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1.
Expert Opin Investig Drugs ; 33(2): 95-104, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38299551

RESUMEN

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.


Asunto(s)
Biosimilares Farmacéuticos , Uveítis , Humanos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Uveítis/tratamiento farmacológico , Adalimumab , Factor de Necrosis Tumoral alfa
2.
Prev Med Rep ; 36: 102519, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38116289

RESUMEN

The purpose of this study, based in the United States, was to evaluate knowledge gaps and barriers related to diagnosis and care of inflammatory breast cancer (IBC), a rare but lethal breast cancer subtype, amongst Primary Care Providers (PCP) as they are often the first point of contact when patients notice initial symptoms. PCP participants in the Duke University Health System, federally qualified health center, corporate employee health and community practices, nearby academic medical center, Duke physician assistant and advanced practice nurse leadership program alumni were first selected in a convenience sample and for semi-structured interviews (n = 11). Based on these data, an online survey tool was developed and disseminated (n = 78) to assess salient measures of IBC diagnosis, health disparity factors, referral and care coordination practices, COVID-19 impact, and continuing medical education (CME). PCP reported access to care and knowledge gaps in symptom recognition (mean = 3.3, range 1-7) as major barriers. Only 31 % reported ever suspecting IBC in a patient. PCP (n = 49) responded being challenged with referral delays in diagnostic imaging. Additionally, since the COVID-19 pandemic started, 63 % reported breast cancer referral delays, and 33 % reported diagnosing less breast cancer. PCP stated interest in CME in their practice for improved diagnosis and patient care, which included online (53 %), lunch time or other in-service training (33 %), patient and provider-facing websites (32 %). Challenges communicating rare cancer information, gaps in confidence in diagnosing IBC, and timely follow-up with patients and specialists underscores the need for developing PCP educational modules to improve guideline-concordant care.

3.
Expert Opin Emerg Drugs ; 28(4): 297-309, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38129984

RESUMEN

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.


Asunto(s)
Uveítis , Humanos , Uveítis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Ensayos Clínicos Fase II como Asunto
4.
BMC Health Serv Res ; 23(1): 924, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37649084

RESUMEN

BACKGROUND: Prevalence of health workers with occupational health issues ranked fourth among all careers resulting in a reduction in quality of life. However, tools to measure professional quality of life (ProQoL) are unavailable in Vietnamese. This study aims to develop a Vietnamese version of the ProQoL, and examine ProQoL and its associated factors among doctors and nurses. METHODS: The ProQoL is comprised of 30 items measures compassion satisfaction (CS), burnout (BO), and secondary traumatic stress (STS). The tool was translated into Vietnamese following the Guideline by Guillemin et. al (1993), reviewed by expert panels, and validated for internal consistency and test-retest reliability among 38 health workers working at hospitals in HCMC. The validated tool was then used in a cross-sectional study to measure the ProQoL of full-time doctors and nurses working in clinical departments at the University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. In addition to the ProQoL, self-reported data about demographic and occupational characteristics were collected. RESULTS: The Vietnamese version of ProQoL achieved high internal consistency (alphas between 0.85 and 0.91) and Intra-class Correlation Coefficients (ICCs between 0.71 and 0.89) for all subscales. Among 316 health workers, mean scores of CS, BO, STS were 36.4 (SD = 5.4), 24.9 (SD = 5.1), 25.9 (SD = 5.3), respectively, indicating moderate levels of CS, BO and STS. Participants who were older (b = 0.17, 95%CI = 0.08, 0.26), had sufficient perceived income (b = 2.59, 95%CI = 0.93, 4.24), and > 10 years of working experience (b = 2.15, 95%CI = 0.68, 3.62), had higher CS scores. Those who were older (b=-0.15, 95%CI=-0.23, -0.07), had sufficient perceived income (b=-2.64, 95%CI=-4.18, -1.09), > 10 years of experience (b=-1.38, 95%CI=-2.76, -0.01), worked in surgical department (b=-1.46, 95%CI=-2.54, -0.38) and 8 hours/day (b=-1.52, 95%CI=-2.61, -0.44), had lower BO scores. Moreover, those in a relationship (b=-2.27, 95%CI=-3.53, -1.01) and had sufficient perceived income (b=-1.98, 95%CI=-3.64, -0.32) had lower STS scores. CONCLUSIONS: The Vietnamese version of ProQoL is valid and reliable for use among Vietnamese health workers. Age, marital status, perceived income status, years of working experience, daily working hours, and specialty was associated with at least one component of ProQoL but gender, religion, education level, and monthly income were not.


Asunto(s)
Enfermeras y Enfermeros , Médicos , Calidad de Vida , Humanos , Estudios Transversales , Reproducibilidad de los Resultados , Pueblos del Sudeste Asiático , Vietnam
5.
Neuro Oncol ; 25(3): 508-519, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35976058

RESUMEN

BACKGROUND: Meningioma is the most common primary intracranial tumor in adults. A subset of these tumors recur and invade the brain, even after surgery and radiation, resulting in significant disability. There is currently no standard-of-care chemotherapy for meningiomas. As genomic DNA methylation profiling can prognostically stratify these lesions, we sought to determine whether any existing chemotherapies might be effective against meningiomas with high-risk methylation profiles. METHODS: A previously published dataset of meningioma methylation profiles was used to screen for clinically significant CpG methylation events and associated cellular pathways. Based on these results, patient-derived meningioma cell lines were used to test candidate drugs in vitro and in vivo, including efficacy in conjunction with radiotherapy. RESULTS: We identified 981 genes for which methylation of mapped CpG sites was related to progression-free survival in meningiomas. Associated molecular pathways were cross-referenced with FDA-approved cancer drugs, which nominated Docetaxel as a promising candidate for further preclinical analyses. Docetaxel arrested growth in 17 meningioma cell sources, representing all tumor grades, with a clinically favorable IC50 values ranging from 0.3 nM to 10.7 mM. The inhibitory effects of this medication scaled with tumor doubling time, with maximal benefit in fast-growing lesions. The combination of Docetaxel and radiation therapy increased markers of apoptosis and double-stranded DNA breaks, and extended the survival of mice engrafted with meningioma cells relative to either modality alone. CONCLUSIONS: Global patterns of DNA methylation may be informative for the selection of chemotherapies against meningiomas, and existing drugs may enhance radiation sensitivity in high-risk cases.


Asunto(s)
Antineoplásicos , Neoplasias Meníngeas , Meningioma , Animales , Ratones , Meningioma/tratamiento farmacológico , Meningioma/genética , Meningioma/patología , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Docetaxel/farmacología , Metilación de ADN
6.
Ocul Immunol Inflamm ; 31(9): 1819-1824, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36170559

RESUMEN

PURPOSE: To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients. METHODS: Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales. RESULTS: Mean change in LFP was correlated to those in BCVA (p = .018), SUN scale (p < .001), and MSUN scale (p = .008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p < .05). CONCLUSIONS: LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.


Asunto(s)
Uveítis Anterior , Uveítis , Humanos , Humor Acuoso , Uveítis/diagnóstico , Fotometría , Rayos Láser
7.
JCI Insight ; 7(21)2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36345944

RESUMEN

One of the least-investigated areas of brain pathology research is glycosylation, which is a critical regulator of cell surface protein structure and function. ß-Galactoside α2,6-sialyltransferase (ST6GAL1) is the primary enzyme that α2,6 sialylates N-glycosylated proteins destined for the plasma membrane or secretion, thereby modulating cell signaling and behavior. We demonstrate a potentially novel, protumorigenic role for α2,6 sialylation and ST6GAL1 in the deadly brain tumor glioblastoma (GBM). GBM cells with high α2,6 sialylation exhibited increased in vitro growth and self-renewal capacity and decreased mouse survival when orthotopically injected. α2,6 Sialylation was regulated by ST6GAL1 in GBM, and ST6GAL1 was elevated in brain tumor-initiating cells (BTICs). Knockdown of ST6GAL1 in BTICs decreased in vitro growth, self-renewal capacity, and tumorigenic potential. ST6GAL1 regulates levels of the known BTIC regulators PDGF Receptor ß (PDGFRB), Activated Leukocyte Cell Adhesion Molecule, and Neuropilin, which were confirmed to bind to a lectin-recognizing α2,6 sialic acid. Loss of ST6GAL1 was confirmed to decrease PDGFRB α2,6 sialylation, total protein levels, and the induction of phosphorylation by PDGF-BB. Thus, ST6GAL1-mediated α2,6 sialylation of a select subset of cell surface receptors, including PDGFRB, increases GBM growth.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Animales , Ratones , Ácido N-Acetilneuramínico/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transducción de Señal , beta-D-Galactósido alfa 2-6-Sialiltransferasa
8.
Ocul Immunol Inflamm ; 30(7-8): 1906-1912, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35081012

RESUMEN

PURPOSE: To compare laser flare photometry (LFP) measurements of aqueous flare with Standardization of Uveitis Nomenclature (SUN) and modified SUN grading. METHODS: In this prospective study with multicenter design, uveitis patients were classified according to SUN and modified SUN grading scales. LFP was performed with Kowa FM-700 flaremeter. Mean LFP values were compared with SUN and MSUN scores. RESULTS: The study included 475 LFP measurements, of which 216, 48, 150, 31, 28 and 2 had 0, 0.5+, 1+, 1.5+, 2+ and 3+ flare, respectively. LFP values were significantly different between each two consecutive steps for both clinical gradings (all P < .05). Cut-off values for modified SUN grading steps were defined as 5.7, 9.7, 15.7 and 43.2 for 0/0.5+, 0.5+/ 1+, 1+/1.5+ and 1.5/2+ borders of clinical flare, respectively. CONCLUSIONS: LFP proves to be an objective measurement in analyzing aqueous flare comparable to both SUN and MSUN clinical grading systems.


Asunto(s)
Rayos Láser , Humanos , Estudios Prospectivos
9.
Health Educ Behav ; 48(6): 733-738, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34672827

RESUMEN

INTRODUCTION: We sought to describe how Latina immigrants living in King County coped with the pandemic, including their attitudes and behaviors related to COVID-19, and the impact of the pandemic on their mental health and wellbeing. METHOD: We conducted surveys by phone with adult Spanish-speaking Latina immigrants (n = 137) in the summer of 2020. RESULTS: Very few women had been infected with COVID-19, and 23% reported having been tested. Most frequent reasons for not being tested were not knowing where to go (14%), concerns over the cost (15%), and not wanting to know if they were infected (12%). Most participants had concerns about paying for housing (76%) and food (73%). Depression and anxiety symptoms were in the moderate range. Almost all participants were practicing recommended preventive behaviors. CONCLUSION: Although few participants had COVID-19 infection, the pandemic had significant impacts on their mental health and ability to meet basic needs.


Asunto(s)
COVID-19 , Emigrantes e Inmigrantes , Adaptación Psicológica , Adulto , Femenino , Hispánicos o Latinos , Humanos , Salud Mental , Pandemias , SARS-CoV-2
10.
Artículo en Inglés | MEDLINE | ID: mdl-33921539

RESUMEN

Anti-vaccination attitudes have been an issue since the development of the first vaccines. The increasing use of social media as a source of health information may contribute to vaccine hesitancy due to anti-vaccination content widely available on social media, including Twitter. Being able to identify anti-vaccination tweets could provide useful information for formulating strategies to reduce anti-vaccination sentiments among different groups. This study aims to evaluate the performance of different natural language processing models to identify anti-vaccination tweets that were published during the COVID-19 pandemic. We compared the performance of the bidirectional encoder representations from transformers (BERT) and the bidirectional long short-term memory networks with pre-trained GLoVe embeddings (Bi-LSTM) with classic machine learning methods including support vector machine (SVM) and naïve Bayes (NB). The results show that performance on the test set of the BERT model was: accuracy = 91.6%, precision = 93.4%, recall = 97.6%, F1 score = 95.5%, and AUC = 84.7%. Bi-LSTM model performance showed: accuracy = 89.8%, precision = 44.0%, recall = 47.2%, F1 score = 45.5%, and AUC = 85.8%. SVM with linear kernel performed at: accuracy = 92.3%, Precision = 19.5%, Recall = 78.6%, F1 score = 31.2%, and AUC = 85.6%. Complement NB demonstrated: accuracy = 88.8%, precision = 23.0%, recall = 32.8%, F1 score = 27.1%, and AUC = 62.7%. In conclusion, the BERT models outperformed the Bi-LSTM, SVM, and NB models in this task. Moreover, the BERT model achieved excellent performance and can be used to identify anti-vaccination tweets in future studies.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , Teorema de Bayes , Humanos , Aprendizaje Automático , Pandemias , SARS-CoV-2
11.
J Ophthalmic Inflamm Infect ; 11(1): 11, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33834305

RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

12.
J Bone Miner Res ; 36(2): 283-297, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32916022

RESUMEN

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant in RPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia. In vitro studies on patient-derived dermal fibroblasts harboring RPL13 missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p < 0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p = 0.007) and attenuated global translation (p = 0.017). In line with the human phenotype, our rpl13 mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum of RPL13 mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generated rpl13 mutant zebrafish model corroborates the role of eL13 in skeletogenesis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..


Asunto(s)
Osteocondrodisplasias , Pez Cebra , Animales , Variación Biológica Poblacional , Humanos , Proteínas de Neoplasias , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/genética , Linaje , Proteínas Ribosómicas/genética , Columna Vertebral , Pez Cebra/genética
13.
Ther Adv Ophthalmol ; 12: 2515841420917783, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32524073

RESUMEN

PURPOSE: To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration. METHODS: A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed. RESULTS: Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% (p < 0.05). Twelve cases (70.6%) had an underlying lesion (eight cases: disrupted photoreceptor layer and four cases: normal photoreceptor layer). Mean percent improvement in cases with normal photoreceptor layer (90.8 ± 5.45%) was higher than with abnormal photoreceptor layer (58.5 ± 7.17%) (p < 0.05). Five cases with distortion had no associated underlying lesion. Mean percent improvement in these subjects was significantly higher than those with photoreceptor layer disruption. CONCLUSION: Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.

14.
J Racial Ethn Health Disparities ; 7(5): 937-948, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32040841

RESUMEN

Latina immigrant women in the U.S. are at increased risk for poor mental health status, due to socioeconomic- and immigration-related stressors. We sought to describe the mechanisms linking immigration-related stressors and mental health, including how the current social and political climate affects women's mental health status, and which coping strategies are used to maintain well-being. We conducted four focus groups with Latina immigrants (N = 58) recruited through local community-based organizations. We drew on the stages of migration framework to guide our study design and analysis. Focus group transcripts were analyzed to identify emergent themes across groups. On average, focus group participants were 35.5 years old and had lived in the U.S. for 12.5 years. Most were from Mexico. Participants reported immigration-related stressors including unsafe migration, worry about immigration enforcement, broken social ties, and limited access to health and social services. In the face of these stressors, they relied on transnational social networks and connections with other Latina immigrant women. Social ties with family in the U.S. also helped them alleviate social isolation and overcome barriers to social services. Those who were mothers expressed that their children were a source of encouragement and comfort with feelings of stress. Immigration policies that contribute to unsafe migration, worry about immigration enforcement, limited social ties, and limited access to social services were associated with increased stress among Latina immigrants who participated in the focus groups. These participants could benefit from increased access to mental health care and community-based programs that connect them to resources.


Asunto(s)
Adaptación Psicológica , Emigrantes e Inmigrantes/psicología , Emigración e Inmigración/legislación & jurisprudencia , Hispánicos o Latinos/psicología , Estrés Psicológico/etnología , Adulto , Emigrantes e Inmigrantes/estadística & datos numéricos , Femenino , Grupos Focales , Hispánicos o Latinos/estadística & datos numéricos , Humanos , México/etnología , Estrés Psicológico/psicología
15.
Int J Mol Sci ; 21(2)2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31947698

RESUMEN

The murine macrophage cell line RAW264.7 is extensively used as a progenitor to study osteoclast (OC) differentiation. RAW264.7 is a heterogeneous cell line, containing sub-clones with different abilities to form OCs. The aim of this study was to identify characteristics within the heterogeneous RAW264.7 cells that define sub-clones with an augmented ability to form bone-resorbing OCs (H9), as well as sub-clones representing non-OCs (J8). RAW264.7 sub-clones were isolated by single cell cloning. Selection was based on TRAP/cathepsin K expression in sub-clone cultures without added RANKL. Sub-clones before and after differentiation with RANKL were assayed for multiple OC-characteristics. Sub-clone H9 cells presented a higher expression of OC-markers in cultures without added RANKL compared to the parental RAW264.7. After 6 days of RANKL stimulation, sub-clone H9 cells had equal expression levels of OC-markers with RAW264.7 and formed OCs able to demineralize hydroxyapatite. However, sub-clone H9 cells displayed rapid differentiation of OC already at Day 2 compared to Day 4 from parental RAW264.7, and when cultured on plastic and on bone they were more efficient in resorption. This rapid differentiation was likely due to high initial expression/nuclear translocation of OC master transcription factor, NFATc1. In contrast to H9, J8 cells expressed initially very low levels of OC-markers, and they did not respond to RANKL-stimulation by developing OC-characteristics/OC-marker expression. Hence, H9 is an additional clone suitable for experimental setup requiring rapid differentiation of large numbers of OCs.


Asunto(s)
Resorción Ósea/genética , Factores de Transcripción NFATC/genética , Osteoclastos/metabolismo , Animales , Catepsina K/genética , Catepsina K/metabolismo , Diferenciación Celular , Línea Celular , Células Cultivadas , Expresión Génica , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ratones , Factores de Transcripción NFATC/metabolismo , Especificidad de Órganos , Ligando RANK/genética , Ligando RANK/metabolismo , Células RAW 264.7 , Fosfatasa Ácida Tartratorresistente/genética , Fosfatasa Ácida Tartratorresistente/metabolismo
16.
Sci Rep ; 9(1): 8946, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31222125

RESUMEN

Mutations in isocitrate dehydrogenases 1 and 2 (IDHmut) are present in a variety of cancers, including glioma, acute myeloid leukemia (AML), melanoma, and cholangiocarcinoma. These mutations promote hypermethylation, yet it is only a favorable prognostic marker in glioma, for reasons that are unclear. We hypothesized that the patterns of DNA methylation, and transcriptome profiles, would vary among IDHmut cancers, especially gliomas. Using Illumina 450K and RNA-Seq data from The Cancer Genome Atlas, we show that of 365,092 analyzed CpG sites, 70,591 (19%) were hypermethylated in IDHmut gliomas compared to wild-type (IDHwt) gliomas, and only 3%, 2%, and 4% of CpG sites were hypermethylated in IDHmut AML, melanoma, and cholangiocarcinoma, relative to each of their IDHwt counterparts. Transcriptome differences showed pro-malignant genes that appear to be unique to IDHmut gliomas. However, genes involved in differentiation and immune response were suppressed in all IDHmut cancers. Additionally, IDHmut caused a greater degree of hypermethylation in undifferentiated neural progenitor cells than in mature astrocytes. These data suggest that the extent and targets of IDHmut-induced genomic hypermethylation vary greatly according to the cellular context and may help explain why IDHmut is only a favorable prognostic marker in gliomas.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Metilación de ADN , Glioma/metabolismo , Isocitrato Deshidrogenasa/genética , Mutación , Neoplasias/genética , Neoplasias Encefálicas/genética , Estudios de Cohortes , Femenino , Glioma/genética , Humanos , Masculino , Transcriptoma
17.
J Nurses Prof Dev ; 35(3): 152-159, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30829741

RESUMEN

A nurse leadership program provides advanced practice nurses, many of whom have nursing professional development roles within their agencies, with a year of education, mentoring, and guidance to create and implement innovative models of care designed to improve population health. This article highlights program participants' leadership development outcomes, along with strategies to educate and mentor rising nurse leaders.


Asunto(s)
Enfermería de Práctica Avanzada/educación , Liderazgo , Recursos Humanos/normas , Adulto , Enfermería de Práctica Avanzada/métodos , Educación de Postgrado en Enfermería/métodos , Educación de Postgrado en Enfermería/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermeras y Enfermeros/psicología , Enfermeras y Enfermeros/estadística & datos numéricos , Desarrollo de Personal/métodos , Encuestas y Cuestionarios
18.
J Ophthalmic Inflamm Infect ; 9(1): 1, 2019 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-30617430

RESUMEN

PURPOSE: The aim of this study is to evaluate the differences in the fundus autofluorescence (FAF) signal between the blue light autofluorescence (BAF) from Spectralis® (Heidelberg, CA) and green light autofluorescence (GAF) 200TxTM (OPTOS, UK, in normal subjects and in patients with retinochoroidopathies (RC). METHODS: In this prospective study, FAF was performed using BL (λ = 488 nm) and GL (λ = 532 nm) on normal subjects and patients with RC. The corresponding pairs of BAF and GAF images from both groups were analyzed using Photoshop. The strength of the FAF signal was measured on a gray scale, where optic disc was a standard to indicate absence of AF. In addition, gray values obtained from three identical points (foveal center, and points of hypo and hyper autofluorescence) in the corresponding BAF and GAF images of normal and RC subjects were divided by the optic disc value to calculate autofluorescence signal ratio (R). The R values at fovea (R1), hypoautofluorescent point (R2), and hyperautofluorescent point (R3) were compared between BAF and GAF modalities, in normal and in RC subjects separately. RESULTS: One hundred six pairs (106 eyes) of FAF images analyzed (37 pairs: normal and 69 pairs: RC subjects). In normal subjects, the mean R1, R2, and R3 values for BAF were (1.5 ± 0.88, 1.23 ± 0.58, and 4.73 ± 2.85, respectively) and for GAF were (0.78 ± 0.20, 0.78 ± 0.20, and 1.62 ± 0.39, respectively). Similarly, in subjects with RC, the mean R1, R2, and R3 values for BAF were (1.68 ± 1.02, 1.66 ± 1.15, and 7.75 ± 6.82, respectively) and for GAF were (0.95 ± 0.59, 0.79 ± 0.45, and 2.50 ± 1.65, respectively). The mean difference in the R1, R2, and R3 ratios between BAF and GAF in normal and in RC subjects was statistically significant (p < 0.001). The strength of the correlation (r) between ratios for BAF and GAF was weak or not statistically significant in both normal and RC subjects (p > 0.05). CONCLUSION: The distribution and intensity of the AF signal differ in BAF and GAF and cannot be used interchangeably. In BAF, optic disc signal is always weaker than in other areas, which was not true for GAF where optic disc signal was stronger than fovea and hypoautofluorescent point in both groups.

19.
Int J Psychiatry Med ; 54(3): 188-202, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30269631

RESUMEN

OBJECTIVE: Behavioral health services frequently delivered by primary care providers include care for mental health and substance abuse disorders and assistance with behavioral risk factor reduction. Internal medicine residencies in the United States lack formal expectations regarding training in behavioral health for residents. This qualitative study aimed to determine learners' and teachers' perceptions about appropriate behavioral health curricular components for internal medicine residents. METHOD: Focus groups and interviews were conducted with the following individuals from the Duke Outpatient Clinic: residents with continuity practice (n = 27), advanced practice providers (n = 2), internal medicine attending physicians (n = 4), internal medicine/psychiatry attending physicians (n = 2), and behavioral health clinicians (n = 4). A focus group leader asked regarding residents' successes and challenges in managing behavioral health issues and about specific learning components considered necessary to understand and manage these behavioral health conditions. Transcripts were coded using an editing analysis style to identify central themes and concordance/discordance between groups. RESULTS: Regarding mental health management (Theme 1), residents emphasized a need for better care coordination with specialty mental health, while attendings and behavioral health clinicians gave priority to residents' skills in primary management of mental health. Residents, attendings, and behavioral health clinicians all emphasized advanced interviewing skills (Theme 2) with subthemes: eliciting the patient's perspective, managing time in encounters, improving patients' understanding, and patient counseling. CONCLUSIONS: Internal medicine residents, attendings, and behavioral health clinicians may differ significantly in their perceptions of primary care's role in mental health care. Future internal medicine behavioral health curricula should specifically address these attitudinal differences. Curricula should also emphasize interview skills training as an essential component of behavioral health learning.


Asunto(s)
Curriculum/estadística & datos numéricos , Docentes , Medicina Interna/educación , Internado y Residencia/métodos , Trastornos Mentales/terapia , Psiquiatría/educación , Estudios de Evaluación como Asunto , Femenino , Grupos Focales , Humanos , Masculino , Investigación Cualitativa , Estados Unidos
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