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1.
Clin Teach ; : e13759, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494981

RESUMO

BACKGROUND: Paramedics are expected to record electrocardiograms (ECGs) as part of their clinical assessment; however, it is an extremely difficult skill to learn and understand as it has a high intrinsic cognitive load which can also be challenging to teach effectively. AIMS: This article will explore the use of cognitive load theory to assist in the teaching of ECG interpretation within the context of paramedical education. DESCRIPTION: Cognitive load theory can be useful to aid teaching within complex medical and health science domains including clinical skills teaching. CONCLUSIONS: The application of cognitive load theory to the teaching of ECG interpretation can be useful as it allows for the development of understanding, building schemata linking information currently being learned to knowledge already gained within the long-term memory, which can maximise germane load by the appropriate selection of intrinsic load, minimising extraneous load therefore not overloading the working memory.

2.
Pathology ; 55(7): 917-921, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37805343

RESUMO

Complete biomarker workup of non-small cell lung cancer (NSCLC) specimens is essential for appropriate and timely clinical management decisions. This can be challenging to achieve from small cytology and histology specimens, with increasing numbers of molecular and immunohistochemical biomarkers required. We conducted a 5 year retrospective audit of cases at our institution to assess the diagnostic and biomarker testing adequacy rates, particularly those specimens obtained with rapid onsite evaluation (ROSE), performed by a cytopathologist and a cytology scientist or pathology trainee, including all endobronchial ultrasound guided transbronchial needle aspirations (EBUS-TBNA), CT guided lung fine needle aspirations (FNA) and CT guided lung core biopsies. A total of 5,354 cases were identified, of which 92.2% had sufficient material for diagnosis. Of the 1506 cases identified with a recorded diagnosis of lung adenocarcinoma or NSCLC, not otherwise specified, 1001 (66.5%) had biomarker testing requested. Sufficient material was available in 89.5% of cases for a complete biomarker workup which included EGFR and KRAS mutational testing (all cases), ALK, ROS1 and PD-L1 immunohistochemistry (all cases), and ALK and ROS1 FISH (as required). For EGFR and KRAS mutational testing across both cytology and histology specimens, 99% of cases were sufficient. Of the samples in which a complete biomarker workup was unable to be performed, approximately half were only insufficient due to inadequate numbers of tumour cells for PD-L1 immunohistochemistry. Excluding PD-L1 IHC, 952 (95.1%) of samples obtained with ROSE were sufficient for the remainder of the testing requirements. Next generation sequencing using a 33 gene custom AmpliSeq panel was achieved in up to 72% of cases. In conclusion, small cytology and histology specimens obtained with ROSE are suitable for predictive biomarker testing in NSCLC, although attention needs to be paid to obtaining sufficient cells (>100) for PD-L1 immunohistochemistry.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Estudos Retrospectivos , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas p21(ras) , Proteínas Proto-Oncogênicas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Biomarcadores Tumorais , Receptores ErbB , Receptores Proteína Tirosina Quinases
3.
PLoS One ; 17(12): e0278867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584160

RESUMO

We experimentally created a particle size dataset that is based on reduction sequences and raw materials typical of the Middle and Later Stone Age in southern Africa. The reason for creating this new dataset is that current particle size frameworks are based, almost exclusively, on flint and western European knapping methods. We produced the dataset using knapping methods and raw materials frequently encountered in the southern African archaeological record because we wanted to test whether it has the same distribution as particle size datasets experimentally created in Europe, and to initialise the production of a database for use in the analysis of lithic assemblages from southern African Late Pleistocene deposits. We reduced 117 cores of quartz, quartzite, jasper, chalcedony, hornfels, and rhyolite. The knapping methods selected were unidirectional, discoidal, Levallois recurrent and bipolar flaking. In this article we compare this new particle size distribution dataset with the results obtained from previous experiments. We found that the southern African dataset shows a wider size range distribution, which seems to be explained by differences in knapping methods and raw materials. Our results show that there is overlap between the distribution of the southern African experimental knapping dataset and the sorting experiment conducted by Lenoble on flint artefacts in a runoff context. This article shows that a particle size analysis is not sufficient on its own to assess the perturbation of an archaeological assemblage and must be coupled with other analytical tools.


Assuntos
Arqueologia , Tecnologia , Tamanho da Partícula , Europa (Continente) , África Austral , Fósseis
4.
Rofo ; 194(10): 1088-1099, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35545103

RESUMO

Osteoporosis is a highly prevalent systemic skeletal disease that is characterized by low bone mass and microarchitectural bone deterioration. It predisposes to fragility fractures that can occur at various sites of the skeleton, but vertebral fractures (VFs) have been shown to be particularly common. Prevention strategies and timely intervention depend on reliable diagnosis and prediction of the individual fracture risk, and dual-energy X-ray absorptiometry (DXA) has been the reference standard for decades. Yet, DXA has its inherent limitations, and other techniques have shown potential as viable add-on or even stand-alone options. Specifically, three-dimensional (3 D) imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), are playing an increasing role. For CT, recent advances in medical image analysis now allow automatic vertebral segmentation and value extraction from single vertebral bodies using a deep-learning-based architecture that can be implemented in clinical practice. Regarding MRI, a variety of methods have been developed over recent years, including magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) that enable the extraction of a vertebral body's proton density fat fraction (PDFF) as a promising surrogate biomarker of bone health. Yet, imaging data from CT or MRI may be more efficiently used when combined with advanced analysis techniques such as texture analysis (TA; to provide spatially resolved assessments of vertebral body composition) or finite element analysis (FEA; to provide estimates of bone strength) to further improve fracture prediction. However, distinct and experimentally validated diagnostic criteria for osteoporosis based on CT- and MRI-derived measures have not yet been achieved, limiting broad transfer to clinical practice for these novel approaches. KEY POINTS:: · DXA is the reference standard for diagnosis and fracture prediction in osteoporosis, but it has important limitations.. · CT- and MRI-based methods are increasingly used as (opportunistic) approaches.. · For CT, particularly deep-learning-based automatic vertebral segmentation and value extraction seem promising.. · For MRI, multiple techniques including spectroscopy and chemical shift imaging are available to extract fat fractions.. · Texture and finite element analyses can provide additional measures for vertebral body composition and bone strength.. CITATION FORMAT: · Sollmann N, Kirschke JS, Kronthaler S et al. Imaging of the Osteoporotic Spine - Quantitative Approaches in Diagnostics and for the Prediction of the Individual Fracture Risk. Fortschr Röntgenstr 2022; 194: 1088 - 1099.


Assuntos
Osteoporose , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Absorciometria de Fóton/métodos , Densidade Óssea , Humanos , Vértebras Lombares , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/diagnóstico por imagem , Prótons , Fraturas da Coluna Vertebral/diagnóstico por imagem , Água
5.
Ecol Evol ; 12(4): e8825, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35441006

RESUMO

Higher education in evolutionary anthropology involves providing students with in-depth knowledge of biological and cultural heritage sites and collections that are frequently inaccessible. Indeed, most sites, fossils, and archaeological remains can be visited or manipulated only rarely and solely by specialists with extensive experience. Owing to the development of 3D and medical imaging techniques, this fragile heritage is now more widely accessible, and in a dynamic way. However, exclusive adoption of virtual teaching and learning has a negative impact on student engagement and, naturally, on exchanges with instructors, and thus cannot be used without some reservations. In the ITAP (Immersion dans les Terrains de l'Anthropologie biologique et de la Préhistoire) project of the higher education STEP (Soutien à la Transformation et à l'Expérimentation Pédagogiques) transformation program at the University of Bordeaux, we combine student-active teaching with Master's students fully immersed in ongoing fieldwork, laboratory study, and dissemination of research results in order to develop more individually shaped learning curricula and to foster both professional and new interdisciplinary skills. Here, we present examples of experiments conducted in the ITAP project using both authentic and virtual collections of archaeological, experimental, and reference materials that help to break down the barriers between research activities and higher education, as well as providing a more general appraisal of the appropriate use of virtual tools in higher education by combining them with real-life situations.

6.
BMJ Open ; 11(12): e054075, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-37185327

RESUMO

INTRODUCTION: Grades 2 and 3 gliomas (G2/3 gliomas), when combined, are the second largest group of malignant brain tumours in adults. The outcomes for G2/3 gliomas at progression approach the dismal outcomes for glioblastoma (GBM), yet there is a paucity of trials for Australian patients with relapsed G2/3 gliomas compared with patients with GBM. LUMOS will be a pilot umbrella study for patients with relapsed G2/3 gliomas that aims to match patients to targeted therapies based on molecular screening with contemporaneous tumour tissue. Participants in whom no actionable or no druggable mutation is found, or in whom the matching drug is not available, will form a comparator arm and receive standard of care chemotherapy. The objective of the LUMOS trial is to assess the feasibility of this approach in a multicentre study across five sites in Australia, with a view to establishing a national molecular screening platform for patient treatment guided by the mutational analysis of contemporaneous tissue biopsies METHODS AND ANALYSIS: This study will be a multicentre pilot study enrolling patients with recurrent grade 2/3 gliomas that have previously been treated with radiotherapy and chemotherapy at diagnosis or at first relapse. Contemporaneous tumour tissue at the time of first relapse, defined as tissue obtained within 6 months of relapse and without subsequent intervening therapy, will be obtained from patients. Molecular screening will be performed by targeted next-generation sequencing at the reference laboratory (PathWest, Perth, Australia). RNA and DNA will be extracted from representative formalin-fixed paraffin embedded tissue scrolls or microdissected from sections on glass slides tissue sections following a review of the histology by pathologists. Extracted nucleic acid will be quantified by Qubit Fluorometric Quantitation (Thermo Fisher Scientific). Library preparation and targeted capture will be performed using the TruSight Tumor 170 (TST170) kit and samples sequenced on NextSeq 550 (Illumina) using NextSeq V.2.5 hi output reagents, according to the manufacturer's instructions. Data analysis will be performed using the Illumina BaseSpace TST170 app v1.02 and a custom tertiary pipeline, implemented within the Clinical Genomics Workspace software platform from PierianDx (also refer to section 3.2). Primary outcomes for the study will be the number of patients enrolled and the number of patients who complete molecular screening. Secondary outcomes will include the proportion of screened patients enrolled; proportion of patients who complete molecular screening; the turn-around time of molecular screening; and the value of a brain tumour specific multi-disciplinary tumour board, called the molecular tumour advisory panel as measured by the proportion of patients in whom the treatment recommendation was refined compared with the recommendations from the automated bioinformatics platform of the reference laboratory testing. ETHICS AND DISSEMINATION: The study was approved by the lead Human Research Ethics Committee of the Sydney Local Health District: Protocol No. X19-0383. The study will be conducted in accordance with the principles of the Declaration of Helsinki 2013, guidelines for Good Clinical Practice and the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2007, updated 2018 and as amended periodically). Results will be disseminated using a range of media channels including newsletters, social media, scientific conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12620000087954; Pre-results.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Glioma , Adulto , Humanos , Antineoplásicos/uso terapêutico , Austrália , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioma/tratamento farmacológico , Glioma/genética , Estudos Multicêntricos como Assunto , Projetos Piloto , Recidiva , Literatura de Revisão como Assunto
8.
Pathology ; 52(6): 686-693, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32782216

RESUMO

Molecular profiling was performed in 50 problematic ovarian sex cord-stromal tumours (SCSTs) most of which were seen in consultation. Following analysis, 17 were classified as adult granulosa cell tumour (AGCT), 16 of which showed a FOXL2 sequence variant (mutation); the initial favoured diagnosis in five of the cases was benign thecoma/fibrothecoma. Thirteen tumours ultimately classified as cellular fibroma or thecoma were FOXL2 sequence variant negative which was helpful in excluding AGCT. All six Sertoli-Leydig cell tumours (SLCTs) demonstrated DICER1 'hot spot' sequence variants, and one case each of AGCT and SLCT showed high grade histological transformation associated with a concurrent TP53 sequence variant. All eight unclassified SCSTs were negative for FOXL2 mutations and the six tested cases were DICER1 wild type; however, three tumours demonstrated MET, CTNNB1 or TP53 sequence variants. Four cases were classified as juvenile granulosa cell tumour, and one of these harboured a GNAS sequence variant. The single gynandroblastoma and microcystic stromal tumours in the series demonstrated FOXL2 and CTNNB1 alterations, respectively. In summary, molecular analysis aids in accurate classification of challenging ovarian SCSTs and sometimes leads to revision of the favoured provisional diagnosis. TP53 sequence variants may be associated with dedifferentiation in both SLCTs and AGCTs.


Assuntos
Neoplasias Ovarianas/classificação , Tumores do Estroma Gonadal e dos Cordões Sexuais/classificação , Tumor da Célula Tecal/classificação , Proteína Supressora de Tumor p53/genética , beta Catenina/genética , Desdiferenciação Celular , RNA Helicases DEAD-box/genética , Feminino , Proteína Forkhead Box L2/genética , Humanos , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/patologia , Ribonuclease III/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumor da Célula Tecal/genética , Tumor da Célula Tecal/patologia
9.
J Cell Biochem ; 120(1): 848-860, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30161276

RESUMO

Expression of the transcriptional regulator, E26 transformation-specific 1 (ETS1), is elevated in human prostate cancers, and this is associated with more aggressive tumor behavior and a rapid progression to castrate-resistant disease. Multiple ETS1 isoforms with distinct biological activities have been characterized and in 44 matched nonmalignant and malignant human prostate specimens, messenger RNAs for two ETS1 isoforms, ETS1p51 and ETS1p42, were detected, with ETS1p51 levels significantly lower in prostate tumor compared to matched nonmalignant prostate tissues. In contrast, ETS1p51 protein, the only ETS1 isoform detected, was expressed at significantly higher levels in malignant prostate. Analysis of epithelial-to-mesenchymal transition (EMT)-associated genes regulated following overexpression of ETS1p51 in the LNCaP prostate cancer cell line predicted promotion of transforming growth factor ß (TGFß) signaling and of EMT. ETS1p51 overexpression upregulated cellular levels of the EMT transcriptional regulators, ZEB1 and SNAIL1, resulted in reduced expression of the mesenchymal marker vimentin with concomitantly elevated levels of claudin 1, an epithelial tight junction protein, and increased prostate cancer cell migration and invasion. ETS1p51-induced activation of the pro-EMT TGFß signaling pathway that was predicted in polymerase chain reaction arrays was verified by demonstration of elevated SMAD2 phosphorylation following ETS1p51 overexpression. Attenuation of ETS1p51 effects on prostate cancer cell migration and invasion by inhibition of TGFß pathway signaling indicated that ETS1p51 effects were in part mediated by induction of TGFß signaling. Thus, overexpression of ETS1p51, the predominant ETS1 isoform expressed in prostate tumors, promotes an EMT program in prostate cancer cells in part via activation of TGFß signaling, potentially accounting for the poor prognosis of ETS1-overexpressing prostate tumors.


Assuntos
Transição Epitelial-Mesenquimal/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Benzamidas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Dioxóis/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Proteína Smad2/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Transfecção , Fator de Crescimento Transformador beta1/farmacologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
10.
Ann Thorac Surg ; 105(3): 779-784, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29258677

RESUMO

BACKGROUND: To examine short-term and midterm outcomes after the David and Bentall procedures in patients with an acute type A aortic dissection. METHODS: Between 2001 and 2017, patients (n = 135) with acute type A aortic dissection underwent an aortic root replacement with either the David (n = 40) or Bentall (n = 95) procedure. Perioperative outcome, reoperation rate, aortic valve function, and long-term survival were evaluated. RESULTS: The median age of the entire cohort was 56 years. Rates of malperfusion (21%), shock (16%), history of renal failure (4%), and extent of surgery were similar between David and Bentall groups. However, the David group was significantly younger (45 versus 61 years) with less hypertension (45% versus 66%), coronary artery disease (0% versus 17%), valvulopathy (5% versus 19%), and prior cardiac surgery (5% versus 21%). Overall operative mortality was 9.6% (David 3% and Bentall 13%). Composite outcome comprising myocardial infarction, stroke, new-onset renal failure, and operative mortality was 18% in the entire cohort (David 5% and Bentall 23%). In the David group, the freedom of moderate aortic insufficiency was 95% at 10 years. The rate of reoperation for pathology of the proximal aorta or aortic valve was 0% and 2% for the David and Bentall groups, respectively. Ten-year Kaplan-Meier survival was 66% (95% confidence interval: 51% to 77%) for the entire cohort, with 98% (95% confidence interval: 84% to 99%) survival in the David group and 57% (95% confidence interval: 42% to 70%) survival in the Bentall group. CONCLUSIONS: Both the David and Bentall procedures are appropriate surgical approaches for aortic root replacement in select patients with an acute type A aortic dissection.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Implante de Prótese de Valva Cardíaca , Adulto , Idoso , Dissecção Aórtica/complicações , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento
11.
J Dent Child (Chic) ; 84(3): 120-124, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29282167

RESUMO

PURPOSE: To describe pediatric dental residents education as it pertains to children with special healthcare needs (CSHCN). METHODS: A web-based survey was administered to 80 program directors of pediatric dental residencies recognized by the American Academy of Pediatric Dentistry (AAPD). The survey identified demographic data and education and training methods pertaining to CSHCN. RESULTS: Forty surveys (50 percent) were received from programs in all six AAPD regions. Programs that treated 4,500 patients or less/year were statistically less likely to require a specific assessment and were less likely to use written tests to assess competency treating CSHCN. A specific special needs didactic course (88 percent) and journal articles (85 percent) were the most common didactic training methods. The majority of the programs (69 percent) offered more than 20 hours of didactic education. On average 36.3 percent of the patients treated in residencies reported to be CSHCN and each resident clinically treated and average of 13 CSHCN/week. One-third of the respondents planned to increase CSHCN education in the next three years. Almost 70 percent of respondents supported the standardization of a national curriculum regarding CSHCN. CONCLUSIONS: A wide disparity exists among residencies regarding education related to CSHCN. Most pediatric dental residency directors support the national standardization of CSHCN education.


Assuntos
Assistência Odontológica para a Pessoa com Deficiência , Internato e Residência , Odontopediatria/educação , Criança , Currículo , Humanos , Inquéritos e Questionários , Estados Unidos
12.
Nat Commun ; 8: 15481, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28541271

RESUMO

Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.


Assuntos
Valva Aórtica/anormalidades , Fator de Transcrição GATA4/genética , Variação Genética , Doenças das Valvas Cardíacas/genética , Substituição de Aminoácidos , Valva Aórtica/embriologia , Valva Aórtica/metabolismo , Doença da Válvula Aórtica Bicúspide , Sistemas CRISPR-Cas , Estudos de Casos e Controles , Transdiferenciação Celular/genética , Feminino , Fator de Transcrição GATA4/deficiência , Fator de Transcrição GATA4/metabolismo , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Cardiopatias Congênitas/genética , Doenças das Valvas Cardíacas/embriologia , Doenças das Valvas Cardíacas/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Masculino , Mutação de Sentido Incorreto , Fenótipo , RNA não Traduzido/genética
13.
BMJ Case Rep ; 20172017 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-28455460

RESUMO

BRAF mutation testing to determine eligibility for treatment with vemurafenib was performed on archival skin lesions of a 54-year-old patient diagnosed with Erdheim-Chester disease (ECD) in 1999. Sanger sequencing of DNA extracted from a 2008 skin lesion identified two non-contiguous base substitutions in BRAF, which were shown by next-generation sequencing (NGS) to be located in the same allele. Due to its long-standing duration, molecular evolution of disease was possible; however, both Sanger and NGS of a 2000 skin lesion were unsuccessful due to the poor quality of DNA. Finally, droplet digital PCR using a probe specific for this novel mutation detected the complex BRAF mutation in both the 2000 and 2008 lesions, indicating this case to be ECD with a novel underlying BRAF p.Thr599_Val600delinsArgGlu mutation. Although well at present, molecular modelling of the mutant BRAF suggests suboptimal binding of vemurafenib and hence reduced therapeutic effectiveness.


Assuntos
Doença de Erdheim-Chester/genética , Histiocitose de Células de Langerhans/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Inibidores Enzimáticos/uso terapêutico , Doença de Erdheim-Chester/etiologia , Doença de Erdheim-Chester/patologia , Histiocitose de Células de Langerhans/patologia , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Pele/patologia , Neoplasias Cutâneas/genética , Sulfonamidas/uso terapêutico , Vemurafenib
14.
J Cell Biochem ; 117(10): 2249-59, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26917208

RESUMO

Elevated expression of the efflux transporter, ATP-binding cassette subfamily G isoform 2 (ABCG2) on the plasma membrane of cancer cells contributes to the development of drug resistance and is a key characteristic of cancer stem cells. In this study, gene expression analysis identified that treatment of the MCF-7 and T-47D breast cancer cell lines with the androgen, 5α-dihydrotestosterone (DHT), and the Hedgehog signaling inhibitor, cyclopamine downregulated ABCG2 mRNA levels. In MCF-7 cells, and in Hoechst 33342(lo) /CD44(hi) /CD24(lo) breast cancer stem-like cells isolated from MCF-7 cultures, ABCG2 was accumulated in cell-to-cell junction complexes and in large cytoplasmic aggresome-like vesicles. DHT treatments, which decreased cellular ABCG2 protein levels, led to diminished ABCG2 localization in both cell-to-cell junction complexes and in cytoplasmic vesicles. In contrast, cyclopamine, which did not alter ABCG2 protein levels, induced accumulation of ABCG2 in cytoplasmic vesicles, reducing its localization in cell-to-cell junction complexes. The reduced localization of ABCG2 at the plasma membrane of MCF-7 cells was associated with decreased efflux of the ABCG2 substrate, mitoxantrone, and increased sensitivity of cyclopamine-treated cultures to the cytotoxic effects of mitoxantrone. Together, these findings indicate that DHT and cyclopamine reduce ABCG2 activity in breast cancer cells by distinct mechanisms, providing evidence to advocate the adjunct use of analogous pharmaceutics to increase or prolong the efficacy of breast cancer treatments. J. Cell. Biochem. 117: 2249-2259, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Membrana Celular/metabolismo , Di-Hidrotestosterona/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Alcaloides de Veratrum/farmacologia , Androgênios/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células Tumorais Cultivadas
15.
J Clin Neurosci ; 26: 154-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26633091

RESUMO

This case report presents a 37-year-old man with clinical signs of myelopathy almost 9 years after implantation of a Bryan disc prosthesis (Medtronic Sofamor Danek, Memphis, TN, USA) for C5/C6 soft disc herniation. As demonstrated on MRI and CT scan, spinal cord compression was caused by bony spurs due to heterotopic ossification posterior to the still moving prosthesis. The device, as well as the ectopic bone deposits, had to be removed because of myelopathy and its imminent aggravation. Conversion to anterior spondylodesis was performed.


Assuntos
Prótese Articular/efeitos adversos , Ossificação Heterotópica/etiologia , Doenças da Medula Espinal/etiologia , Substituição Total de Disco/efeitos adversos , Adulto , Vértebras Cervicais/cirurgia , Humanos , Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Imageamento por Ressonância Magnética , Masculino , Osteófito/etiologia , Osteófito/patologia , Compressão da Medula Espinal/etiologia , Doenças da Medula Espinal/cirurgia , Fusão Vertebral , Tomografia Computadorizada por Raios X
16.
Langmuir ; 31(49): 13426-32, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26569145

RESUMO

The temperature-dependent switching behavior of poly(N,N-dimethylaminoethyl methacrylate) brushes in alkaline, neutral, and acidic solutions is examined. A novel microscopic laser temperature-jump technique is employed in order to study characteristic thermodynamic and kinetic parameters. Static laser micromanipulation experiments allow one to determine the temperature-dependent variation of the swelling ratio. The data reveal a strong shift of the volume phase transition of the polymer brushes to higher temperatures when going from pH = 10 to pH = 4. Dynamic laser micromanipulation experiments offer a temporal resolution on a submillisecond time scale and provide a means to determine the intrinsic rate constants. Both the swelling and the deswelling rates strongly decrease in acidic solutions. Complementary experiments using in situ atomic force microscopy show an increased polymer layer thickness at these conditions. The data are discussed on the basis of pH-dependent structural changes of the polymer brushes including protonation of the amine groups and conformational rearrangements. Generally, repulsive electrostatic interactions and steric effects are assumed to hamper and slow down temperature-induced switching in acidic solutions. This imposes significant restrictions for smart polymer surfaces, sensors, and devices requiring fast response times.

17.
J Clin Neurosci ; 21(5): 741-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24256884

RESUMO

We report on 69 retrospectively reviewed patients who received 73 Bryan (Medtronic Sofamor Danek, Memphis, TN, USA) total disc arthroplasties for recent soft cervical disc herniations over a 9.3year period. Three patients returned with radiculopathy due to the redevelopment of uncoforaminal stenosis at the Bryan segment and later underwent posterior decompression of the uncoforaminal area without modification to the prosthesis. They recovered from the radiculopathy after decompression; however, one patient later required adjacent segment fusion to recover from concomitant cervicalgia. After posterior decompression, all prostheses continued to function normally. In one patient, however, bony bridging of the prosthesis is imminent, despite being currently asymptomatic. We normally exclude patients with uncoforaminal stenosis from Bryan arthroplasty. Analysis of three of these patients (4.3% of patients, 4.1% of prostheses) revealed that they received a prosthesis despite slight uncoforaminal stenosis (slight stenosis was known prior to surgery in one instance, two others were only discovered intra-operatively). Our observation raises the suspicion that slight uncoforaminal stenosis could also recur in physiologically working arthroplasty segments, and that in some instances this spur formation may progress into prosthesis bridging. However, more research is required to confirm the significance of uncoforaminal stenosis discovered pre- or intra-operatively in arthroplasty patients. Posterior minimally invasive decompression using the Frykholm-Scoville keyhole approach successfully treats uncoforaminal stenosis without revising the prosthesis.


Assuntos
Descompressão Cirúrgica/métodos , Complicações Pós-Operatórias/cirurgia , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Substituição Total de Disco/efeitos adversos , Adulto , Idoso , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Recidiva , Estudos Retrospectivos , Estenose Espinal/etiologia
18.
Plast Reconstr Surg ; 131(4): 574e-581e, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23542275

RESUMO

BACKGROUND: Normal nasolabial anatomy has received little attention in infants younger than 1 year. However, the notion of an ideal lip and nose is critical to reconstruction of this region, especially for cleft lip and nose repair. The purpose of this study was to quantitatively define the normal nasolabial anatomy in a series of infants younger than 1 year. METHODS: A prospective analysis was performed of infants aged 0 to 12 months from 2011 to 2012. Plaster molds of the nasolabial region were produced from each subject. Anthropometric measurements were performed by two independent, blinded reviewers. Results were compiled and compared statistically using the two-tailed t test and analysis of variance with the post hoc Tukey honestly significant difference test. Correlation coefficients were calculated for the relationship of age and weight to nasolabial measurements. RESULTS: A total of 34 infants were included (mean age, 8.7 months; girls, n = 11). Ten anthropometric measurements of the nasolabial region were performed. Nasal length in boys was significantly longer than in girls (p < 0.05). With the exception of alar base width (p < 0.001), philtrum column height (p < 0.05), and cutaneous upper lip height (p < 0.01), ethnicity had no effect on nasolabial measurements. Alar thickness and nares circumference correlated positively with age and weight (p < 0.05). CONCLUSIONS: The normal nasolabial morphology is anthropometrically described in a population of infants younger than 1 year. Measurements were similar between boys and girls, and alar thickness and nostril circumference correlated with increasing age and weight.


Assuntos
Lábio/anatomia & histologia , Nariz/anatomia & histologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Valores de Referência
19.
Macromol Rapid Commun ; 34(5): 417-22, 2013 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-23300057

RESUMO

A laser temperature-jump technique is used to probe the impact of sodium halides on the temperature-dependent switching kinetics and thermodynamics of poly(N-isopropylacrylamide) brushes. An analysis on the basis of a two-state model reveals van't Hoff enthalpy and entropy changes. Sodium halides increase the endothermicity and the entropic gain of the switching process below and above Tc following the Hofmeister series: NaCl > NaBr > NaI. In contrast, enthalpic and entropic changes at Tc remain virtually unaffected. This provides an unprecedented insight into the underlying switching energetics of this classic stimuli-responsive polymer. Because of its model character, these results represent an essential reference on the way to unpuzzle the molecular driving forces of the Hofmeister effect.


Assuntos
Polímeros/química , Temperatura , Termodinâmica
20.
J Clin Neurosci ; 18(12): 1677-81, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22099076

RESUMO

A highly selected cohort of nine women and five men (mean age±standard error of the mean, 39.6±10.2 years) with discogenic low-back pain (duration: 75.4±97.5 months) and radiculopathy due to disc herniation (duration: 9.4±11.8 months) underwent anterior microdiscectomy and ProDisc-L II arthroplasty (Synthes, Oberdorf, Switzerland) (L5/S1 in 13 patients, L4/5 in one). As reported earlier, initial results were excellent in 11 and good in three patients at 17.8±4.7 months. At an average of 6.5 years after surgery, all were reassessed using the SWISSDISC-questionnaire, which involves the EuroQol-5D and North American Spine Society evaluations (general health, low-back and lower limb status), and a telephone call. Patients reporting an unsatisfactory outcome were re-examined clinically and radiologically. Results were excellent for 10, good for two, satisfactory for one, and poor for one patient. Visual analog scores for back and leg pain at 6.5 years had improved significantly relative to preoperative values (p<0.01), and were only slightly higher than at 1.48 years (p=0.3). This study confirms the initial favorable results.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Substituição Total de Disco , Adulto , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/complicações , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
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