RESUMO
Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Refluxo Gastroesofágico , Masculino , Humanos , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Estudos de Coortes , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/complicações , Azia/complicações , Estudos Prospectivos , Incidência , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar TabacoRESUMO
OBJECTIVE: To present an approach on using electronic health record (EHR) data that assesses how different eligibility criteria, either individually or in combination, can impact patient count and safety (exemplified by all-cause hospitalization risk) and further assist with criteria selection for prospective clinical trials. MATERIALS AND METHODS: Trials in three disease domains - relapsed/refractory (r/r) lymphoma/leukemia; hepatitis C virus (HCV); stages 3 and 4 chronic kidney disease (CKD) - were analyzed as case studies for this approach. For each disease domain, criteria were identified and all criteria combinations were used to create EHR cohorts. Per combination, two values were derived: (1) number of eligible patients meeting the selected criteria; (2) hospitalization risk, measured as the hazard ratio between those that qualified and those that did not. From these values, k-means clustering was applied to derive which criteria combinations maximized patient counts but minimized hospitalization risk. RESULTS: Criteria combinations that reduced hospitalization risk without substantial reductions on patient counts were as follows: for r/r lymphoma/leukemia (23 trials; 9 criteria; 623 patients), applying no infection and adequate absolute neutrophil count while forgoing no prior malignancy; for HCV (15; 7; 751), applying no human immunodeficiency virus and no hepatocellular carcinoma while forgoing no decompensated liver disease/cirrhosis; for CKD (10; 9; 23893), applying no congestive heart failure. CONCLUSIONS: Within each disease domain, the more drastic effects were generally driven by a few criteria. Similar criteria across different disease domains introduce different changes. Although results are contingent on the trial sample and the EHR data used, this approach demonstrates how EHR data can inform the impact on safety and available patients when exploring different criteria combinations for designing clinical trials.
Assuntos
Registros Eletrônicos de Saúde , Infecções por HIV , Definição da Elegibilidade , Humanos , Seleção de Pacientes , Estudos ProspectivosRESUMO
Esophageal squamous cell carcinoma (ESCC) accounts for the large majority of esophageal cancer cases worldwide. In this review, we examine the potential role of non-acidic fluid (NAF) exposure in ESCC carcinogenesis. Esophageal NAF consists of a mixture of salivary, esophageal, gastric, and duodenal fluids, containing inflammatory constituents such as digestive enzymes and bile acids that induce DNA damage, as well as known carcinogens such as acetaldehyde and N-nitrosamines. Exposure to NAF can occur in the setting of increased non-acid reflux, decreased gastric acidity, and decreased esophageal fluid clearance. Non-acid reflux has been associated with ESCC in small observational studies, and in animal models bile reflux can promote the development of ESCC. Associations have been found between increased ESCC risk and atrophic gastritis, a history of partial gastrectomy, and proton pump inhibitor use, all of which raise the pH of refluxate. Additionally, a minimally or non-acidic gastric environment contains an altered microbiome that can increase the production of acetaldehyde and N-nitrosamines. Esophageal motility disorders such as achalasia and opioid-induced esophageal dysfunction result in increased stasis and exposure to these potentially proinflammatory constituents of NAF. NAF may promote the development of ESCC via multiple mechanisms and is an understudied area of research.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Nitrosaminas , Acetaldeído/efeitos adversos , Animais , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/genética , Humanos , Nitrosaminas/efeitos adversosRESUMO
BACKGROUND AND AIMS: After endoscopic eradication of Barrett's esophagus (BE), recurrence of intestinal metaplasia at the gastroesophageal junction (GEJIM) is common. The clinical significance of this finding is unclear. We assessed whether recurrent GEJIM is associated with increased risk of subsequent dysplasia and whether endoscopic treatment lowers this risk. METHODS: A retrospective, multicenter, cohort study was performed of treated BE patients who achieved complete eradication of intestinal metaplasia (IM). Postablation follow-up was performed at standard intervals. Recurrent GEJIM was defined as nondysplastic IM on gastroesophageal junction biopsy specimens without endoscopic evidence of BE. Patients were categorized as "never-GEJIM," "GEJIM-observed," or "GEJIM-treated." Endoscopic treatment for recurrent GEJIM was at the endoscopists' discretion. The primary outcome was dysplasia recurrence. Analyses were performed using log-rank tests and Cox proportional hazards modeling. RESULTS: Six hundred thirty-three patients were analyzed; median follow-up was 47 months (interquartile range, 24-69). Most patients (81%) had high-grade dysplasia or intramucosal adenocarcinoma before treatment. Dysplasia recurrence was 2.2% per year. GEJIM-observed patients had the lowest rate of recurrence (.6%/y) followed by GEJIM-treated (2.2%/y) and never-GEJIM (2.6%/y) (log-rank P = .07). In multivariate analyses, compared with never-GEJIM, the risk of dysplasia recurrence was significantly lower in GEJIM-observed patients (adjusted hazard ratio, .19; 95% confidence interval, .05-.81) and not different in GEJIM-treated patients (adjusted hazard ratio, .81; 95% confidence interval, .39-1.67). Older age and longer initial BE length were independently associated with recurrence. CONCLUSIONS: Recurrent GEJIM after endoscopic eradication of BE was not associated with an increased risk of subsequent dysplasia. Future studies are warranted to determine if observation is appropriate for this finding.
Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Idoso , Esôfago de Barrett/cirurgia , Estudos de Coortes , Junção Esofagogástrica/cirurgia , Esofagoscopia , Humanos , Metaplasia , Recidiva Local de Neoplasia/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Although age is often used as a clinical risk stratification tool, recent data have suggested that adverse outcomes are driven by frailty rather than chronological age. AIMS: In this nationwide cohort study, we assessed the prevalence of frailty, and factors associated with 30-day readmission and mortality among hospitalized IBD patients. METHODS: Using the Nationwide Readmission Database, we examined all patients with IBD hospitalized from 2010 to 2014. Based on index admission, we defined IBD and frailty using previously validated ICD codes. We used univariable and multivariable regression to assess risk factors associated with all-cause 30-day readmission and 30-day readmission mortality. RESULTS: From 2010 to 2014, 1,405,529 IBD index admissions were identified, with 152,974 (10.9%) categorized as frail. Over this time period, the prevalence of frailty increased each year from 10.20% (27,594) in 2010 to 11.45% (33,507) in 2014. On multivariable analysis, frailty was an independent predictor of readmission (aRR 1.16, 95% CI: 1.14-1.17), as well as readmission mortality (aRR 1.12, 95% CI 1.02-1.23) after adjusting for relevant clinical factors. Frailty also remained associated with readmission after stratification by IBD subtype, admission characteristics (surgical vs. non-surgical), age (patients ≥ 60 years old), and when excluding malnutrition, weight loss, and fecal incontinence as frailty indicators. Conversely, we found older age to be associated with a lower risk of readmission. CONCLUSIONS: Frailty, independent of age, comorbidities, and severity of admission, is associated with a higher risk of readmission and mortality among IBD patients, and is increasing in prevalence. Given frailty is a potentially modifiable risk factor, future studies prospectively assessing frailty within the IBD patient population are needed.
Assuntos
Fragilidade/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Readmissão do Paciente , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Feminino , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/mortalidade , Fragilidade/terapia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/mortalidade , Doenças Inflamatórias Intestinais/terapia , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Clinical instructors have an important role in advancing nursing students to achieve the program objectives. Nursing student perceptions about the characteristics of an effective clinical instructors may help programs improve clinical instruction. As such, the purpose of this study was to understand the characteristics perceived by students to define an effective clinical instructor. METHODS: In this qualitative descriptive study, semi-structured interviews were conducted with undergraduate and postgraduate nursing students. The sample was purposefully selected. MAXQDA software was used for the content analysis. The codes were organized into subcategories and consolidated into categories. RESULTS: Data saturation was reached with twelve participants, including seven women and five men, between 21 and 36 years of age. General and special characteristics were the two main categories that emerged from the data. These categories were defined by nine subcategories including internal motivation, professional acceptability, clinical competency, teaching skill, clinical experience, values, being a faculty member, appropriate appearance, and communication skills. CONCLUSIONS: Effective clinical instructors have a specific characteristics identified by student. The most important characteristics of effective clinical instructors were related to communication and teaching skills, internal motivation, and professional appearance. More research is necessary to determine the relationship between the characteristics, instructor competency, and student learning outcomes.
RESUMO
BACKGROUND: Coordination of various physical and mental aspects of individuals, including the ability to control difficult conditions and situations has an effect in the prevention and development of various diseases, such as diabetes, and the improvement of the quality of life. Therefore, the purpose of this study was is to determine the effect of emotional intelligence on the quality of life of elderly diabetic patients. METHODS: This study was conducted in 2018. The statistical population in this cross-sectional study consisted of elderly people referred to the health centers of Kermanshah province in western Iran, who were divided via available sampling into two groups with diabetes and without diabetes. Data gathering tools were a couple of LIPAD Quality of Life and Shrink Emotional Intelligence standard questionnaires. The Data was analysed using software SPSS, 23 th version. Tests were used (T-test, Chi-square, Anova and regression). RESULTS: Most of them were male (52.72%) and the mean age of the patients was 65.01(±6.08) years old and married. The quality of life score in diabetics and non-diabetics was respectively 51.9 and 50.37 with a standard deviation of 17.73 and 20.54. The mean total score of emotional intelligence in the elderly with diabetes was 99.42 with a standard deviation of 10.37 and non-diabetic subjects were 97.18 with a standard deviation of 18.4. CONCLUSION: There was no significant difference between the mean scores of quality of life (0.652) and emotional intelligence (0.421) in diabetic and non-diabetic individuals. But, the emotional intelligence has an effect on the quality of life of the elderly people.
Assuntos
Diabetes Mellitus , Qualidade de Vida , Idoso , Estudos Transversais , Inteligência Emocional , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Self-medication associates with many problems and complications, and is considered as a global health issue. Regarding a lack of information about perception of nursing students, as a part of healthcare workers, in this issue, the current study was aimed to explore the perceived consequences of self-medication from the perspective of nursing students. METHODS: This qualitative study was conducted using semi-structured individual face-to-face interviews. Purposeful sampling method was used for selection of participants. Twelve nursing students in the age range of 21-36 years were enrolled. Five participants were male and seven were female, seven master's degree and five were undergraduate of bachelor degree. Data were collected using semi-structured interviews and analyzed as content analyses. RESULTS: Two categories and seven sub-categories were emerged from the data analysis. The main categories included; positive consequences and negative consequences, and subcategories included; time saving, cost savings, disease treatment, harming the health system, drug resistance, physical complications and death. CONCLUSION: The participants believed that self-medication has some positive and negative consequences in viewpoints of nursing students. Regarding, Self-medication that potentially has dangerous consequences, it is suggested the students will be educated and warned about the adverse effects of self-medication, and the nursing teachers should try to rectify students' misconceptions about self-medication.
RESUMO
The number of people undergoing cosmetic procedures (CP) has been growing around the world in recent years. The aim of this study was to determine factors involved in the desire of nurses to undergo CP. A total of 360 nurses were recruited in this cross-sectional study. Stratified random sampling was used to select the samples. The data were collected using the Social Appearance Anxiety Scale and a questionnaire addressing social factors affecting the desire to undergo CP. More than half of the nurses (56.7%) were willing. Gender, social factors, and social appearance anxiety (SAA) were associated with undergoing CP. The results of logistic regression indicated that women were four times more willing to undergo CP than men, and for each unit increase in SAA score, the odds of desiring to undergo CP increased by 1.04. The Hosmer-Lemeshow test confirmed the goodness-of-fit of the regression model. Moreover, 3 independent variables of gender, SAA, and social factors were powerful predictors of the desire to undergo CP that could explain 39.9%-53.6% of changes in the desire to undergo CP. Further studies are needed to investigate the amount of CP and motivations to undergo CP in nurses.
Assuntos
Motivação , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cirurgia Plástica/métodos , Adulto , Estudos Transversais , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cirurgia Plástica/psicologia , Cirurgia Plástica/normas , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Dream, as a kind of mental activity, includes various functions such as mood regulation, adjustment and integration of new information with the available memory system. The study was done for assessing the relationship between physiological and psychological components of cardiac diseases with emotionally negative dreams in cardiac rehabilitation. METHODS: At the baseline of this cross-sectional study, 156 patients from Western Iran participated during April-November 2016. People 20 years-80 years able to recall the emotional content of dreams after cardiac surgery entered the study. The Beck depression inventory (BDI), Beck anxiety inventory (BAI), Buss and Perry's aggression questionnaire (BPAQ) and Schredl's dream emotions manual were used for collecting data. A binary logistic regression analysis used for the study of the relationship between risk factors and emotionally negative dreams. RESULTS: The mean age of participants was 59 (SD = 9) years (men: 64.1%). The results showed that 25% of patients have negative emotional content. After adjustment for demographic variables, the results showed that increased anxiety [adjusted odds ratio (adj OR) = 1.08 [1.01-1.16], P = 0.020] and anger (adj OR = 1.03 [1.00-1.06], P = 0.024) and hypertension (adj OR = 2.71 [1.10-6.68], P = 0.030) can predict the dreams with negative content significantly. CONCLUSION: The increasing rates of anxiety and anger and history of hypertension are related to increasing dreams with the negative emotional load. The control of risk factors of dreams with negative emotional load can be the target of future interventions.
RESUMO
Quality indicators have been proposed for endoscopic eradication therapy of Barrett's esophagus (BE). One such measure suggests that complete eradication of intestinal metaplasia (CE-IM) should be achieved within 18 months of starting treatment. The aim of this study was to assess whether achievement of CE-IM within 18 months is associated with improved long-term clinical outcomes. This was a retrospective cohort study of BE patients who underwent endoscopic eradication. Time to CE-IM was recorded and categorized as ≤ or > 18 months. The main outcome measures were recurrence of IM and of dysplasia after CE-IM, defined as a single endoscopy without endoscopic evidence of BE or histologic evidence of intestinal metaplasia. Recurrence was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards modeling. A total of 290 patients were included in the analyses. The baseline histology was high-grade dysplasia or intramucosal carcinoma in 74.2% of patients. CE-IM was achieved in 85.5% of patients, and 54.1% of the cohort achieved CE-IM within 18 months. Achieving CE-IM within 18 months was not associated with reduced risk of recurrence of IM or dysplasia in both unadjusted and adjusted analyses. In this cohort, older age and increased BE length were associated with IM recurrence, and increased hiatal hernia size was associated with dysplasia recurrence. Compared to longer times, achieving CE-IM within 18 months was not associated with a reduced risk of recurrence of IM or dysplasia. Alternative evidence-based quality metrics for endoscopic eradication therapy should be identified.
Assuntos
Esôfago de Barrett/cirurgia , Carcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/estatística & dados numéricos , Intestinos/patologia , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Feminino , Humanos , Intestinos/cirurgia , Estimativa de Kaplan-Meier , Masculino , Metaplasia/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Caesarean section without medical indication imposes many problems to families, personnel and medical equipment causing some side effects to pregnant woman and foetus, compared to natural childbirth. The present study aimed to evaluate the interventions in reducing caesarean section in the world. This study was a systematic review using Embase, PubMed, Scopus, Web of Science, Science Direct, Magiran and SID databases and grey literature. All studies conducted during 2000-2018 were reviewed and finally the studies with inclusion and exclusion criteria were selected. A total of 19 studies were selected among 5,559 studies. The interventions conducted for reducing caesarean section included training the specialists and women by using Six Sigma method, changing the guidelines, reviewing the definition of natural childbirth various stages, encouraging the natural childbirth and expanding painless childbirth. All interventions were divided into educational strategy and managerial strategy. The interventions can be implemented to change the behaviour of physicians and attitude of pregnant women in order to reduce caesarean section. In this regard, the authorities are recommended to make more efforts.
RESUMO
Stevia rebaudiana Bertoni is One of the most important biologically sourced and low-calorie sweeteners that known as "Sweet Weed". It contains steviol glycosides that they are about 200-300 times sweeter than sucrose. Tissue culture is the best method with high efficiency that can overcome to problems of traditional methods, and it is the most useful tools for studying stress tolerance mechanisms under in vitro conditions to obtain drought tolerance. In the present research, we investigated the impact of life cycle, leaves location and the harvesting time on expression of UGT74G1 and UGT76G1 as well as steviol glycosides accumulation. The highest gene expression of both UGT74G1 and UGT76G1 (207.677 and 208.396 Total Lab unit, respectively) was observed in young leaves in the second vegetative year. Also, the highest amount of stevioside accumulation (13.04) was due to the old leaves in vegetative stage which had significant differences with other effects whereas the lowest accumulation (7.47) was seen at young leaves at vegetative stage. Interestingly, the highest level of rebaudioside a production (15.74) was occurred at the young leaves at vegetative stage. There was significant differences between life cycle and leaves location on steviol glycoside production in stevia.
Assuntos
Diterpenos do Tipo Caurano/biossíntese , Regulação da Expressão Gênica de Plantas/fisiologia , Glucosídeos/biossíntese , Estágios do Ciclo de Vida/fisiologia , Folhas de Planta/fisiologia , Stevia/crescimento & desenvolvimento , Diterpenos do Tipo Caurano/análise , Diterpenos do Tipo Caurano/genética , Genes de Plantas/genética , Glucosídeos/análise , Glucosídeos/genética , Stevia/genética , Stevia/metabolismo , Fatores de TempoRESUMO
BACKGROUND: Self-medication is the use of one or more medications without physician's diagnosis, opinion, or prescription and supervision, which includes the use of herbal or chemical drugs. Todays, self-medication is one of the biggest socio-health and economic problems among nursing students of various societies, including Iran, and because this issue can affected by contextual factors, this study aimed to explore the perceived factors that affect self-medication among nursing students. METHODS: In this qualitative study, a semi-structured interview was conducted with 11 nursing students. The transcript of each interview was reviewed several times and classified into main categories and sub-categories by content analysis. To evaluate this study, Guba and Lincoln's four criteria, including credibility, transferability, dependability, and confirmability were considered for trustworthiness. RESULTS: After analyzing the qualitative content of the interviews, four main categories, including educational backgrounds, nature of the disease, access to the media, and beliefs and personal experiences, and ten subcategories, including contact with clinical environment, relative knowledge about medications, simplicity of the disease, recurrence of the disease, influence of the media, use of the internet, believing in own knowledge, positive experiences of traditional medicine, and using own and others' experiences, were extracted. CONCLUSIONS: It seems that, having a relative awareness about various diseases and medications, which is sometimes associated with taking a few educational courses with an internship, creates a false confidence in student for self-medication and prescribing drugs to others. It would be beneficial if the education system and associated tutors could inform the students about the possible consequences of this issue. By knowing the internal and subjective factors that influence the self-medication, this arbitrary practice can be largely prevented.
RESUMO
A significant portion of the various communities, especially developing countries, is involved in drug abuse and receive formal drug treatments. Although the benefits of available therapeutics such as methadone maintenance treatment (MMT) for controlling infectious diseases have been confirmed, treatment failure has been seen in a large range of the patients. This review addresses the importance of a less attentive behavioural approach in reducing treatment withdrawal. The executive protocol, the outcomes and challenges, and the benefits of this approach are debatable.
RESUMO
Autophagy is a highly conserved mechanism that is activated during cellular stress. We hypothesized that autophagy may be induced by acid reflux, which causes injury, and inflammation, and therefore, contributes to the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Currently, the role of autophagy in BE and EAC is poorly studied. We quantitatively define autophagy levels in human BE cell lines, a transgenic mouse model of BE, and human BE, and EAC biopsies. Human non-dysplastic BE had the highest basal number of autophagic vesicles (AVs), while AVs were reduced in normal squamous cells and dysplastic BE cells, and nearly absent in EAC. To demonstrate a functional role for autophagy in BE pathogenesis, normal squamous (STR), non-dysplastic BE (CPA), dysplastic BE (CPD), and EAC (OE19) cell lines were exposed to an acid pulse (pH 3.5) followed by incubation in the presence or absence of chloroquine, an autophagy inhibitor. Acid exposure increased reactive oxygen species (ROS) levels in STR and CPA cells. Chloroquine alone had a small impact on intracellular ROS or cell survival. However, combination of chloroquine with the acid pulse resulted in a significant increase in ROS levels at 6 h in STR and CPA cells, and increased cell death in all cell lines. These findings establish increased numbers of AVs in human BE compared to normal squamous or EAC, and suggest that autophagy functions to improve cell survival after acid reflux injury. Autophagy may thus play a critical role in BE pathogenesis and progression. © 2015 Wiley Periodicals, Inc.
Assuntos
Ácidos/efeitos adversos , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Espécies Reativas de Oxigênio/metabolismo , Adenocarcinoma/metabolismo , Animais , Autofagia/efeitos dos fármacos , Esôfago de Barrett/metabolismo , Linhagem Celular , Sobrevivência Celular , Cloroquina/farmacologia , Modelos Animais de Doenças , Progressão da Doença , Neoplasias Esofágicas/metabolismo , Humanos , Camundongos , Estresse OxidativoRESUMO
Hepatitis delta virus (HDV) replication and packaging require interactions between the unbranched rodlike structure of HDV RNA and hepatitis delta antigen (HDAg), a basic, disordered, oligomeric protein. The tendency of the protein to bind nonspecifically to nucleic acids has impeded analysis of HDV RNA protein complexes and conclusive determination of the regions of HDAg involved in RNA binding. The most widely cited model suggests that RNA binding involves two proposed arginine-rich motifs (ARMs I and II) in the middle of HDAg. However, other studies have questioned the roles of the ARMs. Here, binding activity was analyzed in vitro using HDAg-160, a C-terminal truncation that binds with high affinity and specificity to HDV RNA segments in vitro. Mutation of the core arginines of ARM I or ARM II in HDAg-160 did not diminish binding to HDV unbranched rodlike RNA. These same mutations did not abolish the ability of full-length HDAg to inhibit HDV RNA editing in cells, an activity that involves RNA binding. Moreover, only the N-terminal region of the protein, which does not contain the ARMs, was cross-linked to a bound HDV RNA segment in vitro. These results indicate that the amino-terminal region of HDAg is in close contact with the RNA and that the proposed ARMs are not required for binding HDV RNA. Binding was not reduced by mutation of additional clusters of basic amino acids. This result is consistent with an RNA-protein complex that is formed via numerous contacts between the RNA and each HDAg monomer.
Assuntos
Motivos de Aminoácidos , Vírus Delta da Hepatite/fisiologia , Antígenos da Hepatite delta/metabolismo , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Arginina/genética , Arginina/metabolismo , Linhagem Celular , Análise Mutacional de DNA , Vírus Delta da Hepatite/genética , Antígenos da Hepatite delta/genética , Humanos , Mutagênese Sítio-Dirigida , Ligação Proteica , Proteínas de Ligação a RNA/genética , Deleção de SequênciaRESUMO
INTRODUCTION: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities. METHODS: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines. RESULTS: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95). DISCUSSION: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.
RESUMO
Over the past year, the emergence of state-of-the-art large language models (LLMs) in tools like ChatGPT has ushered in a rapid acceleration in artificial intelligence (AI) innovation. These powerful AI models can generate tailored and high-quality text responses to instructions and questions without the need for labor-intensive task-specific training data or complex software engineering. As the technology continues to mature, LLMs hold immense potential for transforming clinical workflows, enhancing patient outcomes, improving medical education, and optimizing medical research. In this review, we provide a practical discussion of LLMs, tailored to gastroenterologists. We highlight the technical foundations of LLMs, emphasizing their key strengths and limitations as well as how to interact with them safely and effectively. We discuss some potential LLM use cases for clinical gastroenterology practice, education, and research. Finally, we review critical barriers to implementation and ongoing work to address these issues. This review aims to equip gastroenterologists with a foundational understanding of LLMs to facilitate a more active clinician role in the development and implementation of this rapidly emerging technology.
Large language models in gastroenterology: a simplified overview for clinicians This text discusses the recent advancements in large language models (LLMs), like ChatGPT, which have significantly advanced artificial intelligence. These models can create specific, high-quality text responses without needing extensive training data or complex programming. They show great promise in transforming various aspects of clinical healthcare, particularly in improving patient care, medical education, and research. This article focuses on how LLMs can be applied in the field of gastroenterology. It explains the technical aspects of LLMs, their strengths and weaknesses, and how to use them effectively and safely. The text also explores how LLMs could be used in clinical practice, education, and research in gastroenterology. Finally, it discusses the challenges in implementing these models and the ongoing efforts to overcome them, aiming to provide gastroenterologists with the basic knowledge needed to engage more actively in the development and use of this emerging technology.
RESUMO
Objective: To automate scientific claim verification using PubMed abstracts. Materials and Methods: We developed CliVER, an end-to-end scientific Claim VERification system that leverages retrieval-augmented techniques to automatically retrieve relevant clinical trial abstracts, extract pertinent sentences, and use the PICO framework to support or refute a scientific claim. We also created an ensemble of three state-of-the-art deep learning models to classify rationale of support, refute, and neutral. We then constructed CoVERt, a new COVID VERification dataset comprising 15 PICO-encoded drug claims accompanied by 96 manually selected and labeled clinical trial abstracts that either support or refute each claim. We used CoVERt and SciFact (a public scientific claim verification dataset) to assess CliVER's performance in predicting labels. Finally, we compared CliVER to clinicians in the verification of 19 claims from 6 disease domains, using 189 648 PubMed abstracts extracted from January 2010 to October 2021. Results: In the evaluation of label prediction accuracy on CoVERt, CliVER achieved a notable F1 score of 0.92, highlighting the efficacy of the retrieval-augmented models. The ensemble model outperforms each individual state-of-the-art model by an absolute increase from 3% to 11% in the F1 score. Moreover, when compared with four clinicians, CliVER achieved a precision of 79.0% for abstract retrieval, 67.4% for sentence selection, and 63.2% for label prediction, respectively. Conclusion: CliVER demonstrates its early potential to automate scientific claim verification using retrieval-augmented strategies to harness the wealth of clinical trial abstracts in PubMed. Future studies are warranted to further test its clinical utility.