Discovering Hair Biomarkers of Alzheimer's Disease Using High Resolution Mass Spectrometry-Based Untargeted Metabolomics.

Hair may be a potential biospecimen to discover biomarkers for Alzheimer's disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol/phosphate-buffered saline 50/50 (v/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD.

Using social media data in diabetes care: bridging the conceptual gap between health providers and the network population.

BACKGROUND: Patients with diabetes who have poor health literacy about the disease may exhibit poor compliance and thus subsequently experience more complications. However, the conceptual gap of diabetes between health providers and the general population is still not well understood. Decoding concerns about diabetes on social media may help to close this gap. METHODS: Social media data were collected from the OpView social media platform. After checking the quality of the data, we analyzed the trends in people's discussions on the internet using text mining. The natural language process includes word segmentation, word counting and counting the relationships between the words. A word cloud was developed, and clustering analyses were performed. RESULTS: There were 19,565 posts about diabetes collected from forums, community websites, and Q&A websites in the summer (June, July, and August) of 2017. The three most popular aspects of diabetes were diet (33.2%), life adjustment (21.2%), and avoiding complications (15.6%). Most discussions about diabetes were negative. The negative/positive ratios of the top three aspects were avoiding complications (7.60), problem solving (4.08), and exercise (3.97). In terms of diet, the most popular topics were Chinese medicine and special diet therapy. In terms of life adjustment, financial issues, weight reduction, and a less painful glucometer were discussed the most. Furthermore, sexual dysfunction, neuropathy, nephropathy, and retinopathy were the most worrisome issues in avoiding complications. Using text mining, we found that people care most about sexual dysfunction. Health providers care about the benefits of exercise in diabetes care, but people are mostly concerned about sexual functioning. CONCLUSION: A conceptual gap between health providers and the network population existed in this real-world social media investigation. To spread healthy diabetic education concepts in the media, health providers might wish to provide more information related to the network population's actual areas of concern, such as sexual function, Chinese medicine, and weight reduction.

Association between Outpatient Visits and Initiating Medication among Elderly Patients after an Osteoporotic Vertebral Fracture.

PURPOSE: A treatment gap exists in vertebral fracture (VF) patients. An outpatient visit is a necessary step to initiate treatment. The study aimed to evaluate factors associated with an outpatient visit following a VF diagnosis, and the association between the interval of an outpatient visit after VF diagnosis and its impact on prescribing of anti-osteoporosis medications (AOMs). METHODS: Subjects 65 years and older from Tianliao Township in Taiwan with newly diagnosed VF between 2009 and 2010 were included. Information about outpatient visits and AOMs prescriptions were derived from the National Health Insurance Research database and followed up for 2 years. Factors associated with outpatient visits and the initiation of AOMs were assessed using the multivariable Cox proportional regression model analysis. The receiver operating characteristic curve (ROC curve) was analyzed to determine the predictive effects of the interval between an outpatient visit following the diagnosis of a new VF on initiating AOMs and the potential optimal cutoff point. RESULTS: Of 393 participants, 42.2% had outpatient visits within 2 years after a new VF diagnosis, for which the mean interval was 4.8 ± 4.8 months. Patients who were female and reported a current use of supplements were positively associated with visits after a new VF diagnosis, but the bone mineral density (BMD) T-score was negatively associated with visits. Furthermore, 140 (35.6%) patients had initiated AOMs within 2 years after the diagnosis of a new VF. It was found that a higher BMD T-score and a longer interval between an outpatient visit following diagnosis was negatively associated with initiation of AOMs. The ROC curve analysis showed outpatient visits within 3 months after a VF diagnosis had the highest Youden index and maximum area under the curve. CONCLUSIONS: Patients who were female, were currently taking supplements, and those who had a lower BMD T-score were more likely to visit doctors after being diagnosed with a new VF. Furthermore, a lower BMD T-score and a shorter interval, within 3 months and not more than 8 months, between an outpatient visit following the diagnosis of VF increased the likelihood of being prescribed AOMs.

Body-Weight Gain in Women During Smoking Cessation Is a Sex-Specific Predictor of 6-Month Abstinence: A Retrospective Cohort Study.

Background: Smoking behavior differs between the sexes. Weight control is one of the main reasons leading to tobacco abuse in women but not in men. Studies on the predictive factors of cessation failure between sexes are scarce. This study is aim to investigate whether there are sex differences in the effect of weight gain on smoking cessation rate. Methods: Participants in the smoking-cessation program at a Medical Center in Taiwan between 2018 and 2019 were included. Details of age, sex, comorbidities, depression screening, nicotine dependence, body weight, and cessation medications of the participants were collected. The participants were classified based on their sex, and multivariable logistic regression analyses were conducted. Multivariable logistic regression analyses were performed for sensitivity analysis after stratifying the participants according to their weight loss (weight loss ≥ 1.5 kg and weight loss ≥ 3.0 kg). Results: A total of 1,475 participants were included. The body-weight gain in women was associated with failed abstinence (adjusted odds ratio (OR): 3.10, 95% CI: 1.10-9.04). In contrast, body-weight gain in men was associated with successful 6-month prolonged abstinence (adjusted OR: 0.77, 95% CI: 0.61-0.98). The adjusted ORs for any body-weight loss, body-weight loss ≥1.5 kg, and body-weight loss ≥3.0 kg were 0.28 (95% CI: 0.09-0.88), 0.14 (95% CI: 0.03-0.55), and 0.03 (95% CI: 0.01-0.42), respectively. Conclusion: Body-weight gain in women during a hospital-based smoking-cessation program is associated with abstinence failure. Further multicenter studies, including participants of different races and cultural backgrounds, are warranted.

Association of Egr-1 and autophagy-related gene polymorphism in men with chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Autophagy is important in cellular homeostasis and control of inflammatory immune response. Increased autophagy has recently been associated with increased cell death and chronic obstructive pulmonary disease (COPD) pathogenesis. Two autophagy regulator genes have been identified: Egr-1 (early growth response), associated with different phenotype expressions in asthma; and, Atg16L1 (autophagy related 16-like 1), a candidate gene responsible for susceptibility to chronic inflammatory diseases. We will explore the role of the Egr-1 and Atg16L1 gene polymorphisms in COPD. METHODS: The genotypes of 151 male smoking patients with COPD and 100 male smoking controls were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the Egr-1 (-4071 A → G) rs7729723 and Atg16L-1 (T300A) rs2241880 variants. RESULTS: The G allele of the Egr-1 gene polymorphism was associated with an increased risk of developing COPD [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.15-3.72], and participants with the G allele polymorphism (GG and GA genotypes) had a 2.56-fold higher risk (OR, 2.56; 95% CI, 1.31-5.16) of having COPD than those homozygous for the A allele [35.8% (54/151) vs. 24.0% (24/100); p = 0.007]. Participants with the A allele of the Atg16L1 gene polymorphism (AA and AG genotypes) had a 3.34-fold higher risk (OR, 3.34; 95% CI, 1.32-8.97) of having COPD than those homozygous for the G allele [93.4% (141/151) vs. 81.0% (81/100); p = 0.013]. CONCLUSION: The Egr-1 and Atg16L1 genes' polymorphisms were significant risk factors for susceptibility to COPD. These results demonstrate that autophagy regulator genetic mutations are associated with COPD in male smokers.

HBsAg expression of liver correlates with histological activities and viral replication in chronic hepatitis B.

INTRODUCTION: The intrahepatic hepatitis B surface antigens (HBsAg) expression is related to disease progression of chronic hepatitis B. We examined the features of intrahepatic HBsAg expression. MATERIAL AND METHODS: A total of 181 patients with e antigen positive chronic hepatitis B were enrolled. Patterns and semi-quantitative measurement of intrahepatic HBsAg expression were analyzed. The association of intrahepatic hepatitis HBsAg expression with clinical, viral, and histological characteristics was evaluated. RESULTS: Higher necroinflammation grade and greater fibrosis stage accompanied with lower serum HBV DNA and HBsAg levels were observed in patients with type II ground glass hepatocytes and 2+/3+ scales of intrahepatic HBsAg expression. Basal core promoter T1762/A1764 mutations were strongly associated with the pattern of type II ground glass hepatocytes expression (P < 0.001) and higher level of HBsAg expression (9.3 ± 8.0% vs. 4.3 ± 5.0%, P = 0.008). In multivariate analysis, basal core promoter mutations (Odds ratio: 6.356, 95% confidence interval: 1.204 ~ 33.356, P = 0.029) was associated with 2+/3+ scale of HBsAg expression. CONCLUSION: Both pattern and levels of intrahepatic HBsAg expression were associated with severity of liver disease in e antigen positive chronic hepatitis B. Strong relationship between intrahepatic HBsAg expression and basal core promoter 1762/A1764 mutations indicated that HBsAg expression may be the histological manifestation of hepatitis B virus genomic evolution under host immune surveillance.

High uric acid level associated with increased arterial stiffness in apparently healthy women.

OBJECTIVES: Increased serum uric acid level is regarded as a risk factor for cardiovascular disease, and found to be associated with increased arterial stiffness. While previous studies investigated the relationship between serum uric acid and arterial stiffness, most did not exclude the confounding factors, such as history or medications of hypertension, diabetes, dyslipidemia and hyperuricemia. The aim of this study was to explore the association of uric acid with arterial stiffness in an apparently healthy population. METHODS: This cross-sectional study enrolled 7025 participants during health examinations from October 2006 to August 2009. A total of 5150 apparently healthy subjects were enrolled in the final analysis. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV). Uric acid was divided into quartiles in men (Q1: 59.5-333.1, Q2: 333.2-380.7, Q3: 380.8-428.3, Q4: 428.4-701.9 µmol/L) and women (Q1: 113.0-236.4, Q2: 236.5-273.6, Q3:273.7-315.2, Q4:315.3-585.0 µmol/L). RESULTS: Uric acid level was significantly different between women with and without increased arterial stiffness, but not in men. ANCOVA showed that women with Q3 and Q4 of serum uric acid had greater baPWV level. In multiple logistic regression analysis, Q4 (OR = 1.53, 95% CI = 1.04-2.26) of uric acid was positively associated with increased baPWV in women, but not in men. In addition, age and high blood pressure were also independently associated factors of increased arterial stiffness for both genders. CONCLUSION: In apparently healthy women, high-normal serum uric acid or greater was associated with greater risk of arterial stiffness. However, the relationship between hyperuricemia and increased arterial stiffness was not significant in men.

The relationship between different glycemic statuses and colon polyps in a Taiwanese population.

BACKGROUND: While diabetes is considered as a risk factor for colorectal cancer, there are few studies that address the association between glycemic statuses and different colon polyps, ranging from non-neoplastic polyps to advanced adenomatous polyps. METHODS: A total of 6,348 participants, consisting of 3,777 men and 2,571 women, with a mean age of 50.5 years, were included for final analysis after excluding subjects with a past history of colorectal cancer, colon polyps/polypectomy, familial adenomatous polyposis, and colorectomy, or missing data. Diabetes and pre-diabetes were defined using the 2011 American Diabetes Association criteria. Subjects were classified into four groups: polyp-free, non-neoplastic polyps, non-advanced and advanced adenomatous polyps. RESULTS: There were significant differences in the prevalence of diabetes and pre-diabetes among groups with different kinds of colon polyps. In addition, significant differences were also noted in age, total cholesterol, body mass index, triglyceride, high density lipoprotein-cholesterol, fasting plasma glucose, and the prevalence of male gender, hypertension, obesity, current smoking and alcohol drinking among groups. In the multinomial logistic regression analyses, diabetes was related to both non-advanced and advanced adenomatous polyps, while pre-diabetes was only related to non-advanced adenomatous polyps. In addition, age ≥65 years and male gender were associated with both non-advanced and advanced adenomatous polyps, while hypertension and current smoking were independently related to advanced and non-advanced adenomatous polyps, respectively. CONCLUSIONS: Diabetes, but not pre-diabetes, was associated with a higher risk of advanced adenomatous polyps. In addition, both diabetes and pre-diabetes were important correlates of non-advanced adenomatous polyps.

Short sleep duration associated with a higher prevalence of metabolic syndrome in an apparently healthy population.

OBJECTIVE: To examine the association between sleep duration and metabolic syndrome in an apparently healthy Chinese population. METHOD: The baseline data were collected from a health examination center in Tainan, Taiwan, from October 1, 2006, to August 31, 2009. A total of 7100 adults were recruited. Subjects were classified into three groups according to their sleep duration: short (<6 h), normal (6-8 h), and long sleepers (>8 h). RESULTS: There were significant differences in age, gender, education level, fasting plasma glucose, and the proportion of smoking status and exercise frequency among different sleep groups. Based on multiple logistic regression, short sleepers were positively associated with metabolic syndrome (OR=1.28, 95% CI: 1.01-1.63) in males but not in females (OR=1.04, 95% CI: 0.72-1.51). Long sleepers were not related with metabolic syndrome in both genders. Short sleep duration was independently related to hyperglycemia (OR=1.39, 95% CI: 1.10-1.74) also in males only. Other components such as hypertriglyceridemia, low high density lipoprotein cholesterol, high blood pressure and central obesity were not associated with short sleep duration. CONCLUSION: Males with short sleep duration are positively associated with metabolic syndrome and they also exhibited a higher prevalence of hyperglycemia.

The role of bactericidal/permeability-increasing protein in men with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Bactericidal/permeability-increasing protein (BPI) is a member of the pattern recognition receptors of the innate immune system. Recently, an association between genetic polymorphism in the BPI gene and a risk of airflow decline after transplantation was demonstrated, but whether these findings are reproducible in nontransplantation populations, such as those with COPD, is still unknown. The aim of this study is to explore the role of BPI in COPD. METHODS: The genotypes of 107 patients with COPD and 110 control subjects were evaluated by polymerase chain reaction and polymorphism analysis of the BPI genes and ELISA analysis of the plasma BPI level. All subjects were men over 40 years old who smoked. RESULTS: BPI mutation PstI (T→C) polymorphism in intron 5 was associated with an increased risk of developing COPD (OR 3.73, 95%CI: 1.62-9.10), and the frequency was significantly increased in the COPD group compared with the control group (26/107 [24.3%] vs 12/110 [10.9%], p = 0.002). In addition, COPD patients exhibited a decreased plasma level of BPI compared with the control group (10.6 ± 2.2 vs 23.4 ± 2.1 ng/ml, p < 0.0001). CONCLUSIONS: BPI mutation (PstI in intron 5) and a decreased plasma BPI level were significant risk factors in susceptibility to COPD. These results demonstrate that BPI genetic mutation and impaired BPI production or release may result in airflow obstruction in smokers.

Polymorphism of microsomal epoxide hydrolase is associated with chronic obstructive pulmonary disease and bronchodilator response.

BACKGROUND/PURPOSE: Microsomal epoxide hydrolase (EPHX) is an important enzyme that metabolizes harmful reactive epoxides from smoking. Genetic variations of this enzyme are thought to increase the risk of developing chronic obstructive pulmonary disease (COPD). The aim of this study was to confirm and advance our knowledge of the role of this genetic variation in COPD. In addition, the association between this gene and important COPD-related phenotype bronchodilator responses (BDRs) was studied. METHODS: This was a hospital-based case-control study. The EPHX1 genetic mutations of 105 smokers with COPD and 103 control smokers without COPD were evaluated by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. The association of genetic mutations and COPD phenotypes was also studied. RESULTS: Subjects with EPHX1 113 (His(113)/His(113)) homozygote mutation had a strong correlation with COPD (odds ratio: 2.7, 95% confidence interval: 1.5-5.2). In addition, compared with other genotypes, the His(113) homozygote mutation patients had significantly lower BDRs, as shown by the absolute and percentage changes from baseline, in COPD patients (91.7 ± 12.5 mL vs. 141.6 ± 15.1 mL, p = 0.01 and 8.3 ± 1.2% vs. 13.4 ± 1.4%, p = 0.006). CONCLUSION: A strong correlation between the EPHX1 113 mutant homozygote and smoking-related COPD was noted. This genetic polymorphism was also associated with lower BDRs in COPD patients.

Sleep duration is a potential risk factor for newly diagnosed type 2 diabetes mellitus.

U-shaped patterns have been observed for the relationship between sleep duration and diabetes. In addition, prediabetes is associated with the risk of cardiovascular diseases and diabetes. However, there are few studies investigating the relationship between sleep duration and prediabetes/newly diagnosed diabetes. The aim of this study is to examine the relationship between sleep duration and prediabetes/newly diagnosed diabetes in a Taiwanese population. After excluding the subjects with a high risk of obstructive sleep apnea, those with a positive history of diabetes, or those taking hypnotic drugs, a total of 3470 adults were recruited from a health checkup center. Each subject completed a self-administrated structured questionnaire on sleep duration and lifestyle factors. Prediabetes/diabetes was defined following the definition of the American Diabetes Association. Subjects with different sleep durations were classified into short (<6.0 hours), normal (6.0∼8.49 hours), and long sleepers (≥8.5 hours). The proportion of subjects with normal glucose tolerance, prediabetes, and newly diagnosed diabetes was 71.9%, 22.9%, and 5.2%, respectively. There were significant differences in age, sex, weight, education level, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, alcohol and coffee drinking habits, family history of diabetes, and sleep duration among the 3 glycemic groups. In multinomial regression, both short and long sleepers had a higher risk of newly diagnosed diabetes; and the odds ratio were 1.55 (95% confidence interval, 1.07-2.24) and 2.83 (1.19-6.73), respectively. However, sleep duration was not found to relate to prediabetes. In conclusion, both short and long sleep durations were independently associated with newly diagnosed diabetes, but not with prediabetes.

Population-based study on the prevalence and risk factors of orthostatic hypotension in subjects with pre-diabetes and diabetes.

OBJECTIVE: The aim of this study was to investigate the relationship between pre-diabetes and orthostatic hypotension and to examine the prevalence and correlates of orthostatic hypotension in community dwellers with normal glucose tolerance (NGT), pre-diabetes, and diabetes. RESEARCH DESIGN AND METHODS: All participants were classified as having NGT (n = 1,069), pre-diabetes (n = 412), or diabetes (n = 157). Orthostatic hypotension was defined as a decline in systolic/diastolic blood pressure of > or =20/10 mmHg when an individual changed from a supine to a standing position. The cardiovagal response to standing was the ratio between the longest RR interval around beat 30 and the shortest RR interval around beat 15 after standing (30 max-to-15 min ratio). RESULTS: The prevalences of orthostatic hypotension were 13.8, 17.7, and 25.5% in subjects with NGT, pre-diabetes, and diabetes, respectively. For all subjects, age, diabetes, hypertension, and a decreased 30 max-to-15 min ratio, but not pre-diabetes, were independently associated with orthostatic hypotension. Age, hypertension, and 30 max-to-15 min ratio were the correlates of orthostatic hypotension in NGT subjects. Age and hypertension were related to orthostatic hypotension in pre-diabetic subjects. A1C and hypertension were the determinants of orthostatic hypotension in diabetic subjects. Supine blood pressure was related to orthostatic hypotension in all subjects and subgroups. CONCLUSIONS: Pre-diabetic subjects do not have a higher risk of orthostatic hypotension than subjects with NGT, although the risk of orthostatic hypotension is higher in diabetic subjects. Hypertension and supine blood pressure were risk factors for orthostatic hypotension in both pre-diabetic and diabetic subjects. Age and A1C were the correlates of orthostatic hypotension in pre-diabetic and diabetic subjects, respectively. The cardiovagal response to standing is an important determinant of orthostatic hypotension in subjects with NGT but not in pre-diabetic and diabetic subjects.

Seroprevalence of hepatitis E virus infection among institutionalized psychiatric patients in Taiwan.

BACKGROUND: Hepatitis E virus infection (HEV) remains unclear in institutionalized psychiatric patients. OBJECTIVES: To investigate the prevalence and risk factors of HEV infection in a psychiatric institution in Taiwan. STUDY DESIGN: A total of 754 patients with psychiatric disorders were enrolled in the study. Clinical features, review of patient charts, and interviews with families were recorded for analysis. Antibody to HEV was tested using a commercial enzyme-linked immunosorbent assays. RESULTS: The prevalence of HEV infection in institutionalized patients was as high as 14.5%. Males had higher prevalence than females. It was also found prevalence increased significantly by age group. When compared with patients 30 years old or less, those in the 31-40 year old age group had an odds ratio of 4.89 [95% confidence interval (CI), 1.15-20.82], 41-50 years old of 6.30 (95% CI, 1.48-26.83), and 50 years or older of 6.20 (95% CI, 1.44-26.74). In multivariate logistic regression analysis, age and male gender were the independent risk factors. CONCLUSIONS: Institutionalized psychiatric patients had higher prevalence of HEV infection. In addition, there was an age-related increase in exposure to HEV with males that had a higher HEV seropositivity.

Relationship among habitual tea consumption, percent body fat, and body fat distribution.

OBJECTIVE: To disclose the possible relationship between habitual tea consumption and changes in total body fat and fat distribution in humans. RESEARCH METHODS AND PROCEDURES: A cross-sectional survey of 1,210 epidemiologically sampled adults (569 men and 641 women) were enrolled in our study. Tea consumption and other lifestyle characteristics were obtained by structured questionnaires. Percent body fat (BF%) was measured using bioelectrical impedance analysis. Body fat distribution was assessed using waist-to-hip ratio (WHR). RESULTS: Among the 1,103 analyzed subjects, 473 adults (42.9%) consumed tea once or more per week for at least 6 months. The habitual tea drinkers were male-dominant, more frequently current smokers, and alcohol or coffee drinkers than the nonhabitual tea drinkers. Habitual tea drinkers for more than 10 years showed a 19.6% reduction in BF% and a 2.1% reduction in WHR compared with nonhabitual tea drinkers. The multiple stepwise regression models revealed that men, older age, higher BMI, and current smokers were positive factors for BF% and WHR. In contrast, longer duration of habitual tea consumption and higher total physical activity were negative factors for BF%. Longer duration of habitual tea consumption, higher socioeconomic status, and premenopausal status were negative factors for WHR. DISCUSSION: An inverse relationship may exist among habitual tea consumption, BF%, and body fat distribution, especially for subjects who have maintained the habit of tea consumption for more than 10 years.