Evaluation of anti-hypertensive activity of Ulmus wallichiana extract and fraction in SHR, DOCA-salt- and L-NAME-induced hypertensive rats.

Ethnopharmacological Relevance: Ulmus wallichiana Planchon (Himalayan Elm), a traditional medicinal plant, used in fracture healing in folk tradition of Uttarakhand, Himalaya, India. It is also used as diuretic. U.

Antibacterial FabH Inhibitors with Mode of Action Validated in Haemophilus influenzae by in Vitro Resistance Mutation Mapping.

Fatty acid biosynthesis is essential to bacterial growth in Gram-negative pathogens. Several small molecules identified through a combination of high-throughput and fragment screening were cocrystallized with FabH (β-ketoacyl-acyl carrier protein synthase III) from Escherichia coli and Streptococcus pneumoniae. Structure-based drug design was used to merge several scaffolds to provide a new class of inhibitors.

Systematic Quality Assessment of Published Antishivering Protocols.

Shivering is a common side effect of targeted temperature modulation and general anesthesia. Antishivering strategies often employ a stepwise approach involving both pharmacological and physical interventions. However, approaches to treat shivering are often empiric and vary widely across care environments.

Transcranial Doppler Changes in Patients Treated with Extracorporeal Membrane Oxygenation.

Background: Transcranial Doppler (TCD) has significant implications for neurovascular assessment in patients being treated with venoarterial-extracorporeal membrane oxygenation (VA-ECMO). However, there have been no studies demonstrating the changes in pulsatility indices (PIs) seen in these patients. Nonpulsatile waveforms are seen during on-pump coronary artery bypass graft, but low or low-normal PIs have never been reported.

Optimizing Outcomes for Mechanically Ventilated Patients in an Era of Endovascular Acute Ischemic Stroke Therapy.

Endovascular mechanical thrombectomy is a new standard of care for acute ischemic stroke (AIS). The majority of these patients receive mechanical ventilation (MV), which has been associated with poor outcomes. The implication of this is significant, as most neurointerventionalists prefer general compared to local anesthesia during the procedure.

Pentobarbital-Induced Myocardial Stunning in Status Epilepticus Requiring Extracorporeal Membrane Oxygenation: A Case Report and Literature Review.

Introduction. Mild hypotension is a well-recognized complication of intravenous pentobarbital; however fulminant cardiopulmonary failure has not been previously reported. Case Report.

Identification of non-PBP2a resistance mechanisms in Staphylococcus aureus after serial passage with ceftaroline: involvement of other PBPs.

Objectives: Ceftaroline (the active metabolite of ceftaroline fosamil) is a cephalosporin that possesses activity against MRSA due to its differentiating high affinity for PBP2a. It is known that PBP2a sequence variations, including some outside of the transpeptidase-binding pocket, impact ceftaroline susceptibility and recent evidence suggests involvement of non-PBP2a mechanisms in ceftaroline resistance. This study evaluated the potential of ceftaroline to select for resistant Staphylococcus aureus clones during serial passage.

Use of Intra-aortic- Balloon Pump Counterpulsation in Patients with Symptomatic Vasospasm Following Subarachnoid Hemorrhage and Neurogenic Stress Cardiomyopathy.

Introduction: Intra-aortic counterpulsation balloon pumps (IABPs) have been widely used to augment hemodynamics in critically ill patients with cardiogenic shock and have recently been proposed as a management strategy for subarachnoid hemorrhage (SAH) patients with neurogenic stress cardiomyopathy (NSC). Prior case series have described the use of IABP as a means to manage cardiogenic shock in this patient population; however, we sought to describe our experience with IABP as a means to wean vasopressor requirement while augmenting hemodynamics and maintaining pressures at goal.

Methods: Five patients were identified from a single center, prospective, observational cohort study that received an IABP for the management of ischemia related to cerebral vasospasm in the setting of NSC.

Structural and sequence analysis of class A β-lactamases with respect to avibactam inhibition: impact of Ω-loop variations.

Background: There exists a significant diversity among class A β-lactamases and the proliferation of these enzymes is a significant medical concern due to the ability of some members to efficiently hydrolyse both extended-spectrum cephalosporins and carbapenems. Avibactam is a novel non-β-lactam β-lactamase inhibitor that, in combination with ceftazidime, has recently obtained regulatory approval in the USA. Although avibactam is known to efficiently inhibit key class A enzymes, the diversity of this enzyme family warranted a more complete investigation to understand the breadth of the potential spectrum of inhibition.

ERK2 phosphorylates Krüppel-like factor 8 protein at serine 48 to maintain its stability.

Krüppel-like factor 8 (KLF8) plays important roles in cancer and is strictly regulated by various post-translational modifications such as sumoylation, acetylation, ubiquitylation and PARylation. Here we report a novel phosphorylation of KLF8 by ERK2 responsible and critical for the stability of KLF8 protein. The full-length KLF8 protein displays a doublet in SDS-PAGE gel.

Multi-center and multi-method evaluation of in vitro activities of ceftaroline against S. aureus.

This five-site study was performed to assess the reproducibility of ceftaroline MIC and disk results for Staphylococcus aureus. Three commercial broth microdilution, three gradient diffusion and ceftaroline 5μg disk diffusion methods were compared to a reference broth microdilution method against challenge isolates (n = 41) and isolates collected at four European sites (n = 30/site). For four MIC methods (Sensititre and three gradient diffusion methods), 99.

Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage.

OBJECTIVE The clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome. METHODS The authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013.

Prognostication of long-term outcomes after subarachnoid hemorrhage: The FRESH score.

Objective: To create a multidimensional tool to prognosticate long-term functional, cognitive, and quality of life outcomes after spontaneous subarachnoid hemorrhage (SAH) using data up to 48 hours after admission.

Methods: Data were prospectively collected for 1,619 consecutive patients enrolled in the SAH outcome project July 1996 to March 2014. Linear models (LMs) were applied to identify factors associated with outcome in 1,526 patients with complete data.

Thermodynamic inference based on coarse-grained data or noisy measurements.

Fluctuation theorems have become an important tool in single-molecule biophysics to measure free-energy differences from nonequilibrium experiments. When significant coarse-graining or noise affect the measurements, the determination of the free energies becomes challenging. In order to address this thermodynamic inference problem, we propose improved estimators of free-energy differences based on fluctuation theorems, which we test on a number of examples.

Krüppel-like factor 8 activates the transcription of C-X-C cytokine receptor type 4 to promote breast cancer cell invasion, transendothelial migration and metastasis.

Krüppel-like factor 8 (KLF8) has been strongly implicated in breast cancer metastasis. However, the underlying mechanisms remain largely unknown. Here we report a novel signaling from KLF8 to C-X-C cytokine receptor type 4 (CXCR4) in breast cancer.

The influence of humanitarian crises on social functioning among civilians in low- and middle-income countries: A systematic review.

Our aim was to systematically review how social functioning is measured, conceptualised, impacted, and associated with mental disorders in populations affected by humanitarian crises. Quantitative studies conducted with civilian populations affected by humanitarian crises in low- and middle-income countries with outcomes of social functioning were examined up to 2014. Data sources included Medline, Embase, PsycInfo, and Global Health, and 8 grey literature sources, yielding 14,350 records, of which 20 studies met inclusion criteria.

Identification of Novel VEB β-Lactamase Enzymes and Their Impact on Avibactam Inhibition.

Ceftazidime-avibactam has activity against Pseudomonas aeruginosa and Enterobacteriaceae expressing numerous class A and class C β-lactamases, although the ability to inhibit many minor enzyme variants has not been established. Novel VEB class A β-lactamases were identified during characterization of surveillance isolates. The cloned novel VEB β-lactamases possessed an extended-spectrum β-lactamase phenotype and were inhibited by avibactam in a concentration-dependent manner.

Dietary sugar intake increases liver tumor incidence in female mice.

Overnutrition can promote liver cancer in mice and humans that have liver damage caused by alcohol, viruses, or carcinogens. However, the mechanism linking diet to increased liver tumorigenesis remains unclear in the context of whether tumorigenesis is secondary to obesity, or whether nutrients like sugar or fat drive tumorigenesis independent of obesity. In male mice, liver tumor burden was recently found to correlate with sugar intake, independent of dietary fat intake and obesity.

MALDI imaging mass spectrometry as a novel tool for detecting histone modifications in clinical tissue samples.

Histone post-translational modifications (PTMs), histone variants and enzymes responsible for the incorporation or the removal of the PTMs are being increasingly associated with human disease. Combinations of histone PTMs and the specific incorporation of variants contribute to the establishment of cellular identity and hence are potential markers that could be exploited in disease diagnostics and prognostics and therapy response prediction. Due to the scarcity of suitable antibodies and the pre-requirement of tissue homogenization for more advanced analytical techniques, comprehensive information regarding the spatial distribution of these factors at the tissue level has been lacking.

Patient-Powered Reporting of Modified Rankin Scale Outcomes Via the Internet.

Background And Purpose: The modified Rankin Scale (mRS) is a common and resource-intensive measure of functional outcome in stroke-related conditions. In this observational prospective cohort feasibility study, mRS scores are generated using a patient-powered online survey and compared to scores obtained by structured telephonic interview.

Materials And Methods: Fifty-one patients with subarachnoid hemorrhage (SAH) or their surrogates responded to an online survey following discharge from the hospital.

In situ detection of histone variants and modifications in mouse brain using imaging mass spectrometry.

Histone posttranslational modifications and histone variants control the epigenetic regulation of gene expression and affect a wide variety of biological processes. A complex pattern of such modifications and variants defines the identity of cells within complex organ systems and can therefore be used to characterize cells at a molecular level. However, their detection and identification in situ has been limited so far due to lack of specificity, selectivity, and availability of antihistone antibodies.