innovación OrganizacionalRESUMEN
OBJECTIVES: Inadvertent intra-arterial injection is a rare and serious complication of sclerotherapy. Multiple treatments have been used in reported cases, with varying levels of success. We report a rare case of intra-arterial injection being treated with steroids and pulsed dye laser therapy and present a plan for future incidences. METHOD/CASE: A 52-year-old woman presented to the clinic looking for aesthetic improvement to telangiectatic veins on the anterior aspect of the right leg. She developed cutaneous necrosis after sclerotherapy injection with 4 mL of 0.5% liquid polidocanol. RESULTS: After 23 months of pulsed dye laser therapy and a course of oral prednisolone, the patient made a good recovery and is left with minimal lasting tissue damage. CONCLUSIONS: More research is needed into the area of treating cutaneous necrosis with a pulsed dye laser, but this case report indicates a possible future therapeutic use after a successful outcome.
Asunto(s)
Inyecciones Intraarteriales/métodos , Soluciones Esclerosantes/efectos adversos , Escleroterapia/efectos adversos , Telangiectasia/terapia , Femenino , Humanos , Terapia por Láser/métodos , Pierna/irrigación sanguínea , Polidocanol , Polietilenglicoles/uso terapéutico , Soluciones Esclerosantes/uso terapéuticoAsunto(s)
Betacoronavirus , Defensa Civil , Control de Enfermedades Transmisibles/organización & administración , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Activismo Político , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/epidemiología , SARS-CoV-2 , Reino Unido/epidemiologíaRESUMEN
The role of bacteria in the pathogenesis of chronic, nonhealing wounds is unclear. All wounds are colonized with bacteria, but differentiating colonizers from invading organisms is difficult, if not impossible, at the present time. Furthermore, robust new molecular genomic techniques have shown that only 1% of bacteria can be grown in culture; anaerobes are especially difficult to identify using standard culture methods. Recent studies utilizing microbial genomic methods have demonstrated that chronic wounds are host to a wide range of microorganisms. New techniques also show that microorganisms are capable of forming highly organized biofilms within the wound that differ dramatically in gene expression and phenotype from bacteria that are typically seen in planktonic conditions. The aim of this review is to present a concise description of infectious agents as defined by new molecular techniques and to summarize what is known about the microbiology of chronic wounds in order to relate them to the pathophysiology and therapy of chronic wounds.
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Bacterias/genética , Infecciones Bacterianas/fisiopatología , Dermatitis/fisiopatología , Microbiología/tendencias , Biología Molecular/tendencias , Cicatrización de Heridas/fisiología , Animales , Regulación Bacteriana de la Expresión Génica , HumanosRESUMEN
We tested here the hypothesis that calcitonin and glucocorticoids, known to modulate bone metabolism, could have opposite actions on bone cells regulating expression of cytokine receptor activator of nuclear factor-kappaBeta ligand (RANKL) and osteoprotegerin (OPG). In the U2OS osteosarcoma cell line, calcitonin (10(-11) to 10(-9) mol/L) reduced RANKL and augmented OPG both at the mRNA and protein levels. Cell incubation with prednisolone (10(-8) to 10(-6) mol/L), the glucocorticoid chosen for this study, produced opposite results. These molecular studies prompted more functional analyses whereby osteoclast bone resorptive activity was determined. Calcitonin (10(-10) mol/L) abrogated the stimulating effect of 10 ng/ml RANKL or 10(-9) mol/L prednisolone; similar results were obtained with OPG. Assessment of calcitonin and prednisolone effects in an in vivo model of rheumatoid arthritis revealed partially surprising results. In fact, calcitonin not only preserved bone morphology (as assessed on day 18) in rats subjected to arthritis and treated with prednisolone (0.8 to 4 mg/kg daily from day 13) but also synergized with the steroid to elicit its antiarthritic effects. These results suggest that calcitonin could be used as a novel cotreatment to augment efficacy and reduce side effects associated with the prolonged use of steroids.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Conservadores de la Densidad Ósea/farmacología , Huesos/efectos de los fármacos , Calcitonina/farmacología , Glucocorticoides/farmacología , Prednisolona/farmacología , Animales , Artritis Experimental/patología , Resorción Ósea/patología , Huesos/patología , Línea Celular , Sinergismo Farmacológico , Humanos , Masculino , Osteoclastos/efectos de los fármacos , Osteoprotegerina/efectos de los fármacos , Osteoprotegerina/metabolismo , Ligando RANK/efectos de los fármacos , Ligando RANK/metabolismo , Ratas , Ratas Endogámicas Lew , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes.