Multiplexed Antibody Glycosylation Profiling Using Dual Enzyme Digestion and Liquid Chromatography-Triple Quadrupole Mass Spectrometry Method.

Antibody glycosylation plays a crucial role in the humoral immune response by regulating effector functions and influencing the binding affinity to immune cell receptors. Previous studies have focused mainly on the immunoglobulin G (IgG) isotype owing to the analytical challenges associated with other isotypes. Thus, the development of a sensitive and accurate analytical platform is necessary to characterize antibody glycosylation across multiple isotypes. In this study, we have developed an analytical workflow using antibody-light-chain affinity beads to purify IgG, IgA, and IgM from 16 µL of human plasma. Dual enzymes, trypsin and Glu-C, were used during on-bead digestion to obtain enzymatic glycopeptides and protein-specific surrogate peptides. Ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry was used in order to determine the sensitivity and specificity. Our platform targets 95 glycopeptides across the IgG, IgA, and IgM isotypes, as well as eight surrogate peptides representing total IgG, four IgG classes, two IgA classes, and IgM. Four stable isotope-labeled internal standards were added after antibody purification to calibrate the preparation and instrumental bias during analysis. Calibration curves constructed using serially diluted plasma samples showed good curve fitting (R2 > 0.959). The intrabatch and interbatch precision for all the targets had relative standard deviation of less than 29.6%. This method was applied to 19 human plasma samples, and the glycosylation percentages were calculated, which were comparable to those reported in the literature. The developed method is sensitive and accurate for Ig glycosylation profiling. It can be used in clinical investigations, particularly for detailed humoral immune profiling.

A phenomenological comparison of auditory hallucinations between borderline personality disorder and schizophrenia: A systematic review.

OBJECTIVE: Borderline personality disorder (BPD) with auditory hallucinations (AHs) may inadvertently be misdiagnosed with a primary psychotic disorder, such as schizophrenia (SZ). This misidentification can lead to challenges in providing effective psychological treatment. This review therefore aims to identify the phenomenological characteristics of AHs in BPD in comparison to SZ, as well as psychological interventions that explicitly target AHs in BPD. METHODS: A systematic review was conducted to summarise the existing evidence base regarding the phenomenological similarities and differences of AHs in BPD and SZ, along with the identification of psychological interventions for AHs in BPD. RESULTS: Eighteen studies were eligible for inclusion. Compared to the SZ group, BPD clients were characterised by more persistent and repetitive AHs, significantly more voice-related distress and appraisals of omnipotence, and an earlier age of onset of AHs. The BPD group also reported more severe depression and anxiety, a higher incidence of childhood trauma, and more negative self-schema. Cognitive Behaviour Therapy Coping Strategy Enhancement (CBT-CSE) might be a promising intervention to reduce AH-related distress in BPD, although further studies are required to determine its effectiveness. CONCLUSION: In order to prevent misdiagnosis of AHs in BPD, the DSM-5 may need to acknowledge the broader and more frequent occurrence of psychosis symptoms in BPD clients. Such clarification may enhance diagnostic practices and facilitate more timely access to treatment. There is also a need to develop and trial psychological interventions that explicitly target AHs in BPD.

Targeting HR Repair as a Synthetic Lethal Approach to Increase DNA Damage Sensitivity by a RAD52 Inhibitor in BRCA2-Deficient Cancer Cells.

BRCA mutation, one of the most common types of mutations in breast and ovarian cancer, has been suggested to be synthetically lethal with depletion of RAD52. Pharmacologically inhibiting RAD52 specifically eradicates BRCA-deficient cancer cells. In this study, we demonstrated that curcumin, a plant polyphenol, sensitizes BRCA2-deficient cells to CPT-11 by impairing RAD52 recombinase in MCF7 cells. More specifically, in MCF7-siBRCA2 cells, curcumin reduced homologous recombination, resulting in tumor growth suppression. Furthermore, a BRCA2-deficient cell line, Capan1, became resistant to CPT-11 when BRCA2 was reintroduced. In vivo, xenograft model studies showed that curcumin combined with CPT-11 reduced the growth of BRCA2-knockout MCF7 tumors but not MCF7 tumors. In conclusion, our data indicate that curcumin, which has RAD52 inhibitor activity, is a promising candidate for sensitizing BRCA2-deficient cells to DNA damage-based cancer therapies.

Oxidative stress markers in type 2 diabetes patients with diabetic nephropathy.

BACKGROUND: Epidemiological studies show that 5-40 % of type 2 diabetes (T2DM) patients have diabetic nephropathy, and oxidative stress is one of several underlying mechanisms. We investigated associations between oxidative stress markers and severity of diabetic nephropathy. METHODS: Fifty-nine T2DM patients from the endocrinology outpatient department were included, and their levels of oxidative stress markers were measured. Three groups were determined by their urine albumin-to-creatinine ratio (UACR): group A (UACR < 30 mg/g, n = 22); group B (30 ≤ UACR < 300 mg/g, n = 22); and group C (UACR ≥ 300 mg/g, n = 15). RESULTS: Vitamin C levels correlated negatively and moderately with serum creatinine (γ = -0.459, p < 0.001), urine albumin (γ s = -0.458, p = 0.001) and UACR (γ s = -0.408, p = 0.001), but only weakly with hydroxy-2-deoxyguanosine (8-OHdG) and estimated glomerular filtration rate (eGFR). Vitamin C levels decreased as 8-OHdG, serum creatinine, albumin and UACR increased. T2DM patients with more severe diabetic nephropathy had lower vitamin C levels. CONCLUSION: Our results identified several oxidative stress markers that may be clinically important in diabetic nephropathy. Studies with larger sample sizes should be undertaken to confirm these findings.

SH3-like motif-containing C-terminal domain of staphylococcal teichoic acid transporter suggests possible function.

The negatively charged bacterial polysaccharides-wall teichoic acids (WTAs) are synthesized intracellularly and exported by a two-component transporter, TagGH, comprising a transmembrane subunit TagG and an ATPase subunit TagH. We determined the crystal structure of the C-terminal domain of TagH (TagH-C) to investigate its function. The structure shows an N-terminal SH3-like subdomain wrapped by a C-terminal subdomain with an anti-parallel ß-sheet and an outer shell of α-helices. A stretch of positively charged surface across the subdomain interface is flanked by two negatively charged regions, suggesting a potential binding site for negatively charged polymers, such as WTAs or acidic peptide chains. Proteins 2016; 84:1328-1332. © 2016 Wiley Periodicals, Inc.

Risks after Gestational Diabetes Mellitus in Taiwanese Women: A Nationwide Retrospective Cohort Study.

OBJECTIVE: An increasing trend in the prevalence of gestational diabetes mellitus (GDM) has been reported in Taiwan. GDM has been linked to various adverse maternal outcomes over a long period, including cardiovascular disease (CVD) and chronic kidney disease (CKD). However, evidence implies that the effects of GDM on the mid-term surrogate risk factors for these diseases are limited. Furthermore, data from nationwide cohort studies are limited. The primary aim of this study was to investigate the risk of developing type 2 diabetes mellitus (T2DM), arterial hypertension (aHTN), and hyperlipidemia (HL) through a 5-year follow-up post-delivery of women with GDM in a nationwide cohort study in Taiwan. The second objective was to investigate the risk of developing insulin resistance syndrome (IRS)-related diseases, including CVD, acute myocardial infarction (AMI), peripheral artery occlusive disease (PAOD), non-alcoholic fatty liver diseases (NAFLD), and CKD. METHODS: This was a retrospective, population-based nationwide cohort study. The data source comprises a merge of the Birth Certificate Application Database (BCA) and the National Health Insurance Research Database in Taiwan. Women aged between 15 and 45 years who gave birth in Taiwan between 2004 and 2011 were included. Women who were enrolled and had a GDM diagnosis were assigned to the exposure group. Women who were enrolled without a GDM diagnosis were assigned to the comparison group. The relative risk of developing T2DM, aHTN, HL, and IRS-related diseases, including CVD, AMI, PAOD, NAFLD, and CKD, were analyzed and presented as hazard ratio (HR) through Cox regression and log-rank regression analyses. RESULTS: A total of 1,180,477 women were identified through the BCA database between 2004 and 2011. Of those, 71,611 GDM-diagnosed women and 286,444 women without GDM were included in the final analysis. After adjusting for age, pre-existing cancer, and parity, developing T2DM, aHTN, and HL were still significantly increased in the GDM group (HR and interquartile range (IQR): 2.83 (2.59, 3.08), 1.09 (1.01, 1.06), and 1.29 (1.20, 1.38), accordingly). CVD, NAFLD, and CKD had a very low incidence and showed insignificant results. CONCLUSION: Our findings provide nationwide cohort data showing that GDM increased the risk of developing T2DM, aHTN, and HL 5 years after delivery within the same group. The GDM complications and risk of CVD, AMI, PAOD, NAFLD, and CKD need further investigation.

Quantification of skeletal muscle fibrosis at different healing stages using sonography: a morphologic and histologic study in an animal model.

OBJECTIVES: This study attempted to quantify the degree of muscle fibrosis on sonograms of injured gastrocnemius muscles at different healing stages in a rat model. Correlations between the quantifications and histologic assessments of the injured muscles were also determined. METHODS: Sonograms and histologic findings of gastrocnemius muscle fibrosis were obtained during the second, third, and fourth weeks after surgically induced lesions in the right gastrocnemius muscles of 15 Wistar rats. The echo intensity, reflecting the degree of brightness on a sonogram, was divided into 256 gray levels instead of decibels. The mean echo intensity of each pixel in the region of interest was calculated as a summation of the echo intensities in all pixels divided by the pixel numbers in the region. To control individual variations among the rats, we calculated a K value, defined as the difference in the mean echo intensity between normal and affected muscles. RESULTS: Significant correlations (r > 0.7; P < .05) between mean echo intensity and K values and the fibrous tissue percentage were identified. The mean echo intensity in the injured gastrocnemius muscles was significantly (P = .029) greater than that in the normal muscles 3 weeks after injury. In histologic assessments, muscle fibrosis was most prominent 3 weeks after injury. However, the differences in fibrosis at different healing stages were not significant. CONCLUSIONS: Mean echo intensity and K values can reflect the extent of fibrosis in affected muscles and may be valuable for quantifying muscle fibrosis in clinical practice.

Correction: Lin et al. Grounding the Body Improves Sleep Quality in Patients with Mild Alzheimer's Disease: A Pilot Study. Healthcare 2022, 10, 581.

The authors would like to make the following corrections to the published paper [...].

Grounding the Body Improves Sleep Quality in Patients with Mild Alzheimer's Disease: A Pilot Study.

BACKGROUND: Grounding refers to having direct contact with the Earth, such as by walking barefoot or lying on the ground. Research has found that grounding can improve inflammation, free radical damage, blood pressure, sleep quality, pain, stress, mood, and wound healing. However, there has been no research on the effect of utilizing grounding for patients with Alzheimer's disease (AD). Thus, in this study, we investigated the effectiveness of grounding as a non-pharmacological therapy for treating sleep disturbances, anxiety, and depression in patients with mild AD. METHODS: Patients with mild AD were enrolled in the study. The electrochemical analyzer CHI 1205b was employed to check the electrochemical signals at acupoints KI1 and GV16. We used the Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II) to evaluate sleep quality, anxiety, and depression, respectively, at weeks 0 and 12. RESULTS: This 12-week placebo-controlled study enrolled 22 patients, but only 15 patients completed the 12-week intervention and survey. Grounding significantly improved PSQI scores compared to the sham-grounding group (mean ± SD: 0.3 ± 0.7 vs. 3.0 ± 1.9, p = 0.006). The scores on the BAI and BDI-II did not change significantly after grounding in comparison to the sham-grounding group. CONCLUSIONS: Grounding can improve sleep quality, but it does not significantly improve anxiety and depression among patients with mild AD.

Effect of moxibustion on meridian in a warm needling model: A protocol for a prospective observational study.

BACKGROUND: Warm needling is a type of traditional Chinese medicine (TCM), which uses burned moxa to generate warmth and exerts a therapeutic effect on human skin. Additionally, based on TCM theory, warm needling could improve deficiency-cold syndrome. Research has found that warm needling has analgesic effects as well as effects on the immune system, endocrine system, nervous system, and lower urinary tract symptoms. However, the mechanism of warm needling on the meridians is not fully understood. In modern studies, the electric characteristics of the meridians have been discovered and the combination of semiconductor and TCM theory could explain the meridian phenomena through physics. However, there is no known research exploring the relationship between thermal effect and electric property on the meridians. METHODS: A total of 30 healthy participants older than 20 years of age will be recruited for this study. The participants would first be administered acupuncture, following which the electric characteristics will be measured using the semiconductor analyzer Agilent B1500A/Agilent 4156C. The visual analog score (VAS) will also be rated. Thereafter, a burned moxa will be added to the acupuncture needles as a method for warm needling. The electric characteristics and VAS will be measured again. We will use the paired t-test and repeated measure two-way ANOVA to compare the electric characteristics and VAS before and after warm needling in each participant. OBJECTIVES: This protocol aims to explore the thermal effect on the electric characteristics of meridians in a warm needling model and provide a scientific explanation of TCM through the aspect of physics.

Meridian study on the response current affected by acupuncture needling direction.

Acupuncture manipulation with needling direction is important for the therapeutic effect based on traditional Chinese medicine theory. However, there is controversy over directional manipulation and therapeutic effect, despite some research showing that acupuncture manipulations may have something to do with therapeutic effect. Moreover, research usually focuses on the therapeutic effects on the acupoints and acupuncture time rather than exploring the manipulation method. This study applies a semiconductor analyzer to investigate the effects of acupuncture manipulation. 10 healthy participants were recruited for the study. We used a cross-over design to compare the effect of different manipulation on individuals. This study employed an Agilent B1500A semiconductor analyzer to investigate the electric characteristics of meridians under directional supplementation and draining manipulation. We measured the electric current of meridians under different manipulation, and compared the difference between supplementation and draining manipulation in healthy individuals. The electric current was significantly larger in supplementation manipulation compared to draining manipulation in the meridians (P < .001). The measured electric current in the same manipulation methods did not show a statistical difference between meridians (P = .094). The different directional manipulation result in different electric currents in humans. Our finding implies that the supplementation and draining manipulation may result in different therapeutic effects clinically as the description of traditional Chinese medicine theory. Therefore, directional manipulation may need to be taken into consideration in future acupuncture studies and clinical management.

Long-term exposure to particulate matter was associated with increased dementia risk using both traditional approaches and novel machine learning methods.

Air pollution exposure has been linked to various diseases, including dementia. However, a novel method for investigating the associations between air pollution exposure and disease is lacking. The objective of this study was to investigate whether long-term exposure to ambient particulate air pollution increases dementia risk using both the traditional Cox model approach and a novel machine learning (ML) with random forest (RF) method. We used health data from a national population-based cohort in Taiwan from 2000 to 2017. We collected the following ambient air pollution data from the Taiwan Environmental Protection Administration (EPA): fine particulate matter (PM2.5) and gaseous pollutants, including sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), nitrogen oxide (NOx), nitric oxide (NO), and nitrogen dioxide (NO2). Spatiotemporal-estimated air quality data calculated based on a geostatistical approach, namely, the Bayesian maximum entropy method, were collected. Each subject's residential county and township were reviewed monthly and linked to air quality data based on the corresponding township and month of the year for each subject. The Cox model approach and the ML with RF method were used. Increasing the concentration of PM2.5 by one interquartile range (IQR) increased the risk of dementia by approximately 5% (HR = 1.05 with 95% CI = 1.04-1.05). The comparison of the performance of the extended Cox model approach with the RF method showed that the prediction accuracy was approximately 0.7 by the RF method, but the AUC was lower than that of the Cox model approach. This national cohort study over an 18-year period provides supporting evidence that long-term particulate air pollution exposure is associated with increased dementia risk in Taiwan. The ML with RF method appears to be an acceptable approach for exploring associations between air pollutant exposure and disease.

Increasing trend in the prevalence of gestational diabetes mellitus in Taiwan.

AIMS/INTRODUCTION: Maternal hyperglycemia leads to adverse pregnancy outcomes, and also subsequently affects both mothers and their offspring in later life. The prevalence of type 2 diabetes mellitus is increasing worldwide, and gestational diabetes mellitus (GDM) is also believed to be increasing. More precise nationwide and up-to-date data on GDM are required. MATERIALS AND METHODS: A population-based retrospective cohort study was carried out with the Birth Certificate Application database and linked to the National Health Insurance Research Database to explore trends in the annual crude prevalence of GDM in all women who gave birth between 1 January 2004 and 31 December 2015 in Taiwan and their pregnancy outcomes. The registry is considered complete, reliable and accurate. RESULTS: A total of 2,468,793 births from 2,430,307 pregnancies were reported between 1 January 2004 and 31 December 2015. Finally, 2,053,305 pregnancies were included for further analysis. The annual prevalence of GDM increased by 1.8-fold during the 12 years from 2004 to 2015, with a significant continuous increasing trend (from 7.6% to 13.4%, P < 0.001). The annual prevalence of GDM significantly increased in each age group (all trends P < 0.001), particularly for women with maternal ages of 31 years and older. Urbanization level, geographic risk factors and seasonal variations were also noted. CONCLUSION: The annual prevalence of GDM increased by 1.8-fold in the 12-year period from 2004 to 2015 in Taiwan, with a significant continuous increasing trend (from 7.6% to 13.4%, P < 0.001).

Chinese Herbal Products for Non-Motor Symptoms of Parkinson's Disease in Taiwan: A Population-Based Study.

Objective: Combinations of Chinese herbal products (CHPs) are widely used for Parkinson's disease (PD) in Taiwan. Thereby, we investigated the use of CHPs in patients with PD. Methods: This study was a population-based cohort study that analyzed the data of patients with PD from the National Health Insurance Research Database. A total of 9,117 patients were selected from a random sample of one million individuals included in this database. We used multiple logistic regression models to estimate the adjusted odds ratios of the demographic factors and analyzed the formula and single CHPs commonly used for PD. Results: Traditional Chinese medicine users were more commonly female, younger, of white-collar status, and residents of Central Taiwan. Chaihu-Jia-Longgu-Muli-Tang was the most commonly used formula, followed by Ma-Zi-Ren-Wan and then Shao-Yao-Gan-Cao-Tang. The most commonly used single herb was Uncaria tomentosa (Willd. ex Schult.) DC., followed by Gastrodia elata Blume and then Radix et Rhizoma Rhei (Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill.). Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. have shown neuroprotective effects in previous studies, and they have been used for managing non-motor symptoms of PD. Conclusion: Chaihu-Jia-Longgu-Muli-Tang and U. tomentosa (Willd. ex Schult.) DC. are the most commonly used CHPs for PD in Taiwan. Our results revealed the preferences in medication prescriptions for PD. Further studies are warranted to determine the effectiveness of these CHPs for ameliorating the various symptoms of PD, their adverse effects, and the mechanisms underlying their associated neuroprotective effects.

Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse pregnancy outcomes in high-risk Taiwanese women.

BACKGROUND: The objective of this study was to investigate the associations among the mid-pregnancy glycated hemoglobin A1c (HbA1c) level, gestational diabetes (GDM), and risk of adverse pregnancy outcomes in women without overt diabetes and with positive 50-g, 1-h glucose challenge test (GCT) results (140 mg/dL or greater). METHODS: This prospective study enrolled 1,989 pregnant Taiwanese women. A two-step approach, including a 50-g, 1-h GCT and 100-g, 3-h oral glucose tolerance test (OGTT), was employed for the diagnosis of GDM at weeks 23-32. The mid-pregnancy HbA1c level was measured at the time the OGTT was performed. A receiver operating characteristic (ROC) curve was used to determine the relationship between the mid-pregnancy HbA1c level and GDM. Multiple logistic regression models were implemented to assess the relationships between the mid-pregnancy HbA1c level and adverse pregnancy outcomes. RESULTS: An ROC curve demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM, as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was 5.7%. The area under the ROC curve of the mid-pregnancy HbA1c level for GDM was 0.70. Compared with the levels of 4.5-4.9%, higher mid-pregnancy HbA1c levels (5.0-5.4, 5.5-5.9, 6.0-6.4, 6.5-6.9, and >7.0%) were significantly associated with increased risks of gestational hypertension or preeclampsia, preterm delivery, admission to the neonatal intensive care unit, low birth weight, and macrosomia (the odds ratio [OR] ranges were 1.20-9.98, 1.31-5.16, 0.88-3.15, 0.89-4.10, and 2.22-27.86, respectively). CONCLUSIONS: The mid-pregnancy HbA1c level was associated with various adverse pregnancy outcomes in high-risk Taiwanese women. However, it lacked adequate sensitivity and specificity to replace the two-step approach in the diagnosis of GDM. The current study comprised a single-center prospective study; thus, additional, randomized control design studies are required.

Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.

OBJECTIVE: The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA1c and other traditional risk factors in such patients. RESEARCH DESIGN AND METHODS: Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. RESULTS: During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA1c, drug-related variables, and comorbidities, both FPG CV and HbA1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA1c CV. CONCLUSIONS: FPG CV and HbA1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA1c CV can be valuable therapeutic targets for patients with T2DM at risk.

Relationship between several surrogate estimates of insulin sensitivity in non-diabetic patients with coronary artery disease.

BACKGROUND AND PURPOSE: Insulin resistance plays an important role in the pathogenesis of coronary artery disease (CAD). Thus, there is a need for accurate and accessible tools for measurement of insulin sensitivity in patients with this disease. This study explored the relationship between several surrogate estimates of insulin sensitivity in non-diabetic patients with angiographic evidence of CAD. METHODS: The study population consisted of 1363 non-diabetic subjects with angiography results which revealed evidence of CAD in 660 and no evidence of CAD in 703 subjects. After overnight fasting, blood samples were drawn for determination of glucose and insulin concentrations in order to determine the homeostasis model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). In addition, steady-state plasma glucose (SSPG) concentrations obtained from insulin suppression tests were carried out in 54 subjects with and 194 subjects without CAD. The correlation of QUICKI with other surrogate estimates of insulin sensitivity in obese and non-obese subjects was also evaluated. RESULTS: The QUICKI correlated significantly with other methods for estimating insulin sensitivity in the CAD and non-CAD groups. The QUICKI also had a closer correlation with SSPG and log fasting plasma insulin (log FPI) in subjects with CAD (r = -0.573 and -0.869, respectively) than HOMA-IR (r = 0.508 and 0.777, respectively). QUICKI had a closer correlation with SSPG in the obese subjects than in the non-obese subjects, irrespective of the presence of CAD. CONCLUSIONS: The QUICKI was more closely related with SSPG, insulin area, and log FPI than other measurements of insulin sensitivity. These findings suggest that the QUICKI may provide a convenient, efficient method to measure insulin sensitivity in non-diabetic patients with CAD.

Risk factors associated with diabetic retinopathy onset and progression in diabetes patients: a Taiwanese cohort study.

Diabetic retinopathy (DR) is a common complication of type 2 diabetes mellitus (T2DM) and the leading cause of adult blindness. This study aimed to clarify the risk factors associated with DR onset and progression in patients with T2DM in Taiwan. This retrospective analysis enrolled 743 T2DM patients, including 170 with DR and 573 without DR at baseline who were enrolled in the Diabetes Shared-Care Program. The average follow-up period was 2.9 years. Variables, including demographic characteristics, DM duration, anthropometric data and clinical laboratory results, were compared between patients with DR at baseline, those with new-onset DR, and patients without DR using a chi-squared test and one-way ANOVA. A multivariate Cox proportional hazards model was performed to identify risk factors associated with progression of preexisting DR or new-onset DR. During the follow-up period, 38 (22.4%) patients with preexisting DR experienced disease progression, and 91 (15.9%) patients had new-onset DR. Multivariate analysis revealed that the presence of neuropathy (HR: 3.96, 95% CI: 1.84, 8.53) and diastolic blood pressure (HR: 1.05, 95% CI: 1.02, 1.08) were associated with increased risk of DR progression (both P < 0.001). Factors associated with new-onset DR included neuropathy, systolic BP, cholesterol, and updated mean of HbA1c (all P ≤ 0.001). The risk factors associated with DR onset and progression in Taiwanese patients with T2DM are different. Neuropathy and blood pressure increased the risk of both DR onset and progression; however, the risk of DR onset was also increased with updated mean of HbA1c and cholesterol.

Association of inflammation and oxidative stress with obstructive sleep apnea in ischemic stroke patients.

OBJECTIVE: The role of obstructive sleep apnea (OSA) in the mortality and further cardiovascular risk in subjects with ischemic stroke remains a contentious issue. Oxidative stress and inflammatory reaction due to OSA have seldom been studied in stable ischemic stroke patients. PATIENTS/METHODS: This cross-sectional, prospective study involved 92 consecutive ischemic stroke patients who were admitted to the Rehabilitation ward. All subjects received polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers, including: C-reactive protein (CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC), and urinary 8-hydroxy-2-deoxyguanosine. Differences in study variables between patients with or without severe OSA were compared, and multivariate linear regression analyses were used to assess the relationship between OSA severity and target biomarkers. RESULTS: Participants in the severe OSA group were significantly older (p = 0.002), had a significantly higher risk of hypertension (p = 0.021) and a lower level of CRP (p = 0.006). Among the subjects with ischemic stroke and severe OSA, the levels of CRP, IL-6, and TAC were positively correlated with the desaturation index (DI) and the TAC levels were negatively correlated with mean arterial oxygen saturation (SaO2). Regression analysis results indicated that the TAC levels remained significantly and negatively correlated with mean SaO2 levels. Moreover, the CRP levels remained significantly correlated with the apnea-hypopnea index and DI after controlling for covariates. CONCLUSIONS: The present study demonstrated that a preferentially adaptive antioxidative response to hypoxia emerges, and the role of OSA with respect to inflammatory reaction is attenuated, in ischemic stroke patients with OSA.