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We developed and validated an abbreviated version of the Coma Recovery Scale-Revised (CRS-R), the CRS-R For Accelerated Standardized Testing (CRSR-FAST), to detect conscious awareness in patients with severe traumatic brain injury in the intensive care unit. In 45 consecutively enrolled patients, CRSR-FAST administration time was approximately one-third of the full-length CRS-R (mean [SD] 6.5 [3.3] vs 20.1 [7.2] minutes, p < 0.0001). Concurrent validity (simple kappa 0.68), test-retest (Mak's ρ = 0.76), and interrater (Mak's ρ = 0.91) reliability were substantial. Sensitivity, specificity, and accuracy for detecting consciousness were 81%, 89%, and 84%, respectively. The CRSR-FAST facilitates serial assessment of consciousness, which is essential for diagnostic and prognostic accuracy. ANN NEUROL 2023;94:919-924.
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Coma , Estado de Consciência , Humanos , Coma/diagnóstico , Reprodutibilidade dos Testes , Estudos de Viabilidade , Recuperação de Função Fisiológica , Unidades de Terapia Intensiva , Transtornos da Consciência/diagnósticoRESUMO
BACKGROUND: With a steady rise in the number of urgent care centers in the United States and the establishment of urgent care medicine as a specialty, research in the field is likely to emerge. OBJECTIVES: To perform a bibliometric analysis of published studies in the field of urgent care medicine over the past two decades. METHODS: A comprehensive literature review was conducted, including original and review articles pertaining to urgent care medicine published 2000-2020. Data abstracted from each article included publication year, journal, research study design, study population, clinical relevance (clinical or non-clinical), and study topics. RESULTS: A total of 144 publications from 94 peer-reviewed journals were analyzed. There has been a steady increase in the annual number of publications from 2010 to 2019. The most common study designs were retrospective (55.5%), study specific (24.3%), prospective (15.3%), and quality improvement (4.9%). Adults were the most frequently identified study population (33.3%), followed by pediatrics (18%), and both adults and pediatrics (16.7%). Publications were categorized as clinical (48.6%) and non-clinical (51.4%). The most common research topics were urgent care utilization [n = 34, 23.6%; especially effectiveness (n = 9) and disease based (n = 7)], diagnostic testing [(n = 20, 13.9%; especially HIV (n = 7) and sexually transmitted infections (n = 6)], and antibiotic stewardship (n = 17, 11.8%). CONCLUSION: Based on our sample, published research in the field of urgent care medicine has evolved. By describing current trends, we hope that clinicians and researchers continue to advance the field by developing high quality research, including prospective, multi-institutional/center studies involving both clinical and non-clinical topics.
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Assistência Ambulatorial , Bibliometria , Editoração/estatística & dados numéricos , Animais , HumanosRESUMO
AIMS: As previous reports show an association of chronic hepatitis C (HCV) with hepatocellular carcinoma (HCC) and non-liver cancers, we examine the association of HCV with liver cancer and non-liver cancers. METHODS: Retrospective cross-sectional study at Kaiser Permanente Southern California (KPSC) evaluating HCV and non-HCV patients from 1 January 2008 to 12 December 2012. Cancer diagnoses were obtained from the KPSC-SEER-affiliated registry. Logistic regression analyses were used for rate ratios and time-to-event analyses were performed using Cox proportional hazards models, adjusted for age, gender, race, smoking and cirrhosis. Cancer rate ratios were stratified by tobacco, alcohol abuse, diabetes and body mass index (BMI). RESULTS: The initial population and final population of multivariable analysis were N = 5 332 903 and N = 2 080 335 respectively. Cancer burden (all sites) was significantly higher in HCV than in non-HCV patients and HCV patients had a high rate of liver cancer. When liver cancer was excluded, cancer rates remained significantly increased in HCV. Unadjusted cancer rates were significantly higher in HCV compared to non-HCV for oesophageal, stomach, colorectal, pancreas, myeloma, non-Hodgkin's lymphoma, head/neck, lung, renal and prostate cancer. After stratification for alcohol abuse, tobacco, diabetes and BMI, increased cancer rates remained significant for all cancer sites, liver cancer and non-Hodgkin's lymphoma. Multivariable analyses demonstrated a strong correlation between cirrhosis and cancer. Tobacco use and diabetes were also associated with cancer. In the absence of cirrhosis, HCV, tobacco use and diabetes significantly increased the cancer risk. Mediation analyses showed that cirrhosis was responsible for a large proportion on the effect of HCV on cancer risk. CONCLUSION: This study supports the concept of HCV as a systemic illness and treating HCV regardless of disease severity and prior to progression to cirrhosis.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Estudos Transversais , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Frontotemporal dementia refers to a group of progressive neurodegenerative syndromes usually caused by the accumulation of pathological tau or TDP-43 proteins. The effects of these proteins in the brain are complex, and each can present with several different clinical syndromes. Clinical efficacy trials of drugs targeting these proteins must use endpoints that are meaningful to all participants despite the variability in symptoms across patients. There are many candidate clinical measures, including neuropsychological scores and functional measures. Brain imaging is another potentially attractive outcome that can be precisely quantified and provides evidence of disease modification. Most imaging studies in frontotemporal dementia have been cross-sectional, and few have compared longitudinal changes in cortical volume with changes in other measures such as perfusion and white matter integrity. The current study characterized longitudinal changes in 161 patients with three frontotemporal dementia syndromes: behavioural variant frontotemporal dementia (n = 77) and the semantic (n = 45) and non-fluent (n = 39) variants of primary progressive aphasia. Visits included comprehensive neuropsychological and functional assessment, structural MRI (3 T), diffusion tensor imaging, and arterial spin labelled perfusion imaging. The goal was to identify measures that are appropriate as clinical trial outcomes for each group, as well as those that might be appropriate for trials that would include more than one of these groups. Linear mixed effects models were used to estimate changes in each measure, and to examine the correlation between imaging and clinical changes. Sample sizes were estimated based on the observed effects for theoretical clinical trials using bootstrapping techniques to provide 95% confidence intervals for these estimates. Declines in functional and neuropsychological measures, as well as frontal and temporal cortical volumes and white matter microstructure were detected in all groups. Imaging changes were statistically significantly correlated with, and explained a substantial portion of variance in, the change in most clinical measures. Perfusion and diffusion tensor imaging accounted for variation in clinical decline beyond volume alone. Sample size estimates for atrophy and diffusion imaging were comparable to clinical measures. Corpus callosal fractional anisotropy led to the lowest sample size estimates for all three syndromes. These findings provide further guidance on selection of trial endpoints for studies in frontotemporal dementia and support the use of neuroimaging, particularly structural and diffusion weighted imaging, as biomarkers. Diffusion and perfusion imaging appear to offer additional utility for explaining clinical change beyond the variance explained by volume alone, arguing for considering multimodal imaging in treatment trials.
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Determinação de Ponto Final/métodos , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/epidemiologia , Imagem Multimodal/métodos , Idoso , Estudos Transversais , Imagem de Tensor de Difusão/métodos , Imagem de Tensor de Difusão/tendências , Determinação de Ponto Final/tendências , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/tendênciasRESUMO
INTRODUCTION: The Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial-frontotemporal lobar degeneration due to autosomal dominant mutations. METHODS: We examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non-mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia. RESULTS: Asymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self-monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects. DISCUSSION: Imaging changes appear to precede clinical changes in familial-frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.
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Atrofia/patologia , Degeneração Lobar Frontotemporal , Predisposição Genética para Doença , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Testes Neuropsicológicos/estatística & dados numéricos , Proteína C9orf72/genética , Feminino , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/patologia , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Progranulinas/genética , Lobo Temporal/patologia , Proteínas tau/genéticaRESUMO
INTRODUCTION: Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset. METHODS: We created dementia risk scores in 268 familial frontotemporal lobar degeneration family members by entering covariate-adjusted standardized estimates of brain atrophy into a logistic regression to classify asymptomatic versus demented participants. The score's predictive value was tested in a separate group who were followed up longitudinally (stable vs. converted to dementia) using Cox proportional regressions with dementia risk score as the predictor. RESULTS: Cross-validated logistic regression achieved good separation of asymptomatic versus demented (accuracy = 90%, SE = 0.06). Atrophy scores predicted conversion from asymptomatic or mildly/questionably symptomatic to dementia (HR = 1.51, 95% CI: [1.16,1.98]). DISCUSSION: Individualized quantification of baseline brain atrophy is a promising predictor of progression in asymptomatic familial frontotemporal lobar degeneration mutation carriers.
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Atrofia/patologia , Demência Frontotemporal , Predisposição Genética para Doença , Mutação/genética , Testes Neuropsicológicos/estatística & dados numéricos , Encéfalo/patologia , Proteína C9orf72/genética , Feminino , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/genética , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Progranulinas/genética , Proteínas tau/genéticaRESUMO
OBJECTIVES: Direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) lead to cure in more than 95% of recipients; however, payers may limit access to these lifesaving drugs due to high initial cost. Here, the cost-effectiveness of treating HCV with DAAs vs no treatment over a lifetime horizon is evaluated from the perspective of Kaiser Permanente Southern California (KPSC). STUDY DESIGN: A hybrid decision-tree Markov model. METHODS: The model simulated the health and economic outcomes for a real cohort of patients with HCV treated with either ledipasvir-sofosbuvir or sofosbuvir-velpatasvir between November 1, 2014, and October 31, 2019, at KPSC. Patients entered the model at different stages of liver disease and received either active treatment with DAAs or no treatment. Patients who did not achieve sustained virological response experienced disease progression; those who achieved sustained virological response experienced either significantly slower or no disease progression depending on the stage of fibrosis at model start. Demographics, treatment experience, genotype, baseline fibrosis stage, treatment rates, and treatment efficacy were sourced from KPSC real-world data. Costs and utilities were sourced from published literature. RESULTS: A total of 7255 patients with a mean age of 59 years were treated during the study period. Over a lifetime horizon, DAAs resulted in significant reduction in advanced liver disease events and a total cost savings of $1 billion compared with no treatment based on a hybrid decision-tree Markov state-transition model. Cost savings were achieved after only 3 years. DAA intervention dominated no treatment on a per-patient and cohort basis. CONCLUSIONS: DAA treatment at KPSC is predicted to significantly reduce HCV-related morbidity and mortality, providing an anticipated return on investment in drug costs after 3 years of treatment.
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Hepatite C Crônica , Sofosbuvir , Humanos , Pessoa de Meia-Idade , Sofosbuvir/uso terapêutico , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepacivirus , Quimioterapia Combinada , California , Fibrose , GenótipoRESUMO
INTRODUCTION: Behavioral variant frontotemporal dementia (bvFTD) can be computationally divided into four distinct anatomic subtypes based on patterns of frontotemporal and subcortical atrophy. To more precisely predict disease trajectories of individual patients, the temporal stability of each subtype must be characterized. METHODS: We investigated the longitudinal stability of the four previously identified anatomic subtypes in 72 bvFTD patients. We also applied a voxel-wise mixed effects model to examine subtype differences in atrophy patterns across multiple timepoints. RESULTS: Our results demonstrate the stability of the anatomic subtypes at baseline and over time. While they had common salience network atrophy, each subtype showed distinctive baseline and longitudinal atrophy patterns. DISCUSSION: Recognizing these anatomically heterogeneous subtypes and their different patterns of atrophy progression in early bvFTD will improve disease course prediction in individual patients. Longitudinal volumetric predictions based on these anatomic subtypes may be used as a more accurate endpoint in treatment trials.
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Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. However, the natural history of NAFLD is incomplete. This is a retrospective cohort study of patients identified with NAFLD by diagnosis codes in a large, community-based health care delivery system. The objectives were (1) to follow patients from initial NAFLD presentation through progression to cirrhosis and/or decompensated cirrhosis to liver cancer, liver transplant, and death for up to 10 years; and (2) to conduct disease progression analysis restricted to patients with NAFLD identified as having diabetes at baseline. A total of 98,164 patients with full NAFLD and 26,488 with diabetes were divided into three baseline prevalent states: (1) no cirrhosis, (2) compensated cirrhosis, and (3) decompensated cirrhosis. In baseline patients without cirrhosis, annual rates of compensated cirrhosis, decompensated cirrhosis, and death were 0.28%, 0.31%, and 0.63% per year, respectively. With baseline compensated cirrhosis, the annual rates of decompensation and death were 2.4% and 6.7% per year. Finally, in those with decompensated cirrhosis at baseline, the death rate was 8.0% per year. In those without cirrhosis and with cirrhosis at baseline, the rates of liver cancer and death were increased approximately 2-fold in the diabetic subpopulation compared with the full NAFLD cohort. Age and comorbidities increased with increasing disease severity. Cox proportional hazards regression analysis showed that cirrhosis was strongly associated with death and liver cancer, and that diabetes was associated with a significant increase in the hazard of both liver cancer and death (2.56 [2.04-3.20] and 1.43 [1.35-1.52]), respectively. Conclusion: The findings of this community-based study further our understanding of the natural history of NAFLD and demonstrate that diabetes is a major factor in the progression of this disease.
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Diabetes Mellitus/epidemiologia , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Idoso , Comorbidade , Diabetes Mellitus/mortalidade , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Análise de Regressão , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados Unidos/epidemiologiaRESUMO
This study analyzes in-state retention rates at Penn State University (PSU) and nationally. Data were taken from the PSU handbook with location information of graduated residents and compared to data from the Association of American Medical Colleges (AAMC). The retention rate at PSU was lower than that nationally in all but three specialties. PSU retention rate was lower than that of Pennsylvania. Pennsylvania's retention rate was lower than the national average. Community size and physician per capita may play a role in graduating resident retention rate.
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This study examines gender representation and in-state retention rates of practicing residency graduates from Pennsylvania State University (PSU), as well as at the national level. PSU and national data were collected from a PSU handbook and the Association of American Medical Colleges (AAMC), respectively. There were significant differences between male and female representation both at PSU and at the national level. Furthermore, there was a significant difference between male and female retention rates nationally. This study demonstrates a true gender discrepancy for graduates from PSU and at the national level. Moving forward, investigating potential causes of this discrepancy may help minimize gender differences.
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PURPOSE: Previous studies have shown that research can be used as a predictive factor for an academic career for physicians in the fields of radiation oncology, orthopedic surgery, and diagnostic radiology. We seek to determine if this factor is predictive for all medical specialties based on an analysis of public data on physicians who have trained at Hershey Medical Center (HMC) and public National Resident Matching Program (NRMP) charting outcomes. METHODS: We determined the location and job title of all graduates of HMC residency training programs through a combination of publicly available information on HMC's website and other institutions' websites. We separated these into academic and non-academic positions and performed Chi-square analysis to determine if the number of research experiences was predictive of an academic career. RESULTS: Participating in the residency specialties of general surgery, pathology, internal medicine, and neurological surgery are statistically significant predictors of an academic career upon graduation. The average number of research experiences obtained by matched U.S. medical students is not a statistically significant predictor of an academic career upon graduation. CONCLUSION: In contrast to previously published studies, a higher number of research experiences in medical school is not a significant predictor of an academic career for attending physicians who graduated residency at HMC.
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BACKGROUND: The decision to emergently operate on nonagenarian patients (NONAs) can be complex due to the uncertainty about outcomes and goals of care at this advanced age. We sought to study: (1) the outcomes and predictors of mortality for NONAs undergoing emergency general surgery (EGS) and (2) the accuracy of ACS-NSQIP mortality risk calculator in this special population. METHODS: Using the 2007 to 2015 ACS-NSQIP database, we included all patients older than 90 years of age who underwent an emergent operation with a Current Procedural Terminology (CPT) code for "digestive system." Multivariable logistic regression analyses were performed to identify independent predictors of 30-day mortality. NONAs' mortality rates for different combinations of risk factors were also studied and compared to the ACS-NSQIP calculator-predicted mortality rates. RESULTS: Out of a total of 4,456,809 patients, 4,724 NONAs were included. The overall 30-day patient mortality and morbidity rates were 21% and 45%, respectively. In multivariable analyses, several independent predictors of 30-day mortality were identified, including recent history of weight loss, history of steroid use, smoking, functional dependence, hypoalbuminemia and sepsis or septic shock. The mortality among NONAs with a history of steroid use and a recent history of weight loss was 100%. Similarly, the mortality of NONAs with recent history of weight loss who presented with preoperative septic shock was 93%. The ACS-NSQIP calculator significantly and consistently underestimated the risk of mortality in all NONAs undergoing EGS. CONCLUSION: Most NONAs undergoing EGS survive the hospital stay and the first 30 postoperative days, even in the presence of significant preexisting comorbidities. However, the combination of recent weight loss with either steroid use or septic shock nearly ensures mortality and should be used in the discussions with patients and families before a decision to operate is made. The ACS-NSQIP surgical risk calculator should be used with caution in these high-risk patients. LEVEL OF EVIDENCE: Prognostic study, level III.
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Tratamento de Emergência/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidade , Fatores Etários , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: The study sought to develop a criteria-based scoring tool for assessing drug-disease knowledge base content and creation of a subset and to implement the subset across multiple Kaiser Permanente (KP) regions. MATERIALS AND METHODS: In Phase I, the scoring tool was developed, used to create a drug-disease alert subset, and validated by surveying physicians and pharmacists from KP Northern California. In Phase II, KP enabled the alert subset in July 2015 in silent mode to collect alert firing rates and confirmed that alert burden was adequately reduced. The alert subset was subsequently rolled out to users in KP Northern California. Alert data was collected September 2015 to August 2016 to monitor relevancy and override rates. RESULTS: Drug-disease alert scoring identified 1211 of 4111 contraindicated drug-disease pairs for inclusion in the subset. The survey results showed clinician agreement with subset examples 92.3%-98.5% of the time. Postsurvey adjustments to the subset resulted in KP implementation of 1189 drug-disease alerts. The subset resulted in a decrease in monthly alerts from 32 045 to 1168. Postimplementation monthly physician alert acceptance rates ranged from 20.2% to 29.8%. DISCUSSION: Our study shows that drug-disease alert scoring resulted in an alert subset that generated acceptable interruptive alerts while decreasing overall potential alert burden. Following the initial testing and implementation in its Northern California region, KP successfully implemented the disease interaction subset in 4 regions with additional regions planned. CONCLUSIONS: Our approach could prevent undue alert burden when new alert categories are implemented, circumventing the need for trial live activations of full alert category knowledge bases.
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Sistemas de Apoio a Decisões Clínicas , Quimioterapia Assistida por Computador , Registros Eletrônicos de Saúde , Sistemas de Registro de Ordens Médicas , Erros de Medicação/prevenção & controle , Fadiga de Alarmes do Pessoal de Saúde/prevenção & controle , California , Interações Medicamentosas , HumanosRESUMO
According to the cognitive reserve theory, intellectual stimuli acquired during life can prevent against developing cognitive impairment. The underlying cognitive reserve mechanisms were underexplored in low-educated individuals. Because episodic memory impairment due to hippocampal dysfunction is a key feature of Alzheimer's dementia (AD), we sought to look at a possible cognitive reserve mechanism by determining whether few years of education moderated the relationship between the hippocampal volumes and the episodic-memory scores. The sample was composed by 183 older adults, 40.1% male, with the median age of 78[76,82] years and the median years of education of 4[2,10] who had undergone an episodic-memory test and a 3-Tesla MRI scan to access the hippocampal volumes. Overall, 112 were cognitively healthy, 26 had cognitive impairment-no dementia (CIND) and 45 had dementia. We used multiple linear regression to assess whether the interaction between years of education and each hippocampal volume significantly predicted the episodic-memory scores' variance, controlling for cognitive diagnosis and nuisance variables. The interaction term with the left hippocampus (ß = 0.2, p = 0.043, CI = 1.0, 1.4), but not with the right (ß = 0.1, p = 0.218, CI = 0.9, 1.2) significantly predicted the variation on memory scores. The mechanism by which the left hippocampus seems to play a more important role on memory processing in more educated individuals needs to be further investigated and might be associated with a better use of mnemonic strategies or higher hippocampal connectivity. Because the sample's median years of education was four, which corresponds to primary school, we may infer that this level might be sufficient to contribute for building cognitive reserve.
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With the advent of high throughput technology, a huge amount of microRNA information has been added to the growing body of knowledge for non-coding RNAs. Here we present the Dietary MicroRNA Databases (DMD), the first repository for archiving and analyzing the published and novel microRNAs discovered in dietary resources. Currently there are fifteen types of dietary species, such as apple, grape, cow milk, and cow fat, included in the database originating from 9 plant and 5 animal species. Annotation for each entry, a mature microRNA indexed as DM0000*, covers information of the mature sequences, genome locations, hairpin structures of parental pre-microRNAs, cross-species sequence comparison, disease relevance, and the experimentally validated gene targets. Furthermore, a few functional analyses including target prediction, pathway enrichment and gene network construction have been integrated into the system, which enable users to generate functional insights through viewing the functional pathways and building protein-protein interaction networks associated with each microRNA. Another unique feature of DMD is that it provides a feature generator where a total of 411 descriptive attributes can be calculated for any given microRNAs based on their sequences and structures. DMD would be particularly useful for research groups studying microRNA regulation from a nutrition point of view. The database can be accessed at http://sbbi.unl.edu/dmd/.
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Bases de Dados Genéticas , Dieta , Alimentos , MicroRNAs/genética , Animais , Sequência de Bases , Bovinos , Redes Reguladoras de Genes , HumanosRESUMO
MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.
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Exossomos/genética , MicroRNAs/sangue , MicroRNAs/genética , Sequência de Bases , Biologia Computacional , Dieta , Ingestão de Alimentos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Análise de Sequência de RNARESUMO
MicroRNAs, a class of short non-coding RNAs, are able to regulate more than half of human genes and affect many fundamental biological processes. It has been long considered synthesized endogenously until very recent discoveries showing that human can absorb exogenous microRNAs from dietary resources. This finding has raised a challenge scientific question: which exogenous microRNAs can be integrated into human circulation and possibly exert functions in human? Here we present a well-designed ensemble manifold ranking model for identifying human absorbable exogenous miRNAs from 14 common dietary species. Specifically, we have analyzed 4,910 dietary microRNAs with 1,120 features derived based on the microRNA sequence and structure. In total, 70 discriminative features were selected to characterize the circulating microRNAs in human and have been used to infer the possibility of a certain exogenous microRNA getting integrated into human circulation. Finally, 461 dietary microRNAs have been identified as transportable exogenous microRNAs. To assess the performance of our ensemble model, we have validated the top predictions through a milk-feeding study. In addition, 26 microRNAs from two virus species were predicted as transportable and have been validated in two external experiments. The results demonstrate the data-driven computational model is highly promising to study transportable microRNAs while bypassing the complex mechanistic details.
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BACKGROUND: Achievement of sustained virologic response (SVR) and factors associated with treatment failure in hepatitis C virus (HCV) genotype 3 have been described in tertiary and referral care settings, with rates of SVR reported to range between 72% and 89%. Fewer data exist on SVR outside of these settings. OBJECTIVE: To describe rates of SVR and characterize factors associated with achievement of SVR within an integrated health care delivery system. METHODS: A retrospective cohort study of genotype 3 HCV patients treated with dual therapy (pegylated interferon-alpha plus ribavirin) was conducted at Kaiser Permanente Southern California. Adult patients diagnosed with HCV and testing positive for HCV-RNA genotype 3 were identified from electronic medical records. Data were collected on patient demographics, baseline health status, and comorbid conditions. A multivariate logistic regression model was used to determine the association between baseline patient factors and SVR. RESULTS: A total of 484 HCV genotype 3 patients met the eligibility criteria. The median age was 49 years, and 65.7% were male. Overall, 252 (52.1%) achieved SVR. Aged ≥ 45 years and male gender were associated with lower rates of SVR; cirrhosis and chronic diseases (diabetes and chronic obstructive pulmonary disease) were also associated with lower rates of SVR. CONCLUSIONS: SVR was lower in patients within an integrated care delivery system than in those in tertiary and referral centers. Males and older patients had lower rates of SVR, as well as patients with cirrhosis, diabetes, and chronic obstructive pulmonary disease.