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1.
J Clin Med ; 13(15)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39124569

RESUMEN

Epithelial-to-mesenchymal transition (EMT) is a major axis of phenotypic plasticity not only in diseased conditions such as cancer metastasis and fibrosis but also during normal development and wound healing. Yet-another important axis of plasticity with metastatic implications includes the cancer stem cell (CSCs) and non-CSC transitions. However, in both processes, epithelial (E) and mesenchymal (M) phenotypes are not merely binary states. Cancer cells acquire a spectrum of phenotypes with traits, properties, and markers of both E and M phenotypes, giving rise to intermediary hybrid (E/M) phenotypes. E/M cells play an important role in tumor initiation, metastasis, and disease progression in multiple cancers. Furthermore, the hybrid phenotypes also play a major role in causing therapeutic resistance in cancer. Here, we discuss how a systems biology perspective on the problem, which is implicit in the 'Team Medicine' approach outlined in the theme of this Special Issue of The Journal of Clinical Medicine and includes an interdisciplinary team of experts, is more likely to shed new light on EMT in cancer and help us to identify novel therapeutics and strategies to target phenotypic plasticity in cancer.

2.
Cells ; 13(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38786043

RESUMEN

Epigenetic alterations that lead to differential expression of microRNAs (miRNAs/miR) are known to regulate tumour cell states, epithelial-mesenchymal transition (EMT) and the progression to metastasis in breast cancer. This study explores the key contribution of miRNA-18a in mediating a hybrid E/M cell state that is pivotal to the malignant transformation and tumour progression in the aggressive ER-negative subtype of breast cancer. The expression status and associated effects of miR-18a were evaluated in patient-derived breast tumour samples in combination with gene expression data from public datasets, and further validated in in vitro and in vivo breast cancer model systems. The clinical relevance of the study findings was corroborated against human breast tumour specimens (n = 446 patients). The down-regulated expression of miR-18a observed in ER-negative tumours was found to drive the enrichment of hybrid epithelial/mesenchymal (E/M) cells with luminal attributes, enhanced traits of migration, stemness, drug-resistance and immunosuppression. Further analysis of the miR-18a targets highlighted possible hypoxia-inducible factor 1-alpha (HIF-1α)-mediated signalling in these tumours. This is a foremost report that validates the dual role of miR-18a in breast cancer that is subtype-specific based on hormone receptor expression. The study also features a novel association of low miR-18a levels and subsequent enrichment of hybrid E/M cells, increased migration and stemness in a subgroup of ER-negative tumours that may be attributed to HIF-1α mediated signalling. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing miRNA signatures.


Asunto(s)
Neoplasias de la Mama , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Transición Epitelial-Mesenquimal/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Progresión de la Enfermedad , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Línea Celular Tumoral , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Fenotipo , Animales , Ratones , Movimiento Celular/genética
3.
Artículo en Ruso | MEDLINE | ID: mdl-38640223

RESUMEN

The article considers stages of becoming of Soviet nephrology as independent scientific educational clinical discipline. The role of M. I. Vikhert in becoming of nephrology as independent clinical direction within the framework of the clinic of internal diseases is demonstrated. Also the role of E. M. Tareev as the founder of nephrology in the USSR as institutionalized clinical discipline is revealed.


Asunto(s)
Nefrología , Moscú , U.R.S.S.
4.
Biochem Biophys Res Commun ; 709: 149829, 2024 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-38552553

RESUMEN

The microRNA-200 (miR-200) family is a potent suppressor of epithelial-to-mesenchymal transition (EMT). While its role as a tumor suppressor has been well documented, recent studies suggested that it can promote cancer progression in several stages. In this study, we investigated whether the miR-200 family members play a role in the acquisition of a hybrid epithelial/mesenchymal (E/M) state, which is reported to be associated with cancer malignancy, in mesenchymal MDA-MB-231 cells. Our results demonstrated that the induction of miR-200c-141, a cluster of the miR-200 family member, can induce the expression of epithelial gene and cell-cell junction while mesenchymal markers are retained. Moreover, induction of miR-200c-141 promoted collective migration accompanied by the formation of F-actin cables anchored by adherens junction. These results suggest that the miR-200 family can induce a hybrid E/M state and endows with the ability of collective cell migration in mesenchymal cancer cells.


Asunto(s)
Células MDA-MB-231 , MicroARNs , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Genes Supresores de Tumor , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica
5.
Am J Rhinol Allergy ; 38(4): 203-210, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38544422

RESUMEN

BACKGROUND: The concept of "time toxicity" has emerged to address the impact of time spent in the healthcare system; however, little work has examined the phenomenon in the field of otolaryngology. OBJECTIVE: To validate the use of Evaluation and Management (E/M) current procedural terminology codes as a method to assess time burden and to pilot this tool to characterize the time toxicity of office visits associated with a diagnosis of pituitary adenoma between 2016 and 2019. METHODS: A retrospective cohort study of outpatient office visits quantified differences between timestamps documenting visit length and their associated E/M code visit length. The IBM MarketScan database was queried to identify patients with a diagnosis of pituitary adenoma in 2016 and to analyze their new and return claims between 2016 and 2019. One-way ANOVA and two-sample t-tests were used to examine claim quantity, time in office, and yearly visit time. RESULTS: In the validation study, estimated visit time via E/M codes and actual visit time were statistically different (P < 0.01), with E/M codes underestimating actual time spent in 79.0% of visits. In the MarketScan analysis, in 2016, 2099 patients received a primary diagnosis of pituitary adenoma. There were 8490 additional-related claims for this cohort from 2016 to 2019. The plurality of new office visits were with endocrinologists (n = 857; 29.3%). Total time spent in office decreased yearly, from a mean of 113 min (2016) to 69 min (2019) (P < 0.001). CONCLUSIONS: E/M codes underestimate the length of outpatient visits; therefore, time toxicity experienced by pituitary patients may be greater than reported. Further studies are needed to develop additional assessment tools for time toxicity and promote increased efficiency of care for patients with pituitary adenomas.


Asunto(s)
Adenoma , Visita a Consultorio Médico , Neoplasias Hipofisarias , Humanos , Visita a Consultorio Médico/estadística & datos numéricos , Estudios Retrospectivos , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/terapia , Femenino , Masculino , Adenoma/epidemiología , Adenoma/terapia , Adenoma/diagnóstico , Persona de Mediana Edad , Adulto , Factores de Tiempo , Current Procedural Terminology , Anciano
6.
ACS Appl Mater Interfaces ; 16(7): 8365-8377, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38319067

RESUMEN

Inorganic nanoparticles (NPs) have been widely recognized for their stability and biocompatibility, leading to their widespread use in biomedical applications. Our study introduces a novel approach that harnesses inorganic magnetic nanoparticles (MNPs) to stimulate apical-basal polarity and induce epithelial traits in cancer cells, targeting the hybrid epithelial/mesenchymal (E/M) state often linked to metastasis. We employed mesocrystalline iron oxide MNPs to apply an external magnetic field, disrupting normal cell polarity and simulating an artificial cellular environment. These led to noticeable changes in the cell shape and function, signaling a shift toward the hybrid E/M state. Our research suggests that apical-basal stimulation in cells through MNPs can effectively modulate key cellular markers associated with both epithelial and mesenchymal states without compromising the structural properties typical of mesenchymal cells. These insights advance our understanding of how cells respond to physical cues and pave the way for novel cancer treatment strategies. We anticipate that further research and validation will be instrumental in exploring the full potential of these findings in clinical applications, ensuring their safety and efficacy.


Asunto(s)
Polaridad Celular , Neoplasias , Transición Epitelial-Mesenquimal , Células Epiteliales/metabolismo , Fenotipo , Integrinas/metabolismo , Neoplasias/metabolismo
7.
Int J Mol Sci ; 24(24)2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38139138

RESUMEN

ZEB1 plays a pivotal role in epithelial-to-mesenchymal transition (EMT), (cancer) cell stemness and cancer therapy resistance. The M13HS tumor hybrids, which were derived from spontaneous fusion events between the M13SV1-EGFP-Neo breast epithelial cells and HS578T-Hyg breast cancer cells, express ZEB1 and exhibit prospective cancer stem cell properties. To explore a possible correlation between the ZEB1 and stemness/ EMT-related properties in M13HS tumor hybrids, ZEB1 was knocked-out by CRISPR/Cas9. Colony formation, mammosphere formation, cell migration, invasion assays, flow cytometry and Western blot analyses were performed for the characterization of ZEB1 knock-out cells. The ZEB1 knock-out in M13HS tumor cells was not correlated with the down-regulation of the EMT-related markers N-CADHERIN (CDH2) and VIMENTIN and up-regulation of miR-200c-3p. Nonetheless, both the colony formation and mammosphere formation capacities of the M13HS ZEB1 knock-out cells were markedly reduced. Interestingly, the M13HS-2 ZEB1-KO cells harbored a markedly higher fraction of ALDH1-positive cells. The Transwell/ Boyden chamber migration assay data indicated a reduced migratory activity of the M13HS ZEB1-knock-out tumor hybrids, whereas in scratch/ wound-healing assays only the M13SH-8 ZEB1-knock-out cells possessed a reduced locomotory activity. Similarly, only the M13HS-8 ZEB1-knock-out tumor hybrids showed a reduced invasion capacity. Although the ZEB1 knock-out resulted in only moderate phenotypic changes, our data support the role of ZEB1 in EMT and stemness.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Fenotipo , Células Epiteliales/metabolismo , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , MicroARNs/genética , Regulación Neoplásica de la Expresión Génica
8.
Cell Rep ; 42(12): 113470, 2023 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-37979166

RESUMEN

Epithelial-mesenchymal transition (EMT) empowers epithelial cells with mesenchymal and stem-like attributes, facilitating metastasis, a leading cause of cancer-related mortality. Hybrid epithelial-mesenchymal (E/M) cells, retaining both epithelial and mesenchymal traits, exhibit heightened metastatic potential and stemness. The mesenchymal intermediate filament, vimentin, is upregulated during EMT, enhancing the resilience and invasiveness of carcinoma cells. The phosphorylation of vimentin is critical to its structure and function. Here, we identify that stabilizing vimentin phosphorylation at serine 56 induces multinucleation, specifically in hybrid E/M cells with stemness properties but not epithelial or mesenchymal cells. Cancer stem-like cells are especially susceptible to vimentin-induced multinucleation relative to differentiated cells, leading to a reduction in self-renewal and stemness. As a result, vimentin-induced multinucleation leads to sustained inhibition of stemness properties, tumor initiation, and metastasis. These observations indicate that a single, targetable phosphorylation event in vimentin is critical for stemness and metastasis in carcinomas with hybrid E/M properties.


Asunto(s)
Carcinoma , Filamentos Intermedios , Humanos , Vimentina/metabolismo , Fosforilación , Filamentos Intermedios/metabolismo , Filamentos Intermedios/patología , Carcinoma/patología , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal , Células Madre Neoplásicas/metabolismo , Línea Celular Tumoral , Metástasis de la Neoplasia/patología
9.
Orv Hetil ; 164(31): 1213-1221, 2023 Aug 06.
Artículo en Húngaro | MEDLINE | ID: mdl-37543973

RESUMEN

INTRODUCTION: Scapular motion abnormality in rotator cuff tears is a well-known symptom, but its significance is not clear. Some authors consider it as a cause of rotator cuff tear, others as a consequence of the disease. OBJECTIVE: The aim of our study was to assess the changes in scapular motion in medium size full-thickness rotator cuff tear of degenerative origin compared to a healthy control group. MATERIAL AND METHOD: 10 healthy (control group) and 9 subjects with a medium size (1-3 cm), complaining rotator cuff tear (study group) were included in our study, in whom we analyzed the movements of the shoulder girdle, including the scapula, during sagittal and scapular plane flexion using a VICON 3D motion capture system and U.L.E.M.A. motion analysis software. A two-sample t-test was used to test whether significant differences in scapular posterior tilting, upward rotation and protraction values were observed between the two groups for each humeral flexion angular position. RESULTS: In the study group, a significant increase in scapular protraction was demonstrated in sagittal arm elevations at 40 and 50 degrees of arm elevation compared to the control group (p<0.05), whereas no significant difference in scapular upward rotation and posterior tilting was demonstrated. During scapular plane flexion, no significant difference in scapular movements was demonstrated compared to the control group. CONCLUSION: Scapular dyskinesis is already present in cases of medium size rotator cuff tears. In scapular dyskinesis, a significant difference in protraction is first observed, which may affect scapular upward rotation and tilting as the tear continues to grow. Orv Hetil. 2023; 164(31): 1213-1221.


Asunto(s)
Lesiones del Manguito de los Rotadores , Articulación del Hombro , Humanos , Manguito de los Rotadores , Escápula , Rotura , Fenómenos Biomecánicos , Rango del Movimiento Articular/fisiología
10.
BMC Bioinformatics ; 24(1): 228, 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37268887

RESUMEN

BACKGROUND: Mathematical models of haematopoiesis can provide insights on abnormal cell expansions (clonal dominance), and in turn can guide safety monitoring in gene therapy clinical applications. Clonal tracking is a recent high-throughput technology that can be used to quantify cells arising from a single haematopoietic stem cell ancestor after a gene therapy treatment. Thus, clonal tracking data can be used to calibrate the stochastic differential equations describing clonal population dynamics and hierarchical relationships in vivo. RESULTS: In this work we propose a random-effects stochastic framework that allows to investigate the presence of events of clonal dominance from high-dimensional clonal tracking data. Our framework is based on the combination between stochastic reaction networks and mixed-effects generalized linear models. Starting from the Kramers-Moyal approximated Master equation, the dynamics of cells duplication, death and differentiation at clonal level, can be described by a local linear approximation. The parameters of this formulation, which are inferred using a maximum likelihood approach, are assumed to be shared across the clones and are not sufficient to describe situation in which clones exhibit heterogeneity in their fitness that can lead to clonal dominance. In order to overcome this limitation, we extend the base model by introducing random-effects for the clonal parameters. This extended formulation is calibrated to the clonal data using a tailor-made expectation-maximization algorithm. We also provide the companion  package RestoreNet, publicly available for download at https://cran.r-project.org/package=RestoreNet . CONCLUSIONS: Simulation studies show that our proposed method outperforms the state-of-the-art. The application of our method in two in-vivo studies unveils the dynamics of clonal dominance. Our tool can provide statistical support to biologists in gene therapy safety analyses.


Asunto(s)
Algoritmos , Modelos Teóricos , Funciones de Verosimilitud , Simulación por Computador , Células Clonales , Procesos Estocásticos
11.
Cancers (Basel) ; 15(3)2023 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-36765641

RESUMEN

PURPOSE: Cancer progression, invasiveness, and metastatic potential have been associated with the activation of the cellular development program known as epithelial-to-mesenchymal transition (EMT). This process is known to yield not only mesenchymal cells, but instead an array of cells with different degrees of epithelial and mesenchymal phenotypes with high plasticity, usually referred to as E/M hybrid cells. The characteristics of E/M hybrid cells, their importance in tumor progression, and the key regulators in the tumor microenvironment that support this phenotype are still poorly understood. METHODS: In this study, we established an in vitro model of EMT and characterized the different stages of differentiation, allowing us to identify the main genomic signature associated with the E/M hybrid state. RESULTS: We report that once the cells enter the E/M hybrid state, they acquire stable anoikis resistance, invasive capacity, and tumorigenic potential. We identified the hepatocyte growth factor (HGF)/c-MET pathway as a major driver that pushes cells in the E/M hybrid state. CONCLUSIONS: Herein, we provide a detailed characterization of the signaling pathway(s) promoting and the genes associated with the E/M hybrid state.

12.
Agron Sustain Dev ; 43(1): 15, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36714044

RESUMEN

Sorghum is an important food and feed crop in the dry lowland areas of Ethiopia. Farmers grow both early-sown long-duration landraces and late-sown short-duration improved varieties. Because timing and intensity of drought stress can vary in space and time, an understanding of major traits (G), environments (E), management (M), and their interactions (G×E×M) is needed to optimize grain and forage yield given the limited available resources. Crop simulation modeling can provide insights into these complex G×E×M interactions and be used to identify possible avenues for adaptation to prevalent drought patterns in Ethiopia. In a previous study predictive phenology models were developed for a range of Ethiopian germplasm. In this study, the aims were to (1) further parameterize and validate the APSIM-sorghum model for crop growth and yield of Ethiopian germplasm, and (2) quantify by simulation the productivity-risk trade-offs associated with early vs late sowing strategies in the dry lowlands of Ethiopia. Field experiments involving Ethiopian germplasm with contrasting phenology and height were conducted under well-watered (Melkassa) and water-limited (Miesso) conditions and crop development, growth and yield measured. Soil characterization and weather records at the experimental sites, combined with model parameterization, enabled testing of the APSIM-sorghum model, which showed good correspondence between simulated and observed data. The simulated productivity for the Ethiopian dry lowlands environments showed trade-offs between biomass and grain yield for early and late sowing strategies. The late sowing strategy tended to produce less biomass except in poor seasons, whereas it tended to produce greater grain yield except in very good seasons. This study exemplified the systems approach to identifying traits and management options needed to quantify the production-risk trade-offs associated with crop adaptation in the Ethiopian dry lowlands and further exemplifies the general robustness of the sorghum model in APSIM for this task.

13.
J Law Med Ethics ; 51(4): 786-797, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38477273

RESUMEN

Medical-legal partnership (MLP) embeds attorneys and paralegals into care delivery to help clinicians address root causes of health inequities. Notwithstanding decades of favorable outcomes, MLP is not as well-known as might be expected. In this essay, the authors explore ways in which strategic alignment of legal services with healthcare services in terms of professionalism, information collection and sharing, and financing might help the MLP movement become a more widespread, sustainable model for holistic care delivery.


Asunto(s)
Servicios Legales , Natación , Humanos , Atención a la Salud , Abogados
14.
Cells ; 11(24)2022 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-36552758

RESUMEN

Epithelial-mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many carcinomas depend on EMT activation, partial EMT, or hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGFß signal and EMT-inducing transcription factors, such as ZEB1/2, in tumor cells. However, reverse EMT factors are less studied. We demonstrate that prostate epithelial transcription factor SCAND1 can reverse the cancer cell mesenchymal and hybrid E/M phenotypes to a more epithelial, less invasive status and inhibit their proliferation and migration in DU-145 prostate cancer cells. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and the transcriptional co-repression of target genes. We found that SCAND1 expression correlated with maintaining epithelial features, whereas the loss of SCAND1 was associated with mesenchymal phenotypes of tumor cells. SCAND1 and MZF1 were mutually inducible and coordinately included in chromatin with hetero-chromatin protein HP1γ. The overexpression of SCAND1 reversed hybrid E/M status into an epithelial phenotype with E-cadherin and ß-catenin relocation. Consistently, the co-expression analysis in TCGA PanCancer Atlas revealed that SCAND1 and MZF1 expression was negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBRs, in prostate adenocarcinoma specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, in a mouse tumor xenograft model, SCAND1 overexpression significantly reduced Ki-67(+) and Vimentin(+) tumor cells and inhibited migration and lymph node metastasis of prostate cancer. Kaplan-Meier analysis showed high expression of SCAND1 and MZF1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that SCAND1 induces expression and coordinated heterochromatin-binding of MZF1 to reverse the hybrid E/M status into an epithelial phenotype and, inhibits tumor cell proliferation, migration, and metastasis, potentially by repressing the gene expression of EMT drivers and the MAP3K-MEK-ERK signaling pathway.


Asunto(s)
Transición Epitelial-Mesenquimal , Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Cromatina , Transición Epitelial-Mesenquimal/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Neoplasias de la Próstata/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
15.
Front Cell Dev Biol ; 10: 1038841, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36467417

RESUMEN

Epithelial-mesenchymal plasticity (EMP) refers to the ability of cells to dynamically interconvert between epithelial (E) and mesenchymal (M) phenotypes, thus generating an array of hybrid E/M intermediates with mixed E and M features. Recent findings have demonstrated how these hybrid E/M rather than fully M cells play key roles in most of physiological and pathological processes involving EMT. To this regard, the onset of hybrid E/M state coincides with the highest stemness gene expression and is involved in differentiation of either normal and cancer stem cells. Moreover, hybrid E/M cells are responsible for wound healing and create a favorable immunosuppressive environment for tissue regeneration. Nevertheless, hybrid state is responsible of metastatic process and of the increasing of survival, apoptosis and therapy resistance in cancer cells. The present review aims to describe the main features and the emerging concepts regulating EMP and the formation of E/M hybrid intermediates by describing differences and similarities between cancer and normal hybrid stem cells. In particular, the comprehension of hybrid E/M cells biology will surely advance our understanding of their features and how they could be exploited to improve tissue regeneration and repair.

16.
Healthcare (Basel) ; 10(12)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36553961

RESUMEN

According to the American College of Cardiology/American Heart Association (ACC/AHA) new cholesterol management guidelines in 2019, statin regimen was prescribed to only about 46.4% and 30% of diabetes (DM) patients and patients with atherosclerotic cardiovascular disease (ASCVD), respectively. Atherosclerotic cardiovascular disease accounts for most deaths and disabilities in North America. This study argues that a systematic approach to identifying targeted interventions to adhere to the statin regimen for ASCVD is sparse in previous studies. This study seeks to address the research gap. Besides, the study argues that the statin regimen could improve cholesterol management with the enablers of pharmacy, providers, electronic medical records (E.M.R.), and patients. It paves the way for future research on cardiovascular and statin regimens from different perspectives. Current study has adopted the Qualitative observation method. Accordingly, the study approached the charity care primary clinic serving a large population in the northeastern part of the United States, which constitutes the project's setting. The facility has 51 internal medicine residents. The facility has E.H.R., which is used by the clinical staff. Besides, providers use electronic medication prescribing (E-Scribe). Four PDSA cycles were run in six months. Here, the interventions were intensified during each subsequent cycle. The interventions were then incorporated into routine clinical practice. Based on the observation, the study found a 25% relative improvement by six months based on the baseline data of the appropriate intensity statin prescription for patients with ASCVD or DM by medical resident trainees in our single-center primary care clinic. A total of 77% of cardiovascular disease patients were found to be on an appropriate statin dose at baseline. On the other hand, the proportion of patients with DM who were on proper dose statin was 80.4%. According to the study's findings, PDSA could result in a faster uptake and support of the ACC/AHA guidelines. Evidence indicates that overmedication of persons at low risk and time constraints are some of the most significant impediments to the greater use of prescription medications. Proactive panel management can help improve statins' use by ensuring they are used appropriately.

17.
Camb Q Healthc Ethics ; : 1-10, 2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36524377

RESUMEN

There are many authors who consider the so-called "moral nose" a valid epistemological tool in the field of morality. The expression was used by George Orwell, following in Friedrich Nietzsche's footsteps and was very clearly described by Leo Tolstoy. It has also been employed by authors such as Elisabeth Anscombe, Bernard Williams, Noam Chomsky, Stuart Hampshire, Mary Warnock, and Leon Kass. This article examines John Harris' detailed criticism of what he ironically calls the "olfactory school of moral philosophy." Harris' criticism is contrasted with Jonathan Glover's defense of the moral nose. Glover draws some useful distinctions between the various meanings that the notion of moral nose can assume. Finally, the notion of moral nose is compared with classic notions such as Aristotelian phronesis, Heideggerian aletheia, and the concept of "sentiment" proposed by the philosopher Thomas Reid. The conclusion reached is that morality cannot be based only on reason, or-as David Hume would have it-only on feelings.

18.
Biochim Biophys Acta Gen Subj ; 1866(11): 130215, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35905921

RESUMEN

BACKGROUND: Breast cancer is a heterogenous disease composed of multiple clonal populations and the mechanism by which the tumor microenvironment induces cancer stem cell plasticity is not fully understood. METHODS: MCF7 breast cancer cells were treated with macrophage conditioned medium (MɸCM). PD98059 and SB431542 were used for ERK and TGF-ßR inhibition respectively. Epithelial-mesenchymal transition (EMT) and cancer stem cell markers (CSC) were studied using qRT-PCR and flowcytometry. SCID mice were used for animal experiments. RESULTS: MɸCM- induced ERK/TGF-ß1 signaling led to enrichment of CSC and EMT in MCF7 cells and mammospheres. These effects were abrogated by both MEK inhibitor PD98059 (TGF-ß1 synthesis) and SB431542 (TGF-ß1 signaling). The increase in CSC was both hybrid (ALDH1+) and mesenchymal (CD44+ CD24- cells). Increase in hybrid E/M state was at a single cell level as confirmed by the increase in both claudin-1 (E) and vimentin (M). This did not have any growth advantage in SCID mice and monitoring of CSC and EMT markers before and after growth in SCID mice indicated reversal of these markers in tumor cells recovered from mice. Removal of MɸCM and neutralization of TNF-α, IL-6 and IL-1ß in MɸCM abrogated ERK phosphorylation, TGF-ß and CSC enrichment indicating the requirement of continuous signaling for maintenance. CONCLUSIONS: ERK signaling plays an important role in MɸCM- induced EMT and CSC plasticity which is completely reversible upon withdrawal of signals. GENERAL SIGNIFICANCE: Our experimental observations support the semi-independent nature of EMT-stemness connection which is very dynamic and reversible depending on the microenvironment.


Asunto(s)
Transición Epitelial-Mesenquimal , Neoplasias , Animales , Humanos , Células MCF-7 , Macrófagos , Ratones , Ratones SCID , Células Madre Neoplásicas , Factor de Crecimiento Transformador beta1
19.
Cureus ; 14(4): e24148, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35582556

RESUMEN

Background Competent medical coding is key to maintaining a successful dermatology practice. Resident billing performance can have significant financial implications for the academic institutions employing them. During their residency training, dermatology residents commonly find themselves responsible for the billing of patient encounters. However, despite the importance of adequate knowledge and skill in medical coding, recent data show inadequacies in this aspect of resident education. The goal of this study is to evaluate the impact of an interventional coding curriculum on dermatology residents' billing accuracy at our institution. Methodology Billing data, including evaluation and management (E/M) level of service, procedural codes, and current procedural terminology modifiers (if applicable) were queried from the electronic medical records (EMR) at a resident clinic seeing patients on three half-days each week. Billing codes were gathered from patient visits occurring in two separate time periods, before and after the intervention. The intervention consisted of monthly resident lectures on E/M and procedural billing in outpatient dermatology with associated quizzes. Billing accuracy was verified by three attending dermatologists through chart review and compared between the two time periods. Results Overall, billing data from 532 patient visits, 267 from the pre-intervention period and 265 from the post-intervention period, were checked for accuracy. The accuracy of resident-billed E/M levels of service was similar between the pre- and post-intervention periods (44.3% vs. 44.8%). Similar rates of undercoding and overcoding were noted between the pre- and post-intervention periods (35.2% undercoded and 8% overcoded vs. 35.7% and 8.9%, respectively). However, substantial improvements were noted in the rate of errors with procedural codes and modifiers in the post-intervention period. Overall, 21.9% of procedural codes were incorrectly billed pre-intervention compared to 3.7% post-intervention (p < 0.05). Moreover, 55.2% of modifiers were incorrectly billed pre-intervention versus 27.3% post-intervention (p < 0.05). Conclusions Our analysis suggests that billing lectures yielded a clear improvement in resident billing accuracy at our institution. While there was no improvement in E/M coding, there was a significant improvement in the usage of procedural codes and modifiers. Similar analyses can be used by other residency programs to monitor resident billing performance and the efficacy of educational programs on medical billing.

20.
Prev Vet Med ; 200: 105594, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35180449

RESUMEN

Since 2003, the Sustainable Control Of Parasites in Sheep (SCOPS) group have provided the UK sheep farming industry with guidance on ways to mitigate the development and dissemination of anthelmintic resistance (AR). However our empirical understanding of sheep farmers' influences towards such 'best practice' parasite control approaches is limited, and therefore requires further assessment and evaluation to identify the potential factors influencing their implementation. In 2015, a telephone questionnaire was conducted in order to elicit Scottish sheep farmers' attitudes and behaviours regarding the SCOPS recommended practices, as well as gauging farmers' general attitudes to gastrointestinal nematodes (GIN; term roundworm used in questionnaire) control. A quantitative structural equation modelling (SEM) approach was employed to determine the influences of socio-psychological factors and the uptake of individual anthelmintic resistance mitigating practices including: the implementation of a quarantine strategy for parasite control and the use of parasite diagnostic testing for monitoring faecal egg counts (FEC) and detecting AR. The proposed models established a good fit with the observed data and explained 61%, 54% and 27% of the variance in the adoption of AR testing, FEC monitoring, and quarantine behaviours respectively. The results presented highlight a number of consistent and distinct factors significantly influencing the implementation of selected SCOPS recommended practices. The negative influences of topography and farmer experience was frequently demonstrated in relation to multiple GIN control practices, as well as the positive influences of social norms, worm control knowledge, AR risk perception and positive attitudes to the services provided by the veterinary profession. Factors that were shown to have the greatest relative effects on individual parasite control practices included: the perceived expectation of others (i.e. Social norms) for implementing a quarantine strategy, farmer's suspicions to the presence of AR on the holding for instigating AR testing and the confirmation of AR for adopting FEC monitoring. Determining the influences of behaviour-specific factors on farmers' decision making processes will help to identify and address positive and negative influences concerning implementation of AR mitigating practices, as well as contribute to the development of more evidence based intervention strategies in the future.


Asunto(s)
Infecciones por Nematodos , Enfermedades de las Ovejas , Animales , Control de Enfermedades Transmisibles/métodos , Agricultores/psicología , Humanos , Infecciones por Nematodos/prevención & control , Infecciones por Nematodos/veterinaria , Escocia , Ovinos , Enfermedades de las Ovejas/parasitología , Enfermedades de las Ovejas/prevención & control
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