Validation of the Framingham General Cardiovascular Risk Score and Pooled Cohort Equations in a Community-Based Population: A Prospective Cohort Study Analysis 2006-2017.

Background: The 10-year atherosclerotic cardiovascular disease (ASCVD) risk - as assessed using the Framingham general cardiovascular risk score (FRS-CVD) or pooled cohort equations (PCE) - is commonly used in Western cohorts for the primary prevention of cardiovascular disease (CVD). However, the FRS-CVD and PCE have not been validated in Taiwanese cohorts. Objectives: We aimed to validate the FRS-CVD and PCE for assessing the 10-year ASCVD risk using a Taiwanese community-based population. Methods: We extracted patient data from the Landseed Integrated Outreaching Neighborhood Screening registry, a community-based prospective cohort study established in 2006. Cardiovascular events from 2006 to 2017 were determined from electronic medical records. The discriminative power and calibration of the FRS-CVD and PCE were evaluated. Results: Overall, 5,139 subjects were analyzed; the 10-year follow-up rate was 99.6%. The mean age at baseline was 52.8 ± 13.1 years, and 44.6% of the subjects were male. In total, 430 of 4,631 (9.3%) and 227 of 4,022 (5.6%) of the FRS-CVD- and PCE-like cohorts, respectively, had ASCVD events. The calibration χ2 of the FRS-CVD was 7.0267 (p = 0.6343) in males and 7.8845 (p = 0.5458) in females; the χ2 of PCE was 13.007 (p = 0.1623) in males and 38.785 (p < 0.001) in females. The area under the receiver operating characteristic curve (AUROC) of the FRS-CVD was 0.76 (0.72-0.79) in males and 0.71 (0.67-0.74) in females; the AUROC of PCE was 0.68 (0.62-0.73) in males and 0.61 (0.56-0.67) in females. Conclusions: Except for PCE in females, the FRS-CVD and PCE provided good calibration and modest discrimination in statin-naïve Taiwanese individuals without prior CVD.

IL-6/p-BTK/p-ERK signaling mediates calcium phosphate-induced pruritus.

Uremic pruritus with elevated levels of calcium phosphate (CaP) in skin is a common symptom in patients with chronic kidney disease (CKD). In this study, we demonstrate that intradermal injection of CaP into mice triggered scratching by up-regulating the IL-6 in skin and phosphorylation of ERKs in dorsal root ganglion (DRG) in a dose-dependent manner. IL-6 is essential because the CaP-induced up-regulation of phosphorylated (p)-ERK in DRG was considerably reduced in the IL-6 knockout mice. Microarray analysis in conjunction with real-time PCR revealed a higher mRNA expression of Bruton's tyrosine kinase (BTK) gene in DRG after CaP injection. The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice. A high amount of IL-6 was detected in itchy skin and blood of patients with CKD. The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib. The mechanism by which the CaP-induced pruritus mediated by the IL-6/p-BTK/p-ERK signaling was revealed.-Keshari, S., Sipayung, A. D., Hsieh, C.-C., Su, L.-J., Chiang, Y.-R., Chang, H.-C., Yang, W.-C., Chuang, T.-H., Chen, C.-L., Huang, C.-M. IL-6/p-BTK/p-ERK signaling mediates calcium phosphate-induced pruritus.

Midshaft clavicle fracture following osteosynthesis with a hook plate: a retrospective case analysis.

PURPOSE: The clavicle hook plate has been commonly used to treat distal clavicle fractures and acromioclavicular (AC) joint dislocations; however, midshaft clavicle fracture at the medial end of the hook plate remains an underestimated complication. We aimed to discover the risk factors for this complication and the influence of these risk factors on patients and to suggest preventive surgical techniques. METHODS: We retrospectively reviewed the records of 150 patients with acute distal clavicle fractures or acute AC joint dislocations treated by internal fixation with a clavicle hook plate. The patient demographics, the occurrence of midshaft clavicle fracture at the medial end of the hook plate, and functional outcomes were analyzed. The functional outcomes were evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score and grading of the Constant shoulder score after the hook plate was removed. RESULTS: In total, 17 patients had complicating midshaft clavicle fractures at the medial end of the hook plate. Elderly patients had a higher risk of developing this complication than young patients. The odds ratio was 4.4 (p < 0.05). The average ASES score and grading of Constant score of these patients were 74.1 and 16.3 points, respectively, which were significantly inferior to those of patients without complications (p < 0.001). CONCLUSION: The incidence of midshaft clavicle fractures following osteosynthesis with a clavicle hook plate was not negligible, especially in elderly patients. This complication may impair shoulder function and quality of life. Awareness of this complication and the risk factors for this complication reminds us to perform such operations with caution.

Plasma miRNA profile is a biomarker associated with urothelial carcinoma in chronic hemodialysis patients.

The incidence of urothelial carcinoma (UC) is higher in patients undergoing chronic dialysis than in the general population. This study investigated plasma miRNA profiling as the ancillary diagnosis biomarker associated with UC in patients undergoing chronic hemodialysis. We successfully screened out and detected miRNA expression from plasma in eight patients undergoing dialysis through quantitative real-time PCR array analysis and identified eight candidate miRNAs. The candidate miRNAs were then validated using single quantitative RT-PCR assays from 52 plasma samples. The miRNA classifier for ancillary UC detection was developed by multiple logistic regression analyses. Moreover, we validated the classifier by testing another nine samples. Expression levels of miR-150-5p, miR-150-5p/miR-155-5p, miR-378a-3p/miR-150-5p, miR-636/miR-150-5p, miR-150-5p/miR-210-3p, and miR-19b-1-5p/miR-378a-3p were shown to be significantly different between UC and non-UC samples (P = 0.035, 0.0048, 0.016, 0.024, 0.038, and 0.048). Kaplan-Meier curve analysis also showed that low miR-19b-1-5p expression was associated with a worse prognosis (P = 0.0382). We also developed a miRNA classifier based on five miRNA expression levels to predict UC and found that the area under curve was 0.882. The classifier had a sensitivity of 80% (95% confidence interval: 0.5191% to 0.9567%) and a specificity of 83.7% (95% confidence interval: 0.6799% to 0.9381%). This classifier was tested by nine samples with 100% accuracy. The miRNA classifier offers higher sensitivity and specificity than the existing makers. Thus, this approach will improve the prospective diagnosis of UC in patients undergoing chronic hemodialysis.

Identification of sugar response complex in the metallothionein OsMT2b gene promoter for enhancement of foreign protein production in transgenic rice.

KEY MESSAGE: A 146-bp sugar response complex MTSRC is identified in the promoter of rice metallothionein OsMT2b gene conferring high-level expression of luciferase reporter gene and bioactive recombinant haFGF in transgenic rice. A rice subfamily type 2 plant metallothionein (pMT) gene, OsMT2b, encoding a reactive oxygen species (ROS) scavenger protein, has been previously shown to exhibit the most abundant gene expression in young rice seedling. Expression of OsMT2b was found to be regulated negatively by ethylene and hydrogen peroxide in rice stem node under flooding stress, but little is known about its response to sugar depletion. In this study, transient expression assay and transgenic approach were employed to characterize the regulation of the OsMT2b gene expression in rice. We found that the expression of OsMT2b gene is induced by sugar starvation in both rice suspension cells and germinated embryos. Deletion analysis and functional assay of the OsMT2b promoter revealed that the 5'-flanking region of the OsMT2b between nucleotides - 351 and - 121, which contains the sugar response complex (- 266 to - 121, designated MTSRC) is responsible for high-level promoter activity under sugar starvation. It was also found that MTSRC significantly enhances the Act1 promoter activity in transgenic rice cells and seedlings. The modified Act1 promoter, Act1-MTSRC, was used to produce the recombinant human acidic fibroblast growth factor (haFGF) in rice cells. Our result shows that the bioactive recombinant haFGF is stably produced in transformed rice cell culture and yields are up to 2% of total medium proteins. Our studies reveal that MTSRC serves as a strong transcriptional activator and the Act1-MTSRC promoter can be applicable in establishing an efficient expression system for the high-level production of foreign proteins in transgenic rice cells and seedlings.

microRNA expression pattern as an ancillary prognostic signature for radiotherapy.

BACKGROUND: In view of the limited knowledge of plasma biomarkers relating to cancer resistance to radiotherapy, we have set up screening, training and testing stages to investigate the microRNAs (miRNAs) expression profile in plasma to predict between the poor responsive and responsive groups after 6 months of radiotherapy. METHODS: Plasma was collected prior to and after radiotherapy, and the microRNA profiles were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) arrays. Candidate miRNAs were validated by single qRT-PCR assays from the training and testing set. The classifier for ancillary prognosis was developed by multiple logistic regression analysis to correlate the ratios of miRNAs expression levels with clinical data. RESULTS: We revealed that eight miRNAs expressions had significant changes after radiotherapy and the expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p showed significant differences between the responsive and poor responsive groups in the pre-radiotherapy samples. The Kaplan-Meier curve analysis also showed that low miR-342-5p and miR-519d-3p expressions were associated with worse prognosis. Our results revealed two miRNA classifiers from the pre- and post-radiotherapy samples to predict radiotherapy response with area under curve values of 0.8923 and 0.9405. CONCLUSIONS: The expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p in plasma are associated with radiotherapy responses. Two miRNA classifiers could be developed as a potential non-invasive ancillary tool for predicting patient response to radiotherapy.

Risk of Autoimmune Disease in Adults with Chronic Insomnia Requiring Sleep-Inducing Pills: A Population-Based Longitudinal Study.

BACKGROUND: Recent studies indicate that chronic insomnia is associated with the development of certain somatic diseases. Whether it would be associated with the development of an autoimmune disease (AID) was unknown. OBJECTIVE: We aimed to examine the association and quantify the magnitude of risk for AID in individuals suffering from chronic insomnia requiring sleep-inducing pills. DESIGN: This was a population-based, nationwide longitudinal study. PARTICIPANTS: Using a claims data set containing 1 million randomly sampled, insured subjects derived from the National Health Insurance Research Database, we assembled a chronic insomnia group and a 1:3 propensity score-matched comparison group (CP), which were balanced in terms of sex, age, insurance premium, urbanization, alcohol use disorder, smoking-related diagnoses, and morbid obesity. MAIN MEASURES: Person-time data with incidence rate, adjusted hazard ratios (aHR) by the Cox model, AID-free survival functions compared with the log-rank test, and a sensitivity analysis on the time lag effect were presented. Incident AID within the first year of follow-up were excluded. The error rate was controlled using the Benjamini-Hochberg procedure. KEY RESULTS: With 39,550 and 129,914 person-years' follow-up for the chronic insomnia and CP groups (n = 5,736 and 17,208), respectively, we found an increased risk for subsequent AID, representing a 70 % increase in the aHR (1.7; 95 % confidence interval [CI], 1.5-1.9, p < 0.0001). A positive association between chronic insomnia and primary Sjögren's syndrome (pSS) was observed (aHR, 1.3; 95 % CI, 1.1-1.6). Sensitivity analysis disclosed that AID risk was even stronger after 5 years of follow-up (aHR, 2.0; 95 % CI, 1.7-2.4). CONCLUSION: Chronic insomnia requiring sleep-inducing pills may be associated with a 70 % increased risk for future AID, particularly pSS.

Use of noninvasive brain stimulation and neurorehabilitation devices to enhance poststroke recovery: review of the current evidence and pitfalls.

Neurorehabilitation devices and technologies are crucial for enhancing stroke recovery. These include noninvasive brain stimulation devices that provide repetitive transcranial magnetic stimulation or transcranial direct current stimulation, which can remodulate an injured brain. Technologies such as robotics, virtual reality, and telerehabilitation are suitable add-ons or complements to physical therapy. However, the appropriate application of these devices and technologies, which target specific deficits and stages, for stroke therapy must be clarified. Accordingly, a literature review was conducted to evaluate the theoretical and practical evidence on the use of neurorehabilitation devices and technologies for stroke therapy. This narrative review provides a practical guide for the use of neurorehabilitation devices and describes the implications of use and potential integration of these devices into healthcare.

Concurrent Imaging and Clinical Study of the Efficacy of Hyaluronic Acid Injection for Knee Osteoarthritis: A Synovial Membrane Investigation with Ultrasound Imaging.

We investigated whether hyaluronic acid (HA) injections can ameliorate ultrasound-detected synovitis in knee osteoarthritis (OA). We recruited 103 patients with symptomatic knee OA and ultrasound-detected synovitis and performed two ultrasound-guided fluid drainage procedures, followed by the administration of a low-molecular-weight HA injection (2.5 mL) in the subpatellar bursa, at a 2-week interval. Knee ultrasound imaging evaluations were performed before injection (baseline) and at 1 and 6 months after the second injection and included the measurements of synovial vascularity by using color Doppler ultrasound, synovial fluid depth over the suprapatellar bursa (SF), and synovial hypertrophy (SH). Initial clinical assessments included a visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). VAS scores decreased significantly at both 1-month and 6-month evaluations (p < 0.001). WOMAC scores also significantly decreased at 1 month (p < 0.001), but not at 6 months (p = 0.23). The ultrasound parameters did not significantly change, except color Doppler grading, which tended to decrease at the 6-month evaluation (p = 0.059). Our findings revealed that two ultrasound-guided HA injections following fluid drainage improved pain and knee function but did not considerably influence imaging-detected synovitis in patients with knee OA.

MicroRNA regulators of vascular pathophysiology in chronic kidney disease.

Coronary artery disease (CAD) is a severe comorbidity in chronic kidney disease (CKD) due to heavy calcification in the medial layer and inflamed plaques. Chronic inflammation, endothelial dysfunction and vascular calcification are major contributors that lead to artherosclerosis in CKD. The lack of specific symptoms and signs of CAD and decreased accuracy of noninvasive diagnostic tools result in delayed diagnosis leading to increased mortality. MicroRNAs (miRNAs) are post-transcriptional regulators present in various biofluids throughout the body. In the circulation, miRNAs have been reported to be encapsulated in extracellular vesicles and serve as stable messengers for crosstalk among cells. miRNAs are involved in pathophysiologic mechanisms including CAD and can potentially be extended from basic research to clinical translational practice.

The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis.

BACKGROUND: Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells. METHODS: We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. RESULTS: We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0.033). CONCLUSIONS: Our current study showed that COX Va may play a role in migration and invasion of NSCLC cells and can be used as a biomarker to predict aggressiveness of NSCLC.

Increased risk of chronic kidney disease among users of non-prescribed Chinese herbal medicine in Taiwan.

BACKGROUND: Taiwan has the highest incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Chinese herbal medicine (CHM) has been linked to CKD/ESRD in Taiwan. The specific effects and frequency of CHM on the risk of CKD are unknown. METHODS: A hospital-based case-control study was performed from August 2006 through December 2009. The cases were consecutive nephrology outpatients 20years of age or older, with a first-time diagnosis of CKD, and without cancer or pre-existing renal disease. The controls were randomly selected outpatients that did not have CKD and were matched 1:1 to cases for age, gender and date of outpatient visit. RESULTS: Four hundred and twenty-four patients were recruited. Among 212 cases, 23.6% took non-prescribed CHM, compared to 6.6% among the controls (p<0.001). Multivariate analysis showed that illiteracy [odds ratio (OR) 6.3, 95% confidence interval (CI) 2.4-16.6], hypertension (OR 5.4, 95% CI 2.9-9.8) and occasional use of non-prescribed CHM (OR 6.2, 95% CI 1.8-21.6) were positively associated with CKD, whereas regular exercise was inversely associated with CKD (OR 0.5, 95% CI 0.3-0.9). CONCLUSION: Occasional use of non-prescribed CHM was associated with the risk of CKD in Taiwan.

Peritoneal effluent MicroRNA profile for detection of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS. METHODS: We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning. RESULTS: Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-ß signaling pathway. CONCLUSION: The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS.

Health Utilities in Patients with Type 2 Diabetes in Taiwan.

We aimed to measure health utilities in patients with diabetes mellitus (DM) in Taiwan and to estimate the impact of common DM-related complications and adverse effects (AEs) on health utilities. The present study was a cross-sectional survey of DM patients at a metropolitan hospital. Respondents' health-related quality of life (HRQoL) was assessed by the EQ-5D-5L, and ordinary least-squares (OLS) regression was used to estimate the impact of self-reported DM-related complications and AEs on health utilities after controlling for age, gender, and duration of DM. A total of 506 eligible adults with type 2 DM (T2DM) were enrolled. The EQ-5D index values in our study sample ranged from -0.13 to 1, with a mean ± standard deviation of 0.88 ± 0.20. As indicated by the negative regression coefficients, the presence of any complication or AE was associated with lower EQ-5D index values, and the greatest impact on the score was made by amputation (-0.276), followed by stroke (-0.211), and blindness (-0.203). In conclusion, the present study elicited health utilities in patients with T2DM in Taiwan using the EQ-5D-5L. These estimated utility decrements provided essential data for future DM cost-utility analyses that are needed as a result of the increasing prevalence and health expenditures of DM.

Urine phthalate metabolites are associated with urothelial cancer in chronic kidney disease patients.

BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population. METHODS: In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs. RESULTS: We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21-1.68). CONCLUSION: Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC.

The MicroRNA Prediction Models as Ancillary Diagnosis Biomarkers for Urothelial Carcinoma in Patients With Chronic Kidney Disease.

Urothelial carcinoma is a common urological cancer in chronic kidney disease patients. Cystoscopy and urine cytology are the clinical diagnostic tools for UC. However, cystoscopy is an invasive procedure, while urine cytology showed low sensitivity for low-grade urothelial tumors. High accuracy with non-invasive tools for UC is needed for CKD patients. Our study collected a total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from CKD patients. Seventeen candidate miRNAs of biofluids were selected and confirmed by qRT-PCR. Our results showed that urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378, and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595. Two miRNA classifiers and the nomograms could improve the drawbacks of current UC biomarker screenings for patients with CKD.

The Misconceptions and Determinants of Diabetes Knowledge in Patients with Diabetes in Taiwan.

AIM: This study aimed at (1) examining the misconceptions of patients with diabetes in Taiwan and (2) examining the association between patients' diabetes knowledge and their demographic characteristics. METHODS: A cross-sectional survey was conducted at a metropolitan hospital in northern Taiwan. A total of 501 outpatients with diabetes were recruited, mostly from the hospital's endocrinology and metabolism clinic, nephrology clinic, and dialysis center. A self-developed questionnaire that consisted of demographic information and a diabetes knowledge test was administered. The knowledge test included 10 True/False questions and 6 multiple-choice questions that aimed at identifying patients' common misconceptions about diabetes. RESULTS: A perfect score on the diabetes knowledge test was 16 points, and the mean ± SD score of the respondents was 11.5 ± 2.8. The most common misconception was "People can always feel when their blood sugar level is high." (64%), followed by "Taking insulin hurts the kidneys and may result in a need for dialysis." (52%) and "Being a vegetarian helps control blood sugar levels." (48%). The total knowledge scores were significantly associated with education levels (r s = 0.39, p < 0.001), average monthly income (r s = 0.28, p < 0.001), and age (r s = -0.34, p < 0.001). CONCLUSIONS: Certain misconceptions are prevalent among patients with diabetes, particularly in those with older age, lower education levels, or lower income. Healthcare providers need to work to eliminate common misconceptions and modify diabetes educational programs accordingly to help patients manage diabetes more effectively.

Repurposing INCI-registered compounds as skin prebiotics for probiotic Staphylococcus epidermidis against UV-B.

Repurposing existing compounds for new indications may facilitate the discovery of skin prebiotics which have not been well defined. Four compounds that have been registered by the International Nomenclature of Cosmetic Ingredients (INCI) were included to study their abilities to induce the fermentation of Staphylococcus epidermidis (S. epidermidis), a bacterial species abundant in the human skin. Liquid coco-caprylate/caprate (LCC), originally used as an emollient, effectively initiated the fermentation of S. epidermidis ATCC 12228, produced short-chain fatty acids (SCFAs), and provoked robust electricity. Application of LCC plus electrogenic S. epidermidis ATCC 12228 on mouse skin significantly reduced ultraviolet B (UV-B)-induced injuries which were evaluated by the formation of 4-hydroxynonenal (4-HNE), cyclobutane pyrimidine dimers (CPD), and skin lesions. A S. epidermidis S2 isolate with low expressions of genes encoding pyruvate dehydrogenase (pdh), and phosphate acetyltransferase (pta) was found to be poorly electrogenic. The protective action of electrogenic S. epidermidis against UV-B-induced skin injuries was considerably suppressed when mouse skin was applied with LCC in combination with a poorly electrogenic S. epidermidis S2 isolate. Exploring new indication of LCC for promoting S. epidermidis against UV-B provided an example of repurposing INCI-registered compounds as skin prebiotics.

Comparative functional genomic analysis of Alzheimer's affected and naturally aging brains.

BACKGROUND: Alzheimer's disease (AD) is a prevalent progressive neurodegenerative human disease whose cause remains unclear. Numerous initially highly hopeful anti-AD drugs based on the amyloid-ß (Aß) hypothesis of AD have failed recent late-phase tests. Natural aging (AG) is a high-risk factor for AD. Here, we aim to gain insights in AD that may lead to its novel therapeutic treatment through conducting meta-analyses of gene expression microarray data from AG and AD-affected brain. METHODS: Five sets of gene expression microarray data from different regions of AD (hereafter, ALZ when referring to data)-affected brain, and one set from AG, were analyzed by means of the application of the methods of differentially expressed genes and differentially co-expressed gene pairs for the identification of putatively disrupted biological pathways and associated abnormal molecular contents. RESULTS: Brain-region specificity among ALZ cases and AG-ALZ differences in gene expression and in KEGG pathway disruption were identified. Strong heterogeneity in AD signatures among the five brain regions was observed: HC/PC/SFG showed clear and pronounced AD signatures, MTG moderately so, and EC showed essentially none. There were stark differences between ALZ and AG. OXPHOS and Proteasome were the most disrupted pathways in HC/PC/SFG, while AG showed no OXPHOS disruption and relatively weak Proteasome disruption in AG. Metabolic related pathways including TCA cycle and Pyruvate metabolism were disrupted in ALZ but not in AG. Three pathogenic infection related pathways were disrupted in ALZ. Many cancer and signaling related pathways were shown to be disrupted AG but far less so in ALZ, and not at all in HC. We identified 54 "ALZ-only" differentially expressed genes, all down-regulated and which, when used to augment the gene list of the KEGG AD pathway, made it significantly more AD-specific.