Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis.

Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant.

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of ELX-02 in Healthy Subjects.

ELX-02 is an investigational compound being developed as a therapy for genetic diseases caused by nonsense mutations such as cystic fibrosis. Structurally, ELX-02 is an aminoglycoside analogue that induces read-through of nonsense mutations through interaction with the ribosome, resulting in the production of full-length functional proteins. This phase 1 multiple-ascending-dose trial evaluated the safety and pharmacokinetics of ELX-02 in 62 healthy volunteers.

Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX-02 in Patients With Nephropathic Cystinosis.

The aim of this study was to assess the pharmacokinetics (PK) and safety of ELX-02 in a renally impaired population and apply these findings to the individualized dosing of patients with nephropathic cystinosis. This phase 1 renal impairment (RI; mild, moderate, or severe), single-dose, PK, and safety evaluation included 6 participants assigned to each RI group. Six healthy controls with normal renal function were matched to participants with renal impairment.

Transient ischemic attack presenting as recurrent migratory numbness by seconds: a rare case confirmed by transcranial Doppler micro-emboli monitoring.

Background: Transient ischemic attack (TIA) is a brief episode of cerebral ischemia. However, if a symptom is not presented as drop attack or hemiplegia, and alarming to the patient and the physician, how short of a symptom duration would raise the concern of a physician for TIA? It will be more complicated if the location of the neurological deficit is vagrant. This report highlights a rare TIA case which presented a very short duration of migratory patchy distribution numbness.

Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial.

To evaluate, post hoc, the efficacy and safety of abaloparatide by degree of renal impairment. ACTIVE was a phase 3, 18-month, randomized, double-blind, active-comparator, placebo-controlled study of postmenopausal women with osteoporosis who received subcutaneous abaloparatide 80 µg, placebo, or open-label teriparatide 20 µg daily. Patients with serum creatinine >2.

Up-regulated microRNA-199b-3p represses the apoptosis of cerebral microvascular endothelial cells in ischemic stroke through down-regulation of MAPK/ERK/EGR1 axis.

MicroRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. Therefore, the purpose of present study was to explore the effect of microRNA-199b-3p (miR-199b-3p) on the cerebral microvascular endothelial cells (CMECs) in middle cerebral artery occlusion-reperfusion (MCAO-R) mice by regulating MAPK/ERK/EGR1 axis. Mice were used to establish MCAO-R models and to measure the expression of miR-199b-3p and the MAPK/ERK/EGR1 axis-related genes.

Abaloparatide is an Effective Treatment Option for Postmenopausal Osteoporosis: Review of the Number Needed to Treat Compared with Teriparatide.

Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data.

ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis.

Purpose: In women with postmenopausal osteoporosis, we investigated the effects of 24 months of treatment with alendronate (ALN) following 18 months of treatment with abaloparatide (ABL) or placebo (PBO).

Methods: Women who completed ABL or PBO treatment in ACTIVE were eligible to receive up to 24 months of ALN. We evaluated the incidence of vertebral and nonvertebral fractures and changes in bone mineral density (BMD) during the entire 43-month period from ACTIVE baseline to the end of ACTIVExtend and for the 24-month extension only.

Fe(Ⅲ) ions enhanced catalytic properties of (BiO)CO nanowires and mechanism study for complete degradation of xanthate.

The wire-like Fe-doped (BiO)CO photocatalyst was synthesized by a hydrothermal method. The photocatalytic property of Fe-doped (BiO)CO nanowires was evaluated through degradation of sodium isopropyl xanthate under UV-visible light irradiation. The as-prepared Fe-doped (BiO)CO nanowires were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), UV-visible diffuse reflectance spectroscopy (UV-vis DRS), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) in detail.

Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial.

Objective: To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).

Patients And Methods: ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients.

Results: Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012.

Effects of Abaloparatide-SC on Fractures and Bone Mineral Density in Subgroups of Postmenopausal Women With Osteoporosis and Varying Baseline Risk Factors.

Abaloparatide-SC is a novel 34-amino acid peptide created to be a potent and selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway. In the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) Phase 3 trial (NCT01343004), abaloparatide reduced new morphometric vertebral fractures by 86% compared with placebo (p < 0.001) and nonvertebral fractures by 43% (p = 0.

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

Importance: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.

Objective: To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.

Intravenous Clopidogrel (MDCO-157) Compared with Oral Clopidogrel: The Randomized Cross-Over AMPHORE Study.

Background: The extent of P2Y12 inhibition during coronary intervention is an important determinant of ischemic complications. The currently available oral P2Y12 inhibitors are limited by a relatively slow onset of action and variable on-treatment response.

Objective: Our objective was to determine the pharmacodynamic (PD) dose-antiplatelet response relationship and the pharmacokinetics of MDCO-157, an intravenous formulation of clopidogrel complexed with sulphobutylether betacyclodextrin, and to identify the dose level of MDCO-157 that matches the PD effect of oral clopidogrel 300 mg.

Clevidipine in acute heart failure: Results of the A Study of Blood Pressure Control in Acute Heart Failure-A Pilot Study (PRONTO).

Background: Rapid blood pressure (BP) control improves dyspnea in hypertensive acute heart failure (AHF). Although effective antihypertensives, calcium-channel blockers are poorly studied in AHF. Clevidipine is a rapidly acting, arterial selective intravenous calcium-channel blocker.

Clevidipine rapidly and safely reduces blood pressure in acute intracerebral hemorrhage: the ACCELERATE trial.

Background: Intracerebral hemorrhage (ICH) causes 10-15% of primary strokes, with mortality related to hematoma volume. Blood pressure (BP) reduction may attenuate hematoma expansion. ACCELERATE (the Evaluation of Patients with Acute Hypertension and Intracerebral Hemorrhage with Intravenous Clevidipine Treatment) is a pilot study representing the first evaluation of safety and efficacy of intravenous clevidipine for the rapid treatment of hypertension in ICH patients.

Improved perioperative blood pressure control leads to reduced hospital costs.

Background: Perioperative hypertension affects 80% of cardiac surgery patients and is associated with an increased risk of complications.

Objective: To determine the relationship between perioperative blood pressure (BP) control and hospital costs for cardiac surgery in the United States (US) and estimate the potential cost reductions associated with effective therapies.

Methods: The analysis estimated hospitalization costs (2011 US dollars (USD)) for cardiac surgery when BP was controlled with intravenous (IV) antihypertensives.

Accounting for the relationship between per diem cost and LOS when estimating hospitalization costs.

Background: Hospitalization costs in clinical trials are typically derived by multiplying the length of stay (LOS) by an average per-diem (PD) cost from external sources. This assumes that PD costs are independent of LOS. Resource utilization in early days of the stay is usually more intense, however, and thus, the PD cost for a short hospitalization may be higher than for longer stays.

Pharmacokinetics, pharmacodynamics, and safety of clevidipine after prolonged continuous infusion in subjects with mild to moderate essential hypertension.

Purpose: Clevidipine is a rapidly-acting intravenous dihydropyridine antihypertensive acting via calcium channel blockade. This was a randomized, single-blind, parallel-design study of a 72-h continuous clevidipine infusion.

Method: Doses of 2, 4, 8, or 16.

Does perioperative systolic blood pressure variability predict mortality after cardiac surgery? An exploratory analysis of the ECLIPSE trials.

Background: Few studies describe an association of perioperative blood pressure stability with postoperative outcome. We tested the hypothesis that systolic blood pressure (SBP) variability in patients undergoing cardiac surgery is associated with 30-day mortality.

Methods: Perioperative blood pressure variability was evaluated in the 1512 patients who were randomized and had perioperative hypertension in the ECLIPSE trials.