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Systems with occlusion capabilities, such as those used in vision augmentation, image processing, and optical see-through head-mounted display (OST-HMD), have gained popularity. Achieving precise (hard-edge) occlusion in these systems is challenging, often requiring complex optical designs and bulky volumes. On the other hand, utilizing a single transparent liquid crystal display (LCD) is a simple approach to create occlusion masks. However, the generated mask will appear defocused (soft-edge) resulting in insufficient blocking or occlusion leakage. In our work, we delve into the perception of soft-edge occlusion by the human visual system and present a preference-based optimal expansion method that minimizes perceived occlusion leakage. In a user study involving 20 participants, we made a noteworthy observation that the human eye perceives a sharper edge blur of the occlusion mask when individuals see through it and gaze at a far distance, in contrast to the camera system's observation. Moreover, our study revealed significant individual differences in the perception of soft-edge masks in human vision when focusing. These differences may lead to varying degrees of demand for mask size among individuals. Our evaluation demonstrates that our method successfully accounts for individual differences and achieves optimal masking effects at arbitrary distances and pupil sizes.
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Purpose: This study aims to minimize monitor units (MUs) of intensity-modulated treatments in the Monaco treatment planning system while preserving plan quality by optimizing the "Minimum Segment Width" (MSW) and "Fluence Smoothing" parameters. Materials and Methods: We retrospectively analyzed 30 prostate, 30 gynecological, 15 breast cancer, 10 head and neck tumor, 11 radiosurgery, and 10 hypo-fractionated plans. Original prostate plans employed "Fluence Smoothing" = Off and were reoptimized with Low, Medium, and High settings. The remaining pathologies initially used MSW = 0.5 cm and were reoptimized with MSW = 1.0 cm. Plan quality, including total MU, delivery time, and dosimetric constraints, was statistically analyzed with a paired t-test. Results: Prostate plans exhibited the highest MU variation when changing "Fluence Smoothing" from Off to High (average ΔMU = -5.1%; P < 0.001). However, a High setting may increase overall MU when MSW = 0.5 cm. Gynecological plans changed substantially when MSW increased from 0.5 cm to 1.0 cm (average ΔMU = -29%; P < 0.001). Organs at risk sparing and planning target volumes remained within 1.2% differences. Replanning other pathologies with MSW = 1.0 cm affected breast and head and neck tumor plans (average ΔMU = -168.38, average Δt = -11.74 s, and average ΔMU = -256.56, average Δt = -15.05 s, respectively; all with P < 0.004). Radiosurgery and hypofractioned highly modulated plans did not yield statistically significant results. Conclusions: In breast, pelvis, head and neck, and prostate plans, starting with MSW = 1.0 cm optimally reduces MU and treatment time without compromising plan quality. MSW has a greater impact on MU than the "Fluence Smoothing" parameter. Plans with high modulation might present divergent behavior, requiring a case-specific analysis with MSW values higher than 0.5 cm.
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Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK, KIT, and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT, CTNNB1, EGFR, ALK, HRAS, or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy.
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Melanoma , Mutação , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Espanha , Adulto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Proteínas Proto-Oncogênicas B-raf/genética , Biomarcadores Tumorais/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
This paper explores the connections between traditional Large Deformation Diffeomorphic Metric Mapping methods and unsupervised deep-learning approaches for non-rigid registration, particularly emphasizing diffeomorphic registration. The study provides useful insights and establishes connections between the methods, thereby facilitating a profound understanding of the methodological landscape. The methods considered in our study are extensively evaluated in T1w MRI images using traditional NIREP and Learn2Reg OASIS evaluation protocols with a focus on fairness, to establish equitable benchmarks and facilitate informed comparisons. Through a comprehensive analysis of the results, we address key questions, including the intricate relationship between accuracy and transformation quality in performance, the disentanglement of the influence of registration ingredients on performance, and the determination of benchmark methods and baselines. We offer valuable insights into the strengths and limitations of both traditional and deep-learning methods, shedding light on their comparative performance and guiding future advancements in the field.
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Aprendizado Profundo , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Aprendizado de Máquina não Supervisionado , AlgoritmosRESUMO
BACKGROUND: Patient navigation is an evidence-based intervention that reduces cancer health disparities by directly addressing the barriers to care for underserved patients with cancer. Variability in design and integration of patient navigation programs within cancer care settings has limited this intervention's utility. The implementation science evaluation framework, RE-AIM, allows quantitative and qualitative examination of effective implementation of patient navigation programs into cancer care settings. METHODS: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to evaluate implementation of a community-focused patient navigation intervention at an NCI-designated cancer center between June 2018 and October 2021. Using a 3-month longitudinal, non-comparative measurement period, univariate and bivariate analyses were conducted to examine associations between participant-level demographics and primary (i.e., barrier reduction) and secondary (i.e., patient-reported outcomes) effectiveness outcomes. Mixed methods analyses were used to examine adoption and delivery of the intervention into the cancer center setting. Process-level analyses were used to evaluate maintenance of the intervention. RESULTS: Participants (n = 311) represented a largely underserved population, as defined by the National Cancer Institute, with the majority identifying as Hispanic/Latino, having a household income of $35,000 or less, and being enrolled in Medicaid. Participants were diagnosed with a variety of cancer types and most had advanced staged cancers. Pre-post-intervention analyses indicated significant reduction from pre-intervention assessments in the average number of reported barriers, F(1, 207) = 117.62, p < .001, as well as significant increases in patient-reported physical health, t(205) = - 6.004, p < .001, mental health, t(205) = - 3.810, p < .001, self-efficacy, t(205) = - 5.321, p < .001, and satisfaction with medical team communication, t(206) = - 2.03, p = .029. Referral patterns and qualitative data supported increased adoption and integration of the intervention into the target setting, and consistent intervention delivery metrics suggested high fidelity to intervention delivery over time. Process-level data outlined a successful transition from a grant-funded community-focused patient navigation intervention to an institution-funded program. CONCLUSIONS: This study utilized the implementation science evaluation framework, RE-AIM, to evaluate implementation of a community-focused patient navigation program. Our analyses indicate successful implementation within a cancer care setting and provide a potential guide for other oncology settings who may be interested in implementing community-focused patient navigation programs.
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Institutos de Câncer , National Cancer Institute (U.S.) , Neoplasias , Navegação de Pacientes , Humanos , Navegação de Pacientes/métodos , Navegação de Pacientes/organização & administração , Masculino , Feminino , Estados Unidos , Pessoa de Meia-Idade , Neoplasias/terapia , Institutos de Câncer/organização & administração , Estudos Longitudinais , Avaliação de Programas e Projetos de Saúde , Adulto , Acessibilidade aos Serviços de Saúde , IdosoRESUMO
INTRODUCTION/OBJECTIVES: Colonoscopy completion rates after an abnormal fecal immunochemical test (FIT) are suboptimal, resulting in missed opportunities for early detection and prevention of colorectal cancer. Patient navigation and structured follow-up may improve colonoscopy completion, but implementation of these strategies is not widespread. METHODS: We conducted a quality improvement study using a Plan-Do-Study-Act (PDSA) Model to increase colonoscopy completion after abnormal FIT in a large federally qualified health center serving a diverse and low-income population. Intervention components included patient navigation, and a checklist to promote completion of key steps required for abnormal FIT follow-up. Primary outcome was proportion of patients achieving colonoscopy completion within 6 months of abnormal FIT, assessed at baseline for 156 patients pre-intervention, and compared to 208 patients during the intervention period from April 2017 to December 2019. Drop offs at each step in the follow-up process were assessed. RESULTS: Colonoscopy completion improved from 21% among 156 patients with abnormal FIT pre-intervention, to 38% among 208 patients with abnormal FIT during the intervention (P < .001; absolute increase: 17%, 95% CI: 6.9%-25.2%). Among the 130 non-completers during the intervention period, lack of completion was attributable to absence of colonoscopy referral for 7.7%; inability to schedule a pre-colonoscopy specialist visit for 71.5%; failure to complete a pre-colonoscopy visit for 2.3%; the absence of colonoscopy scheduling for 9.2%; failure to show for a scheduled colonoscopy for 9.2%. CONCLUSIONS: Patient navigation and structured follow-up appear to improve colonoscopy completion after abnormal FIT. Additional strategies are needed to achieve optimal rates of completion.
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Neoplasias Colorretais , Melhoria de Qualidade , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Instalações de Saúde , Colonoscopia , Sangue Oculto , Programas de Rastreamento/métodosRESUMO
Predictors of health across the life-course do not maintain the same significance in very late life and the role of financial strain in health outcomes of very old adults remain unclear. Data from adults aged 74 + in waves 5 and 7 of the Hispanic Established Population for the Epidemiological Study of the Elderly (n = 772) study was used to evaluate the role of financial strain on the health of older Mexican Americans who have the highest poverty rate of any racial or ethnic group in the United States. We evaluate the association between episodic (one wave) and persistent financial strain (two waves), with follow-up health outcomes (self-rated health, ADL (limitations in activities of daily living)/IADL (limitations in instrumental activities of daily living) disability, and depressive symptoms). Adults with persistent strain were twice as likely to experience depressive symptoms and three times more likely to experience IADL limitations than the unstrained. Our findings highlight the role of stress proliferation and allostatic load processes leading to deteriorated health over time.
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Atividades Cotidianas , Depressão , Nível de Saúde , Americanos Mexicanos , Humanos , Masculino , Idoso , Feminino , Americanos Mexicanos/estatística & dados numéricos , Americanos Mexicanos/psicologia , Atividades Cotidianas/psicologia , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Depressão/etnologia , Depressão/psicologia , Estados Unidos/epidemiologia , Estados Unidos/etnologia , Estresse Financeiro/etnologia , Estresse Financeiro/psicologiaRESUMO
Botryosphaeria dieback, caused by a group of pathogens in the Botryosphaeriaceae family, is one of the most common grapevine trunk disease complexes (GTDs) found in Oregon vineyards. To understand the period of spores released by Botryosphaeria spp. in Oregon vineyards, four Burkard 7-day recording volumetric spore traps were placed in vineyard blocks in northern and southern Oregon. Each trap was placed near a younger (<10 years) and older (>30 years) block in both regions. Spore traps were deployed at the beginning of December 2019 and continued until March 2021. Between these timeframes, 475 and 477 days of samples were collected from each spore trap in northern and southern Oregon, respectively. DNA extraction was performed from individual day samples and followed by qPCR analysis of Botryosphaeria spores trapped in each tape sample. Weather data such as temperature, precipitation, relative humidity (RH), and wind speed were collected from nearby weather stations. Association between these data and number of spores detected were analyzed using Pearson correlation analysis. In northern Oregon, the detection occurred between December and February, and the first spore detection occurred when cumulative growing degree day (GDD) totaled to 4,357 and 4,351 units (TBase = 0°C, biofix date = January 1) during the first and second seasons, respectively. Similarly, in southern Oregon, the detection occurred between November and January, and the first spore detection occurred when cumulative GDD was 4,405 units during the second season. Hours of continuous RH >86% was significantly associated with number of spores released (P = 0.026; r = 0.42). During the spore detected dates, the RH was >86% for at least 19 consecutive hours. These findings provide an important implication to manage Botryosphaeria dieback by protecting pruning wounds during the most-spore-released periods. Furthermore, the knowledge of weather variables and their possible association with spore detection provides important information towards developing predictive models in future studies.
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OBJECTIVE: We developed a MHAS (Mexican Health and Aging Study) and O*NET (Occupational Information Network) linkage to allow global researchers using MHAS data to assign lifetime occupation domains for older Mexicans. MATERIALS AND METHODS: Three bilingual raters independently matched 440 records with 132 unique occupation codes from the 2012 MHAS. We used a modified Delphi technique to reach agreements. To assess reliability, we compared the distribution of observations between the MHAS file and the MHAS-O*NET linked file across five job categories (upper white collar, lower white collar, upper blue collar, low blue collar, and agriculture/fishing/forestry). The Institutional Review Board at the University of Texas Medical Branch reviewed and approved the research (IRB # 21-0268). RESULTS: Using the developed 1:1 MHAS-ONET linkage, consistency between MHAS and ONET was 97.4% across the five job categories. CONCLUSION: This MHAS-O*NET linkage will allow researchers to analyze the association between lifetime occupation and multiple dimensions of health, functionality, and retirement determinants for a low-middle income country with a large proportion of workers in the informal sector.
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Envelhecimento , Ocupações , Humanos , Reprodutibilidade dos Testes , MéxicoRESUMO
The rise in population and aging has led to a significant increase in the number of individuals affected by common causes of vision loss. Early diagnosis and treatment are crucial to avoid the consequences of visual impairment. However, in early stages, many visual problems are making it difficult to detect. Visual adaptation can compensate for several visual deficits with adaptive eye movements. These adaptive eye movements may serve as indicators of vision loss. In this work, we investigate the association between eye movement and blurred vision. By using Electrooculography (EOG) to record eye movements, we propose a new tracking model to identify the deterioration of refractive power. We verify the technical feasibility of this method by designing a blurred vision simulation experiment. Six sets of prescription lenses and a pair of flat lenses were used to create different levels of blurring effects. We analyzed binocular movements through EOG signals and performed a seven-class classification using the ResNet18 architecture. The results revealed an average classification accuracy of 94.7% in the subject-dependent model. However, the subject-independent model presented poor performance, with the highest accuracy reaching only 34.5%. Therefore, the potential of an EOG-based visual quality monitoring system is proven. Furthermore, our experimental design provides a novel approach to assessing blurred vision.
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Movimentos Oculares , Baixa Visão , Humanos , Eletroculografia/métodos , Transtornos da VisãoRESUMO
Prior research indicate that emotional states can alter taste perception, but the underlying mechanisms remain unclear. This study explores whether taste perception changes due to the mere evocation of emotions or the cognitive awareness of emotions. The first experiment investigated how anxiety affects taste perception when individuals are aware of their anxiety. Participants watched videos inducing relaxation or anxiety, then were divided into groups focusing on their emotions and those who did not, and the taste perception was measure. The second experiment investigated the influence of awareness directed toward emotions on taste evaluation, without manipulating emotional states. This focused on cognitive processing of taste through evaluations of visual stimuli. Results showed that sweetness perception is suppressed by the evocation of anxiety, whereas bitterness perception is enhanced only by anxiety with awareness. These findings indicate that the mechanisms by which emotional states affect taste perception may differ depending on taste quality.
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Facial neuromuscular electrical stimulation (fNMES), which allows for the non-invasive and physiologically sound activation of facial muscles, has great potential for investigating fundamental questions in psychology and neuroscience, such as the role of proprioceptive facial feedback in emotion induction and emotion recognition, and may serve for clinical applications, such as alleviating symptoms of depression. However, despite illustrious origins in the 19th-century work of Duchenne de Boulogne, the practical application of fNMES remains largely unknown to today's researchers in psychology. In addition, published studies vary dramatically in the stimulation parameters used, such as stimulation frequency, amplitude, duration, and electrode size, and in the way they reported them. Because fNMES parameters impact the comfort and safety of volunteers, as well as its physiological (and psychological) effects, it is of paramount importance to establish recommendations of good practice and to ensure studies can be better compared and integrated. Here, we provide an introduction to fNMES, systematically review the existing literature focusing on the stimulation parameters used, and offer recommendations on how to safely and reliably deliver fNMES and on how to report the fNMES parameters to allow better cross-study comparison. In addition, we provide a free webpage, to easily visualise fNMES parameters and verify their safety based on current density. As an example of a potential application, we focus on the use of fNMES for the investigation of the facial feedback hypothesis.
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Purpose: The study is intended to perform an end-to-end test of the entire intraoperative process using cadaver heads. A simulation of tumor removal was performed, followed by irradiation of the bed and measurement of absorbed doses with radiochromic films. Materials and Methods: Low-energy X-ray intraoperative radiotherapy (IORT) was used for irradiation. A computed tomography study was performed at each site and the absorbed doses calculated by the treatment planning system, as well as absorbed doses with radiochromic films, were studied. Results: The absorbed doses in the organs at risk (OAR) were evaluated in each case, obtaining maximum doses within the tolerance limits. The absorbed doses in the target were verified and the deviations were <1%. Conclusions: These tests demonstrated that this comprehensive procedure is a reproducible quality assurance tool which allows continuous assessment of the dosimetric and geometric accuracy of clinical brain IORT treatments. Furthermore, the absorbed doses measured in both target and OAR are optimal for these treatments.
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Experiences of virtual reality (VR) can easily break if the method of evaluating subjective user states is intrusive. Behavioral measures are increasingly used to avoid this problem. One such measure is eye tracking, which recently became more standard in VR and is often used for content-dependent analyses. This research is an endeavor to utilize content-independent eye metrics, such as pupil size and blinks, for identifying mental load in VR users. We generated mental load independently from visuals through auditory stimuli. We also defined and measured a new eye metric, focus offset, which seeks to measure the phenomenon of "staring into the distance" without focusing on a specific surface. In the experiment, VR-experienced participants listened to two native and two foreign language stimuli inside a virtual phone booth. The results show that with increasing mental load, relative pupil size on average increased 0.512 SDs (0.118 mm), with 57% reduced variance. To a lesser extent, mental load led to fewer fixations, less voluntary gazing at distracting content, and a larger focus offset as if looking through surfaces (about 0.343 SDs, 5.10 cm). These results are in agreement with previous studies. Overall, we encourage further research on content-independent eye metrics, and we hope that hardware and algorithms will be developed in the future to further increase tracking stability.
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Realidade Virtual , Humanos , Percepção Auditiva , Idioma , Interface Usuário-Computador , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Several studies indicate that the anterior visual pathway provides information about the dynamics of axonal degeneration in Multiple Sclerosis (MS). Current research in the field is focused on the quest for the most discriminative features among patients and controls and the development of machine learning models that yield computer-aided solutions widely usable in clinical practice. However, most studies are conducted with small samples and the models are used as black boxes. Clinicians should not trust machine learning decisions unless they come with comprehensive and easily understandable explanations. MATERIALS AND METHODS: A total of 216 eyes from 111 healthy controls and 100 eyes from 59 patients with relapsing-remitting MS were enrolled. The feature set was obtained from the thickness of the ganglion cell layer (GCL) and the retinal nerve fiber layer (RNFL). Measurements were acquired by the novel Posterior Pole protocol from Spectralis Optical Coherence Tomography (OCT) device. We compared two black-box methods (gradient boosting and random forests) with a glass-box method (explainable boosting machine). Explainability was studied using SHAP for the black-box methods and the scores of the glass-box method. RESULTS: The best-performing models were obtained for the GCL layer. Explainability pointed out to the temporal location of the GCL layer that is usually broken or thinning in MS and the relationship between low thickness values and high probability of MS, which is coherent with clinical knowledge. CONCLUSIONS: The insights on how to use explainability shown in this work represent a first important step toward a trustworthy computer-aided solution for the diagnosis of MS with OCT.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Células Ganglionares da Retina , Inteligência Artificial , Tomografia de Coerência Óptica/métodos , Fibras NervosasRESUMO
Objective: To measure the association between housing insecurity and foregone medication due to cost among Medicare beneficiaries aged 65+ during the Recession. Methods: Data came from Medicare beneficiaries aged 65+ years from the 2006-2012 waves of the Health and Retirement Study (HRS). Two-wave housing insecurity changes are evaluated as follows: (i) No insecurity, (ii) Persistent insecurity, (iii) Onset insecurity, and (iv) Onset security. We implemented a series of four weighted longitudinal General Estimating Equation (GEE) models, two minimally adjusted and two fully adjusted models, to estimate the probability of foregone medications due to cost between 2008 and 2012. Results: Our study sample was restricted to non-proxy interviews of non-institutionalized Medicare beneficiaries aged 65+ in the 2006 wave (n = 9936) and their follow up visits (n = 8753; in 2008; n = 7464 in 2010; and n = 6594 in 2012). Results from our fully adjusted model indicated that the odds of foregone medication was 64% higher among individuals experiencing Onset insecurity versus No insecurity in 2008, and also generally larger for individuals experiencing Onset Insecurity versus Persistent Insecurity. Odds of foregone medication was also larger among females, minority versus non-Hispanic white adults, those reporting a chronic condition, those with higher medical expenditures, and those living in the South versus Northeast. Conclusion: This study drew from nationally representative data to elucidate the disparate health and financial impacts of a crisis on Medicare beneficiaries who, despite health insurance coverage, displayed variability in foregone medication patterns. Our findings suggest that the onset of housing insecurity is most closely linked with unexpected acute economic shocks leading households with little time to adapt and forcing trade-offs in their prescription and other needs purchases. Both housing and healthcare policy implications exist from these findings including expansion of low-income housing units and rent relief post-recession as well as wider prescription drug coverage for Medicare adults.
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Previously, functional coatings on 3D-printed titanium implants were developed to improve their biointegration by separately incorporating Ga and Ag on the biomaterial surface. Now, a thermochemical treatment modification is proposed to study the effect of their simultaneous incorporation. Different concentrations of AgNO3 and Ga(NO3)3 are evaluated, and the obtained surfaces are completely characterized. Ion release, cytotoxicity, and bioactivity studies complement the characterization. The provided antibacterial effect of the surfaces is analyzed, and cell response is assessed by the study of SaOS-2 cell adhesion, proliferation, and differentiation. The Ti surface doping is confirmed by the formation of Ga-containing Ca titanates and nanoparticles of metallic Ag within the titanate coating. The surfaces generated with all combinations of AgNO3 and Ga(NO3)3 concentrations show bioactivity. The bacterial assay confirms a strong bactericidal impact achieved by the effect of both Ga and Ag present on the surface, especially for Pseudomonas aeruginosa, one of the main pathogens involved in orthopedic implant failures. SaOS-2 cells adhere and proliferate on the Ga/Ag-doped Ti surfaces, and the presence of gallium favors cell differentiation. The dual effect of both metallic agents doping the titanium surface provides bioactivity while protecting the biomaterial from the most frequent pathogens in implantology.
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Gálio , Titânio , Titânio/farmacologia , Titânio/química , Prata/farmacologia , Prata/química , Osseointegração , Porosidade , Gálio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Antibacterianos/farmacologia , Antibacterianos/química , Propriedades de SuperfícieRESUMO
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of fluoropyrimidines. Variations in the encoding DPYD gene are associated with severe fluoropyrimidine toxicity and up-front dose reductions are recommended. We conducted a retrospective study to evaluate the impact of implementing DPYD variant testing for patients with gastrointestinal cancers in routine clinical practice in a high volume cancer centre in London, United Kingdom. METHODS: Patients receiving fluoropyrimidine chemotherapy for gastrointestinal cancer prior to, and following the implementation of DPYD testing were identified retrospectively. After November 2018, patients were tested for DPYD variants c.1905+1G>A (DPYD*2A), c.2846A>T (DPYD rs67376798), c.1679T>G (DPYD*13), c.1236G>A (DPYD rs56038477), c.1601G>A (DPYD*4) prior to commencing fluoropyrimidines alone or in combination with other cytotoxics and/or radiotherapy. Patients with a DPYD heterozygous variant received an initial dose reduction of 25-50%. Toxicity by CTCAE v4.03 criteria was compared between DPYD heterozygous variant and wild type carriers. RESULTS: Between 1st December 2018 and 31st July 2019, 370 patients who were fluoropyrimidine naïve underwent a DPYD genotyping test prior to receiving a capecitabine (n = 236, 63.8%) or 5FU (n = 134, 36.2%) containing chemotherapy regimen. 33 patients (8.8%) were heterozygous DPYD variant carriers and 337 (91.2%) were wild type. The most prevalent variants were c.1601G > A (n = 16) and c.1236G > A (n = 9). Mean relative dose intensity for the first dose was 54.2% (range 37.5-75%) for DPYD heterozygous carriers and 93.2% (42.9-100%) for DPYD wild type carriers. Overall grade 3 or worse toxicity was similar in DPYD variant carriers (4/33, 12.1%) as compared to wild-type carriers (89/337, 25.7%; P = 0.0924). CONCLUSIONS: Our study demonstrates successful routine DPYD mutation testing prior to the initiation of fluoropyrimidine chemotherapy with high uptake. In patients with DPYD heterozygous variants with pre-emptive dose reductions, high incidence of severe toxicity was not observed. Our data supports routine DPYD genotype testing prior to commencement of fluoropyrimidine chemotherapy.
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Di-Hidrouracila Desidrogenase (NADP) , Neoplasias Gastrointestinais , Humanos , Di-Hidrouracila Desidrogenase (NADP)/genética , Estudos Retrospectivos , Fluoruracila/efeitos adversos , Farmacogenética , Capecitabina , Genótipo , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genéticaRESUMO
The UK National Diagnostic Service for Ehlers-Danlos Syndromes (EDS) was established in 2009 for the rare types of EDS. Vascular EDS (vEDS) is an inherited connective tissue disorder caused by pathogenic variants in the COL3A1 gene. Associated tissue fragility affects multiple organ systems, increasing the risk of blood vessel dissection and rupture, with potentially fatal consequences. The diagnosis of vEDS has improved with advances in genetic testing, however this is most often suspected following an acute event. We provide data on the clinical features of vEDS for 180 patients (full cohort) seen in our service with confirmed molecular diagnoses. Increased awareness of this rare condition will prompt genetic testing essential to confirm the diagnosis. Outcomes are improved by early diagnosis followed by appropriate management. Fragile connective tissues make invasive procedures potentially dangerous, particularly in an emergency setting. Lifestyle advice from a young age can help acceptance and understanding of the diagnosis and inform choices. There is currently limited evidence for the use of drug therapy to reduce vascular events. We report on the incidence of vascular events in 126 patients (statistical analysis cohort) in our care and the use of medication. Our retrospective data showed that those patients on a long-term angiotensin II receptor blocker and/or beta-blocker had fewer vascular events than those not on cardiac medication who received the same lifestyle and emergency care advice.