The role of microbiome in the pathogenesis of oral-gut-liver axis between periodontitis and nonalcoholic fatty liver disease.

Periodontitis and nonalcoholic fatty liver disease (NAFLD) are two prevalent non-communicable diseases affecting people worldwide. The delicate interplay between oral microbiome, intestinal barrier, immune system, and liver is susceptible to disruption by environmental and genetic factors which could result in the onset of systemic diseases. The oral-liver and liver-gut axes have been proposed as the possible mechanisms to explain the links among these factors. Many evidences are mounting to support the role of imbalanced interactions between microbiota and immune system in the development of immune-mediated diseases. The emerging concept of the oral-gut-liver axis is gaining recognition as a means to explore the interconnections among NAFLD, periodontitis, and gut dysbiosis. There is substantial evidence indicating that oral and gut dysbiosis are the significant risk factors for liver disease. Therefore, the role of inflammatory mediators in linking these organs cannot be overlooked. Understanding these complex relationships is crucial in the development of effective strategies for the prevention and management of liver diseases.

Clinical and Metabolic Characteristics of Hyperuricemia with Risk of Liver Fibrosis: A Cross-Sectional Study.

The role of serum uric acid (SUA) in the role of advanced fibrosis is not fully explored. The study assesses the risk of advanced fibrosis according to SUA in an Asian population with a total of 3612 subjects enrolled in one health management center between 2006 and 2008. The fibrosis-4 score was used for the prediction of the high risk of advanced fibrosis. SUA scores higher than 7.6 mg/dL in men and 6.6 mg/dL in women were defined as hyperuricemia. A proportional odds model was used to assess cumulative risks of advanced fibrosis. The prevalence of high risk of advanced fibrosis was 2.5% in the hyperuricemia group and 0.6% in the normal SUA group (p < 0.001). After adjustment for confounding factors, the odds ratios (OR) for more severe advanced fibrosis were 1.37 (95% confidence interval [CI]: 1.07−1.78) in the hyperuricemia group. Hyperuricemia only increased the risk of advanced fibrosis in the non-T2DM group (OR, 1.29; 95% CI, 1.04 to 1.74) instead of T2DM group (OR, 1.85; 95% CI, 0.97 to 3.53). SUA is a risk factor for a higher risk of advanced fibrosis, with the disease likely progressing from a steatotic to a fibrotic picture. The focus should be more emphasized in non-T2DM groups.

Association between obesity and chronic periodontitis: A nationwide population-based cohort study in Taiwan.

ABSTRACT: Previous studies have suggested that obesity might be associated with chronic periodontitis (CP); however, no clear conclusions have been reached so far. In this retrospective cohort study, we aimed to investigate the association between obesity and CP by using a large population-based dataset in Taiwan.A population-based retrospective cohort study was conducted using the Longitudinal Health Insurance Database 2010 (LHID2010) derived from the National Health Insurance Research database in Taiwan, from 2000 to 2013. Obesity and non-obesity groups were matched with sex, age, urbanization level, socioeconomic status, and the related comorbidities by using the propensity score method at a 1:2 ratio.An obese cohort (n = 4140) and a non-obese cohort (n = 8280) were included in this study, with an average age of 41.7 ±â€Š13.8 years and 42.0 ±â€Š14.0 years, respectively. The risk of CP for the patients with obesity was 1.12-fold compared with those without obesity (hazard ratio, 1.12; 95% confidence interval, 1.01-1.25). In the subgroup analysis according to age and sex, the hazard ratio of CP were 1.98 (95% confidence interval, 1.22-3.22) in the subgroup of age equal to or older than 65 years. The risk of CP showed no difference between obesity and non-obesity groups in both sex.This population-based cohort study demonstrated that obesity was associated with the development of CP in Taiwan.

Metabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat.

BACKGROUND AND AIM: Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population. METHODS: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. RESULTS: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79). CONCLUSION: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level.

Enhanced home palliative care could reduce emergency department visits due to non-organic dyspnea among cancer patients: a retrospective cohort study.

BACKGROUND: Dyspnea is a common trigger of emergency department visits among terminally ill and cancer patients. Frequent emergency department (ED) visits at the end of life are an indicator of poor-quality care. We examined emergency department visit rates due to dyspnea symptoms among palliative patients under enhanced home palliative care. METHODS: Our home palliative care team is responsible for patient management by palliative care specialists, residents, home care nurses, social workers, and chaplains. We enhanced home palliative care visits from 5 days a week to 7 days a week, corresponding to one to two extra visits per week based on patient needs, to develop team-based medical services and formulate standard operating procedures for dyspnea care. RESULTS: Our team cared for a total of 762 patients who exhibited 512 ED visits, 178 of which were due to dyspnea (mean ± SD age, 70.4 ± 13.0 years; 49.4% male). Dyspnea (27.8%) was the most common reason recorded for ED visits, followed by pain (19.0%), GI symptoms (15.7%), and fever (15.3%). The analysis of Group A versus Group B revealed that the proportion of nonfamily workers (42.9% vs. 19.4%) and family members (57.1% vs. 80.6%) acting as caregivers differed significantly (P < 0.05). Compared to the ED visits of the Group A, the risk was decreased by 30.7% in the Group B (P < 0.05). CONCLUSIONS: This study proves that enhanced home palliative care with two additional days per week and formulated standard operating procedures for dyspnea could significantly reduce the rate of ED visits due to non-organic dyspnea during the last 6 months of life.

Metabolic profiles and fibrosis of nonalcoholic fatty liver disease in the elderly: A community-based study.

BACKGROUND AND AIMS: There are sparse data on the epidemiology of fatty liver in the elderly Asian population. We evaluated for predictors of fatty liver and high risk of advanced fibrosis in a community-based elderly population. METHODS: A total of 1091 participants (mean age was 74.6 ± 6.3 years) were enrolled from 2017 to 2018. Subjects with age younger than 65 years, alcoholism, and history of hepatitis B and hepatitis C were excluded. Fatty liver was diagnosed with abdominal ultrasound by using ultrasonographic fatty liver indicator, a semi-quantitative measurement grading the severity (normal, mild, and moderate-to-severe). Fibrosis-4 score was used for the prediction of the high risk of advanced fibrosis. Using a multivariable logistic regression model, we identified predictors of fatty liver and high risk of advanced fibrosis. RESULTS: In this ambulatory elderly Asian population, the prevalence of fatty liver is 41.9% and of high risk of advanced fibrosis is 12.3%. The prevalence of fatty liver decreases (44.5% to 31.8%), and the high risk of advanced fibrosis increases (3.9% to 27.0%) with aging significantly (both P < 0.05). Metabolic syndrome is a risk factor for fatty liver (odds ratio [OR], 3.19; 95% CI, 2.41-4.22) but not for high risk of advanced fibrosis (OR, 0.67; 95% CI, 0.41-1.08). Hypertriglyceridemia decreases the risk for high risk of advanced fibrosis (OR, 0.53; 95% CI, 0.33-0.87). CONCLUSION: Fatty liver is prevalent in the ambulatory elderly Asian population, affecting over 40% of this population. Age is a risk factor for high risk of advanced fibrosis, with the disease likely progressing from a steatotic to a fibrotic picture with age.

Association between Peptic Ulcer Disease and Periodontitis: A Nationwide Population-Based Case-Control Study in Taiwan.

Previous studies have suggested that peptic ulcer disease (PUD) including stomach and duodenal ulcers might be associated with periodontitis (PD); however, no clear conclusions have been reached thus far. In this retrospective case-control study, we aimed to investigate the association between PUD and PD by using a large population-based dataset in Taiwan. A population-based retrospective case control study was conducted using the Longitudinal Health Insurance Database 2010 (LHID2010) derived from the National Health Insurance Research database (NHIRD) in Taiwan from 2000 to 2013. The case and control group were matched with gender, age, urbanization level, socioeconomic status, and Charlson comorbidity index (CCI) by using the propensity score method at a 1:1 ratio. A total of 177,240 cases and 177,240 control patients were included in this study, with an average age of 46.96 ± 11.76 years. The risk of PUD for patients diagnosed with PD was 1.15-fold when compared with those without PD (OR, 1.15; 95% CI, 1.12⁻1.18). This population-based case control study demonstrated a significantly positive association between PUD and PD in Taiwan.

Inflammatory bowel disease as a risk factor for periodontitis under Taiwanese National Health Insurance Research database.

BACKGROUND/PURPOSE: Inflammatory bowel disease (IBD), comprised Crohn's disease and ulcerative colitis, is a mucosal immune response that affects gastroenterological tract. The association between IBD and periodontitis was inconclusive. In this study, we aimed to investigate the association between IBD and periodontitis by using a register-based dataset. MATERIALS AND METHODS: The dataset conducting in this retrospective cohort study was obtained from the National Health Insurance Research database (NHIRD) in Taiwan. For IBD group, conditionally selected control subjects were matched in 1:4 ratio from general population. The risk of periodontitis among IBD group comparing with non-IBD group was calculated by multivariable Cox proportional hazards model. RESULTS: In IBD cohort, 27 IBD patients (7 Crohn's disease and 20 ulcerative colitis) with catastrophic illness registry were identified. 108 controls were selected as non-IBD cohort. The median follow-up period was 3.00 years in the IBD group and 3.15 years in the non-IBD group. The cumulative incidence of IBD was 4.32 per 100,000 persons. After adjusting for several confounding factors, IBD group had higher risk for developing periodontitis than non-IBD group (adjusted HR: 1.82; 95% CI: 1.09-3.03). To further stratification with subtype, Crohn's disease group had significantly higher risk of periodontitis (adjusted HR: 3.95; 95% CI: 1.59-9.82). CONCLUSIONS: Taken together, this retrospective cohort study showed that patients with IBD increase risk of having periodontitis comparing with non-IBD group, especially in Crohn's disease subgroup.

Association of intercellular adhesion molecule-1 single nucleotide polymorphisms with hepatocellular carcinoma susceptibility and clinicopathologic development.

Intercellular adhesion molecule-1 (ICAM-1) is a human protein encoded by the ICAM-1 gene and is typically expressed on endothelial cells and immune cells. ICAM-1 is associated with episode, growth, invasion, and metastasis of hepatocellular carcinoma (HCC). However, the association between ICAM-1 genetic variants and the risk of HCC is undetermined. In this study, we investigated the potential associations of ICAM-1 single nucleotide polymorphisms (SNPs) with susceptibility to HCC and its clinicopathological characteristics. A total of 918 participants, including 613 controls participants and 305 patients with HCC, were selected for the analysis of ICAM-1 SNPs (rs3093030, rs5491, rs281432, and rs5498) by using real-time PCR genotyping. After adjusting for covariants of age, sex, and alcohol consumption, 125 smoker patients with HCC carrying at least one G genotype (AG and GG) in rs5498 were observed to have a higher HCC risk compared with 231 smoker control participants carrying the wild-type allele AA (adjusted odds ratio (AOR), 1.713; 95 % confidence interval (CI), 1.091-2.690; P = 0.019). However, patients who possess at least one polymorphic allele of rs5498 are less prone to develop vascular invasive (AOR, 0.309; 95 % CI, 0.103-0.926; P = 0.036). The results suggest that the genetic polymorphism in ICAM-1 rs5498 SNPs with genotype AG and GG is associated with HCC risk among smokers. Moreover, gene and environment interactions of ICAM-1 rs5498 polymorphisms might alter susceptibility to liver cancer. Therefore, ICAM-1 rs5498 may serve as a marker to predict the vascular invasion risk in smoker patients with HCC.

Helicobacter Pylori Infection is Positively Associated with Metabolic Syndrome in Taiwanese Adults: a Cross-Sectional Study.

BACKGROUND: Helicobacter pylori infection and metabolic syndrome have been reported to be positively associated. However, only a few studies have focused on this issue, and H. pylori serum antigen was used to diagnose infection in most of them. We aimed to investigate the association between metabolic syndrome factors and H. pylori infection, as diagnosed via a (13)C-urea breath test. MATERIALS AND METHODS: This cross-sectional study consisted of 3578 subjects (18-64 years old) enrolled from one health management center between 2008 and 2013. H. pylori infection was defined as a positive urea breath test. The risk of metabolic syndrome from H. pylori infection was assessed using a multiple logistic regression model. RESULTS: The prevalence of the H. pylori was similar in both genders (20.6% in men and 19.7% in women). H. pylori -infected participants had significantly higher body mass index, fasting glucose, low-density lipoprotein, and triglycerides, and lower high-density lipoprotein (p < 0.05), than uninfected ones (p < 0.05). The prevalence of metabolic syndrome was higher in H. pylori -infected subjects than uninfected ones (men: 12.4% vs. 7.4%, p < 0.001; women: 7.4% vs. 2.5%, p < 0.001). Furthermore, H. pylori infection prevalence increased with metabolic score (P for trend <0.001, both sexes). Moreover, the association between metabolic syndrome and UBT positivity was significant in females (OR 1.91, 95% CI:1.03-3.53), but only borderline significant in males (OR 1.38, 95% CI: 0.97-1.95). CONCLUSION: H. pylori infection is positively associated with metabolic syndrome, especially in females. The causal relationship between H. pylori infection and metabolic syndrome warrants further investigation.

A4383C and C76G SNP in Cathepsin B is respectively associated with the high risk and tumor size of hepatocarcinoma.

Single nucleotide polymorphism (SNP) in some genes is a candidate for having or developing a cancer. Cathepsin B (CTSB) is considered to be the biomarker of cancers. The study aimed to evaluate the impacts of three SNPs in CTSB gene on the risk and progress of hepatocellular carcinoma (HCC). The SNPs of CTSB C76G (rs12338), CTSB A4383C (rs13332), and CTSB A8422G (rs8898) from 135 patients with HCC and 520 control participants in Taiwan were determined by real-time PCR. Through analyzing by statistics, we found that the polymorphism of rs13332 was significantly associated to the risk of HCC cancer; a significantly high frequent tumor size development was observed in HCC patients carrying rs12338 polymorphic genotype than those carrying ancestral genotype. The SNPs of rs12338, rs13332, and rs8898 were irrelevant to the frequencies of HCC clinical status and the levels of HCC clinicopathological markers. In conclusions, CTSB A4383C SNP is observed modestly more often in patients who developed HCC than in healthy controls and might be associated with the risk of HCC. The association between CTSB C76G SNP and greater tumor size may warrant further study in regards to the biology of HCC.

Semi-automatic segmentation and classification of Pap smear cells.

Cytologic screening has been widely used for detecting the cervical cancers. In this study, a semiautomatic PC-based cellular image analysis system was developed for segmenting nuclear and cytoplasmic contours and for computing morphometric and textual features to train support vector machine (SVM) classifiers to classify four different types of cells and to discriminate dysplastic from normal cells. A software program incorporating function, including image reviewing and standardized denomination of file names, was also designed to facilitate and standardize the workflow of cell analyses. Two experiments were conducted to verify the classification performance. The cross-validation results of the first experiment showed that average accuracies of 97.16% and 98.83%, respectively, for differentiating four different types of cells and in discriminating dysplastic from normal cells have been achieved using salient features (8 for four-cluster and 7 for two-cluster classifiers) selected with SVM recursive feature addition. In the second experiment, 70% (837) of the cell images were used for training and 30% (361) for testing, achieving an accuracy of 96.12% and 98.61% for four-cluster and two-cluster classifiers, respectively. The proposed system provides a feasible and effective tool in evaluating cytologic specimens.

The impact of IGF-I gene polymorphisms on coronary artery disease susceptibility.

BACKGROUND: Coronary artery disease (CAD) was the second leading cause of death for the past 3 years in Taiwan. The insulin-like growth factor (IGF) system is considered a new risk factor of CAD because investigations show that the levels and bioactivity of IGF-I and IGFBP-3 (where IGFBP is insulin-like growth factor-binding protein) may be involved in elevating the risk of CAD. This study investigated the relationships among IGF-I +1770, IGF-I +6093, and IGFBP-3 -202 genetic polymorphisms and CAD in the Taiwanese population. METHODS: A total of 581 subjects, including 390 non-CAD controls and 191 patients with CAD, were recruited and the isolated DNA was subjected to real-time polymerase chain to evaluate the effects of these three polymorphic variants on CAD. RESULTS: Our results showed a significant association between the IGF-I +1770 gene polymorphism and increased risk of CAD. Furthermore, CAD patients with a minimum of one mutant C allele, T/C or C/C, in IGF-I +1770 gene polymorphism had significantly high blood pressure including systolic blood pressure (SBP; P = 0.025) and diastolic blood pressure (DBP; P = 0.004), compared to CAD patients with T/T homozygotes. Moreover, CAD patients with a minimum of one mutant A allele, G/A or A/A, in the IGF-I +6093 gene polymorphism had a 1.695-fold elevated risk of congestive heart failure (CHF), compared to CAD patients with the G/G homozygote. CONCLUSIONS: Polymorphism of IGF-I +1770 was associated with increased CAD risk. In CAD patients, the contributions of IGF-I +1770 and +6093 could be through the effect on blood pressure in CAD patients.

Pseudo three-dimensional vision-based nail-fold morphological and hemodynamic analysis.

In this study, a Pseudo three-dimensional Vision-based Nail-fold Morphological and Hemodynamic Analysis (PTVNMHA) is proposed to automatically extract morphological/hemodynamic features from a microscopic nail-fold image sequence, reconstruct the corresponding pseudo three-dimensional microvascular models, and visualize the dynamic blood flow in the model constructed. The morphological features extracted include the number, width/height, density, arteriolar limb caliber, curved segment caliber, venular limb caliber, blood color, tortuosity, and width of the curved segment of capillaries. The hemodynamic features identified are blood flow velocity and blood flow rate. All are significant pathological indicators with a spatial precision up to 1.6 µm. The diameters of cross-sections along the centerlines of capillaries are identified and employed to reconstruct the pseudo three-dimensional microvascular surface meshes. The microscopic image sequence acquired is mapped to the corresponding microvascular model constructed to perform dynamic blood flow visualization. Compared with laser Doppler velocimetry, PTVNMHA can derive blood flow velocities for each capillary across the microscopic range separately in much higher precision and obtain diversified morphological and hemodynamic features of capillaries with a low-cost equipment setup. In addition to the blood flow velocity, blood flow rate, which keeps almost constant no matter where the measuring position is in a capillary, has also been measured and proposed as a useful feature to discriminate patients with hypertension from the normal with great significance (p<0.001). In the future, large scale experiments will be conducted to diagnose patients with anemia as well as patients with essential and secondary hypertension to verify effectiveness of the PTVNMHA system.