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0026 and P=0.0093) and Mexican American boys and girls (P < 0.0001 and P < 0.0001), respectively. Despite these findings, both insulin and homeostatic model assessment of insulin resistance were greater in non-Hispanic Black compared to non-Hispanic White participants.
Here we describe fasting C-peptide levels in a non-diabetic adolescent population. These data provide crucial insight into evaluating racial differences in endogenous insulin release and clearance and will provide novel information which can be used in assessing residual β-cell function and response to intervention therapy.
Here we describe fasting C-peptide levels in a non-diabetic adolescent population. These data provide crucial insight into evaluating racial differences in endogenous insulin release and clearance and will provide novel information which can be used in assessing residual β-cell function and response to intervention therapy.
To conduct a pooled analysis to assess the performance of intermittently scanned continuous glucose monitoring (isCGM) in association with the rate of change in sensor glucose in a cohort of children, adolescents, and adults with type 1 diabetes.
In this pooled analysis, isCGM system accuracy was assessed depending on the rate of change in sensor glucose. Clinical studies that have been investigating isCGM accuracy against blood glucose, accompanied with collection time points were included in this analysis. isCGM performance was assessed by means of median absolute relative difference (MedARD), Parkes error grid (PEG) and Bland-Altman plot analyses.
Twelve studies comprising 311 participants were included, with a total of 15 837 paired measurements. The overall MedARD (interquartile range) was 12.7% (5.9-23.5) and MedARD differed significantly based on the rate of change in glucose (P < 0.001). An absolute difference of -22 mg/dL (-1.2 mmol/L) (95% limits of agreement [LoA] 60 mg/dL (3.3 mmol/L), -103 mg/dL (-5.7 mmol/L)) was found when glucose was rapidly increasing (isCGM glucose minus reference blood glucose), while a -32 mg/dL (1.8 mmol/L) (95% LoA 116 mg/dL (6.4 mmol/L), -51 mg/dL (-2.8 mmol/L)) absolute difference was observed in periods of rapidly decreasing glucose.
The performance of isCGM was good when compared to reference blood glucose measurements. The rate of change in glucose for both increasing and decreasing glucose levels diminished isCGM performance, showing lower accuracy during high rates of glucose change.
The performance of isCGM was good when compared to reference blood glucose measurements. The rate of change in glucose for both increasing and decreasing glucose levels diminished isCGM performance, showing lower accuracy during high rates of glucose change.
To investigate the association between treatment with dulaglutide and glycaemic variability (GV) in adult patients with type 2 diabetes mellitus (T2D).
Post hoc analyses of six randomized, phase 3 studies were conducted to investigate the association between treatment with dulaglutide 1.5 mg once weekly and GV in adult patients with T2D. Using data from seven- and eight-point self-monitored plasma glucose (SMPG) profiles over up to 28 weeks of treatment, GV in within- and between-day SMPG, and between-day fasting glucose from SMPG (FSMPG) was assessed according to standard deviation and coefficient of variation.
Pooled data from five studies with dulaglutide as monotherapy or added to oral glucose-lowering medication, without concomitant insulin treatment, revealed clinically meaningful reductions in within- and between-day SMPG, and between-day FSMPG variability from baseline in the dulaglutide group. Comparisons between treatment groups in two studies demonstrated that reductions from baseline in withe was associated with a reduction in GV to a greater degree than insulin glargine. When added to insulin glargine, treatment with dulaglutide was associated with greater decreases in GV compared with insulin glargine alone. As reduced GV may be associated with better outcomes, these findings may have clinical relevance.
With the rapid increase in the average age of society, the number of people with dementia has increased in Japan. Thus, the need to prevent dementia is greater, and prevention programs have been implemented throughout Japan. This study aims to evaluate both the short-term and the long-term effects of a dementia prevention program on physical and cognitive function in community-dwelling elderly.
Cognitive and physical assessments were carried out at baseline for a sample including 57 elderly participants. The participants underwent an intensive training program lasting for 2 h per week for 10 days. After the last period of training, the assessment performed was reapplied. The outcome measures used to establish effectiveness were a Mini-Mental State Examination, Five Cognitive Tests, a Cognitive Function Instrument, a Timed Up & Go Test, a grip strength evaluation, a Geriatric Depression Scale, an EQ-5D and a Physical Activity Scale for the Elderly. Participants were then divided randomly into two groupthough the effect of the booster training was not clear, the functions of the elderly participants were found to be maintained during a follow-up assessment. The study findings recommend conducting intensive training for the community-dwelling elderly without follow-up training.
This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self-monitoring fetal heart rate (FHR) in low-risk singleton pregnant women.
This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self-monitoring FHR using the mobile CTG device.
A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4-100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self-monitoring using the iCTG.
The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.
The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.Nonglioblastomatous diffuse glioma (non-GDG) is a heterogeneous neuroepithelial tumor that exhibits a varied survival range from 4 to 13 years based on the diverse subtypes. Recent studies demonstrated novel molecular markers can predict prognosis for non-GDG patients; however, these findings as well as pathological classification strategies show obvious limitations on malignant transition due to the heterogeneity among non-GDGs. Therefore, developing reliable prognostic biomarkers and therapeutic targets have become an urgent need for precisely distinguishing non-GDG subtypes, illuminating the underlying mechanism. Nuclear factor κβ (NF-κB) has been proved to be a significant nuclear transcriptional regulator with specific DNA-binding sequences to participate in multiple pathophysiological processes. However, the underlying mechanism of NF-κB activation still needs to be further investigated. Herein, our results indicated retinol-binding protein 1 (RBP1) was significantly upregulated in the IDHWT and 1p19qNon co-del non-GDG subtypes and enriched RBP1 expression was markedly correlated with more severe outcomes. Additionally, malignant signatures of the non-GDG cells including proliferation, migration, invasion, and self-renewal were significantly suppressed by lentiviral knockdown of RBP1. To further explore the underlying molecular mechanism, bioinformatics analysis was performed using databases, and the results demonstrated RBP1 was strongly correlated with tumor necrosis factor α (TNFα)-NF-κB signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB-kinase α (IKKα) and thus decreased NF-κB expression via decreasing the degradation of the IκBα protein. Altogether, these data suggested RBP1-dependent activation of NF-κB signaling promoted malignancy of non-GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for non-GDG.Extramammary Paget's disease (EMPD) is a rare adnexal neoplasm commonly seen in the genital areas among the senior population. The prognosis of advanced EMPD is not favorable; thus, the development of potential treatments has long been sought. Cyclin-dependent kinase (CDK) 4/6 inhibitors such as abemaciclib and palbociclib have been proven effective against metastatic breast cancer; however, no studies have addressed CDK4/6 inhibitors as an EMPD treatment. We herein examine the efficacy of CDK4/6 inhibitors against an EMPD patient-derived xenograft (PDX) model. Abemaciclib (50 mg/kg/day) or palbociclib (120 mg/kg/day) was given orally to tumor-bearing NOD/Scid mice over a 3-week period. We also investigated the protein expression levels of CDK4/6 and cyclin D1 through immunohistochemical staining using EMPD clinical samples. Treatment with abemaciclib or palbociclib as a single agent was found to significantly suppress tumor growth in EMPD-PDX. The Ki-67-positive ratio of the treated EMPD-PDX tumors was significantly lower than that of the nontreated tumors. Clinically, the expression levels of CDK4 and cyclin D1 were significantly higher in the EMPD tumor cells than in the normal epidermis. Our results suggest that CDK4/6 inhibitors could be novel and potent therapeutics for the treatment of EMPD.Candida albicans is the principal opportunistic fungal pathogen in nosocomial settings and resistance to antifungal drugs is on the rise. Antimicrobial peptides from natural sources are promising novel therapeutics against C. albicans. OsDef2 defensin was previously found to be active against only Gram-positive bacteria, whereas derived fragments Os and its cysteine-free analogue, Os-C, are active against Gram-positive and Gram-negative bacteria at low micromolar concentrations. In this study, OsDef2-derived analogues and fragments were screened for anticandidal activity with the aim to identify peptides with antifungal activity and in so doing obtain a better understanding of the structural requirements for activity and modes of action. Os, Os-C and Os(11-22)NH2 , a Os-truncated carboxy-terminal-amidated fragment, had the most significant antifungal activities, with minimum fungicidal concentrations (MFCs) in the micromolar range (6-28 μM). Lirafugratinib C. albicans killing was rapid and occurred within 30-60 min. Further investigations showed all three peptides interacted with cell wall derived polysaccharides while both Os and Os(11-22)NH2 permeabilized fungal liposomes.