Evaluation of acoustic radiation force impulse (ARFI) elastography as non-invasive diagnostic tool in living donor liver transplantation

Abdominal Radiology - Role of acoustic radiation force impulse (ARFI) elastography, in transplant setting, is not well established. We aimed to define the normal mean values of the liver stiffness...     

Recent developments in the fabrication,characterization and implementation of MgH2-based solid-hydrogen materials in the Kuwait Institute for Scientific Research

Hydrogen energy holds tremendous promise as a new clean energy option. It is a convenient, safe, versatile fuel source that can be easily converted to the desired form of energy without releasing harmful emissions. Hydrogen storage, which spans both hydrogen production and hydrogen applications, plays a critical role in initiating a hydrogen economy. Apart from the traditional methods used for hydrogen storage, Mg metal has been considered to be the most suitable candidate for application as a safe hydrogen storage material. However, Mg still has several technical problems that must be solved before such an attractive light metal can be considered for use in real applications. This review article aims to present and discuss the most recent research activities (2010–2018) that have been undertaken at the Kuwait Institute for Scientific Research (KISR) to develop and implement new categories of MgH₂-based nanocomposites. Comparisons between different catalytic agents used to enhance MgH₂ properties are presented and discussed in terms of structure, morphology, thermal stability, and kinetics.

Photos taken in November 2018 at NAM-EBRC, KISR, presenting the successful application of the use of a solid-state hydrogen storage nanocomposite for charging 8 batteries of an electric golf cart, using a 1000 W PEM-fuel cell.     

Complete heart block: determinants and clinical impact in patients with hypertrophic obstructive cardiomyopathy undergoing nonsurgical septal reduction therapy

OBJECTIVES: The purpose of this paper is to examine the incidence and determinants of permanent complete heart block (CHB) after nonsurgical septal reduction therapy (NSRT), and to evaluate the clinical impact of permanent pacemaker (PPM) placement. BACKGROUND: Nonsurgical septal reduction therapy with ethanol improves the clinical and hemodynamic parameters in patients with symptomatic hypertrophic obstructive cardiomyopathy. Complete heart block is a common complication after NSRT. METHODS: The database of 261 consecutive patients who underwent NSRT at Baylor College of Medicine was reviewed. Clinical variables that were considered as possible determinants for CHB after NSRT were: age, gender, New York Heart Association (NYHA) functional class, left ventricular outflow tract (LVOT) gradient at rest or with provocation, septal thickness, and baseline exercise duration. For electrocardiographic (ECG) variables, the presence of first-degree atrioventricular (AV) block, bifascicular block, left bundle branch block, atrial fibrillation, and left ventricular hypertrophy were analyzed. In addition, the volume of ethanol injected, the method of administration of ethanol (i.e., bolus vs. slow injection [over 30 to 60 s]), number of septal arteries occluded, use of myocardial echocardiography, and infarct size as determined by peak creatine kinase level. RESULTS: Of 261 consecutive patients, 37 had PPM or automatic implantable cardiac defibrillator placed before NSRT. Of the remaining 224 patients, 31 (14%) developed CHB after the procedure. Multivariate logistic regression analysis showed that female gender (odds ratio [OR] 4.3; P = 0.02), bolus injection of ethanol (OR 51; P = 0.004), injecting more than one septal artery (OR 4.6; P = 0.016), the presence of left bundle branch block (OR 39; P = 0.002), and first-degree AV block (OR 14; P = 0.001) on the baseline ECG are independent predictors of CHB after NSRT. Patients requiring PPM placement had a similar improvement in their NYHA functional class, septal thickness reduction, LVOT gradient reduction, and improvement of exercise capacity when compared with patients who did not require pacing. CONCLUSIONS: Multiple demographic, electrocardiographic, and technical factors seem to increase the risk of CHB after NSRT. Patients with CHB after NSRT derive similar clinical and hemodynamic benefit to patients who did not require permanent pacing.     

Refractory Case of Coronary Artery Spasm with Interesting Findings: A Case Report

This is a case of refractory vasospastic angina with unusual electrocardiographic findings and rare coronary angiographic documentation of diffuse spasm of the left coronary system with a baseline of near normal coronary arteries. A 66-year-old man presented with severe vasospastic angina that eventually progressed to non-ST elevation myocardial infarction (NSTEMI). During the episodes of chest pain, the electrocardiogram revealed ST segment depression rather than elevation. Coronary angiography revealed near normal coronary arteries with initial diffuse spasm of the left coronary system. The patient continues to be symptomatic despite treatment with different forms and doses of nitrates and calcium channel blockers. No financial support was needed or provided by any source.     

Discovering a new MgH2 metastable phase

Formation of a new metastable fcc-MgH₂ nanocrystalline phase upon mechanically-induced plastic deformation of MgH₂ powders is reported. Our results have shown that cold rolling of mechanically reacted MgH₂ powders for 200 passes introduced severe plastic deformation of the powders and led to formation of micro-lathes consisting of γ- and β-MgH₂ phases. The cold rolled powders were subjected to different types of defects, exemplified by dislocations, stacking faults, and twinning upon high-energy ball milling. Long term ball milling (50 hours) destabilized β-MgH₂ (the most stable phase) and γ-MgH₂ (the metastable phase), leading to the formation of a new phase of face centered cubic structure (fcc). The lattice parameter of fcc-MgH₂ phase was calculated and found to be 0.4436 nm. This discovered phase possessed high hydrogen storage capacity (6.6 wt%) and revealed excellent desorption kinetics (7 min) at 275 °C. We also demonstrated a cyclic-phase-transformation conducted between these three phases upon changing the ball milling time to 200 hours.

Effect of mechanically-induced cold-rolling followed by high energy ball milling on cyclic phase transformation.

The worldwide interest in MgH₂ is attributed to the natural abundance of Mg metal, and its capability to store hydrogen up to 7.60 wt% (0.11 kg H₂ L⁻¹).^1–3 Among the metal hydride family, MgH₂ has been considered as a promising candidate for solid-state hydrogen storage.^4–6 Despite the attractive properties of MgH₂, and the simplicity for producing the compound on an industrial scale at ambient temperature via a reactive ball milling (RBM) technique,^7,8 MgH₂ is a very stable compound, and possesses slow kinetics of hydrogenation and dehydrogenation under 300 °C.⁹ Since the 1990s efforts have been made in order to destabilize MgH₂ and improve its hydrogenation and dehydrogenation kinetics upon doping with a long list of catalysts.^10–15 Most of the used catalysts showed significant enhancement of the kinetics behavior for MgH₂, indexed by a decreasing decomposition temperature and a speed-up of its kinetics behavior.^16–20 In spite of the beneficial effects obtained upon adding such foreign catalytic agents, they always lead to a dramatic decrease of the hydrogen storage capacity of MgH₂.^21,22Apart from doping MgH₂ powders with catalysts, it has been experimentally demonstrated by some authors that changing the crystal structure of stable β-tetragonal MgH₂ phase to a less stable phase of γ-orthorhombic MgH₂ led to improve the gas uptake/release kinetics and decrease the hydrogenation temperature without drastic decreasing of the storage capacity.^23–26 The β-to-γ phase transformations can be attained via severe plastic deformation (SPD)²⁷ at ambient temperature by different approaches such as high-energy ball milling (HEBM),²⁸ cold rolling (CRing),²⁹ equal channel angular pressing (ECAP),³⁰ and high pressure torsion (HPT).^22,31 A common result of these employed techniques is the formation of nanocrystalline phase along with introducing high intensity defects, leading to increase of grain boundaries density. Presence of these defects in the lattice leads to create nucleation points for hydrogenation, where existence of large number of grain boundaries assists fast diffusion pathways for hydrogen.The present work has been addressed in part to study the effect of HEBM on the structure and decomposition properties of CRed MgH₂ powders. Moreover, we aimed to investigate experimentally the possibility of formation a new metastable MgH₂ phase rather than the reported g-phase and theoretically calculated δ and ε phases³² upon long term of milling.For the purpose of the present study, 5 g Mg (∼80 μm, 99.8 wt%) powder was balanced inside a He gas atmosphere-glove box and sealed together with fifty hardened steel-balls (11 mm in diameter), using ball-to-powder weight ratio as 40 : 1. The vial was then evacuated to the level of 10⁻³ bar and then filled with 50 bar of H₂. The RBM process was carried out at room temperature, using planetary-type HEBM. After 25 hours (h) of RBM, the vial was open inside the glove box to discharge the powders. The powders were charged and sealed in a stainless steel (SUS304) tube (0.8 cm diameter and 20 cm length) inside the glove box. The tube contained MgH₂ powders were severely CRed for different number of passes (1 to 200 passes), using two-drum type manual cold roller (11 cm wide × 5.5 cm rollers diameter). The as-CRed powders for 200 passes were then HEBMed under hydrogen gas for different milling time, in the range between 3 h to 50 h. All the samples were characterized by means of X-ray diffraction (XRD) with Cu radiation, field-emission high-resolution transmission electron microscope (FE-HRTEM) equipped with energy-dispersive X-ray spectroscopy (EDS), field emission scanning electron microscope (FE-SEM)/EDS, and differential scanning calorimeter (DSC). The absorption/desorption kinetics were investigated via Sievert''s method in different temperatures under hydrogen gas pressure in the range between 200 mbar to 8 bar.The XRD patterns of MgH₂ powders obtained after 25 h of RBM is shown in Fig. 1a. Bragg peaks corresponding to starting hcp-Mg powders were hardly seen and replaced by sharp diffracted lines related to γ- and β-MgH₂ phases, as elucidated in Fig. 1a. The SEM observations indicated the powders tendency to agglomerate, forming large aggregates upon CRing for 25 passes (Fig. 2a). Increasing the CRing passes to 200 times led to grain refinement, as implied by the broadening in the Bragg-peaks presented in Fig. 1b. At this stage, micro-bands with thickness of 143 μm were developed as a result of cold working generated during CRing process, as shown in Fig. 2b. The FE-HRTEM image of as-CRed powders for 200 passes indicated the development of lattice imperfections (e.g. stacking faults and deformation twins). This is implying the mechanically-induced SPD, as elucidated in ESI, Fig. S1.^†Open in a separate windowFig. 1XRD patterns of MgH₂ powders obtained after 25 h of RBMing (a), and then CRed for 200 passes (b). XRD pattern of CRed powders for 200 passes and then HEBMEd for 50 h is presented in (c).Open in a separate windowFig. 2FE-SEM micrographs taken at accelerated voltage of 1 kV of MgH₂ powders obtained after 25 h of RBMing and then CRed for (a) 25, and (b) 200 passes.In order to study the effect of HEBM on the stability of cold-rolled MgH₂ aggregates, the powders were charged into tool steel vial and ball milled under 50 bar of H₂ for different milling time. The XRD pattern of CRed MgH₂ powders obtained after 200 CR passes and then HEBMed for 50 h is displayed in Fig. 1c. Obviously, the Bragg peaks corresponding to γ- and β-MgH₂ phases were completely vanished and replaced by new Bragg peaks of unreported phase, appeared at scattering angles (2θ) of, 35.034, 40.584, 58.758, 70.115, and 73.868 (Fig. 1c). XRD analysis indicated that this discovered MgH₂ phase has face centered cubic structure (fcc) of space group, Fm$\bar{3}$m(225). The lattice parameter (a_o) of this phase, calculated from (111) was 0.44361 nm. The as-synthesized fcc-MgH₂ powders had fine spherical particles with sizes distributed in the range between 0.25 μm to 1 μm, as displayed in Fig. 3.Open in a separate windowFig. 3FE-SEM micrograph of MgH₂ powders obtained after 25 h of RBM, CRed for 200 passes and finally HEBMed for 50 h.

Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making

Background:

Intravenous (IV) acetaminophen is increasingly used around the world for pain control for a variety of indications. However, it is unclear whether IV administration offers advantages over oral administration.

Objective:

To identify, summarize, and critically evaluate the literature comparing analgesic efficacy, safety, and pharmacokinetics for IV and oral dosage forms of acetaminophen.

Data Sources:

A literature search of the PubMed, Embase, and International Pharmaceutical Abstracts databases was supplemented with keyword searches of Science Direct, Wiley Library Online, and Springer Link databases for the period 1948 to November 2014. The reference lists of identified studies were searched manually.

Study Selection and Data Extraction:

Randomized controlled trials comparing IV and oral dosage forms of acetaminophen were included if they assessed an efficacy, safety, or pharmacokinetic outcome. For each study, 2 investigators independently extracted data (study design, population, interventions, follow-up, efficacy outcomes, safety outcomes, pharmacokinetic outcomes, and any other pertinent information) and completed risk-of-bias assessments.

Data Synthesis:

Six randomized clinical trials were included. Three of the studies reported outcomes pertaining to efficacy, 4 to safety, and 4 to pharmacokinetics. No clinically significant differences in efficacy were found between the 2 dosage forms. Safety outcomes were not reported consistently enough to allow adequate assessment. No evidence was found to suggest that increased bioavailability of the IV formulation enhances efficacy outcomes. For studies reporting clinical outcomes, the results of risk-of-bias assessments were largely unclear.

Conclusions:

For patients who can take an oral dosage form, no clear indication exists for preferential prescribing of IV acetaminophen. Decision-making must take into account the known adverse effects of each dosage form and other considerations such as convenience and cost. Future studies should assess multiple-dose regimens over longer periods for patients with common pain indications such as cancer, trauma, and surgery.     

Molecular Basis of Crystal Morphology-Dependent Adhesion Behavior of Mefenamic Acid During Tableting

Purpose

The molecular basis of crystal surface adhesion leading to sticking was investigated by exploring the correlation of crystal adhesion to oxidized iron coated atomic force microscope (AFM) tips and bulk powder sticking behavior during tableting of two morphologically different crystals of a model drug, mefenamic acid (MA), to differences in their surface functional group orientation and energy.

Methods

MA was recrystallized into two morphologies (plates and needles) of the same crystalline form. Crystal adhesion to oxidized iron coated AFM tips and bulk powder sticking to tablet punches was assessed using a direct compression formulation. Surface functional group orientation and energies on crystal faces were modeled using Accelrys Material Studio software.

Results

Needle-shaped morphology showed higher sticking tendency than plates despite similar particle size. This correlated with higher crystal surface adhesion of needle-shaped morphology to oxidized iron coated AFM probe tips, and greater surface energy and exposure of polar functional groups.

Conclusions

Higher surface exposure of polar functional groups correlates with higher tendency to stick to metal surfaces and AFM tips, indicating involvement of specific polar interactions in the adhesion behavior. In addition, an AFM method is identified to prospectively assess the risk of sticking during the early stages of drug development.