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1.
Aging (Albany NY) ; 132021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33819921

RESUMO

PURPOSE: Esophageal cancer is the sixth leading cause of cancer-related death worldwide, and is associated with a poor prognosis. Stromal tumor infiltrating lymphocytes (sTIL) and certain single nucleotide polymorphisms (SNPs) have been found to be predictive of patient survival. In this study, we explored the association between SNPs and sTIL regarding the predictability of disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We collected 969 pathologically confirmed ESCC patients from 2010 to 2013 and genotyped 101 SNPs from 59 genes. The number of sTIL for each patient was determined using an automatic algorithm. A Kruskal-Wallis test was used to determine the association between genotype and sTIL. The genotypes and clinical factors related to survival were analyzed using a Kaplan-Meier curve, Cox proportional hazards model, and log-rank test. RESULTS: The median age of the patients was 67 (42-85 years), there was a median follow-up of 851.5 days and 586 patients died. The univariable analysis showed that 10 of the 101 SNPs were associated with sTIL. Six SNPs were also associated with disease-free survival. A multivariable analysis revealed that sTIL, rs1801131, rs25487, and rs8030672 were independent prognostic markers for ESCC patients. The model combining SNPs, clinical characteristics and sTIL outperformed the model with clinical characteristics alone for predicting outcomes in ESCC patients. CONCLUSION: We discovered 10 SNPs associated with sTIL in ESCC and we built a model of sTIL, SNPs and clinical characteristics with improved prediction of survival in ESCC patients.

2.
Cancer ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823062

RESUMO

BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. METHODS: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

3.
BMC Cancer ; 21(1): 343, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789604

RESUMO

BACKGROUND: Selection of high-risk subjects for endoscopic screening of esophageal squamous cell carcinoma (ESCC) lacks individual predictive tools based on environmental risk factors. METHODS: We performed a large population-based case-control study of 1418 ESCC cases and 1992 controls in a high-risk area of China. Information on potential risk factors was collected via face-to-face interview using an electronic structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, and predictive nomograms were established accordingly. A weighted analysis was further conducted to introduce age into predictive nomograms due to frequency matching study design. RESULTS: Most cases were usually exposed to 4 to 6 risk factors, but most controls were usually exposed to 3 to 5 risk factors. The AUCs of male and female predictive nomograms were 0.75 (95%CI: 0.72, 0.77) and 0.76 (95%CI: 0.73, 0.79), respectively. The weighted analysis adding age in the predictive model improved the AUC in both men and women (0.81 (95%CI: 0.79, 0.84) and 0.88 (95%CI: 0.85, 0.90), respectively). CONCLUSIONS: An easy-to-use preclinical predictive tool is provided to select candidate population with high ESCC risk for endoscopic screening. Its usefulness needs to be further evaluated in future screening practice.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33769467

RESUMO

BACKGROUND: The altered microbiota, considered as quantitative traits, has also been identified to play pivotal roles in the host vascular physiology and might contribute to diseases. To understand the role of gut microbiota on vascular physiology in the sub-clinical elderly population and how lifestyles affect the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. METHODS: Performed a population-based fecal metagenomic study over 569 elderly asymptomatic sub-clinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. RESULTS: Carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were shown essentially in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of taking fresh fruits, fresh vegetables, and more exercise significantly reduces carotid arteries atherosclerosis in terms of IMT, PSV and EDV values the through the mediation of Alistepes, Oligella, and Prevotella. The gut microbes explained 16.5% of the mediation effect of lifestyles on the pathogenesis of carotid atherosclerosis. After adjusted, Faecalicatena (OR = 0.20∼0.30) was shown protective in the formation of carotid athersclerosis independently, while Libanicoccus (OR = 2.39∼2.43) were hazardous to carotid arterial IMTs. KEGG/KO analyses revealed a loss of anti-inflammation function in IMT subjects. CONCLUSIONS: Our study provided a Chinese population-wide phenotype-metagenomic network, revealing association and mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at a therapeutic and preventive potential of microbiota in vascular diseases.

5.
Environ Int ; 151: 106455, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33652252

RESUMO

OBJECTIVES: Given the role of exposures related to residence in the development of nasopharyngeal carcinoma (NPC) has not been well explored, present study aims to investigate the magnitude and pattern of associations for NPC with lifelong residential exposures. MATERIALS AND METHODS: We carried out a multi-center, population-based case-control study with 2533 incident NPC cases and 2597 randomly selected population controls in southern China between 2010 and 2014. We performed multivariate logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with residential exposures. RESULTS: Compared with those living in a building over lifetime, risk of NPC was higher for individuals living in a cottage (OR: 1.56; 95% CI: 1.34-1.81) or in a boat (3.87; 2.07-7.21). NPC risk was also increased in individuals using wood (1.34; 1.03-1.75), coal (1.70; 1.17-2.47), or kerosene (3.58; 1.75-7.36) vs. using gas/electricity as cooking fuel; using well water (1.57; 1.34-1.83), river water (1.80; 1.47-2.21), or spring/pond/stream water (2.03; 1.70-2.41) vs. tap water for source of drinking water; living in houses with smaller-sized vs. larger windows in the bedroom (3.08; 2.46-3.86), hall (1.89; 1.55-2.31) or kitchen (1.67; 1.34-2.08); and increasing exposure to cooking smoke [(1.53; 1.20-1.94) for high exposure)] or burned incense [(1.59; 1.31-1.95) for daily use)]. Weighted Cox regression analysis corroborated these results. CONCLUSION: Poorer residential conditions and household air pollution are associated with an increased risk of NPC. Large-scale studies in other populations or longitudinal studies are warranted to further corroborate these findings.

6.
Genome Med ; 13(1): 15, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33517887

RESUMO

BACKGROUND: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. METHODS: We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. RESULTS: We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support. CONCLUSIONS: This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.

7.
Int J Cancer ; 148(8): 2048-2058, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33411965

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, mainly due to late diagnosis at advanced tumor stages. In this study, we aimed to identify plasma protein biomarkers for early detection of PDAC. Totally, 135 PDAC patients (early PDAC, Stage I/II, n = 71; advanced PDAC, Stage III/IV, n = 64), 13 benign lesions/chronic pancreatitis patients and 72 healthy individuals, with corresponding plasma samples from a case-control study in Sweden were included. A proximity extension assay was used to detect 92 cancer-related proteins, and an enzyme-linked immunosorbent assay/electrochemiluminescence immunoassay was used to detect CA19-9. Predictive features were selected from these 93 candidate proteins and three covariates in the Swedish participants, and then validated in Spanish participants, including 37 early PDAC patients, 38 advanced PDAC patients, 19 chronic pancreatitis patients and 36 healthy controls. A panel of eight proteins discriminating early PDAC from healthy individuals was identified, and the cross-validated area under the curves (AUCs) were 0.85 (95% confidence interval, 95% CI, 0.78-0.91) and 0.81 (95% CI, 0.70-0.92) in the Swedish and Spanish participants, respectively. Another eight-protein panel was predictive for classifying advanced PDAC from healthy controls in two populations, with cross-validated AUCs of 0.89 (95% CI, 0.83-0.95) and 0.90 (95% CI, 0.83-0.98), respectively. In conclusion, eight protein biomarkers were identified and externally validated, potentially allowing early detection of PDAC patients if validated in additional prospective studies.

8.
Neurology ; 96(6): e895-e903, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33408141

RESUMO

OBJECTIVE: To determine whether high baseline dietary antioxidants and total nonenzymatic antioxidant capacity (NEAC) is associated with a lower risk of Parkinson disease (PD) in men and women, we prospectively studied 43,865 men and women from a large Swedish cohort. METHODS: In the Swedish National March Cohort, 43,865 men and women aged 18-94 years were followed through record linkages to National Health Registries from 1997 until 2016. Baseline dietary vitamin E, vitamin C, and beta-carotene intake, as well as NEAC, were assessed by a validated food frequency questionnaire collected at baseline. All exposure variables were adjusted for energy intake and categorized into tertiles. Multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for PD. RESULTS: After a mean follow-up time of 17.6 years, we detected 465 incidence cases of PD. In the multivariable adjusted model, dietary vitamin E (HR 0.68, 95% CI 0.52-0.90; p for trend 0.005) and vitamin C (HR 0.68, 95% CI 0.52-0.89; p for trend 0.004) were inversely associated with the risk of PD when comparing participants in the highest vs the lowest tertiles of exposure. No association was found with estimated intake of dietary beta-carotene or NEAC. CONCLUSION: Our findings suggest that dietary vitamin E and C intake might be inversely associated with the risk of PD. No association was found with dietary beta-carotene or NEAC. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that dietary vitamin E and C intake are inversely associated with the risk of PD.


Assuntos
Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Alimentos/estatística & dados numéricos , Doença de Parkinson/epidemiologia , Sistema de Registros , Vitamina E/administração & dosagem , beta Caroteno/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto Jovem
9.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33414179

RESUMO

OBJECTIVE: Several, but not all studies, have shown a dose-dependent inverse association with alcohol consumption and rheumatoid arthritis (RA), whereas smoking is an established risk factor for RA. We aimed to study the association between alcohol consumption and RA incidence and investigate a potential interaction between alcohol and smoking habits, regarding RA incidence. METHODS: We used a prospective cohort study, based on 41 068 participants with detailed assessment of alcohol intake, smoking and potential confounders at baseline in 1997. We ascertained a total of 577 incident cases of RA during a mean of 17.7 years of follow-up through linkage to nationwide and essentially complete databases. Multivariate Cox proportional hazards models were used to estimate HR with 95% CI. Interaction on the additive scale between alcohol and smoking was estimated by calculating the attributable proportion due to interaction (AP). RESULTS: Overall, alcohol consumption was associated with a 30% reduced incidence of RA (HR 0.69, 95% CI 0.55 to 0.86) with a dose-response relationship (p value for trend <0.001) which remained significant after stratification by age and smoking habits. The positive association between smoking and RA incidence was reduced with increasing alcohol consumption (p value for trend <0.001). A synergistic effect was observed between alcohol and smoking (AP 0.40, 95% CI 0.15 to 0.64), indicating that 40% of the cases among the double exposed are due to the interaction per se. CONCLUSIONS: Our findings suggest an inverse association between alcohol consumption and RA incidence, and a synergistic effect between alcohol and smoking.

10.
Int J Epidemiol ; 49(6): 2041-2050, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33347584

RESUMO

BACKGROUND: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project. METHODS: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use. RESULTS: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount. CONCLUSIONS: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.

11.
Sleep Med ; 77: 1-6, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33285395

RESUMO

OBJECTIVE: Previous studies investigating the association between nightmares and suicide have yielded different results. We aimed to investigate whether nightmares, directly or indirectly, influence the incidence of suicide. METHODS: We used a prospective cohort study, based on 40,902 participants with a mean follow-up duration of 19.0 years. Cox proportional hazards models with attained age as time-scale were fitted to estimate hazard ratios (HR) of suicide with 95% confidence intervals (CI) as a function of the presence or absence of depression and nightmares. Mediation analysis was used to asses to what extent the relationship between nightmares and the incidence rate of suicide could be mediated by depression. RESULTS: No association was observed between nightmares and the incidence of suicide among participants without depression. Compared with non-depressed participants without nightmares, the incidence of suicide among participants with a diagnosis of depression was similar among those with and without nightmares (HR 12.3, 95% CI 5.55-27.2 versus HR 13.2, 95% CI 7.25-24.1). The mediation analysis revealed no significant effects of nightmares on suicide incidence. However, the incidence of depression during follow-up was higher among those who suffered from nightmares than among those who did not (p < 0.001). CONCLUSIONS: Our findings indicate that nightmares have no influence on the incidence rate of suicide, but may reflect pre-existing depression. This is supported by a recent discovery of a strong genetic correlation of nightmares with depressive disorders, with no evidence that nightmares would predispose to psychiatric illness or psychological problems. Interventions targeting both depression and nightmares, when these conditions co-occur, may provide additional therapeutic benefit.

12.
Carcinogenesis ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300568

RESUMO

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling, and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal components analysis (PCA) was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 SNPs in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases, and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17,159 controls). Global variation in the IGF pathway was associated with risk of BE (P=0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; p=0.00046, FDR q=0.0056) and IGF1R (IGF1 receptor; p=0.0090, q=0.0542). These gene-level signals remained significant at q<0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

13.
PLoS Med ; 17(12): e1003392, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33259494

RESUMO

BACKGROUND: In recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991-2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period. METHODS AND FINDINGS: We conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991-2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34-1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29-1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08-1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15-1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14-1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96-10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48-0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51-0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration. CONCLUSIONS: Our findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33303643

RESUMO

BACKGROUND: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial. METHODS: In a population-based case-control study in southern China, we assessed alcohol or tea intake from 2,503 histopathologically confirmed NPC cases and 2,591 controls. We calculated mean daily ethanol (g/day) and tea intake (ml/day). Fully adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression; potential dose-response trends were evaluated using restricted cubic spline analysis. RESULTS: Compared with non-drinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93, 1.25), nor among current heavy drinkers (OR for≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95, 1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64, 0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR 0.53, 0.68 and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant non-linear dose-response relation with NPC risk. CONCLUSIONS: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose-response association complicates causal inference. IMPACT: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.

15.
BMC Gastroenterol ; 20(1): 428, 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33357229

RESUMO

BACKGROUND: End-stage liver disease (ESLD) is a major burden on public health, particularly in sub-Saharan Africa, where hepatitis B virus (HBV) is an important risk factor. We aimed to describe clinical characteristics of ESLD from cirrhosis or hepatocellular carcinoma (HCC) and the performance of aspartate aminotransferase (AST)-platelet ratio index (APRI) and alpha fetoprotein (AFP) in Ghana. METHODS: We performed an observational cross-sectional study in outpatient hepatology clinics at three teaching hospitals in Ghana, West Africa. One hundred and forty-one HCC, 216 cirrhosis and 218 chronic HBV patients were recruited by convenience sampling. Sociodemographic, history and examination, laboratory, and disease staging information were shown using descriptive statistics. Performance of the APRI score in diagnosis of cirrhosis and AFP in the diagnosis of HCC was determined using AUROC analysis. RESULTS: Median age at presentation was 44 years for HCC and 46 years for cirrhosis. HBV was found in 69.5% of HCC and 47.2% of cirrhosis cases, and HCV in 6.4% and 3.7% respectively. APRI cut-off of 2 had sensitivity of 45.4% and specificity of 95% in diagnosis of cirrhosis, and cut-off of 1 had sensitivity of 75.9% and specificity of 89%. AUC of AFP was 0.88 (95% CI 0.81-0.94) in diagnosis of HCC. Low monthly income was associated with lower odds of undertaking AFP. Thirty one percent of cirrhotic persons were Child-Pugh C, and 67.9% of HCC patients had advanced or terminal disease at presentation. CONCLUSIONS: Our findings emphasize the young age of ESLD patients in Ghana and the advanced nature at presentation. It highlights shortcomings in surveillance and the need for policies to address the burden and improve outcomes in Ghana.

16.
Sleep ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216134

RESUMO

STUDY OBJECTIVES: The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep duration and depression into consideration. METHODS: The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time of 19.2 years. Cox proportional hazards models with attained age as time-scale were used to estimate hazard ratios (HRs) of death by suicide with 95% confidence intervals (CI) for participants categorized by frequency of insomnia symptoms. Causal mediation analysis was performed to assess to what extent the relationship between insomnia and suicide risk is mediated by depression. RESULTS: Insomnia was only associated with suicide risk among short sleepers, whereas no significant association was observed among those who slept 7 hours/night or more. The total effect of insomnia in the context of short sleep on suicide risk, expressed on the HR scale, was 2.85 (95% CI 1.42-5.74). The direct effect was 2.25 (95% CI 1.12-4.54) and the indirect effect, mediated by depression, was 1.27 (95% CI 1.05-1.53). Of the total effect, 32% was mediated by depression. The association between insomnia and suicide risk became more pronounced with decreasing depressive symptoms (p value for trend <0.05). CONCLUSIONS: Insomnia in the context of short sleep increases suicide risk, both directly and indirectly by affecting the risk of depression. Abnormalities of sleep duration and insomnia symptoms should be evaluated when assessing suicide risk.

17.
Plant Dis ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910724

RESUMO

An emerging threat to agriculture, Meloidogyne enterolobii Yang & Eisenback, 1983 is a tropical species and considered to be the most damaging root-knot nematode (RKN) in the world because of its wide host range, aggressiveness, and ability to overcome resistance to RKN in many crops. It was first detected in the USA on ornamental plants in Florida in 2001, but has since been identified in North Carolina, South Carolina and Louisiana. Several thousand RKN populations were collected from North Carolina field crops, ornamental plants and turfgrasses for species identification in the Nematode Assay Laboratory in the North Carolina Department of Agriculture & Consumer Services (NCDA&CS). From 2006 to 2019, root systems showing galling symptoms were dissected under the microscope and females were obtained for DNA analysis. When only soil samples were submitted, the second-stage juveniles or males were used instead. Molecular characterization was performed by PCR using species-specific primers and DNA sequencing on the ribosomal DNA 18S-ITS1-5.8S and 28S D2/D3, and mitochondrial DNA CoxII-16S. One hundred and thirty-five representative RKN populations from North Carolina were characterized and identified as M. enterolobii. Six populations from China where the species was originally described were included in this study for identity confirmation and comparison. As of December 2019, M. enterolobii was confirmed from a limited number of fields in 11 North Carolina counties, including Columbus, Craven, Greene, Harnett, Johnston, Lenoir, Nash, Pitt, Sampson, Wayne and Wilson. Currently, M. enterolobii is the most important emerging RKN species in the USA and causes severe damage to agronomic and horticultural crops, especially sweetpotato in North Carolina.

18.
Theranostics ; 10(23): 10589-10605, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32929368

RESUMO

Rationale: The oncogenesis of head and neck squamous cell carcinoma (HNSCC) is believed to result from oncogene activation and tumor suppressor inactivation. Here, we identified a new oncogenic role for the EREG gene in HNSCC. Methods: The TCGA database and immunohistochemistry assay were used to analyze expression of EREG in HNSCC tissues. Immunoblotting was performed to identify the EGFR-mediated pathways altered by EREG. The role of EREG in oncogenesis was investigated in vivo and in vitro. Results: Upregulated EREG expression predicted a poor prognosis and triggered HNSCC oncogenic transformation by activating the epidermal growth factor receptor (EGFR) signaling pathway. We also demonstrated the direct association of EREG with EGFR and that this binding required EGFR domains I and III and the N57 residue of EREG. Moreover, EREG overexpression was shown to promote HNSCC oncogenesis by inducing C-Myc expression, and the pharmacological inhibition of C-Myc rescued EREG-promoted HNSCC oncogenesis. Unlike other EGFR ligands, EREG could mimic EGFR mutations by sustaining the activation of the EGFR-Erk pathway, and high EREG expression was positively associated with the response to treatment with the EGFR inhibitor erlotinib. Furthermore, knockdown of EREG decreased sensitivity to erlotinib treatment in vitro and in vivo. Conclusions: These results identify the EREG-EGFR-C-Myc pathway as a crucial axis that drives HNSCC oncogenesis and show that EREG expression could be a predictive functional marker of sensitivity to erlotinib therapy in HNSCC.

19.
Gastroenterology ; 159(6): 2065-2076.e1, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918910

RESUMO

BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. METHODS: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. RESULTS: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, PBONF = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, PBONF = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals. CONCLUSIONS: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32866565

RESUMO

PURPOSE: The human commensal microbiome has been suggested to be involved in the regulation of response to anticancer therapies. However, little is known regarding changes in commensal microbes in patients with cancer during radiation therapy. We conducted a prospective, longitudinal proof-of-concept cohort study with patients with newly diagnosed nasopharyngeal carcinoma (NPC) who underwent radiation therapy-based treatment. METHODS AND MATERIALS: Nasopharyngeal swabs were collected before radiation therapy, twice per week during radiation therapy, and after radiation therapy. The nasopharyngeal microbiome was assessed using 16S rRNA amplicon sequencing. A patient's response to treatment was measured 3 months after the completion of radiation therapy as a short-term clinical outcome. In total, 39 NPC patients with 445 nasopharyngeal samples were analyzed. RESULTS: There was stable temporal change in the community structure of the nasopharyngeal microbiome among patients with NPC during treatment (P = .0005). Among 73 abundant amplicon sequence variants (ASVs), 7 ASVs assigned to genus Corynebacterium decreased significantly during the treatment (W-statistic >80%); 23 ASVs showed statistically significant changes in the ratio of abundance between early and late responders during treatment (false discovery rate <0.05). CONCLUSIONS: This study addressed stable temporal change in the nasopharyngeal microbiome among patients with NPC during radiation therapy-based treatment and provided preliminary evidence of an association with a short-term clinical outcome.

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