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Obesity is strongly associated with insulin sensitivity in type 2 diabetes (T2D), mainly because free fatty acids (FFAs) are released from excess fat tissue. Long-term exposure to high levels of FFAs and glucose leads to glucolipotoxicity, causing damage to pancreatic β-cells, thus accelerating the progression of T2D. Therefore, the prevention of β-cell dysfunction and apoptosis is essential to prevent the development of T2D. Unfortunately, there are currently no specific clinical strategies for protecting β-cells, highlighting the need for effective therapies or preventive approaches to improve the survival of β-cells in T2D. Interestingly, recent studies have shown that the monoclonal antibody denosumab (DMB), used in osteoporosis, displays a positive effect on blood glucose regulation in patients with T2D. DMB acts as an osteoprotegerin (OPG) by inhibiting the receptor activator of the NF-κB ligand (RANKL), preventing the maturation and function of osteoclasts. However, the exact mechanism by which the RANK/RANKL signal affects glucose homeostasis has not been fully explained. The present study used human 1.4 × 10 7 β-cells to simulate the T2D metabolic condition of high glucose and free fatty acids (FFAs), and it investigated the ability of DMB to protect β-cells from glucolipotoxicity. Our results show that DMB effectively attenuated the cell dysfunction and apoptosis caused by high glucose and FFAs in β-cells. This may be caused by blocking the RANK/RANKL pathway that reduced mammalian sterile 20-like kinase 1 (MST1) activation and indirectly increased pancreatic and duodenal homeobox 1 (PDX-1) expression. Furthermore, the increase in inflammatory cytokines and ROS caused by the RANK/RANKL signal also played an important role in glucolipotoxicity-induced cytotoxicity, and DMB can also protect β-cells by reducing the mechanisms mentioned above. These findings provide detailed molecular mechanisms for the future development of DMB as a potential protective agent of β-cells.

Diabetic neuropathy (DN) is a type of sensory nerve damage that can occur in patients with diabetes. Although the understanding of pathophysiology is incomplete, DN is often associated with structural and functional alterations of the affected neurons. Among all possible causes of nerve damage, Schwann cells (SCs) are thought to play a key role in repairing peripheral nerve injury, suggesting that functional deficits occurring in SCs may potentially exhibit their pathogenic roles in DN. Therefore, elucidating the mechanisms that underlie this pathology can be used to develop novel therapeutic targets. In this regard, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently attracted great attention in ameliorating SCs' dysfunction. However, the detailed mechanisms remain uncertain. In the present study, we investigated how GLP-1 RA Liraglutide protects against RSC96 SCs dysfunction through a diabetic condition mimicked by high glucose and high free fatty acid (FFA). Our results showed that high glucose and high FFAs reduced the viability of RSC96 SCs by up to 51%, whereas Liraglutide reduced oxidative stress by upregulating antioxidant enzymes, and thus protected cells from apoptosis. Liraglutide also inhibited NFκB-mediated inflammation, inducing SCs to switch from pro-inflammatory cytokine production to anti-inflammatory cytokine production. Moreover, Liraglutide upregulated the production of neurotrophic factors and myelination-related proteins, and these protective effects appear to be synergistically linked to insulin signaling. Taken together, our findings demonstrate that Liraglutide ameliorates diabetes-related SC dysfunction through the above-mentioned mechanisms, and suggest that modulating GLP-1 signaling in SCs may be a promising strategy against DN.

The aim of this work was to appraise the potential associations of single nucleotide polymorphisms (SNPs) of long non-coding RNA growth arrest-specific 5 ( GAS5 ) with diabetic retinopathy (DR) in a diabetes mellitus (DM) population. Two loci of the GAS5 SNPs (rs55829688 and rs145204276) were genotyped via TaqMan allelic discrimination in 449 non-DR patients and 273 DR subjects. The SNP rs145204276 Del/Del showed a significantly higher distribution in the DR group compared to the non-DR group (AOR: 2.487, 95% CI: 1.424-4.344, p = 0.001). During subgroup analyses, the non-proliferative diabetic retinopathy (NPDR) subgroup demonstrated a significantly higher ratio of the SNP rs145204276 Del/Del (AOR: 2.917, 95% CI: 1.574-5.406, p = 0.001) and Ins/Del + Del/Del (AOR: 1.242, 95% CI: 1.016-1.519, p = 0.034) compared to the non-DR population, while the proliferative diabetic retinopathy (PDR) subgroup did not reveal significant differences in either SNP rs145204276 or rs55829688 distributions compared to the non-DR group. Furthermore, patients with a GAS5 SNP rs145204276 Del/Del showed a significantly shorter DM duration than the wild type (Ins/Ins) ( p = 0.021). In conclusion, our findings demonstrate that the GAS5 SNP rs145204276 Del/Del variant is associated with an increased susceptibility to DR in DM patients, particularly in those patients with NPDR.

This study aimed to examine the prognostic significance of preoperative inflammation-associated blood cell markers in the metachronous contralateral recurrence of upper tract urothelial carcinoma (UTUC). Patients with nonmetastatic UTUC treated in Taiwan and the U.S. between 1990 and 2017 were included. The Kaplan-Meier method was used to calculate the contralateral recurrence rate, and multivariate logistic regression was performed to study the association of blood cell markers and clinicopathological characteristics with contralateral recurrence. Overall, a total of 1039 patients were included in this study, 52 of whom (5.0%) developed metachronous recurrence of the contralateral side. Kaplan-Meier analysis indicated that a history of bladder cancer ( p = 0.006), multiple tumors ( p = 0.016), advanced chronic kidney disease (CKD; p < 0.001), elevated serum white blood cell (WBC) count ( p < 0.001), and decreased hemoglobin levels ( p = 0.001) significantly reduced the contralateral recurrence-free survival. Multivariate analysis showed that multiple tumors (hazard ratio (HR), 1.87; p = 0.030), advanced CKD (HR, 2.63; p = 0.002) and increased WBC count (HR, 2.60; p = 0.001) were independent risk factors for higher contralateral recurrence rate. Notably, advanced CKD was a significant factor regardless of the patient's region. In summary, multiple tumors, advanced CKD and elevated serum WBC count are independent predictors of contralateral recurrence in patients with UTUC. It is recommended that patients with these adverse characteristics be closely followed up to monitor the opposite upper urinary tract.

Purpose: Sleep disturbance is one of the major complaints among patients with diabetes. The status of diabetes control and associated complications may contribute to sleep disturbance. This study explored night time sleep and excessive daytime sleepiness in adults with type 2 diabetes and examined the association of diabetes control and associated complications on their sleep quality. Methods: A retrospective cohort study design was used. Type 2 diabetic patients (87 females and 79 males, aged 63.1 ± 10.5 years) were recruited from the outpatient clinics of the endocrine department. Sleep quality was assessed by the Pittsburg Sleep Quality Index and the Epworth Sleepiness Scale. Diabetes control and complications were obtained by retrospectively reviewing patients' medical records over 1 year prior to study enrollment. Results: 72.3% of recruited patients had poor glycemic control, and 71.1% had at least one diabetic complication. 56.0% of patients experienced poor sleep quality, and 24.1% had excessive daytime sleepiness. Those who were female (OR = 3.45) and who had ophthalmological problems (OR = 3.17) were associated with poor night time sleep quality, but if they did exercise to the point of sweating (OR = 0.48) reduced the risk of poor sleep quality. Furthermore, poor sleep quality (OR = 4.35) and having nephropathy (OR = 3.78) were associated with a higher risk of excessive daytime sleepiness. Conclusions: Sex, ophthalmological problems, nephropathy, and no exercise to the point of sweating are associated with sleep problems in patients with type 2 diabetes. Both lifestyle behaviors and diabetic complications affect sleep disturbances in patients with diabetes.

This study aimed to determine whether daily physical activity in young and older adults with T2DM is associated with diabetes control. A prospective correlational study involving 206 young (≤65 years) and older (>65 years) adults was conducted. The International Physical Activity Questionnaire was used to assess their daily physical activity levels. Patients' mean HbA1c level was 7.8% (±1.4), and 95.9% of patients had unsatisfactory diabetes control. Performing more minutes per week of moderate-intensity daily physical activity was associated with a lower risk of glycemia in both young and older adults. Furthermore, moderate daily physical activity significantly lowered the risk of glycemia. Health personnel must encourage patients to engage in moderate daily physical activities to improve diabetes control.

We aimed to determine the influence of osteoporosis and stress urinary incontinence in women. We hypothesized that women with osteoporosis had an increased risk of stress urinary incontinence. This retrospective study used data from the Taiwan Longitudinal Health Insurance database from 2005-2009. The study population was screened to identify women (age ≥ 40 years) newly diagnosed with osteoporosis (ICD-9-CM code = 733.0, 733.1). The osteoporosis cohort included 6125, and the non-osteoporosis cohort included 12,250 participants. The newly diagnosed stress urinary incontinence incidence was calculated to determine the influence of osteoporosis and stress urinary incontinence. We used the Cox proportional hazards model to predict the effects of stress urinary incontinence and the Kaplan-Meier analysis to estimate the cumulative incidence of stress urinary incontinence in women. Participants with osteoporosis experienced a 1.79 times higher risk than that of the non-osteoporosis group (95% CI = 1.28-2.51) for stress urinary incontinence, regardless of age. We did not observe a higher risk of stress urinary incontinence in participants with pathological fractures compared to those with simple osteoporosis. Our data emphasized that physicians and nurses should conduct urinary incontinence screening in women with osteoporosis to recommend proper treatment, medical help or to bring the disorder to light.

Blood pressure (BP) control is crucial for minimizing the risk of mortality and hematoma growth in patients with acute intracranial hemorrhage (ICH). We aimed to determine the optimal BP range associated with improved patient outcomes. From the Medical Information Mart for Intensive Care-III database, we identified 1493 patients (age, 18-99 years) admitted to the intensive care unit (ICU) with non-traumatic ICH. The 3-day and 14-day mortality of ICU admissions were compared at different BP ranges. Generalized additive models were used to assess the optimal range of initial mean arterial pressure, systolic blood pressure (SBP), and diastolic blood pressure, and these were identified to be 70-100, 120-150, and 60-100 mmHg, respectively. The 3-day or 14-day mortality showed U-shaped correlations with BP ranges. Our results show that an initial SBP between 120 and 150 mmHg is associated with minimal risk of mortality risk. This recommendation can assist physicians to achieve better outcomes for patients with ICH., Competing Interests: The authors declare no conflict of interest.

We sought to examine the relationship between microtubule-associated proteins (MAPs) and the prognosis of urothelial carcinoma by assessing the microtubule bundle formation genes using a reappraisal transcriptome dataset of urothelial carcinoma (GSE31684). The result revealed that microtubule-associated protein 1b ( MAP1B ) is the most significant upregulated gene related to cancer progression. Real-time reverse-transcription polymerase chain reaction was used to measure MAP1B transcription levels in urothelial carcinoma of the upper tract (UTUC) and the bladder (UBUC). Immunohistochemistry was conducted to detect MAP1B protein expression in 340 UTUC and 295 UBUC cases. Correlations of MAP1B expression with clinicopathological status, disease-specific survival, and metastasis-free survival were completed. To assess the oncogenic functions of MAP1B , the RTCC1 and J82 cell lines were stably silenced against their endogenous MAP1B expression. Study findings indicated that MAP1B overexpression was associated with adverse clinical features and could independently predict unfavorable prognostic effects, indicating its theranostic value in urothelial carcinoma.

In this study, a long carbon chain dimer acid is introduced into a nylon 6 structure and is copolymerized with different structural amines to produce amorphous nylon 6 by 4,4'-methylenebis(2-methylcyclohexylamine) (MMCA) in different copolymerization ratios. The effect of different structures and copolymerization ratios on the properties of nylon 6 is determined, along with the thermal properties, crystallinity, water absorption, dynamic mechanical properties, and optical properties. It is found that the melting point and the thermal cracking temperature Td10 of nylon 6 are respectively between 176 °C and 213 °C and 378 °C to 405 °C. The effect of introducing a bicyclohexane group containing a methyl side chain is greater than that of a meta-benzene ring, so COMM (synthesized by Caprolactam (C), dimer oleic acid (OA), and 4,4'-Methylenebis(2-methylcyclohexylamine) (MMCA)) has the lowest melting point, enthalpy, and crystallinity. As the copolymerization ratio increases, its thermal properties decrease. 10% is the lowest crystallinity. The amine structure containing a bicycloalkyl group has lower water absorption and a 10% copolymerization ratio gives the lowest water absorption. It contains the bicycloalkyl group, COM (synthesized by Caprolactam (C), dimer oleic acid (OA) and 4,4'-Methylenebis(cyclohexylamine) (MCA)), which has the highest loss modulus. The lowest loss modulus is noted for a copolymerization ratio of 7% and the value of tan δ increases as the copolymerization ratio increases. The introduction of nylon 6 with the bicycloalkyl groups, COMM and COM, significantly increases transparency. As the copolymerization ratio increases, the transparency increases and the haze decreases. The best optical properties are achieved for 10% copolymerization.

Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen the differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays in the training phase ( n = 72) and validation phase ( n = 178). The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. The three-plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer., Competing Interests: The authors declare no conflict of interest.

Falls are the primary cause of accidents for the elderly in the living environment. Reducing hazards in the living environment and performing exercises for training balance and muscles are the common strategies for fall prevention. However, falls cannot be avoided completely; fall detection provides an alarm that can decrease injuries or death caused by the lack of rescue. The automatic fall detection system has opportunities to provide real-time emergency alarms for improving the safety and quality of home healthcare services. Two common technical challenges are also tackled in order to provide a reliable fall detection algorithm, including variability and ambiguity. We propose a novel hierarchical fall detection algorithm involving threshold-based and knowledge-based approaches to detect a fall event. The threshold-based approach efficiently supports the detection and identification of fall events from continuous sensor data. A multiphase fall model is utilized, including free fall, impact, and rest phases for the knowledge-based approach, which identifies fall events and has the potential to deal with the aforementioned technical challenges of a fall detection system. Seven kinds of falls and seven types of daily activities arranged in an experiment are used to explore the performance of the proposed fall detection algorithm. The overall performances of the sensitivity, specificity, precision, and accuracy using a knowledge-based algorithm are 99.79%, 98.74%, 99.05% and 99.33%, respectively. The results show that the proposed novel hierarchical fall detection algorithm can cope with the variability and ambiguity of the technical challenges and fulfill the reliability, adaptability, and flexibility requirements of an automatic fall detection system with respect to the individual differences.

Falls are the primary cause of accidents among the elderly and frequently cause fatal and non-fatal injuries associated with a large amount of medical costs. Fall detection using wearable wireless sensor nodes has the potential of improving elderly telecare. This investigation proposes a ZigBee-based location-aware fall detection system for elderly telecare that provides an unobstructed communication between the elderly and caregivers when falls happen. The system is based on ZigBee-based sensor networks, and the sensor node consists of a motherboard with a tri-axial accelerometer and a ZigBee module. A wireless sensor node worn on the waist continuously detects fall events and starts an indoor positioning engine as soon as a fall happens. In the fall detection scheme, this study proposes a three-phase threshold-based fall detection algorithm to detect critical and normal falls. The fall alarm can be canceled by pressing and holding the emergency fall button only when a normal fall is detected. On the other hand, there are three phases in the indoor positioning engine: path loss survey phase, Received Signal Strength Indicator (RSSI) collection phase and location calculation phase. Finally, the location of the faller will be calculated by a k-nearest neighbor algorithm with weighted RSSI. The experimental results demonstrate that the fall detection algorithm achieves 95.63% sensitivity, 73.5% specificity, 88.62% accuracy and 88.6% precision. Furthermore, the average error distance for indoor positioning is 1.15 ± 0.54 m. The proposed system successfully delivers critical information to remote telecare providers who can then immediately help a fallen person.

Background: Liquid crystal display (LCD) manufacturing involves three fabrication processes: array, panel and module processes, which result in different levels of volatile organic compound (VOC) exposure. The aim of this study was to assess the potential reproductive endocrine effects of occupational exposures during LCD manufacturing predictive of menstrual cycles as subclinical markers of female reproductive dysfunction effects of low-dose exposures., Methods: A total of 94 fabrication workers were followed for one complete menstrual cycle using daily urine samples: 23 were from the array, 53 from the panel, and 18 from the module work areas. The menstrual cycle characteristics of the study population were measured using a self-administered questionnaire. Urine samples were collected during the first urination in the morning for at least one complete menstrual cycle. The urine was then analyzed to determine the urinary concentrations of follicular stimulating hormone (FSH), estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG). The results of this analysis were used to assess the potential effects of chemical exposure as determined by handheld volatile organic compound (VOC) monitors and 24 h canisters., Results: The concentration of total VOCs was much higher in the module making area (ND-21,000 ppb) than in panel (ND-766 ppb) and array (58-1,472 ppb) making areas. The concentrations of ethanol and acetone were much higher in the module (1,974.9 and 2,283.2 ppb, respectively) and panel (2256.9 and 592.2 ppb, respectively) making areas. Compared to those in the array making area, we found that E1C (12.55, 95% confidence interval (CI): 8.49, 16.61 μg/mg Cr) and PdG (0.53, 95% CI: 0.29, 0.77 μg/mg Cr) levels in the module group were significantly higher in the early follicular phase; E1C (11.93, 95% CI: 6.21, 17.65 μg/mg Cr) and PdG (0.53, 95% CI: 0.29, 0.77 μg/mg Cr) levels were significantly higher in the periovulatory phase; and all the hormone levels, FSH (1.48, 95% CI: 0.81, 2.15 μg/mg Cr), E1C (9.29, 95% CI: 4.92, 13.66 μg/mg Cr), and PdG (1.01, 95% CI: 0.42, 1.60 μg/mg Cr) were also significantly higher in the luteal phase. In addition, the FSH (0.89, 95% CI: 0.07, 1.71 μg/mg Cr) level in the panel group was significantly higher but E1C (-4.49, 95% CI: -7.90, -1.08 μg/mg Cr) was lower in the early follicular phase; and E1C (-5.16, 95% CI: -9.61, -0.71 μg/mg Cr) level was significantly lower in the periovulatory phase., Conclusions: Our findings add to the evidence that exposure to multiple low-level chemicals is associated with modest changes in reproductive hormone urinary concentrations in healthy premenopausal women. In addition, the FSH (0.89, 95% CI: 0.07, 1.71 μg/mg Cr) level in the panel group was significantly higher but E1C (-4.49, 95% CI: -7.90, -1.08 μg/mg Cr) lower in the early follicular phase; and E1C (-5.16, 95% CI: -9.61, -0.71 μg/mg Cr) level was significantly lower in the periovulatory phase.