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1.
J Vasc Surg Venous Lymphat Disord ; : 101967, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270843

RESUMO

OBJECTIVE: The short-term anatomical success rates of mechanochemical ablation (MOCA) using the Clarivein device (Merit Medical, South Jordan, Utah, United States) in the treatment of great saphenous vein (GSV) incompetence are high. However, the anatomical success rates seem to drop over time. The aim of this study was to determine the long-term outcomes of GSV treatment using the Clarivein and to assess whether specific anatomical features better correlate with clinical or QoL related outcomes. METHODS: This is a single-center, prospective cohort study in follow-up of a multicenter, randomized controlled trial, using Clarivein with liquid polidocanol for the treatment of GSV incompetence. The primary outcome was anatomical success (AS), defined as compete occlusion or a recanalized segment, irrespective of reflux, of <10 cm in length. In addition, reflux-free anatomical success (RF-AS) was determined and defined as a complete occlusion or a recanalized segment with <10 cm of reflux. Clinical success was assessed using the Venous Clinical Severity Score (VCSS) and QoL was assessed using the Dutch version of the Aberdeen Varicose Vein Questionnaire (DAVVQ) and the 36-Item Short Form Health Survey (SF-36). Subgroup analyses were performed based on whether AS or RF-AS was achieved or not. RESULTS: 109 patients (115 limbs) were included. The mean follow-up time was 8.4 ± 0.9 years (range 5.5-10.3 years). AS was seen in 60.5% of limbs and RF-AS was seen in 72.8% of limbs. Compared to baseline, the overall mean VCSS improved from 5.3 ± 2.4 to 4.1 ± 2.4, and the overall median DAVVQ score from 13.1 (7.3-19.4) to 10.5 (4.8-15.8) (p<0.001). Improvement in VCSS was only significant in patients with successful treatment: 5.5 ± 2.4 to 3.7 ± 2.5 (p<.001) if AS was achieved and 5.0 ± 1.7 to 4.5 ± 1.9 (p=.20) if AS was not achieved. The same results were found for DAVVQ scores: 13.5 (8.7-20.6) to 10.3 (3.0-14.5) (p<001) if AS was achieved and 12.9 (8.3-19.3) to 10.8 (6.7-18.2) (p=.35) if AS was not achieved. Regarding the overall SF-36 scores, the domains vitality, mental health and general health worsened significantly. CONCLUSION: In over eight-years of follow-up, anatomical success after the treatment of GSV incompetence using the Clarivein device decreased to 60.5%. However, clinical scores and disease-specific QoL still improved significantly compared to baseline. We found no convincing evidence that the absence of reflux correlates better with clinical and quality of life related outcomes compared to recanalization irrespective of reflux.

2.
Med Educ Online ; 29(1): 2345444, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38678447

RESUMO

Accelerated medical school curricula, such as three-year programs, have gained attention in recent years but studies evaluating their impact are still scarce. This study examines the Fully Integrated Readiness for Service Training (FIRST) program, a three-year accelerated pathway, to assess its impact on students' academic performance preparedness for residency. In this observational study, we compared the academic outcomes of FIRST program students to traditional four-year curriculum students from 2018 to 2023. We analyzed multiple metrics, including exam performance (United States Medical Licensing Examination Step scores, shelf exam scores, and pre-clinical course scores) and clinical performance scores during the application and individualization phases. Analysis of Variance was used to examine the effect of accelerated pathway program experience relative to traditional 4-year medical school curriculum on the learning outcomes. FIRST program students were on average 1.5 years younger upon graduation than their traditional peers. While FIRST program students scored slightly lower on Step 2 Clinical Knowledge (CK), they exhibited no significant differences in other exam scores or clinical performance relative to the traditional students. Notably, FIRST students achieved equivalent clinical performance ratings during critical clerkships and rotations. Our findings suggest that a three-year medical school curriculum can effectively prepare students for residency and produce graduates with comparable medical knowledge and clinical skills, offering potential benefits in terms of financial relief and personal well-being for medical students.


Assuntos
Desempenho Acadêmico , Competência Clínica , Currículo , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Desempenho Acadêmico/estatística & dados numéricos , Estudantes de Medicina/psicologia , Educação de Graduação em Medicina/organização & administração , Avaliação Educacional , Estágio Clínico/organização & administração , Internato e Residência , Masculino , Feminino
3.
Phlebology ; 38(8): 532-539, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37436708

RESUMO

OBJECTIVE: This study aimed to compare patient-reported outcomes after technical success (TS) and technical failure (TF) in treating great saphenous vein incompetence (GSV) with ClariVein. METHODS: A subanalysis of a previous trial was conducted on symptomatic GSV incompetence patients who received ClariVein treatment with 2% or 3% polidocanol (POL) and were followed for 6 months. Blinding was implemented for observers and patients, and data from both POL groups were combined. TS was defined as at least 85% occlusion of the treated vein, while TF indicated failure to meet TS criteria. Secondary outcomes included Venous Clinical Severity Score (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and Short-Form 36 Health Survey Questionnaire (SF-36). RESULTS: Among the 364 patients included, the TS rate was 64.5%. Comparison of VCSS, AVVQ, and SF-36 scores between TS and TF groups did not yield significant differences. CONCLUSION: This study indicates no significant variation in VCSS, AVVQ, and SF-36 scores between patients experiencing TS and TF following ClariVein treatment for GSV insufficiency.


Assuntos
Procedimentos Endovasculares , Varizes , Insuficiência Venosa , Humanos , Polidocanol , Veia Safena/diagnóstico por imagem , Resultado do Tratamento , Varizes/terapia , Medidas de Resultados Relatados pelo Paciente , Insuficiência Venosa/terapia , Qualidade de Vida
4.
Clin Teach ; 20(1): e13553, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36464248

RESUMO

BACKGROUND: Many institutions in undergraduate medical education have developed unique curricula to teach social determinants of health (SDOH). Geographic information system (GIS) mapping is one tool that learners could use to understand our built environment and its correlation with health outcomes through data analysis, visualization and active learning. APPROACH: At the University of North Carolina School of Medicine, medical students participate in a 4-year longitudinal curriculum on social and health systems science with the final year dedicated to self-directed learning. This final year course incorporates a GIS-based online module to help students apply their understanding of the health impacts of SDOH. Students create online maps with simulated patient data and identify 'hotspots' with map overlays using ArcGIS software. Students write reflections on their maps based on the implications of SDOH. Thematic analysis of these reflections identified patterns within the narrative data. EVALUATION: From March 2020 to February 2021, 148 fourth-year medical students participated in the GIS learning module. Five major themes were identified: Explored Social Determinant Topics, Inclusion of Geo-mapping in Curriculum, Utility of Geo-mapping in Healthcare, Future Application of ArcGIS for Personal Use, Impressions of ArcGIS Software. Students showed engagement and interest in the exercise, and responses were overall positive. Responses showed understanding of the application of ArcGIS and demonstrated knowledge of social determinants of health. IMPLICATIONS: A self-directed, active learning online module using GIS mapping offers a generally popular, eye-opening and unique method for teaching SDOH in undergraduate medical education.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Sistemas de Informação Geográfica , Determinantes Sociais da Saúde , Currículo , Aprendizagem Baseada em Problemas , Educação de Graduação em Medicina/métodos , Ensino
5.
Front Psychol ; 13: 898171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719490

RESUMO

The COVID-19 pandemic has significantly changed university students' life routines, such as prolonged stay at home and learning online without prior preparation. Identifying factors influencing student online learning has become a great concern of educators and researchers. The present study aimed to investigate whether family wellbeing (i.e., family support and conflict) would significantly predict university students' online learning effectiveness indicated by engagement and gains. The mediational role of individual wellbeing such as life satisfaction and sleep difficulties was also tested. This study collected data from 511 undergraduate students (Mean age = 20.04 ± 1.79 years, 64.8% female students) via an online survey. Structural equation modeling analysis revealed positive effects of family support on students' learning engagement and gains through the mediational effects of life satisfaction and sleep difficulties. In contrast to our expectation, family conflict during the pandemic also positively predicted students' learning gains, which, however, was not mediated by individual wellbeing. The findings add value to the existing literature by delineating the inter-relationships between family wellbeing, individual wellbeing, and online learning effectiveness. The study also sheds light on the unique meaning of family conflict, which needs further clarification in future studies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35627422

RESUMO

Nowadays, playing both online and offline video games is a popular leisure activity among youngsters, but excessive gaming activity engagement may lead to gaming disorder that disrupts daily functioning. Identifying risk and protective factors of this emerging problem is thus essential for devising prevention and intervention strategies. This mixed-method, cross-sectional study aimed to examine the roles of parental depressive symptoms and children's leisure activity engagement on children's gaming disorder symptoms. Furthermore, the moderating roles of risky and protective leisure activity engagement were investigated. The sample comprised 104 parent-child dyads recruited from a population-based survey (parents: Mage = 45.59 years, SD = 6.70; children: Mage = 11.26 years; SD = 4.12). As predicted, parental depressive symptoms and children's gaming activity engagement were positively associated with children's gaming disorder symptoms, whereas children's literacy activity engagement was negatively associated with these symptoms. Moreover, engagement in these two types of leisure activity moderated the association between parental depressive symptoms and children's gaming disorder symptoms in distinct manners, further indicating literacy activities as beneficial and gaming activities as risk-enhancing. These new findings imply that parental depressive symptoms and children's leisure activity engagement should be considered when designing parent-based programs for gaming disorder prevention and intervention.


Assuntos
Comportamento Aditivo , Jogos de Vídeo , Comportamento Aditivo/epidemiologia , Criança , Estudos Transversais , Depressão/epidemiologia , Humanos , Atividades de Lazer , Pessoa de Meia-Idade
7.
Micromachines (Basel) ; 13(4)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35457810

RESUMO

With multi-foci laser cutting technology for sapphire wafer separation, the entire cross-section is generally scanned with single or multiple passes. This investigation proposes a new separation technique through partial thickness scanning. The energy effectivity and efficiency of the picosecond laser were enhanced through a two-zone partial thickness scanning by exploiting the internal reflection at the rough exit surface. Each zone spanned only one-third thickness of the cross-section, and only two out of three zones were scanned consecutively. A laser beam of 0.57 W and 50 kHz pulse repetition rate was split into 9 foci, each with a 2.20 µm calculated focused spot diameter. By only scanning the top two-thirds sample thickness, first its middle section then upper section, a cleavable sample could result. This was achieved with the lowest energy deposition at the fastest scanning speed of 10 mm/s investigated. Although with partial thickness scanning only, counter intuitively, the cleaved sample had a previously unattained uniform roughened sidewall profile over the entire thickness. This is a desirable outcome in LED manufacturing. As such, this proposed scheme could attain a cleavable sample with the desired uniformly roughened sidewall profile with less energy usage and faster scanning speed.

8.
J Vasc Surg Venous Lymphat Disord ; 10(4): 856-864.e2, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34781008

RESUMO

BACKGROUND: The purpose of the present study was to identify the ideal polidocanol (POL) concentration for mechanochemical ablation (MOCA) of the great saphenous vein (GSV) using the ClariVein system (Merit Medical, South Jordan, Utah). METHODS: We performed a multicenter, randomized, controlled, single-blind trial with a follow-up period of 6 months. Patients with symptomatic primary truncal GSV incompetence were randomized to MOCA + 2% POL liquid (2% group) or MOCA + 3% POL liquid (3% group). The primary outcome was technical success (TS), defined as an open part of the treated vein segment of ≤10 cm in length. The secondary outcomes were alternative TS, defined as ≥85% occlusion of the treated vein segment, postoperative pain, venous clinical severity scores, Aberdeen varicose vein questionnaire scores, and short-form 36-item health survey questionnaire scores, and complications. RESULTS: From 2012 to 2018, 364 patients (375 limbs) were included, of which, 189 limbs were randomly allocated to the 2% group and 186 to the 3% group. The TS rate at 6 months was 69.8% in the 2% group vs 78.0% in the 3% group (P = .027). A higher overall TS rate was seen in GSVs of ≤5.9 mm compared with GSVs >5.9 mm (84.3% vs 59.5%, respectively; P < .001). The alternative TS rate at 6 months was 61.4% in the 2% group and 67.7% in the 3% group (P = .028). The venous clinical severity scores, Aberdeen varicose vein questionnaire scores, and most short-form 36-item health survey questionnaire domains had improved in both groups (P < .002). Postprocedural pain was low. Two pulmonary embolisms and two deep vein thromboses were seen. Superficial venous thrombosis had occurred more often in the 3% group (18 vs 8 in the 2% group; P = .033). CONCLUSIONS: The results from the present study showed a higher success rate for MOCA with 3% POL liquid than for MOCA with 2% POL liquid at 6 months of follow-up. However, the difference in quality of life was not significant. Long-term follow-up studies are required to investigate whether these results will be sustained in the future.


Assuntos
Procedimentos Endovasculares , Varizes , Insuficiência Venosa , Procedimentos Endovasculares/métodos , Humanos , Polidocanol/efeitos adversos , Veia Safena/diagnóstico por imagem , Veia Safena/cirurgia , Método Simples-Cego , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/cirurgia , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/cirurgia
9.
Micromachines (Basel) ; 12(11)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34832740

RESUMO

The multi-foci division of through thickness nonlinear pulse energy absorption on ultrashort pulse laser singulation of single side polished sapphire wafers has been investigated. Firstly, it disclosed the enhancement of energy absorption by the total internal reflection of the laser beam exiting from an unpolished rough surface. Secondly, by optimizing energy distribution between foci and their proximity, favorable multi-foci energy absorption was induced. Lastly, for effective nonlinear energy absorption for wafer separation, it highlighted the importance of high laser pulse energy fluence at low pulse repetition rates with optimized energy distribution, and the inadequacy of increasing energy deposition through reducing scanning speed alone. This study concluded that for effective wafer separation, despite the lower pulse energy per focus, energy should be divided over more foci with closer spatial proximity. Once the power density per pulse per focus reached a threshold in the order of 1012 W/cm2, with approximately 15 µm between two adjacent foci, wafer could be separated with foci evenly distributed over the entire wafer thickness. When the foci spacing reduced to 5 µm, wafer separation could be achieved with pulse energy concentrated only at foci distributed over only the upper or middle one-third wafer thickness.

10.
J Fam Pract ; 70(9): 420-430, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34818149

RESUMO

Which history and exam findings have high predictive value for different causes of chest pain? Which decision tool can best assess for CAD in your practice setting?


Assuntos
Dor no Peito/etiologia , Doença da Artéria Coronariana/diagnóstico , Técnicas de Apoio para a Decisão , Doença da Artéria Coronariana/complicações , Diagnóstico Diferencial , Humanos , Anamnese , Exame Físico
11.
Micromachines (Basel) ; 12(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34577675

RESUMO

Electroosmotic flow (EOF) involving displacement of multiple fluids is employed in micro-/nanofluidic applications. There are existing investigations on EOF hysteresis, i.e., flow direction-dependent behavior. However, none so far have studied the solution pair system of dissimilar ionic species with substantial pH difference. They exhibit complicated hysteretic phenomena. In this study, we investigate the EOF of sodium bicarbonate (NaHCO3, alkaline) and sodium chloride (NaCl, slightly acidic) solution pair via current monitoring technique. A developed slip velocity model with a modified wall condition is implemented with finite element simulations. Quantitative agreements between experimental and simulation results are obtained. Concentration evolutions of NaHCO3-NaCl follow the dissimilar anion species system. When NaCl displaces NaHCO3, EOF reduces due to the displacement of NaHCO3 with high pH (high absolute zeta potential). Consequently, NaCl is not fully displaced into the microchannel. When NaHCO3 displaces NaCl, NaHCO3 cannot displace into the microchannel as NaCl with low pH (low absolute zeta potential) produces slow EOF. These behaviors are independent of the applied electric field. However, complete displacement tends to be achieved by lowering the NaCl concentration, i.e., increasing its zeta potential. In contrast, the NaHCO3 concentration has little impact on the displacement process. These findings enhance the understanding of EOF involving solutions with dissimilar pH and ion species.

12.
Nat Commun ; 12(1): 3146, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035283

RESUMO

Despite its advantages of scalable process and cost-effectiveness, nanoimprinting faces challenges with imprinting hard materials (e.g., crystalline metals) at low/room temperatures, and with fabricating complex nanostructures rapidly (e.g., heterojunctions of metal and oxide). Herein, we report a room temperature ultrasonic nanoimprinting technique (named nanojackhammer) to address these challenges. Nanojackhammer capitalizes on the concentration of ultrasonic energy flow at nanoscale to shape bulk materials into nanostructures. Working at room temperature, nanojackhammer allows rapid fabrication of complex multi-compositional nanostructures made of virtually all solid materials regardless of their ductility, hardness, reactivity and melting points. Atomistic simulations reveal a unique alternating dislocation generation and recovery mechanism that significantly reduces the imprinting force under ultrasonic cyclic loading. As a proof-of-concept, a metal-oxide-metal plasmonic nanostructure with built-in nanogap is rapidly fabricated and employed for biosensing. As a fast, scalable, and cost-effective nanotechnology, nanojackhammer will enable various unique applications of complex nanostructures in optoelectronics, biosensing, catalysis and beyond.

13.
Micromachines (Basel) ; 12(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668402

RESUMO

We conducted a laser parameter study on CO2 laser induced electrical conductivity on a polyimide film. The induced electrical conductivity was found to occur dominantly at the center of the scanning line instead of uniformly across the whole line width. MicroRaman examination revealed that the conductivity was mainly a result of the multi-layers (4-5) of graphene structure induced at the laser irradiation line center. The graphene morphology at the line center appeared as thin wall porous structures together with nano level fiber structures. With sufficient energy dose per unit length and laser power, this surface modification for electrical conductivity was independent of laser pulse frequency but was instead determined by the average laser power. High electrical conductivity could be achieved by a single scan of laser beam at a sufficiently high-power level. To achieve high conductivity, it was not efficient nor effective to utilize a laser at low power but compensating it with a slower scanning speed or having multiple scans. The electrical resistance over a 10 mm scanned length decreased significantly from a few hundred Ohms to 30 Ohms when energy dose per unit length increased from 0.16 J/mm to 1.0 J/mm, i.e., the laser power increased from 5.0 W to 24 W with corresponding power density of 3.44 × 10 W/cm2 to 16.54 W/cm2 respectively at a speed of 12.5 mm/s for a single pass scan. In contrast, power below 5 W at speeds exceeding 22.5 mm/s resulted in a non-conductive open loop.

14.
Micromachines (Basel) ; 11(11)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138301

RESUMO

Electroosmotic flow (EOF) is fluid flow induced by an applied electric field, which has been widely employed in various micro-/nanofluidic applications. Past investigations have revealed that the presence of nanostructures in microchannel reduces EOF. Hitherto, the angle-dependent behavior of nanoline structures on EOF has not yet been studied in detail and its understanding is lacking. Numerical analyses of the effect of nanoline orientation angle θ on EOF to reveal the associated mechanisms were conducted in this investigation. When θ increases from 5° to 90° (from parallel to perpendicular to the flow direction), the average EOF velocity decreases exponentially due to the increase in distortion of the applied electric field distribution at the structured surface, as a result of the increased apparent nanolines per unit microchannel length. With increasing nanoline width W, the decrease of average EOF velocity is fairly linear, attributed to the simultaneous narrowing of nanoline ridge (high local fluid velocity region). While increasing nanoline depth D results in a monotonic decrease of the average EOF velocity. This reduction stabilizes for aspect ratio D/W > 0.5 as the electric field distribution distortion within the nanoline trench remains nearly constant. This investigation reveals that the effects on EOF of nanolines, and by extrapolation for any nanostructures, may be directly attributed to their effects on the distortion of the applied electric field distribution within a microchannel.

15.
FP Essent ; 493: 11-21, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32573182

RESUMO

Primary benign bone tumors are uncommon and most often affect children and young adults. They typically are detected incidentally on imaging, though some patients present with pain, swelling, or other symptoms. The four main categories of benign bone tumor are: bone-forming (eg, osteoid osteoma, osteoblastoma, fibrous dysplasia, enostosis), cartilage-forming (eg, osteochondroma, enchondroma), connective tissue, and vascular; the latter two are rare. A fifth category is idiopathic (eg, giant cell tumor, aneurysmal bone cyst, simple bone cyst). Osteochondromas are the most common, accounting for 30% to 35% of benign bone tumors. Giant cell tumors account for 20%, osteoblastomas for 14%, and osteoid osteomas for 12%. All others are less common. Diagnosis mainly is via imaging; biopsy rarely is required. Management varies with tumor type, location, symptoms, and risk of recurrence. Some (eg, enchondroma, osteochondroma, fibrous dysplasia, enostosis) typically are asymptomatic, and generally require no intervention. Others (eg, osteoid osteoma, aneurysmal bone cyst, simple bone cyst) can cause symptoms and require percutaneous ablation or surgery. Still others (eg, giant cell tumor, osteoblastoma) can be aggressive and require surgery and other therapies. Malignant transformation is rare for all benign bone tumors, but patients with these tumors should be monitored with serial imaging.


Assuntos
Neoplasias Ósseas , Osteoblastoma , Osteoma Osteoide , Biópsia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/terapia , Criança , Diagnóstico Diferencial , Humanos , Osteoblastoma/diagnóstico , Osteoblastoma/terapia , Osteoma Osteoide/diagnóstico , Osteoma Osteoide/terapia , Adulto Jovem
16.
Micromachines (Basel) ; 10(2)2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30736476

RESUMO

Viscous liquid flow in micro-channels is typically laminar because of the low Reynolds number constraint. However, by introducing elasticity into the fluids, the flow behavior could change drastically to become turbulent; this elasticity can be realized by dissolving small quantities of polymer molecules into an aqueous solvent. Our recent investigation has directly visualized the extension and relaxation of these polymer molecules in an aqueous solution. This elastic-driven phenomenon is known as 'elastic turbulence'. Hitherto, existing studies on elastic flow instability are mostly limited to single-stream flows, and a comprehensive statistical analysis of a multi-stream elastic turbulent micro-channel flow is needed to provide additional physical understanding. Here, we investigate the flow field characteristics of elastic turbulence in a 3-stream contraction-expansion micro-channel flow. By applying statistical analyses and flow visualization tools, we show that the flow field bares many similarities to that of inertia-driven turbulence. More interestingly, we observed regions with two different types of power-law dependence in the velocity power spectra at high frequencies. This is a typical characteristic of two-dimensional turbulence and has hitherto not been reported for elastic turbulent micro-channel flows.

17.
Nat Commun ; 10(1): 244, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651561

RESUMO

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzimidazóis/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/uso terapêutico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Epigênese Genética/efeitos dos fármacos , Feminino , GTP Fosfo-Hidrolases/genética , Células HEK293 , Humanos , Concentração Inibidora 50 , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Mutação/genética , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/farmacologia , Piridonas/uso terapêutico , Pirimidinonas/farmacologia , Pirimidinonas/uso terapêutico , Sequências de Repetição em Tandem/genética , Resultado do Tratamento , Sequenciamento do Exoma
18.
Adv Healthc Mater ; 8(6): e1801022, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30511823

RESUMO

Microarrays are widely used in high-throughput analysis of DNA, protein, and small molecules. However, the majority of microarray assays need improved assay speed and sensitivity due to the slow molecular diffusion from bulk solutions to probe surfaces. Here, a new class of magnetic nanomixers in DNA and protein microarray assays is reported to eliminate the diffusion constraint through dynamic mixing. It is demonstrated that the dynamic nanomixers can improve the assay kinetics at least by a factor of 4 and 2 for DNA and protein microarray assays, respectively. By using the dynamic nanomixers, the sensitivities of detecting Escherichia coli O157:H7 DNA and prostate specific antigen increase by more than four-fold. The dynamic mixing also greatly reduces the spot-to-spot variation to below 10% across a broad concentration range, providing more accurate assay results. In comparison with existing methods, this magnetic nanomixer-based approach offers rapid turnaround, improved sensitivity, good accuracy, low cost, simple operation, and excellent compatibility with commercial microarrays.


Assuntos
Magnetismo , Análise em Microsséries/métodos , Nanoestruturas/química , DNA Bacteriano/análise , Difusão , Escherichia coli O157/genética , Humanos , Cinética , Antígeno Prostático Específico/análise
19.
Micromachines (Basel) ; 9(5)2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-30424162

RESUMO

Although electroosmotic flow (EOF) has been applied to drive fluid flow in microfluidic chips, some of the phenomena associated with it can adversely affect the performance of certain applications such as electrophoresis and ion preconcentration. To minimize the undesirable effects, EOF can be suppressed by polymer coatings or introduction of nanostructures. In this work, we presented a novel technique that employs the Dry Etching, Electroplating and Molding (DEEMO) process along with reactive ion etching (RIE), to fabricate microchannel with black silicon nanostructures (prolate hemispheroid-like structures). The effect of black silicon nanostructures on EOF was examined experimentally by current monitoring method, and numerically by finite element simulations. The experimental results showed that the EOF velocity was reduced by 13 ± 7%, which is reasonably close to the simulation results that predict a reduction of approximately 8%. EOF reduction is caused by the distortion of local electric field at the nanostructured surface. Numerical simulations show that the EOF velocity decreases with increasing nanostructure height or decreasing diameter. This reveals the potential of tuning the etching process parameters to generate nanostructures for better EOF suppression. The outcome of this investigation enhances the fundamental understanding of EOF behavior, with implications on the precise EOF control in devices utilizing nanostructured surfaces for chemical and biological analyses.

20.
Nat Commun ; 9(1): 1743, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717124

RESUMO

Microfluidic biochips hold great potential for liquid analysis in biomedical research and clinical diagnosis. However, the lack of integrated on-chip liquid mixing, bioseparation and signal transduction presents a major challenge in achieving rapid, ultrasensitive bioanalysis in simple microfluidic configurations. Here we report magnetic nanochain integrated microfluidic chip built upon the synergistic functions of the nanochains as nanoscale stir bars for rapid liquid mixing and as capturing agents for specific bioseparation. The use of magnetic nanochains enables a simple planar design of the microchip consisting of flat channels free of common built-in components, such as liquid mixers and surface-anchored sensing elements. The microfluidic assay, using surface-enhanced Raman scattering nanoprobes for signal transduction, allows for streamlined parallel analysis of multiple specimens with greatly improved assay kinetics and delivers ultrasensitive identification and quantification of a panel of cancer protein biomarkers and bacterial species in 1 µl of body fluids within 8 min.


Assuntos
Bactérias/metabolismo , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Magnetismo , Microfluídica/instrumentação , Nanoestruturas , Saliva/microbiologia , Bactérias/isolamento & purificação , Líquidos Corporais/química , Humanos , Limite de Detecção , Neoplasias/sangue , Análise Espectral Raman
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