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1.
Artículo en Inglés | MEDLINE | ID: mdl-31597230

RESUMEN

Background/Aims: Since the use of dexlansoprazole in Asian subjects with gastroesophageal reflux disease (GERD) has not been adequately characterized, this study was conducted to evaluate the efficacy and safety of dexlansoprazole modified-release in Asian subjects with non-erosive reflux disease (NERD) and erosive esophagitis (EE). Methods: In this phase 4, open-label, non-randomized, uncontrolled, multicenter, multi-country study sponsored by Takeda, subjects aged ≥ 20 years with persistent typical GERD symptoms for at least 6 months underwent endoscopy. Based on endoscopic findings, they were assigned to either dexlansoprazole modified-release 30 mg once-daily for 4 weeks (NERD group) or dexlansoprazole modified-release 60 mg once-daily for 8 weeks (EE group). The primary endpoint was the percentage of days that subjects did not experience any 24-hour heartburn or acid regurgitation. Results: Of the 445 subjects screened from Hong Kong, South Korea, and Taiwan, 208 were enrolled in the NERD group (mean age: 53.6 years, male: 34.6%) and 88 in the EE group (mean age: 51.7 years, male: 55.7%). Over the treatment period, the median percentage of days that subjects did not experience any 24-hour heartburn or acid regurgitation was 26.9% and 65.5% in the NERD and EE groups, respectively; for nighttime heartburn or acid regurgitation the proportions were 59.3% and 83.3%, respectively. The treatment was well tolerated with low incidence of treatment-related adverse events in NERD and EE groups (6.7% and 5.7%, respectively). Conclusions: In Asian patients with GERD, treatment with dexlansoprazole modified-release indicates a favorable efficacy and safety profile in relieving heartburn and acid regurgitation symptoms.

2.
Lancet Infect Dis ; 19(10): 1109-1120, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31559966

RESUMEN

BACKGROUND: In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4-86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7-88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6-92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters. METHODS: This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879. FINDINGS: Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p<0·0001), and BQ10 (p<0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p<0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% [15/127] to 66% [38/58] for T14, 7% [10/135] to 64% [28/44] for C10), cefazolin (13% [16/127] to 43% [25/58] for T14, 10% [13/135] to 41% [18/44] for C10), cefmetazole (8% [10/127] to 26% [15/58] for T14, 4% [5/135] to 18% [8/44] for C10), levofloxacin (8% [10/127] to 35% [20/58] for T14, 7% [10/135] to 32% [14/44] for C10), gentamicin (13% [19/146] to 47% [27/58] for T14, 15% [22/149] to 45% [20/44] for C10), and trimethoprim-sulfamethoxazole (33% [48/146] to 86% [50/58] for T14, 28% [42/148] to 86% [38/44] for C10; p<0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10. INTERPRETATION: Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.

3.
Artículo en Inglés | MEDLINE | ID: mdl-31408909

RESUMEN

BACKGROUND AND AIM: The reported prevalence of Helicobacter pylori (H. pylori) infection in Taiwan was 54.4% in 1992. An updated prevalence of H. pylori infection in asymptomatic adults is lacking in Taiwan. We aimed to assess the updated age-standardized prevalence of H. pylori infection in asymptomatic subjects and in patients with dyspepsia and to assess the accuracy of H. pylori stool antigen (HpSA) test for screening of H. pylori in Chinese population. METHODS: Asymptomatic adult subjects(N=189) were screened for H. pylori infection using HpSA, serology, and 13 C-Urea Breath Test(13 C-UBT) in 2016-2017. Adult patients with dyspepsia(N=145) were screened for H. pylori using 13 C-UBT, HpSA, serology, rapid urease test, and histology during 2016-2018. Two types of HpSA, including the Diagnostec® HpSA ELISA Kit (HpSA ELISA) and Rapid Test Kit (HpSA Rapid) were used in this study. Sensitivity, specificity and accuracy of the HpSA tests were calculated using the 13 C-UBT as golden standard test. RESULTS: The un-adjusted prevalence of H. pylori was 21.2% in asymptomatic adults and 37.9% in patients with dyspepsia (p<0.001). The age-standardized prevalence of H. pylori was 28.9% in asymptomatic adults in Taiwan. Of the 334 patients included for analysis, the area under the curve of HpSA ELISA test was 0.978, and the optimal cut-off value of OD was 0.03. The sensitivity, specificity, and accuracy of the HpSA ELISA were 0.929, 0.983, and 0.967, respectively. The sensitivity, specificity, and accuracy of the HpSA Rapid were 0.929, 0.958, and 0.949, respectively. CONCLUSIONS: The prevalence of H. pylori infection has decreased in Taiwan. HpSA test is an accurate tool for screening of H. pylori in Chinese population.

4.
Diabetes Care ; 42(9): 1752-1759, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31262951

RESUMEN

OBJECTIVE: Pancreatic cancer-associated diabetes (PCDM) is a paraneoplastic phenomenon accounting for 1% of new-onset diabetes. We aimed to identify the mediators of PCDM and evaluate their usefulness in distinguishing PCDM from type 2 diabetes. RESEARCH DESIGN AND METHODS: Secreted proteins of MIA PaCa-2 cells were identified by proteomics, and those with ≥10-fold overexpression in transcriptome analysis were assessed by bioinformatics and glucose uptake assay to identify candidate factors. Expression of factors was compared between tumors with and without PCDM by immunohistochemistry. Serum levels were measured in a training set including PC with and without PCDM, type 2 diabetes, pancreatitis, other pancreatic/peripancreatic tumors, and control subjects (n = 50 each). Cutoff values for differentiation between PCDM and type 2 diabetes from the training set were validated in a test set (n = 41 each). RESULTS: Galectin-3 and S100A9 were overexpressed in tumors with PCDM and dose-dependently suppressed insulin-stimulated glucose uptake in C2C12 myotubes. In the training set, serum galectin-3 and S100A9 levels were exclusively increased in patients with PCDM and distinguished PCDM from type 2 diabetes (area under the curve [AUC] galectin-3: 0.73 [95% CI 0.64-0.83]; S100A9: 0.79 [95% CI 0.70-0.87]). Similar results were observed in the test set (AUC galectin-3: 0.83 [95% CI 0.74-0.92]; S100A9: 0.77 [95% CI 0.67-0.87]), with sensitivity and specificity 72.1% and 86.1%, respectively, for galectin-3 and 69.8% and 58.1% for S100A9 in differentiating between PCDM and type 2 diabetes. CONCLUSIONS: Galectin-3 and S100A9 are overexpressed in PCDM tumors and mediate insulin resistance. Galectin-3 and S100A9 distinguish PCDM from type 2 diabetes in subjects with new-onset diabetes.

5.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1682-1686, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31270100

RESUMEN

BACKGROUND: Genetic susceptibility is associated with nasopharyngeal carcinoma (NPC). We previously identified rare variants potentially involved in familial NPC and common variants significantly associated with sporadic NPC. METHODS: We conducted targeted gene sequencing of 20 genes [16 identified from the study of multiplex families, three identified from a pooled analysis of NPC genome-wide association study (GWAS), and one identified from both studies] among 819 NPC cases and 938 controls from two case-control studies in Taiwan (independent from previous studies). A targeted, multiplex PCR primer panel was designed using the custom Ion AmpliSeq Designer v4.2 targeting the regions of the selected genes. Gene-based and single-variant tests were conducted. RESULTS: We found that NPC was associated with combined common and rare variants in CDKN2A/2B (P = 1.3 × 10-4), BRD2 (P = 1.6 × 10-3), TNFRSF19 (P = 4.0 × 10-3), and CLPTM1L/TERT (P = 5.4 × 10-3). Such associations were likely driven by common variants within these genes, based on gene-based analyses evaluating common variants and rare variants separately (e.g., for common variants of CDKN2A/2B, P = 4.6 × 10-4; for rare variants, P = 0.04). We also observed a suggestive association with rare variants in HNRNPU (P = 3.8 × 10-3) for NPC risk. In addition, we validated four previously reported NPC risk-associated SNPs. CONCLUSIONS: Our findings confirm previously reported associated variants and suggest that some common variants in genes previously linked to familial NPC are associated with the development of sporadic NPC. IMPACT: NPC-associated genes, including CLPTM1L/TERT, BRD2, and HNRNPU, suggest a role for telomere length maintenance in NPC etiology.

6.
Curr Gastroenterol Rep ; 21(8): 36, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31289917

RESUMEN

PURPOSE OF REVIEW: Colorectal cancer (CRC) remains the third most commonly diagnosed cancer globally, and its incidence and mortality rates have been on the rise in Asia. In this paper, we summarize the recent trends and screening challenges of CRC in this region. RECENT FINDINGS: In 2018, Asia had the highest proportions of both incident (51.8%) and mortality (52.4%) CRC cases (all genders and ages) per 100,000 population in the world. In addition, there has been a rising trend of this disease across Asia with some regional geographic variations. This rise in CRC can be attributed to westernized dietary lifestyle, increasing population aging, smoking, physical inactivity, and other risk factors. In curbing the rising trend, Japan, South Korea, Singapore, and Taiwan have launched nationwide population-based screening programs. CRC screening across this region has been found to be effective and cost-effective compared with no screening at all. The emergence of new therapies has caused a reduction in case fatality; however, these new options have had a limited impact on cure rates and long-term survival due to the great disparity in treatment capacity/resources and screening infrastructures among Asian countries with different degrees of economic development. CRC is still rising in Asia, and implementation of screening is necessary for moderate- to high-incidence countries and construction of treatment capacity is the priority task in low-incidence and low-income countries. Unless countries in Asia implement CRC screening, the incidence and mortality rates of this disease will continue to rise especially with the rapidly rising population growth, economic development, westernized lifestyle, and increasing aging.

7.
Artículo en Inglés | MEDLINE | ID: mdl-31344762

RESUMEN

The human gut microbiota is a functioning endocrine organ and stands at the intersection between dietary components and health or disease. There are tons of microbial metabolites with numerous structures and functions arising from the gut microbial fermentation of foods and become signals for biological communication in the human body. These small molecules can be absorbed and delivered to distant organs through circulatory system to build the gut-systemic axis. The gut microbial metabolomes are thus believed to play important roles in regulating cardiometabolic health and provide opportunities in the mechanistic research and new drug discovery. Measurement of these novel microbial metabolites in clinical samples may serve as a tool to investigate disease biomarkers. In the past decade, the development of untargeted and targeted metabolomics approaches by using NMR, LC-MS, and GC-MS have contributed to the exploration of gut microbial metabolome in cardiometabolic health and disease. Some important targets are currently being translated into clinical applications. In this review article, we introduced an oral carnitine challenge test developed as an example to demonstrate the potential applications in personalized nutrition based on the function of gut microbiota. It is a method taking the gut microbiota as a bioreactor and provides with fermentable materials as inputs and measures the outputs of targeted microbial byproducts in the blood or urine. This challenge test may be extended to measure metabolites from microbial fermentation related to other endocrinological or inflammatory diseases. In this paper, we reviewed current gut metabolome research approaches and proposed a gut microbial functional measurement by using a challenge test. We wish the maturation in measuring gut microbial metabolites may provide an important piece to complete the puzzle of precision medicine.

8.
J Neuroinflammation ; 16(1): 129, 2019 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-31248424

RESUMEN

OBJECTIVE: Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson's disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. METHODS: Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1ß, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. RESULTS: Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102-0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI - 0.043-0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03). CONCLUSIONS: This study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.

9.
J Gerontol A Biol Sci Med Sci ; 74(6): 949-956, 2019 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-31095709

RESUMEN

BACKGROUND: Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism. METHODS: We conducted a prospective study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan. Each participant received baseline measurements of blood HbA1c and inflammatory markers levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. We used generalized linear mixed-effects regression to estimate the adjusted changes in the odds ratio for self-reported physical functioning impairment and Short Physical Performance Battery (SPPB) score according to baseline HbA1c levels (categorized into 0.5% increments from <5.5% to ≥7.0%). RESULTS: HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term < .001). Compared with participants with an HbA1c of 5.5% to <6.0%, those with an HbA1c of <5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04-1.50] and 1.21 [1.04-1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], -0.05 [-0.10 to 0.00] and -0.04 [-0.08 to 0.00]). These relationships were nonlinear only in participants with high soluble interleukin-6 receptor levels (>48,124 pg/mL; p for interaction < .05). CONCLUSIONS: High and low HbA1c levels at baseline are associated with faster physical functioning decline, particularly among individuals with elevated circulating soluble interleukin-6 receptor, a sign of enhanced interleukin-6 trans-signaling.

10.
JAMA Intern Med ; 179(5): 633-640, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30882847

RESUMEN

Importance: Antiviral therapy cannot erase hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B, and it is not indicated for most hepatitis B virus (HBV) carriers. Another effective way of reducing HCC risk needs to be developed. Aspirin may prevent cancer development, but clinical evidence in patients with HBV-related HCC remains limited. Objective: To investigate the association of daily aspirin therapy with HBV-related HCC risk. Design, Setting, and Participants: In this Taiwan nationwide cohort study, we screened 204 507 patients with chronic hepatitis B for the period January 1, 1997, to December 31, 2012. After excluding patients with confounding conditions, 2123 patients who continuously received daily aspirin for 90 or more days (treated group) were randomly matched 1:4 with 8492 patients who had never received antiplatelet therapy (untreated group) by means of propensity scores, consisting of the follow-up index date, baseline characteristics, and potentially chemopreventive drug use during follow-up. Data were analyzed from August 1 to November 30, 2018. Exposures: Daily aspirin therapy during the study period. Main Outcomes and Measures: Both cumulative incidence of and hazard ratios (HRs) for HCC development were analyzed after adjusting patient mortality as a competing risk event. Results: Of the 10 615 patients included in the analysis, 7690 (72.4%) were men; mean (SD) age was 58.8 (11.8) years. The cumulative incidence of HCC in the treated group was significantly lower than that in the untreated group in 5 years (5.20%; 95% CI, 4.11%-6.29% vs 7.87%; 95% CI, 7.15%-8.60%; P < .001). In the multivariable regression analysis, aspirin therapy was independently associated with a reduced HCC risk (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Sensitivity subgroup analyses also verified this association (all HRs <1.0). In addition, older age (HR, 1.01 per year; 95% CI, 1.00-1.02), male sex (HR, 1.75; 95% CI, 1.43-2.14), and cirrhosis (HR, 2.89; 95% CI, 2.45-3.40) were independently associated with an increased HCC risk, but nucleos(t)ide analogue (HR, 0.54; 95% CI, 0.41-0.71) or statin (HR, 0.62; 95% CI, 0.42-0.90) use was correlated with a decreased HCC risk. Conclusions and Relevance: Daily aspirin therapy may be associated with a reduced risk of HBV-related HCC.

11.
Kaohsiung J Med Sci ; 35(2): 73-82, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30848026

RESUMEN

Germ theory of disease and Koch's postulates has been governing our understanding of the role of microbes in human health since 19th century. The discovery of Helicobacter pylori (H. pylori) and H. pylori associated diseases has typically represented the concept and framework of Koch's postulates. Eradication of H. pylori to prevent peptic ulcers recurrence and gastric cancer is the triumph of this microbiology paradigm. Advances of next generation sequencing provide great insight into the unculturable microbes and show trillions of microbes have evolved with human beings. Research into the microbiome-the microbial communities (microbiota) and the host environment that they inhabit-has changed our understanding about microbes in human health and disease. The gut microbiota, the largest reservoir of the microbiome in human, plays a critical role in our catabolic-metabolism and immunity. This review will show the changes of the view of microbes on human health. We will briefly discuss dysbiosis, the disruption of symbiotic relationship between the host and microbiota, and the associated diseases. This leads to an idea to manipulate the microbiota, either by restoring missing functions or by eliminating harmful functions, to prevent or treat a variety of diseases. Current evidences of two common germ therapies, fecal microbiota transplantation and probiotics, in treating diseases will be reviewed.


Asunto(s)
Trasplante de Microbiota Fecal , Teoría del Gérmen de la Enfermedad , Probióticos/farmacología , Ensayos Clínicos como Asunto , Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Humanos
12.
J Proteome Res ; 18(5): 1948-1957, 2019 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-30895795

RESUMEN

The gut microbiota has attracted a great deal of interest in recent years due to its association with many diseases. Short-chain fatty acids (SCFAs), the end products of dietary fiber fermentation by the intestinal microbiota, are among the most frequently discussed gut metabolites. As the sample handling method greatly affects the integrity of data, this study investigated the most important parameters that affect the bias of SCFA comparisons in human fecal studies. An accurate gas chromatography-mass spectrometry (GC-MS) method was first established and validated for quantifying six SCFAs, including acetic, propionic, butyric, isobutyric, isovaleric, and valeric acids. To remove interfering species, we used butanol to extract SCFAs from acidified fecal suspensions. The validated quantification method was then applied to evaluate fecal sample handling protocols. We found that lyophilization of fecal samples can not only minimize bias due to the water content but also provide better stability of SCFAs. Six SCFAs were stable and that their recoveries were higher than 90% after lyophilization. Lyophilization of a large fecal sample is extremely time-consuming, and 1 g of fecal sample is suggested for lyophilization to minimize sampling bias. The interindividual difference was significantly higher than the intra-individual difference when using 1 g of fecal sample to study SCFAs. Finally, an effective protocol from sample collection to GC-MS analysis was proposed. As SCFAs have been shown to play an important role in health maintenance and disease development, the proposed protocol is anticipated to be applicable to clinical studies to delineate the biological functions of each SCFA.

13.
Medicine (Baltimore) ; 98(9): e14672, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30817593

RESUMEN

Atherosclerosis has severe consequences on human health. Carotid artery plaques are a condition typically caused by atherosclerosis. Previous studies showed that nonalcoholic fatty liver disease (NAFLD) and Helicobacter pylori (H pylori) are risks factors for carotid artery plaque formation. We hypothesize that the combination of NAFLD with H pylori infection increases the risk of carotid artery plaque formation.A total of 4669 subjects aged > 40 years who underwent routine health checkups between January 2006 and December 2015 were retrospectively reviewed. A serial examination, including abdominal ultrasound, carotid artery ultrasound and esophago-gastroduodenoscopy (EGD), and biopsy urease testing, was conducted.In total, 2402 subjects were enrolled. There were no differences in H pylori infection status among patients with or without NAFLD. There was a trend of more participants with both NAFLD and H pylori infection (number [N]=583) presenting carotid artery plaque (N = 187,32.08%) than participants without NAFLD and H pylori infection (N = 589) who presented plaque formation (N = 106, 18.00%). Participants who had both H pylori infection and NAFLD had the highest risk of any carotid artery plaque (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.413-2.636) based on a multivariate logistic regression analysis. This analysis also showed that age >60 years, male sex, low-density lipoprotein (LDL) >130 mg/dL, and H pylori infection were independent risk factors for concomitant NAFLD and carotid artery plaque formation.The combination of H pylori infection and NAFLD increases carotid artery plaque formation. H pylori eradication and NAFLD control may be warranted to prevent carotid artery plaque formation.


Asunto(s)
Aterosclerosis/etiología , Estenosis Carotídea/etiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Aterosclerosis/microbiología , Estenosis Carotídea/microbiología , Comorbilidad , Femenino , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/microbiología , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo
14.
PLoS Biol ; 17(3): e2007097, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30883547

RESUMEN

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.

17.
J Formos Med Assoc ; 118(11): 1528-1536, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30635154

RESUMEN

BACKGROUND: Esophageal motility disorders are the major cause of non-obstructive dysphagia (NOD), but may be underdiagnosed. In this high-resolution impedance manometry (HRIM)-based study, we aimed to clarify the etiologies and clinical characteristics of patients presenting with NOD in a Taiwanese population. METHODS: From October 2014 to July 2017, consecutive patients with the chief complaint of dysphagia were prospectively enrolled in the study at a tertiary medical center. All subjects underwent a comprehensive diagnostic work-up, which included validated symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram, and HRIM. Those with obstructive esophageal lesions were excluded. Esophageal motility disorders were diagnosed using the updated Chicago Classification v3.0. We categorized all patients based on the HRIM results, and compared the clinical characteristics and parameters between groups. RESULTS: A total of 120 patients (55 men; mean age [range], 52 [13-87] years) were analyzed. Achalasia was the most common diagnosis by HRIM (n = 66, 55%), followed by ineffective esophageal motility (n = 15, 12.5%), and absent contractility (n = 6, 5%). Patients with achalasia experienced increased vomiting (62.1% vs. 31.5%, p = 0.001), significant weight loss (22.7% vs. 7.4%, p = 0.025), delayed esophageal emptying (90.9% vs. 12.9%, p < 0.001), and abnormal bolus transit (100% vs. 25.9%, p < 0.001) compared with non-achalasia patients. CONCLUSION: Based on HRIM and the updated Chicago Classification, achalasia was the most common diagnosis of NOD in a Taiwanese population. HRIM allows for a more detailed assessment and may assist in the tailoring of further treatment plans.

18.
J Biomed Sci ; 26(1): 4, 2019 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-30611258

RESUMEN

BACKGROUND: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. METHODS: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. RESULTS: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1-6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001). CONCLUSIONS: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer.


Asunto(s)
Proteínas Bacterianas/genética , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/genética , Polimorfismo Genético , Neoplasias Gástricas/epidemiología , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Infecciones por Helicobacter/microbiología , Humanos , Prevalencia , Riesgo , Serina Endopeptidasas/química , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Neoplasias Gástricas/microbiología , Taiwán/epidemiología
19.
J Formos Med Assoc ; 2019 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-30661919

RESUMEN

BACKGROUND/PURPOSE: Although performing balloon enteroscopy soon after the onset of small bowel bleeding appeared to enhance diagnostic rate, the optimal timing was unclear. METHODS: A retrospective cohort study in a single referral center. Patients with overt, suspected small bowel bleeding who underwent primary single-balloon enteroscopy (SBE) were evaluated to determine the association between procedure timing and diagnostic yield rates. RESULTS: A total of 220 patients were enrolled (47.7% males; mean age, 65.6 ± 18.1 years). They were stratified into four groups based on the timing of SBE: emergency (<24 h after onset or continued bleeding, n = 64), 24-72 h (n = 28), 3-7 days (n = 41), and >7 days (n = 87). A significant trend of decreasing diagnostic yields was observed across the groups (90.6%, 67.9%, 68.3%, and 44.8%, respectively, P < 0.0001). Diagnostic yield rates were different between emergency and 24-72 h groups (P < 0.0001), and between 3 and 7 days and >7 days groups (P < 0.05), but not between 24 and 72 h and 3-7 days groups (P = 0.97). In multivariate regression analysis, emergency, ≤ 3 days, and ≤7 days SBEs had greater yield rates than SBEs at later timings. CONCLUSION: The likelihood of diagnostic yield was highest when SBE was performed during continued bleeding or within 24 h of onset, and gradually declined as waiting time increased. We therefore recommend that SBE should be performed as soon as possible, preferably no later than seven days.

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