A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Alogliptin in Pediatric Participants with Type 2 Diabetes Mellitus.

Introduction: There is an unmet need for pharmacological therapies for children with type 2 diabetes mellitus (T2DM). We assessed the efficacy and safety of an oral dipeptidyl peptidase-4 inhibitor, alogliptin, 25 mg once daily (QD), as a potential treatment for pediatric patients with T2DM.

Methods: This phase 3, 52-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in children and adolescents (10-17 years old) with T2DM.

Synthesis and Evaluation of diaryl ether modulators of the leukotriene A hydrolase aminopeptidase activity.

Activation of the aminopeptidase (AP) activity of leukotriene A hydrolase (LTAH) presents a potential therapeutic strategy for resolving chronic inflammation. Previously, ARM1 and derivatives were found to activate the AP activity using the alanine-p-nitroanilide (Ala-pNA) as a reporter group in an enzyme kinetics assay. As an extension of this previous work, novel ARM1 derivatives were synthesized using a palladium-catalyzed Ullmann coupling reaction and screened using the same assay.

Efficient removal of tetracycline hydrochloride through novel Fe/BiOBr/BiWO photocatalyst prepared by dual-strategy under visible-light irradiation.

It is important to investigate whether combining two modification strategies has a synergistic effect on the activity of photocatalysts. In this manuscript, Fe-doped BiOBr/BiWO heterojunctions were synthesized by a one-pot solvothermal method, and excellent photocatalytic performance was obtained for the degradation of tetracycline hydrochloride (TCH) in water without the addition of surfactant. Combining experiments and characterization, the synergistic effect between Fe ion doping and the BiOBr/BiWO heterojunction was elucidated.

Metabolomic Profiling of Human Urine Samples Using LC-TIMS-QTOF Mass Spectrometry.

The identification of metabolites in biological samples is challenging due to their chemical and structural diversity. Ion mobility spectrometry (IMS) separates ionized molecules based on their mobility in a carrier buffer gas giving information about the ionic shape by measuring the rotationally averaged collision cross-section (CCS) value. This orthogonal descriptor, in combination with the /, isotopic pattern distribution, and MS/MS spectrum, has the potential to improve the identification of molecular molecules in complex mixtures.

Glycemic Control Following GLP-1 RA or Basal Insulin Initiation in Real-World Practice: A Retrospective, Observational, Longitudinal Cohort Study.

Introduction: Injectable therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin (BI) are well-established agents for people with type 2 diabetes (T2D). This study aimed to investigate real-world effectiveness of GLP-1 RAs or BI in adults with T2D poorly controlled on oral antihyperglycemic drugs (OADs).

Methods: This was a retrospective, observational, longitudinal cohort study of adults with T2D from the US Optum Humedica® database and UK Clinical Practice Research Datalink, who initiated either injectable between January 1, 2010, and June 30, 2016.

Real-world evidence of the effectiveness on glycaemic control of early simultaneous versus later sequential initiation of basal insulin and glucagon-like peptide-1 receptor agonists.

Aim: To assess the impact of the timing of initiating both basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on reaching glycaemic control targets over 6 and 12 months in people with type 2 diabetes (T2D) uncontrolled on oral antihyperglycaemic drugs with an HbA1c of 9% or higher.

Methods: This retrospective cohort study assessed the impact of the timing of initiating both basal insulin and GLP-1 RA therapies on reaching glycaemic targets (HbA1c < 7% and <8%, and ≥1% and ≥2% HbA1c reduction) over 12 months in people with markedly uncontrolled T2D (HbA1c ≥ 9%) on oral antihyperglycaemic drugs identified on the Optum Humedica database (electronic medical records; 1 January 2011 to 30 June 2017). Study cohorts were defined by the days between initiating each injectable: cohort A, 30 days or less (simultaneous initiation) and cohorts B, 31-90, C, 91-180, D, 181-270 and E, 271-360 days (sequential initiation).

A Real-World Observational Study Evaluating the Probability of Glycemic Control with Basal Insulin or Glucagon-Like Peptide-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes.

Introduction: The effectiveness of basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in providing glycemic control in patients with type 2 diabetes (T2D) in Japanese routine practice is not well known. This real-world observational study evaluated the probability of achieving glycemic control in Japanese patients with T2D uncontrolled by oral antidiabetic drugs (OADs) who initiated BI or GLP-1 RA therapy.

Methods: Patients with T2D aged ≥ 18 years initiating BI or GLP-1 RA therapy following treatment with OADs were selected from real-world data (RWD) retrieved from a large electronic medical record database in Japan, using data from 01 January 2010 to 30 June 2019.

Impact of Simultaneous Versus Sequential Initiation of Basal Insulin and Glucagon-like Peptide-1 Receptor Agonists on HbA1c in Type 2 Diabetes: A Retrospective Observational Study.

Introduction: When and how to intensify treatment in patients with type 2 diabetes (T2D) not achieving glycated hemoglobin (HbA1c) targets with oral antidiabetic drugs (OADs) in clinical practice remains a matter of clinical preference. This pilot study was conducted using the retrospective observational data from such patients to evaluate the impact on HbA1c of three treatment sequences: simultaneous initiation of basal insulin (BI) and a glucagon-like peptide-1 receptor agonist (GLP-1 RA; Cohort 1); BI followed by GLP-1 RA initiation within a 90-day timeframe (Cohort 2); or BI followed by GLP-1 RA initiation beyond 90 days (Cohort 3).

Methods: Data from the regional US electronic medical records database, Research Action for Health Network (REACHnet), were extracted for all patients with T2D aged ≥ 18 years who had encounter dates between January 2011 and August 2017 and ≥ 1 HbA1c laboratory value(s) < 90 days before BI initiation and ≥ 2 HbA1c laboratory values within 1 year after BI initiation and who met the inclusion criteria for GLP-1 RA initiation set for Cohorts 1, 2, or 3.

Probability of Achieving Glycemic Control with Basal Insulin in Patients with Type 2 Diabetes in Real-World Practice in the USA.

Introduction: Basal insulin (BI) plays an important role in treating type 2 diabetes (T2D), especially when oral antidiabetic (OAD) medications are insufficient for glycemic control. We conducted a retrospective, observational study using electronic medical records (EMR) data from the IBM Explorys database to evaluate the probability of achieving glycemic control over 24 months after BI initiation in patients with T2D in the USA.

Methods: A cohort of 6597 patients with T2D who started BI following OAD(s) and had at least one valid glycated hemoglobin (HbA1c) result recorded both within 90 days before and 720 days after BI initiation were selected.

The application of 3D printed surgical guides in resection and reconstruction of malignant bone tumor.

The clinical value of 3D printed surgical guides in resection and reconstruction of malignant bone tumor around the knee joint were studied. For this purpose, a sample of 66 patients from October 2013 to October 2015 were randomly selected and further divided into control group and observation group, each group consisted of 33 cases. The control group was treated by conventional tumor resection whereas, in the observation group, the tumor was resected with 3D printed surgical guide.

The value of computer-assisted navigation for bone reconstruction after tumor resection.

This study was designed to evaluate the use of computer-assisted navigation with computed tomography (CT) images for bone reconstruction after resection in malignant bone tumor treatment. Forty-five patients with malignant bone tumors were recruited for this study. CT scan images in a computer-assisted navigation system were used to assist during the osteotomy, the pairing with allografts, and the monitoring of the allograft and joint lines to perform joint reconstruction.

Combining the G-protein-coupled receptor 40 agonist fasiglifam with sitagliptin improves glycaemic control in patients with type 2 diabetes with or without metformin: A randomized, 12-week trial.

Aims: To evaluate the efficacy and safety of fasiglifam, an orally active G-protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin).

Materials And Methods: In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg. The primary endpoint was change from baseline glycated haemoglobin (HbA1c) at 12 weeks; a key secondary endpoint was change in fasting plasma glucose (FPG).

Evaluation of the pharmacokinetics and safety of a single oral dose of fasiglifam in subjects with normal or varying degrees of impaired renal function.

Introduction: Approximately one-third of patients with type 2 diabetes mellitus (T2DM) have concurrent renal impairment. There are limited therapeutic options for these patients. Fasiglifam is a G protein-coupled receptor 40 agonist that was under investigation for the treatment of T2DM.

The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models.

Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods.

Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel.

Objective: Ramelteon, an MT(1)/MT(2) melatonin receptor agonist, was evaluated for its ability to reduce sleep-onset difficulties associated with eastward jet travel.

Methods: Healthy adults (n=110) with a history of jet lag sleep disturbances were flown eastward across five time zones from Hawaii to the east coast of the US. Ramelteon 1, 4, or 8 mg or placebo was administered 5 min before bedtime (local time) for four nights.

Effect of ramelteon on middle-of-the-night balance in older adults with chronic insomnia.

Study Objectives: To evaluate the effect of ramelteon on middle-of-the-night balance, mobility, and memory in older insomniacs.

Methods: Thirty-three older adults (age > or = 65 years) with insomnia were enrolled in a single-dose, 3-way crossover study of balance after bedtime administration of ramelteon, 8 mg; zolpidem, 10 mg (positive control); or placebo. Subjects were administered study medication 30 minutes before bedtime and were awakened 2 hours after dosing to evaluate balance (Sensory Organization Test), turning speed and stability, memory (immediate and delayed word recall), and adverse events.

Circadian phase-shifting effects of repeated ramelteon administration in healthy adults.

Study Objectives: To assess the ability of repeated daily oral ramelteon to facilitate re-entrainment of human circadian rhythms after an imposed phase advance of the sleep-wake cycle.

Methods: A total of 75 healthy adult volunteers aged 18-45 years remained in a sleep laboratory for 6 days and 5 nights; a 5-h phase advance in their sleep-wake cycle was imposed under dim-light conditions. Oral ramelteon (1,2, 4, or 8 mg once daily for 4 days) or placebo was administered 30 min before bedtime.

Use of computerized dynamic posturography to assess balance in older adults after nighttime awakenings using zolpidem as a reference.

Background: Computerized dynamic posturography (CDP) has been used to detect balance and stability impairments in adults of all ages. The goal of the current pilot study was to evaluate balance in healthy older adults after a middle-of-the-night awakening and to assess the ability of CDP to measure effects of bedtime zolpidem administration.

Methods: Two studies used CDP to evaluate balance in healthy older adults (> or = 65 years) during middle-of-the-night awakenings.

Genome-wide transcriptome expression in the liver of a mouse model of high carbohydrate diet-induced liver steatosis and its significance for the disease.

Purpose: To perform a large-scale gene profiling of the liver in a mouse model of fatty liver induced by high carbohydrate (sucrose) diet (HCD) to gain a deeper insight into potential mechanisms of diet-induced hepatic steatosis.

Methods: C57BL/6 male mice were fed either a purified, control diet or a HCD for 16 weeks. HCD feeding led to marked liver steatosis without inflammation or necrosis.

Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies.

The Hodgkin cells and Reed-Sternberg cells (HRS) of classical Hodgkin lymphoma (CHL) are derived from germinal center B cells. The pathogenesis of CHL is unclear but constitutive activation of NFkappaB may contribute. Proteasome inhibition aimed at inhibiting NFkappaB has been shown to result in apoptosis in HRS cells.

Developing and evaluating genomics- or proteomics-based diagnostic tests: statistical perspectives.

The completion of the Human Genome Project and the ongoing sequencing of mouse, rat, and other genomes have led to an explosion of genetics-related technologies that are finding their way into all areas of biological research in both basic sciences and clinical applications. High-throughput genomics and proteomics technology has been quickly adapted to develop tools for clinical and pharmacological applications. Because molecular alterations usually occur much earlier than histological, physiological, and clinical abnormality, researchers hope to extend the applications of genomics and/or proteomics technology to early diagnosis of diseases and clinical outcome prognosis.

Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl.

Human immunodeficiency virus (HIV) infection continues to rise in drug-abusing populations and causes a dementing illness in a subset of individuals. Factors contributing to the development of dementia in this population remain unknown. We found that HIV-infected individuals with the E4 allele of Apolipoprotein E (ApoE) or history of intravenous drug abuse had increased oxidative stress in the CNS.

Transcriptome profile of macrophages from atherosclerosis-sensitive and atherosclerosis-resistant mice.

We performed a strain intercross between two apoE-deficient mouse strains with a large difference in lesion susceptibility and measured aortic root lesion area in 98 female F(2) progeny. Total RNA was prepared from bone marrow-derived macrophages, and RNA from the five mice with the smallest and largest lesions were used for microarray gene expression profiling. Remarkably, approximately 5% of the 12,288 expressed transcripts were differentially expressed in the atherosclerosis-susceptible and atherosclerosis-resistant bone marrow-derived macrophages (unadjusted p < 0.

Separation of porphyrin-based photosensitizer isomers by laser-induced fluorescence capillary electrophoresis.

Methods for the separation of photosensitizer isomers, such as benzoporphyrin derivative monoacid, benzoporphyrin ethyl monoacid, 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a, diethyleneglycol diester benzoporphyrin derivative, tin ethyl etiopurpurin, and phthalocyanine tetrasulfonate, have been systematically developed by CE. Detection was accomplished by UV absorption at 214 nm or by LIF with excitation at 442/488 nm and emission at 690 nm. The effects of three major experimental parameters of buffer types, organic solvents, and surfactant additives are described.

Permeable guidance channels containing microfilament scaffolds enhance axon growth and maturation.

Successful peripheral nerve regeneration is still limited in artificial conduits, especially for long lesion gaps. In this study, porous poly(L-lactide-co-DL-lactide, 75:25) (PLA) conduits were manufactured with 16 poly(L-lactide) (PLLA) microfilaments aligned inside the lumen. Fourteen and 18 mm lesion gaps were created in a rat sciatic nerve lesion model.