Increasing evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contributes to atherosclerosis. Receptor for advanced glycation end-products (RAGE) has been linked to the pathogenesis of both the macrovascular and microvascular complications of diabetes. Cilostazol is used to treat diabetic vasculopathy by ameliorating HG-induced vascular dysfunction. In this study, we investigated whether the cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism. We investigated the effect of HG and cilostazol on RAGE signaling in A7r5 rat VSMCs. Aortic tissues of streptozotocin (STZ) diabetic mice were also collected. Aortic tissue samples from the diabetic mice exhibited a significantly decreased RAGE expression after cilostazol treatment. HG increased RAGE, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions, and was accompanied with increased reactive oxygen species (ROS), cell proliferation, adhesion and migration. Cilostazol significantly reversed HG-induced RAGE, ROS, downstream gene expressions and cell functions. RAGE knockdown significantly reversed the expressions of HG-induced vasculopathy related gene expressions and cell functions. Cilostazol with RAGE knockdown had additive effects on downstream ERK/NF-κB signaling pathways, gene expressions and cell functions of A7r5 rat VSMCs in HG culture. Both in vitro and in vivo experimental diabetes models showed novel signal transduction of cilostazol-mediated protection against HG-related VSMC dysfunction, and highlighted the involvement of RAGE signaling and downstream pathways.

Objective Although it is known that high uric acid (UA) level is associated with type 2 diabetes (T2DM) and metabolic syndrome (MetS), most of the previous studies were focused on adults. Since aging becomes a major problem for many societies, in this longitudinal study, we investigated the role of UA in future T2DM and MetS in a large cohort of people who were older than 65 years. Design A cross-sectional and longitudinal study. Setting/Participants 18,907 elderly (9,732 men, 9,175 women) aged above 65 years, enrolled from health check-up centers, were classified into three subgroups by 10-year intervals (young old 65-74 years, YO; old old 75-84 years, OO; and oldest old 85-94 years, ODO), with the average follow-up period of 4.3 years. Measurements The optimal cut-off values (CoVs) of baseline UA to predict future MetS and T2DM were determined by receiving operating characteristic (ROC) curve analysis. Using these CoVs of UA, the participants were divided into normal- and high-level groups of UA. Cox proportional hazard analysis was used to calculate hazard ratios (HRs) for the subjects with a high level of UA for the risk of future MetS and T2DM. In addition, Kaplan-Meier plots and log rank test were used to evaluate the time effect on the incidence of developing MetS and T2DM between the two groups. Results In ROC curve analysis, the optimal CoVs of baseline UA were 6.0, 6.3 and 6.7 mg/dl in YO, OO, and ODO men, respectively; 5.5 and 4.9 mg/dl in YO and OO women, respectively (all p < 0.05). However, the CoVs of UA in ODO women (6.1 mg/dl) failed to show its discriminant power (p = 0.13). The Cox regression analysis showed the YO subjects with a higher baseline level of UA had a higher risk of developing MetS (HRs 1.56 and 1.58 for men and women, respectively, both p < 0.001); as for T2DM the HRs were 1.39 and 1.57. In OO men, the HRs was 1.89 for developing future MetS. However, no significant findings could be noted in the ODO group. Kaplan-Meier plots and log rank test also showed the same findings. Conclusion Our study showed that old subjects with high levels of UA will have a higher chance to have MetS and T2DM, particularly in the YO group (6.0 mg/dl for men and 5.5 mg/dl for women, respectively). Using UA as one of the metabolic biomarkers may help clinicians to early detect and prevent MetS and diabetes.

Peripheral intravenous catheterization (PIVC) is pivotal to pediatric medical care; however, it is a challenging technique for pediatricians, and the parameters affecting successful pediatric PIVC establishment have not been fully investigated. This prospective observational study collected data from pediatric patients aged less than 18 years who required PIVC. The participants were categorized into five groups for subgroup analysis: newborn, infant, toddler, pre-school, and student (children and adolescent). Data on demography, biochemistry, and PIVC executors were examined to elucidate the most powerful factors affecting the success of PIVC. A total of 935 peripheral venous cannulations conducted within 1 year were studied. Age-subgroup analysis showed the highest failure rate (FR) of PIVC in the infant group (18.4%). No significant difference in BMI standard deviation score was noted among the groups (p-value = 0.430). Compared with those for the success group, more attempts, longer completion time, and more medical staff were needed for the failure group (all p-values < 0.05). A high serum procalcitonin level was correlated with an increased FR (p-value = 0.016). In addition, the success rate was positively associated with the seniority of the operators, except for the 3-year experienced R3 group (93.5%) showing a higher success rate than the 4-year experienced CR group (84.2%). Difficulty in setting up PIVC was the greatest in infants and even greater than that in newborns. Even though seniority was a cardinal factor in successful PIVC, a high FR was still noted despite the lack of continuous and steady practice.

Background: 20p13 microdeletion syndrome has been reported to be associated with developmental delays, intellectual disability, epilepsy, and unspecific dysmorphic characteristics. However, only a few cases of 20p13 microdeletion have been described, and therefore its typical features and precise pathogenesis remain elusive.Methods and Results: In this article, we report the case of a 9‐month‐old infant who presented with a large fontanelle, facial dysmorphism, and failure to thrive. Array‐comparative genomic hybridization (aCGH) analysis confirmed a 2.01‐Mb microdeletion in chromosome band 20p13 that involved SOX12 and NRSN2, both of which are considered paramount causative genes in patients with 20p13 microdeletion. To elucidate the typical features of 20p13 microdeletion, we further reviewed these previously reported cases and found that motor delay (90%) was the most common manifestation, followed by language delay (60%), abnormal digits (60%), mental retardation (50%), large fontanelle (50%), electroencephalography abnormalities (50%), and seizure (40%).Conclusion: This report highlights the potential of aCGH as a practical and powerful tool with which to detect submicroscopic chromosomal abnormalities in individuals presenting with a wide spectrum of phenotypes, ranging from facial dysmorphism to failure to thrive. Additionally, the literature review casts new light on the clinical features of 20p13 microdeletion.

Introduction: Hypothyroidism is a rare and possible cause of hyponatremia. However, the clinical epidemiology and risk of mortality (ROM) when they coexist still remain elusive. Objectives: We assessed the epidemiology and ROM among index patients with coexisting hypothyroidism and hyponatremia via a national population database. Patients and methods: This retrospective cohort study utilized Taiwan’s National Health Insurance program database. Distributions of definite sociodemographic factors were analyzed. The annual incidence among the overall group and sex-subgroups was investigated. In addition, potential factors influencing the ROM were also evaluated. Results: Of 4,549,226 patients from 1998 to 2015, a total of 3,140 index patients with concurrent hypothyroidism and hyponatremia were analyzed. The incidence rate increased tenfold from 1998 to 2015; average annual incidence rate was 174. Among the total participants, 57.1% were women; mean age was 72.6 ± 14.7 years and 88.8% were aged > 55 years. Although average length of stay (LOS) was 13.1 ± 15.4 days, the mortality group had significantly longer LOS than that in the survival group (12.9 days vs 22.2 days). Old age, catastrophic illness, cardiac dysrhythmia, and low hospital hierarchy were independent predictors of hospital mortality. The optimal LOS cutoff value for ROM prediction was 16 days. Index patients with LOS > 16 days increased ROM by 2.3-fold. Conclusions: Coexistent hypothyroidism and hyponatremia is rare, although the incidence increased gradually. Factors influencing the ROM, such as old age, underlying catastrophic status, cardiac dysrhythmia, hospital hierarchy, and LOS should be considered in clinical care.

Background: Rickets is a growth disorder that imposes a global health burden and causes disability in affected children. However, issues related to the clinical epidemiology and mortality risk of nutritional versus hereditary rickets have not been fully investigated in large population studies, particularly in Asia.Purpose: This study aimed to investigate the nationwide incidence, demographic characteristics, and mortality-related risk factors of pediatric rickets stratified by nutritional and hereditary subtypes.Methods: This study utilized data of subjects aged 0–18 years taken from Taiwan’s National Health Insurance Research Database. The database includes records of 31,488,321 individuals from January 1, 2008, to December 31, 2018. We analyzed all cases and conducted subgroup analyses of nutritional and hereditary rickets to examine how different etiologies affect the risk of mortality (ROM).Results: Among the 1,551 patients with rickets, nutritional rickets accounted for twice as many cases as hereditary rickets. Nutritional rickets primarily affects preschoolers without sex-based differences, whereas hereditary rickets is often diagnosed later with a male predominance. ROM in rickets is associated with a low household income, anemia, chronic kidney disease (CKD), hyperparathyroidism secondary to renal tubulopathy, and a prolonged length of hospital stay (LOS). Between 2012 and 2018, the overall incidence of rickets increased and the mortality rates decreased.Conclusion: Increasing incidence and decreasing mortality rates of rickets were noted, suggesting improvements in clinical awareness and disease management. influencing ROM, such as family income, anemia, CKD, hyperparathyroidism secondary to renal tubulopathy, and LOS are important considerations in the clinical care of rickets.