Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Correlation between central corneal thickness and intraocular pressure in children with congenital glaucoma

Abstract: Objectives: This work aimed to study correlation between central corneal thickness and intraocular pressure in children with congenital glaucoma requiring surgery. Background: Central corneal thickness (CCT) has recently been shown to be important risk factor for development and severity of glaucoma. The clinical use of CCT measurement has become so important that it directly affects glaucoma management strategy in 15% of patients. Patients and methods: Thirty individuals were enrolled in this study, 18 males and 12 females. All children were diagnosed to have primary congenital glaucoma and underwent combined trabeculotomy-trabeculectomy operation. All patients underwent full history taking, thorough clinical examination and ocular examination was doneunder oral sedation and local anaesthetic eye drops with emphasis on IOP and CCT measurements. The central corneal thickness was measured using (PacScan 300 AP ultrasonic pachymetry, Sonomed, USA). IOP was measured by Perkins hand-held applanation tonometer. Results: The mean CCT was 547 μm before operation and decreased to 533.9 μm after operation with P-value (< 0.01). Mean IOP was30.7 mmHg before and decreased to 11.8 mmHg after operation with P-value (< 0.01).There was no significant dependence of CCT on IOP values measured with local anaesthesia and oral sedation before and after operation with p-value (> 0.05). There wasno significant correlation between the decrease of CCT and the decrease of IOP after operation (p-value>0.05, r= -0.139) regarding IOP data obtained with local anaesthesia and oral sedation. Conclusion: Regarding IOP data obtained with local anaesthesia and oral sedation we cannot depend on central corneal thickness as an independent parameter to monitor the follow up of childhood glaucoma cases after surgery

Synthesis and 2D-QSAR Study of Active Benzofuran-Based Vasodilators

A new series of 2-alkyloxy-pyridine-3-carbonitrile-benzofuran hybrids (4a–x) was synthesized. All the new derivatives were examined via the standard technique for their vasodilation activity. Some of the investigated compounds exhibited a remarkable activity, with compounds 4w, 4e, 4r, 4s, 4f and 4g believed to be the most active hits in this study with IC50 values 0.223, 0.253, 0.254, 0.268, 0.267 and 0.275 mM, respectively, compared with amiodarone hydrochloride, the reference standard used (IC50 = 0.300 mM). CODESSA PRO was employed to obtain a statistically significant 2-Dimensional Quantitative Structure Activity Relationship (2D-QSAR) model describing the bioactivity of the newly synthesized analogs (N = 24, n = 4, R2 = 0.816, R2cvOO = 0.731, R2cvMO = 0.772, F = 21.103, s2 = 6.191 × 10−8)

Evaluation of Insecticidal Effects of Plants Essential Oils Extracted from Basil, Black Seeds and Lavender against Sitophilus oryzae

The risk of using synthetic insecticides to the environment, human health, and the emergence of new genera of pests resistant to that kind of drugs, have led to attention in natural compounds. The present study aimed at evaluating the insecticidal activity of 0.25–6 mg/cm2 of basil (Ocimum basilicum), black seeds (Nigella sativa), and lavender (Lavandula angustifolia) essential oils (EOs) against one of the major stored product pests, Sitophilus oryzae (L.). This was done by assessing mortality and repellent percentage assay in the adult stage, as well as analysing up and down-regulated genes associated with toxicity effect of selected EOs. The three studied EOs showed a toxic effect on S. oryzae; where O. basilicum and L. angustifolia EOs explicated 100% mortality at 6 mg/cm2 after 48 and 24 h, respectively. The highest repellence activity was recorded for O. basilicum EO at 0.75 mg/cm2 with value 82.3% after exposure time 5 h. In the highest dose (6 mg/cm2), the maximum up-regulated expression level of detoxification DEGs genes (CL1294 and CL 8) and cytochrome p45o gene (CYP4Q4) in Lavandula angustifolia EOs exhibited 8.32, 6.08, and 3.75 fold changes, respectively, as compared with 4.76 fold at 10 ppm malathion and 1.02 fold change in acetone control