New insights into the regulatory pathways associated with the activation of the stringent response in bacterial resistance to the PBP2-targeted antibiotics, mecillinam and OP0595/RG6080.

Objectives: The diazabicyclooctane β-lactamase inhibitor OP0595 (RG6080) also acts as an antibiotic, targeting PBP2 in Enterobacteriaceae, but this activity is vulnerable to mutational resistance. We used WGS to investigate the basis of this resistance.

Methods: Twenty OP0595-selected mutants, comprising four derived from each of five different Escherichia coli strains, were sequenced on Illumina HiSeq.

Right-Sided and Left-Sided Colon Cancers are Two Distinct Disease Entities: an Analysis of 200 Cases in Pakistan.

Background: There is growing evidence that there are differences in histological and genetic characteristics along with clinical behavior between right- and left-sided colon carcinomas. We have compared various parameters of the two types and assessed associations of the results with prognosis in patients in Pakistan.

Materials And Methods: We reviewed 200 cases from our institutional database; 100 cases of right-sided and 100 cases of left-sided colon cancer.

Effect of Different Surface Treatments and Thermocycling on Bond Strength of a Silicone-based Denture Liner to a Denture Base Resin.

Aim: The aim of this study is to evaluate the effects of three different surface treatments and thermocycling on the tensile strength of a silicone lining material to denture resin.

Materials And Methods: A total of 96 cube-shaped specimens were fabricated using heat-cured polymethyl methacrylate (PMMA) denture base resin. Three millimeters of the material was cut from the midsection.

Highly efficient method for I-radiolabeling of biomolecules using inverse-electron-demand Diels-Alder reaction.

In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give I-labeled product ([I]1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of [I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared.

The presence of remodeled and mixed atherosclerotic plaques at coronary ct angiography predicts major cardiac adverse events - The CAFÉ-PIE Study.

Background: It is still unclear how to exploit information made available by coronary computed tomography angiography (CCTA) on coronary artery disease (CAD) features in order to better predicting major adverse cardiac events (MACEs). Aim of this study was to validate the prognostic role of a comprehensive and simplified CT-derived score in patients evaluated for suspected CAD.

Methods: A prospective registry included 477 consecutive symptomatic patients without known CAD who underwent clinically-indicated CCTA.

Rationale and design of the PERFECTION (comparison between stress cardiac computed tomography PERfusion versus Fractional flow rEserve measured by Computed Tomography angiography In the evaluation of suspected cOroNary artery disease) prospective study.

Background: Non-invasive stress tests are commonly used as gatekeepers to invasive coronary angiography (ICA) in patients with suspected coronary artery disease (CAD). New computed tomography angiography (CTA) techniques such as fractional flow reserve calculated by CTA (FFRCT) and stress myocardial computed tomography perfusion (CTP) have emerged as potential strategies to combine anatomical and functional evaluation of CAD in one technique. The aim of this study is to compare per-vessel diagnostic accuracy of FFRCT versus stress myocardial CTP for the detection of functionally significant coronary artery disease (CAD), using invasive FFR as the reference standard.

In Vitro Activity of Eravacycline against Carbapenem-Resistant Enterobacteriaceae and Acinetobacter baumannii.

Eravacycline and comparators were tested against carbapenem- and tigecycline-resistant Enterobacteriaceae and Acinetobacter isolates received at the United Kingdom's national reference laboratory. Eravacycline MICs correlated closely with those of tigecycline but mostly were around 2-fold lower; both molecules retained full activity against isolates with high-level tetracycline and minocycline resistance. MIC90s of eravacycline and tigecycline were raised ca.

Inactivation or inhibition of AcrAB-TolC increases resistance of carbapenemase-producing Enterobacteriaceae to carbapenems.

Objectives: The objective of this study was to study the contribution of the multidrug resistance AcrAB-TolC efflux system to carbapenem resistance in carbapenemase-producing Enterobacteriaceae and the impact of the efflux inhibitor PABN on this resistance.

Methods: Klebsiella pneumoniae, Escherichia coli, Salmonella enterica serovar Typhimurium and their corresponding AcrAB-TolC mutants, each carrying carbapenemase-carrying plasmids (pKpQIL-UK with blaKPC and pNDM-HK with blaNDM), were tested for their susceptibility to six β-lactam antibiotics according to the BSAC agar dilution method. MICs were also determined in the presence of efflux inhibitors.

Post-traumatic Stress Disorder (PTSD) in Children of Conflict Region of Kashmir (India): A Review.

Post-traumatic stress disorder (PTSD) occurs due to traumatic events. The last two decades have seen various traumatic events in Kashmiri population, which has led to psychological impact on all population, especially children. PTSD is one of the psychiatric disorders occurring after witnessing of traumatic events.

Isolation, characterization and HPLC quantification of compounds from Aquilegia fragrans Benth: Their in vitro antibacterial activities against bovine mastitis pathogens.

Ethno-pharmacological Relevance: The underground parts of Aquilegia fragrans are traditionally used for the treatment of wounds and various inflammatory diseases like bovine mastitis. However, there are no reports on the phytochemical characterization and antibacterial studies of A. fragrans.

Interactions of OP0595, a Novel Triple-Action Diazabicyclooctane, with β-Lactams against OP0595-Resistant Enterobacteriaceae Mutants.

OP0595 is a novel diazabicyclooctane which, like avibactam, inhibits class A and C β-lactamases. In addition, unlike avibactam, it has antibacterial activity, with MICs of 0.5 to 4 μg/ml for most members of the family Enterobacteriaceae, owing to inhibition of PBP2; moreover, it acts synergistically with PBP3-active β-lactams independently of β-lactamase inhibition, via an "enhancer effect.

Prognostic value of dipyridamole stress cardiac magnetic resonance in patients with known or suspected coronary artery disease: a mid-term follow-up study.

Objectives: Dipyridamole stress cardiac magnetic resonance (CMR) evaluates the key phases (perfusion and wall motion) of the ischemic cascade. We sought to determine the prognostic value of dipyridamole stress-CMR in consecutive patients symptomatic for chest pain.

Methods: Seven hundred and ninety-three consecutive patients symptomatic for chest pain underwent dipyridamole stress-CMR and were followed up for 810 ± 665 days.

Susceptibility testing challenges with ceftaroline, MRSA and a 1 mg/L breakpoint.

Objectives: A 1 mg/L susceptibility breakpoint for ceftaroline and staphylococci is universally agreed; EUCAST counts MIC >1 mg/L as resistant whereas CLSI and FDA count 2 mg/L as intermediate and >2 mg/L as resistant. We investigated whether routine diagnostic tests reliably distinguish MICs of 1 versus 2 mg/L.

Methods: Thirty-five UK laboratories collected Staphylococcus aureus isolates and performed tests with 5 μg (as EUCAST) or 30 μg (as CLSI) discs and either confluent growth on Mueller-Hinton agar (as EUCAST and CLSI) or semi-confluent growth on Iso-Sensitest agar (as BSAC).

Activity of OP0595/β-lactam combinations against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing β-lactamases.

Background: OP0595 is a diazabicyclooctane that (i) acts as a PBP2-active antibacterial, (ii) inhibits Class A and C β-lactamases and (iii), like mecillinam, gives β-lactamase-independent potentiation of β-lactams targeting other PBPs. We tested its behaviour against β-lactam-resistant Enterobacteriaceae and non-fermenters.

Methods: Organisms were UK clinical isolates; MICs were determined by CLSI agar dilution for OP0595 alone or combined at 1-4 mg/L with aztreonam, biapenem, cefepime or piperacillin.

N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy through Superoxide Dismutase Regulation.

Objective: Oxidative stress down regulates antioxidant enzymes including superoxide dismutase (SOD) and contributes to the development of cardiac hypertrophy. N-Acetyl cysteine (NAC) can enhance the SOD activity, so the aim of this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1)-induced cardiac hypertrophy.

Materials And Methods: In this experimental study at QAU from January, 2013 to March, 2013.

Pathogens of skin and skin-structure infections in the UK and their susceptibility to antibiotics, including ceftaroline.

Objectives: Bacterial skin and skin-structure infections (SSSIs) are frequent settings for antibiotic use. We surveyed their UK aetiology and pathogen susceptibility, including susceptibility to ceftaroline.

Methods: Consecutive SSSI isolates were collected at 35 UK hospitals, to a maximum of 60/site, together with 15 'supplementary' MRSA/site.

In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase.

Ceftazidime-avibactam is active against most Enterobacteriaceae isolates with KPC carbapenemases. We investigated whether this activity could be compromised by mutation. Single-step and multistep selections were attempted using ceftazidime-avibactam (avibactam fixed at 1 or 4 μg/ml) versus two strains each of Enterobacter cloacae and Klebsiella pneumoniae, all with the KPC-3 enzyme.

Impact of an intra-cycle motion correction algorithm on overall evaluability and diagnostic accuracy of computed tomography coronary angiography.

Objectives: The aim of this study was to evaluate the impact of a novel intra-cycle motion correction algorithm (MCA) on overall evaluability and diagnostic accuracy of cardiac computed tomography coronary angiography (CCT).

Methods: From a cohort of 900 consecutive patients referred for CCT for suspected coronary artery disease (CAD), we enrolled 160 (18 %) patients (mean age 65.3 ± 11.

A Pilot Study to Evaluate Haemostatic Function, following Shock Wave Lithotripsy (SWL) for the Treatment of Solitary Kidney Stones.

Purpose: The number of patients undergoing shock wave lithotripsy (SWL) in the UK for solitary unilateral kidney stones is increasing annually. The development of postoperative complications such as haematuria and sepsis following SWL is likely to increase. Comparing a range of biological markers with the aim of monitoring or predicting postoperative complications following SWL has not been extensively researched.

Ultra-low-dose CT for left atrium and pulmonary veins imaging using new model-based iterative reconstruction algorithm.

Aims: To evaluate the feasibility of ultra-low-dose CT for left atrium and pulmonary veins using new model-based iterative reconstruction (MBIR) algorithm.

Methods And Results: Two hundred patients scheduled for catheter ablation were randomized into two groups: Group 1 (100 patients, Multidetector row CT (MDCT) with MBIR, no ECG triggering, tube voltage and tube current of 100 kV and 60 mA, respectively) and Group 2 [100 patients, MDCT with adaptive statistical iterative reconstruction algorithm (ASIR), no ECG triggering, and kV and mA tailored on patient BMI]. Image quality, CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of left atrium (LA) and pulmonary veins, and effective dose (ED) were evaluated for each exam and compared between two groups.

Insulin over expression induces heart abnormalities via reactive oxygen species regulation, might be step towards cardiac hypertrophy.

Insulin is known to regulate blood—glucose level and promote its utilization as an energy source in cardiac tissues under normal physiological conditions as well as stimulates signaling pathways that involved cell growth and proliferation. Although recently insulin generated free radicals via NAD(P)H has been documented but the molecular mechanism is still under investigation. The aim of present study is to elucidate the reactive oxygen species (ROS) dependent possible role of insulin in cardiac abnormalities, including hypertrophy by regulation of antioxidants enzyme (SOD) activity.

Stress-responsive factor regulation in patients suffering from type 2 diabetes and myocardial infarction.

Background/aim: Pro-free radical oxidative stresses, as well as regulatory factors, are believed to be the key players in the development of diabetes and heart-related disorders such as myocardial infarction. The aim of the present study was to highlight the role of oxidative stress-responsive factors (reactive oxygen species [ROS], super oxide dismutase [SOD], and calpain-1) in type 2 diabetes and myocardial infarction.

Materials And Methods: A total of 100 type 2 diabetes patients with myocardial infarction and 50 normal individuals were selected for this analysis.

Comparison of articaine and lignocaine for uncomplicated maxillary exodontia.

Objective: To compare single buccal articaine injection versus conventional lignocaine buccal and palatal injections for uncomplicated maxillary tooth extractions.

Study Design: Single blinded randomized control trial.

Place And Duration Of Study: The outpatient department of Oral and Maxillofacial Surgery, Armed Forces Institute of Dentistry, Rawalpindi, from February to September 2011.

Low-dose CT coronary angiography with a novel IntraCycle motion-correction algorithm in patients with high heart rate or heart rate variability.

Aims: Motion artefacts due to high or irregular heart rate (HR) are common limitations of coronary computed tomography (CT) angiography (CCTA). The aim of the study was to evaluate the impact of a new motion-correction (MC) algorithm used in conjunction with low-dose prospective ECG-triggering CCTA on motion artefacts, image quality, and coronary assessability.

Methods And Results: Among 380 patients undergoing CCTA for suspected CAD, we selected 120 patients with pre-scanning HR >70 bpm or HR variability (HRv) >10 bpm during scanning irrespective of pre-scanning HR or both conditions.