Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
Genes (Basel) ; 15(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38397230

RESUMO

Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations.


Assuntos
Anticorpos Antiproteína Citrulinada , Artrite Reumatoide , Humanos , México , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/genética , Fator de Transcrição STAT4/genética
2.
Int J Mol Sci ; 24(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38069427

RESUMO

Microorganisms have a close relationship with humans, whether it is commensal, symbiotic, or pathogenic. Recently, it has been documented that microorganisms may influence the response to drug therapy. Pharmacomicrobiomics is an emerging field that focuses on the study of how variations in the microbiome affect the disposition, action, and toxicity of drugs. Two additional sciences have been added to complement pharmacomicrobiomics, namely toxicomicrobiomics, which explores how the microbiome influences drug metabolism and toxicity, and pharmacoecology, which refers to modifications in the microbiome as a result of drug administration. In this context, we introduce the concept of "drug-infection interaction" to describe the influence of pathogenic microorganisms on drug response. This review analyzes the current state of knowledge regarding the relevance of microorganisms in the host's response to drugs. It also highlights promising areas for future research and proposes the term "drug-infection interaction" as an extension of pharmacomicrobiomics.


Assuntos
Anti-Infecciosos , Microbiota , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Preparações Farmacêuticas/metabolismo , Microbiota/fisiologia
3.
Nutrients ; 15(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37960221

RESUMO

Previous studies have highlighted the role of lifestyle on HDL-C concentrations in adults. To our knowledge, the health and nutritional status of emerging adults have been understudied. The present study aimed to explore the most important lifestyle factors, including micronutrient intake adequacy and the percentage of energy from food processing, according to HDL-C concentrations in emerging adults. In this context, a cross-sectional analysis was conducted on 261 Mexican emerging adults who were apparently healthy. Lifestyle factors were collected through a structured survey and the prevalence of micronutrient intake inadequacy was estimated using the estimated average requirement cut-point method. The percentage of energy from ultra-processed foods was assessed using the NOVA system. HDL-C was determined using the enzymatic colorimetric method. Statistical analyses were conducted in SPSS. The results revealed that lifestyle factors do not differ according to HDL-C status. The participants showed a poor nutritional diet that was energy-dense and micronutrient-inadequate. Nearly half of their energy came from processed and ultra-processed foods. Most participants did not meet the recommendations for key nutrients (ϖ3 fatty acids and phytosterols) that promote a healthy lipid status. In conclusion, regardless of their HDL-C levels, emerging adults exhibited lifestyle-related risk factors. The persistence of these findings over time could contribute to the development of metabolic disorders in the future. It is crucial to increase understanding and to develop effective nutritional interventions during this critical phase of life.


Assuntos
Ingestão de Energia , Lipoproteínas HDL , Humanos , Adulto , Estudos Transversais , Estado Nutricional , Estilo de Vida , Dieta , Fast Foods
4.
Viruses ; 15(7)2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37515200

RESUMO

Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the response to several drugs used to treat type 2 diabetes (DM2), such as metformin. The aim of this study was to test whether HAdV-36 affects the response to metformin in a group of obese patients with DM2. METHODS: In a prospective cohort study, 103 obese patients with newly diagnosed DM2 were divided into two groups based on their HAdV-36 seropositivity (+HAdV-36 and -HAdV-36). Weight, glucose, cholesterol, triglycerides, body mass index, body fat percentage, and waist and hip circumference were measured and compared in both groups at baseline and after 45 days of metformin treatment. RESULTS: Only glucose was significantly lower in the +HAdV-36 group at baseline, while all other variables were similar between the two study groups. After 45 days of follow-up, it was observed that the effect of metformin did not differ between the groups, but the variables improved significantly after treatment. CONCLUSIONS: In this study, we did not find that HAdV-36 had an effect on the response to metformin in obese patients with DM2.


Assuntos
Adenovírus Humanos , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Hipoglicemiantes/efeitos adversos , Estudos Prospectivos , Obesidade/complicações , Obesidade/tratamento farmacológico , Glucose
5.
Genes (Basel) ; 14(5)2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37239480

RESUMO

Forensic genomic systems allow simultaneously analyzing identity informative (iiSNPs), ancestry informative (aiSNPs), and phenotype informative (piSNPs) genetic markers. Among these kits, the ForenSeq DNA Signature prep (Verogen) analyzes identity STRs and SNPs as well as 24 piSNPs from the HIrisPlex system to predict the hair and eye color. We report herein these 24 piSNPs in 88 samples from Monterrey City (Northeast, Mexico) based on the ForenSeq DNA Signature prep. Phenotypes were predicted by genotype results with both Universal Analysis Software (UAS) and the web tool of the Erasmus Medical Center (EMC). We observed predominantly brown eyes (96.5%) and black hair (75%) phenotypes, whereas blue eyes, and blond and red hair were not observed. Both UAS and EMC showed high performance in eye color prediction (p ≥ 96.6%), but a lower accuracy was observed for hair color prediction. Overall, UAS hair color predictions showed better performance and robustness than those obtained with the EMC web tool (when hair shade is excluded). Although we employed a threshold (p > 70%), we suggest using the EMC enhanced approach to avoid the exclusion of a high number of samples. Finally, although our results are helpful to employ these genomic tools to predict eye color, caution is suggested for hair color prediction in Latin American (admixed) populations such as those studied herein, principally when no black color is predicted.


Assuntos
Cor de Olho , Cor de Cabelo , Humanos , Cor de Olho/genética , Cor de Cabelo/genética , México , Genótipo , DNA/genética
6.
Sci Rep ; 13(1): 4555, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941337

RESUMO

To develop a novel algorithm based on ray tracing, simulated visual performance and through-focus optimization for an accurate intraocular lens (IOL) power calculation. Custom-developed algorithms for ray tracing optimization (RTO) were used to combine the natural corneal higher-order aberrations (HOAs) with multiple sphero-cylindrical corrections in 210 higher order statistical eye models for developing keratoconus. The magnitude of defocus and astigmatism producing the maximum Visual Strehl was considered as the optimal sphero-cylindrical target for IOL power calculation. Corneal astigmatism and the RMS HOAs ranged from - 0.64 ± 0.35D and 0.10 ± 0.04 µm (0-months) to - 3.15 ± 1.38D and 0.82 ± 0.47 µm (120-months). Defocus and astigmatism target was close to neutral for eyes with low amount of HOAs (0 and 12-months), where 91.66% of eyes agreed within ± 0.50D in IOL power calculation (RTO vs. SRK/T). However, corneas with higher amounts of HOAs presented greater visual improvement with an optimized target. In these eyes (24- to 120-months), only 18.05% of eyes agreed within ± 0.50D (RTO vs. SRK/T). The power difference exceeded 3D in 42.2% while the cylinder required adjustments larger than 3D in 18.4% of the cases. Certain amounts of lower and HOAs may interact favourably to improve visual performance, shifting therefore the refractive target for IOL power calculation.


Assuntos
Astigmatismo , Ceratocone , Lentes Intraoculares , Facoemulsificação , Humanos , Acuidade Visual , Refração Ocular , Córnea , Óptica e Fotônica
7.
Int J Legal Med ; 137(2): 297-301, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36495333

RESUMO

Often bones are the only biological material left for the identification of human remains. As situations may occur where samples need to be stored for an extended period without access to cooling, appropriate storage of the bone samples is necessary for maintaining the integrity of DNA for profiling. To simulate DNA preservation under field conditions, pig rib bones were used to evaluate the effects of bone cleaning, buffer composition, storage temperature, and time on DNA recovery from bone samples. Bones were stored in three different buffers: TENT, solid sodium chloride, and ethanol-EDTA, at 20 °C and 35 °C for 10, 20, and 30 days. Bones were subsequently dried and ground to powder. DNA was extracted and quantified. Results show that temperature and storage time have no significant influence on DNA yield. DNA recovery from bones stored in solid sodium chloride or ethanol-EDTA was significantly higher compared to bones stored in TENT, and grinding of bones was facilitated by the extent of dehydration in solid sodium chloride and ethanol-EDTA compared to TENT. Overall, solid sodium chloride was found to be superior over ethanol-EDTA; when it comes to transportation, dry material such as salt eliminates the risk of leaking; it is non-toxic and in contrast to ethanol not classified as dangerous goods. Based on this study's results, we recommend NaCl as a storage substrate for forensic samples in cases where no cooling/freezing conditions are available.


Assuntos
Preservação Biológica , Cloreto de Sódio , Humanos , Animais , Suínos , Ácido Edético , DNA/genética , Etanol
8.
Nutrients ; 14(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35745096

RESUMO

Nutrition is an essential component when promoting human health. Without a doubt, improving the quality of one's diet can improve one's quality of life as a whole and help postpone the onset or control of many chronic diseases. The volume of publications in this field has increased in recent years, in line with increased awareness of the importance of nutrition in health; however, the quality of the evidence on which most nutritional guidelines are based remains low, due to errors in conducting nutritional interventions or because the information is primarily derived from observational studies. To enhance the evidence supporting clinical guidelines in nutrition, the quality of randomized clinical trials (RCT) based on nutritional interventions must be improved; nevertheless, due to their heterogeneous nature and a lack of specific guidelines for designing, performing, documenting, and reporting on this type of intervention, conducting a nutritional intervention is a real challenge. Following a review of the literature on the methodological and ethical standards, as well as four extensions of the CONSORT (Consolidated Standards of Reporting Trials) guidelines that should be considered when implementing a nutritional intervention, seven essential aspects were identified. The current narrative review includes definitions, examples, diagrams, and algorithms regarding aspects of the appropriate study design, the intervention of the control group, the randomization and blinding processes, the study population selection, as well as a description of the type of intervention and the personnel involved in carrying out the study in order to make the implementation of a nutritional intervention easier.


Assuntos
Dieta , Qualidade de Vida , Doença Crônica , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Am J Cardiovasc Drugs ; 22(6): 615-631, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35570249

RESUMO

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m2, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Piridonas/efeitos adversos , Varfarina/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Administração Oral , Estudos Observacionais como Assunto
10.
Nutrients ; 14(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35268076

RESUMO

Approximately 25-50% of the population worldwide exhibits serum triglycerides (TG) (≥150 mg/dL) which are associated with an increased level of highly atherogenic remnant-like particles, non-alcoholic fatty liver disease, and pancreatitis risk. High serum TG levels could be related to cardiovascular disease, which is the most prevalent cause of mortality in Western countries. The etiology of hypertriglyceridemia (HTG) is multifactorial and can be classified as primary and secondary causes. Among the primary causes are genetic disorders. On the other hand, secondary causes of HTG comprise lifestyle factors, medical conditions, and drugs. Among lifestyle changes, adequate diets and nutrition are the initial steps to treat and prevent serum lipid alterations. Dietary intervention for HTG is recommended in order to modify the amount of macronutrients. Macronutrient distribution changes such as fat or protein, low-carbohydrate diets, and caloric restriction seem to be effective strategies in reducing TG levels. Particularly, the Mediterranean diet is the dietary pattern with the most consistent evidence for efficacy in HTG while the use of omega-3 supplements consumption is the dietary component with the highest number of randomized clinical trials (RCT) carried out with effective results on reducing TG. The aim of this review was to provide a better comprehension between human nutrition and lipid metabolism.


Assuntos
Ácidos Graxos Ômega-3 , Hipertrigliceridemia , Pancreatite , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Estado Nutricional , Pancreatite/tratamento farmacológico , Saúde Pública
11.
Int J Clin Pharm ; 44(2): 439-447, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34977994

RESUMO

Background The World Health Organization considers medication errors to be an issue that requires attention at all levels of care, to reduce the severe and preventable harm related to drug therapy. Different standards for clinical pharmaceutical practices have been proposed by various organizations across the world, where the pharmacist, as part of the multidisciplinary health team, can help improve patient safety. Objective To assess the impact of the introduction of a clinical pharmacy practice model on medication error in patients of a university hospital. Setting The study was conducted in a tertiary care hospital, Medellín, Colombia. Methods A randomized, controlled cluster-wedge staggered trial with a duration of 14 months was conducted to compare the clinical pharmacy practice model with the usual care process in the hospital. Five hospital health care units were included, which were initially assigned to the control group, and after an observation period of 2 months, they were randomly assigned to the intervention group. The trial protocol was registered in ClinicalTrials.gov (identifier NCT03338725). Main outcome measure The incidence of medication errors in hospitalized patients was the main outcome measure. Results The incidence of medication error was 13.3% and 22.8% for the intervention group and control group, respectively. The probability of presenting a medication error was 48% lower when the patient was in the intervention group (RR 0.52; 95% CI: 0.34-0.79). The probability of presenting a medication error over time was 44% lower in the intervention group (p = 0.0005); meanwhile, the resolution of a medication error over time was 70% higher in the intervention group (p = 0. 0029). Conclusion The clinical pharmacy practice model, made up of strategies focused on reducing medication errors, significantly reduces medication errors in patients during hospitalization compared with usual practice. This work assessed the effect of a clinical pharmacy model on the incidence of medication errors and demonstrated its effectiveness in reducing these errors in hospitalized patients. Trial registration ClinicalTrials.gov, NCT03338725. Registered on 9 November 2017. First patient randomized on February 2, 2018.


Assuntos
Serviço de Farmácia Hospitalar , Farmácia , Hospitais Universitários , Humanos , Incidência , Erros de Medicação/prevenção & controle , Farmacêuticos
12.
Entramado ; 17(2): 208-225, jul.-dic. 2021. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1360423

RESUMO

RESUMEN Se presentan resultados del proyecto de investigación, mapa de conocimiento del uso de medios de comunicación en instituciones educativas de básica y media realizado en Cartago, Colombia en la I.E. (Institución educativa) GABO, la I.E Ciudad Cartago y la I.E Antonio Holguín Garcés. La metodología aplicada fue cualitativa y se utiliza la Investigación Acción Participativa para la construcción de biografías mediáticas a modo de síntesis de resultados. Se identifica una desarticulación entre las políticas públicas e iniciativas del estado a nivel nacional con las dinámicas regionales, un interés particular de la Secretaria de Educación municipal en las acciones por la calidad educativa a nivel local y una postura positiva, crítica y significativa en el papel de las TIC y los medios de comunicación en los procesos de aprendizaje en los estudiantes.


ABSTRACT Results of the research project are presented, map of knowledge of the use of media in basic and medium educational institutions carried out in Cartago, Colombia, in I.E GABO, I.E Ciudad Cartago and I.E Antonio Holguín Garcés. The methodology applied was qualitative and Participatory Action Research is used for the construction of Media Biographies as a synthesis of results. A disarticulation is identified between public policies and initiatives of the state at the national level with regional dynamics, a particular interest of the municipal education secretary in actions for educational quality at the local level and a positive, critical posture and significant in the role of ICT and the media in student learning processes.


RESUMO São apresentados os resultados do projecto de investigação, mapa de conhecimento do uso dos media nas instituições de ensino básico e secundário realizado em Cartago, Colômbia, na I.E. (Instituição Educativa) GABO, na I.E. Ciudad Cartago e na I.E. Antonio Holguín Garcés. A metodologia aplicada foi qualitativa e utilizou a Investigação de Acção Participativa para a construção de biografias dos meios de comunicação como síntese de resultados. É identificada uma desarticulação entre políticas públicas e iniciativas estatais a nível nacional com dinâmica regional, um interesse particular da Secretaria Municipal de Educação nas acções para a qualidade educativa a nível local e uma posição positiva, crítica e significativa sobre o papel das TIC e dos media nos processos de aprendizagem dos estudantes.

13.
Andes Pediatr ; 92(2): 288-297, 2021 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-34106170

RESUMO

INTRODUCTION: Medication errors (ME) are preventable incidents of inappropriate use of medications by health per sonnel or by the patient. These events can occur at any stage of drug use generating significant costs to the health system and, in some cases, these can even lead to death. The pediatric population is con sidered susceptible to ME with a prevalence 3 times higher than adult patients. OBJECTIVE: To identify the prevalence of medication errors in hospitalized pediatric patients, as well as their classification according to the stage of use of the medication when they occurred. METHOD: A literature review of ME in pediatrics was carried out through a Pubmed / Medline search using Mesh terms ("Medication Errors" and "Pediatrics") in the last 10 years. Three investigators reviewed independently the identi fied articles considering the STROBE checklist for observational studies. RESULTS: 192 bibliographic references were identified, 22 of them were eligible for review and data collection. Studies reported an error rate between 1% and 58% of the evaluated medication indications, with errors reported in different processes of drug use. 9 articles (41%) described errors related only to prescription, mainly associated with incorrect dosage, 6 (27%) errors related to prescription, administration, and other processes, 3 (14%) related to prescription and administration, 2 (9%) related only to administra tion, 1 (4%) article reported errors related to conciliation, and 1 (4%) described errors related to preparation and administration. CONCLUSION: The studies reported different medication errors in the pediatric population. Most of them reported ME related to prescription followed by ME in the administration. Knowing the proportion of ME allows focusing interventions aimed at reducing their prevalence.


Assuntos
Criança Hospitalizada/estatística & dados numéricos , Erros de Medicação/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Criança , Humanos , Erros de Medicação/classificação
14.
Nutrients ; 13(4)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33916032

RESUMO

Cardiovascular diseases (CVD) remain a serious public health problem and are the primary cause of death worldwide. High-density lipoprotein cholesterol (HDL-C) has been identified as one of the most important molecules in the prevention of CVD due to its multiple anti-inflammatories, anti-atherogenic, and antioxidant properties. Currently, it has been observed that maintaining healthy levels of HDL-C does not seem to be sufficient if the functionality of this particle is not adequate. Modifications in the structure and composition of HDL-C lead to a pro-inflammatory, pro-oxidant, and dysfunctional version of the molecule. Various assays have evaluated some HDL-C functions on risk populations, but they were not the main objective in some of these. Functional foods and dietary compounds such as extra virgin olive oil, nuts, whole grains, legumes, fresh fish, quercetin, curcumin, ginger, resveratrol, and other polyphenols could increase HDL functionality by improving the cholesterol efflux capacity (CEC), paraoxonase 1 (PON1), and cholesteryl ester transfer protein (CETP) activity. Nevertheless, additional rigorous research basic and applied is required in order to better understand the association between diet and HDL functionality. This will enable the development of nutritional precision management guidelines for healthy HDL to reduce cardiovascular risk in adults. The aim of the study was to increase the understanding of dietary compounds (functional foods and bioactive components) on the functionality of HDL.


Assuntos
Doenças Cardiovasculares/etiologia , HDL-Colesterol , Dieta , Alimento Funcional , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Humanos
15.
Nat Genet ; 53(5): 683-693, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33767450

RESUMO

Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma has yet to be defined. Here we studied the single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We defined normal differentiation trajectories from Schwann cell precursors over intermediate states to neuroblasts or chromaffin cells and showed that neuroblastomas transcriptionally resemble normal fetal adrenal neuroblasts. Importantly, neuroblastomas with varying clinical phenotypes matched different temporal states along normal neuroblast differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis. Our work highlights the roles of oncogenic MYCN and loss of TFAP2B in blocking differentiation and may provide the basis for designing therapeutic interventions to overcome differentiation blocks.


Assuntos
Perfilação da Expressão Gênica , Neuroblastoma/genética , Neuroblastoma/patologia , Análise de Célula Única , Glândulas Suprarrenais/embriologia , Glândulas Suprarrenais/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Estudos de Coortes , Regulação Neoplásica da Expressão Gênica , Humanos , Transcriptoma/genética , Resultado do Tratamento
16.
Nat Cancer ; 2(1): 114-128, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-35121888

RESUMO

Half of the children diagnosed with neuroblastoma (NB) have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from NB are lacking. Here, using genome-wide H3K27ac profiles across 60 NBs, covering the different clinical and molecular subtypes, we identified four major super-enhancer-driven epigenetic subtypes and their underlying master regulatory networks. Three of these subtypes recapitulated known clinical groups; namely, MYCN-amplified, MYCN non-amplified high-risk and MYCN non-amplified low-risk NBs. The fourth subtype, exhibiting mesenchymal characteristics, shared cellular identity with multipotent Schwann cell precursors, was induced by RAS activation and was enriched in relapsed disease. Notably, CCND1, an essential gene in NB, was regulated by both mesenchymal and adrenergic regulatory networks converging on distinct super-enhancer modules. Overall, this study reveals subtype-specific super-enhancer regulation in NBs.


Assuntos
Neuroblastoma , Criança , Humanos , Mutação , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/genética , Sequências Reguladoras de Ácido Nucleico
18.
Biol Methods Protoc ; 5(1): bpaa022, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376806

RESUMO

Non-negative matrix factorization (NMF) has been widely used for the analysis of genomic data to perform feature extraction and signature identification due to the interpretability of the decomposed signatures. However, running a basic NMF analysis requires the installation of multiple tools and dependencies, along with a steep learning curve and computing time. To mitigate such obstacles, we developed ShinyButchR, a novel R/Shiny application that provides a complete NMF-based analysis workflow, allowing the user to perform matrix decomposition using NMF, feature extraction, interactive visualization, relevant signature identification, and association to biological and clinical variables. ShinyButchR builds upon the also novel R package ButchR, which provides new TensorFlow solvers for algorithms of the NMF family, functions for downstream analysis, a rational method to determine the optimal factorization rank and a novel feature selection strategy.

19.
Clin Appl Thromb Hemost ; 26: 1076029620952550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33079570

RESUMO

INTRODUCTION: NVAF is estimated to affect between 6.4 and 7.4 million Americans in 2018, and increases the risk of stroke 5-fold. To mitigate this risk, guidelines recommend anticoagulating AF patients unless their stroke risk is very low. Despite these recommendations, 30.0-60.0% of NVAF patients do not receive indicated anticoagulation. To better understand why this may be, we surveyed PCPs and cardiologists nationwide on their attitudes, knowledge and practices toward managing NVAF with warfarin and direct-acting oral anticoagulants (DOACs). METHODS: We surveyed 1,000 PCPs and 500 cardiologists selected randomly from a master list of the American Medical Association, using a paper based, anonymous, self-administered, mailed scannable survey. The survey contained questions on key demographics and data concerning attitudes, knowledge and practices related to prescribing DOACs. The surveys went out in the fall/winter of 2017-8 with a $10 incentive gift card. Survey responses were scanned into an Excel database and analyzed using SAS 9.3 (Cary, NC) for descriptive and inferential statistics. RESULTS: Two hundred and forty-nine providers (167 PCPs, 82 cardiologists) participated in the study with a response rate of 18.8% (249/1320). Respondent mean years ±SD of experience since completing residency was 23.2 ± 13.8. Relative to cardiologists, less PCPs use CHADsVASC (36.8% vs. 74.4%) (p < 0.0001); more have never used HAS-BLED, HEMORR2HAGES, or ATRIA (38.5% vs. 9.8%) (p < .0001); more felt that their lack of knowledge/experience with DOACs was a barrier to prescribing the agents (p = 0.005); and more reported that they could use additional education on DOACs (87.0% vs. 47.0%) (p < 0.0001). Overall, cardiologists were more concerned about ischemic stroke outcomes, while PCPs were more concerned with GI bleeding. Cardiologists also felt that clinical trial data were most helpful in choosing the most appropriate DOAC for their patients, while PCPs felt that Real World Data was most useful. CONCLUSIONS: Cardiologists were more concerned with ischemic stroke while anticoagulating patients and utilized screening instruments like CHADsVASC in a majority of their patients. PCPs were concerned with GI bleeds when anticoagulating but nearly 40.0% utilized no screening tools to assess bleeding risk. Our findings show that future education about DOACs would be warranted especially with PCPs.


Assuntos
Anticoagulantes/uso terapêutico , Cardiologistas/normas , Padrões de Prática Médica/normas , Fibrilação Atrial , Atitude , Feminino , Humanos , Conhecimento , Masculino , Fatores de Risco , Inquéritos e Questionários
20.
Sci Rep ; 10(1): 14641, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887927

RESUMO

This paper presents the simulated performance assessment of an artificial iris embedded on a scleral contact lens using real data from an aniridia patient. The artificial iris is based on guest-host liquid crystal cells (GH-LCD) in order to actively modify the transmittance of the lens and effective pupil size. Experimental validation of the GH-LCD spectrum and iris contrast (determined to be 1:2.1) enabled the development of optical models that include the effect of a small pupil on image quality and visual quality on an optical system with aniridia characteristics. Visual simulations at different light conditions (high/low photopic and mesopic) demonstrated the theoretical capacity of the customized artificial iris smart contact lens to expand the depth-of-focus and decrease the optical aberrations (in particular, the spherical aberration). The visual modelling suggests a maximum depth-of-focus value for a 2-mm pupil diameter for both eyes as follows: 3D (1,000 cd/m2), 2D (10 cd/m2) and 0.75D (1 cd/m2). This work demonstrates the beneficial optical effects of an active artificial iris, based on visual simulations in response to different light levels, and enables further experimental investigation on patients to validate the dynamic light attenuation and visual performance of smart contact lenses with GH-LCD.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...