Spontaneous Left Main Coronary Artery Dissection in a Male.

Spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome (ACS) that is increasingly recognized in young to middle-aged women without typical coronary risk factors. This case report describes a 46-year-old male with a rare presentation of SCAD involving the left main (LM) coronary artery. The patient underwent an emergency coronary angiogram for high-risk ACS and had percutaneous coronary intervention (PCI) of LM due to active ischemia and hemodynamic instability.

Comparative study on thermo-mechanical, structural and functional properties of pectin extracted from immature wasted apples and commercial pectin.

Pectin yield of 22.22 ± 0.98 % (dry basis) was achieved from prematurely dropped Golden Delicious apples, having a light orange hue (hue value: 78.

A multi-institutional retrospective analysis on impact of RV acute mechanical support timing after LVAD implantation on 1-year mortality and predictors of RV acute mechanical support weaning.

Background: There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning.

Methods: A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed.

Increased 2-arachidonoyl-sn-glycerol levels normalize cortical responses to sound and improve behaviors in Fmr1 KO mice.

Background: Individuals with Fragile X syndrome (FXS) and autism spectrum disorder (ASD) exhibit an array of symptoms, including sociability deficits, increased anxiety, hyperactivity, and sensory hyperexcitability. It is unclear how endocannabinoid (eCB) modulation can be targeted to alleviate neurophysiological abnormalities in FXS as behavioral research reveals benefits to inhibiting cannabinoid (CB) receptor activation and increasing endocannabinoid ligand levels. Here, we hypothesize that enhancement of 2-arachidonoyl-sn-glycerol (2-AG) in Fragile X mental retardation 1 gene knock-out (Fmr1 KO) mice may reduce cortical hyperexcitability and behavioral abnormalities observed in FXS.

An Overlap Presentation of Pericardial Decompression Syndrome and Stress Cardiomyopathy Following Therapeutic Pericardiocentesis.

Pericardial decompression syndrome, defined as paradoxical hypotension and pulmonary edema after pericardiocentesis, is a rare complication of pericardiocentesis. Stress cardiomyopathy, caused by excess catecholamine response resulting in left ventricular dysfunction and elevated cardiac enzymes, can overlap with pericardial decompression syndrome, and both might belong to the same spectrum of disease. ().

Complete Revascularization of Stable STEMI Patients Offers a Significant Benefit if Done During the Index PCI, but Not if It's Done as a Staged Procedure.

Background: Complete revascularization (CR) of hemodynamically stable STEMI improves outcomes when compared to culprit-only PCI. However, the optimal timing for CR (CR during index PCI [iCR] versus staged PCI [sCR]) is unknown. sCR is defined as revascularization of non-culprit lesions not done during the index procedure (mean 31.

Prediction of right heart failure after left ventricular assist implantation: external validation of the EUROMACS right-sided heart failure risk score.

Aims: Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant remains a challenge. The EUROMACS right-sided heart failure (EUROMACS-RHF) risk score was proposed as a prediction tool for post-LVAD RHF but lacks from large external validation. The aim of our study was to externally validate the score.

The H domain of syntaxin 3 is a ubiquitin binding domain.

Syntaxins are a family of membrane-anchored SNARE proteins that are essential components required for membrane fusion in eukaryotic intracellular membrane trafficking pathways. Syntaxins contain an N-terminal regulatory domain, termed the H domain that is not highly conserved at the primary sequence level but folds into a three-helix bundle that is structurally conserved among family members. The syntaxin H domain has previously been found to be structurally very similar to the GAT domain present in GGA family members and related proteins that are otherwise completely unrelated to syntaxins.

Radiologic versus Endoscopic Placement of Gastrostomy Tube: Comparison of Indications and Outcomes at a Tertiary Referral Center.

Objectives: Percutaneous gastrostomy tube placement is performed in patients requiring long-term enteral nutrition. Although both endoscopic and fluoroscopic techniques may be used, there are inherent risks and potential complications associated with both procedures that are not generally known to referring physicians. The purpose of this study was to compare and contrast indications for placement and procedurally related complications between fluoroscopic and endoscopic gastrostomy tubes techniques at a tertiary care facility.

A discrete event simulation model to evaluate the treatment pathways of patients with cataract in the United Kingdom.

Background: The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade.

Discovery of a potent, orally active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221).

Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11beta-HSD1 inhibitors. However, the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer. A methyl group was added to the C-5 position to eliminate epimerization, leading to the discovery of (S)-2-((1S,2S,4R)-bicyclo[2.

Different modes of inhibitor binding to prolyl hydroxylase by combined use of X-ray crystallography and NMR spectroscopy of paramagnetic complexes.

In aqueous solution, azaquinolone inhibitors bind to prolyl 4-hydroxylase in two different orientations, as first detected by (19)F spectroscopy. This contrasts with the crystallographic structure where only one orientation has been determined. Dissection of the metal binding properties of the enzyme allowed structures of both complexes to be obtained in solution from (19)F and (13)C dipolar shifts in a labeled ligand.

Hepcidin revisited, disulfide connectivity, dynamics, and structure.

Hepcidin is a tightly folded 25-residue peptide hormone containing four disulfide bonds, which has been shown to act as the principal regulator of iron homeostasis in vertebrates. We used multiple techniques to demonstrate a disulfide bonding pattern for hepcidin different from that previously published. All techniques confirmed the following disulfide bond connectivity: Cys(1)-Cys(8), Cys(3)-Cys(6), Cys(2)-Cys(4), and Cys(5)-Cys(7).

Perinatal outcomes in pregnancy with asthma.

Objective: To examine the relationship between asthmatic pregnancies and selected maternal and neonatal outcomes in a representative cohort.

Methods: A retrospective cohort study was conducted at the Aga Khan University Hospital during the year 2004. A random selection was made of 65 asthmatic and 63 non-asthmatic singleton births.

Discovery of highly selective and potent p38 inhibitors based on a phthalazine scaffold.

Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110.

3-amino-7-phthalazinylbenzoisoxazoles as a novel class of potent, selective, and orally available inhibitors of p38alpha mitogen-activated protein kinase.

The p38 mitogen-activated protein kinase (MAPK) is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, osteoporosis, and many other diseases where aberrant cytokine signaling is the driver of disease. Herein, we describe a novel class of 3-amino-7-phthalazinylbenzoisoxazole-based inhibitors.

The co-crystal approach to improve the exposure of a water-insoluble compound: AMG 517 sorbic acid co-crystal characterization and pharmacokinetics.

Co-crystals are relatively novel in the pharmaceutical field and are not reported extensively. AMG 517 is an insoluble small molecule VR1 (vanilloid receptor 1) antagonist. In animal studies, good exposure of AMG 517 is seen from a 10% (w/v) Pluronic F108 in OraPlus suspension.

Stereoselective synthesis of a MCHr1 antagonist.

Melanin-concentrating hormone (MCH) is implicated in the feeding behavior in mammals affording a potential target to control overeating in people. Compound 1 (AMG 076) has been identified as a potent MCHr1 antagonist for the treatment of obesity. A synthesis suitable for the large-scale preparation of this lead candidate was developed to support preclinical studies.

Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr.

Inhibition of tumor-induced angiogenesis is a promising strategy in anticancer research. Neovascularization is a process required for both tumor growth and metastasis. Enhanced understanding of the underlying molecular mechanisms has led to the discovery of a variety of pharmaceutically attractive targets.

Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2).

Cellular and physiological responses to changes in dioxygen levels in metazoans are mediated via the posttranslational oxidation of hypoxia-inducible transcription factor (HIF). Hydroxylation of conserved prolyl residues in the HIF-alpha subunit, catalyzed by HIF prolyl-hydroxylases (PHDs), signals for its proteasomal degradation. The requirement of the PHDs for dioxygen links changes in dioxygen levels with the transcriptional regulation of the gene array that enables the cellular response to chronic hypoxia; the PHDs thus act as an oxygen-sensing component of the HIF system, and their inhibition mimics the hypoxic response.