Prediction of Clinically Relevant Herb-Drug Clearance Interactions Using Sandwich-Cultured Human Hepatocytes: Case Study.

The Schisandraceae family is reported to have a range of pharmacological activities, including anti-inflammatory effects. As with all herbal preparations, extracts of species are mixtures composed of >50 lignans, especially schizandrins, deoxyschizandrins, and gomisins. In China, extract (SSE) is often coadministered with immunosuppressant treatment of transplant recipients.

Isoform- and cell type-specific structure of apolipoprotein E lipoparticles as revealed by a novel Forster resonance energy transfer assay.

Apolipoprotein E (apoE) has an important role in the pathogenesis of Alzheimer's disease with its three isoforms having distinct effects on disease risk. Here, we assessed the conformational differences between those isoforms using a novel flow cytometry-Forster resonance energy transfer (FRET) assay. We showed that the conformation of intracellular apoE within HEK cells and astrocytes adopts a directional pattern; in other words, E4 adopts the most closed conformation, E2 adopts the most open conformation, and E3 adopts an intermediate conformation.

Review of functional and clinical relevance of intrinsic signal optical imaging in human brain mapping.

Intrinsic signal optical imaging (ISOI) within the first decade of its use in humans showed its capacity as a precise functional mapping tool. It is a powerful tool that can be used intraoperatively to help a surgeon to directly identify functional areas of the cerebral cortex. Its use is limited to the intraoperative setting as it requires a craniotomy and durotomy for direct visualization of the brain.

Study of single and multidigit activation in monkey somatosensory cortex using voltage-sensitive dye imaging.

Toward the goal of understanding cutaneous sensory integration during manual behavior, we used voltage-sensitive dye (VSD) imaging to study the organization and dynamics of anesthetized monkey primary somatosensory cortex (SI) in response to single and multidigit tactile stimulation. We find that in both macaque and squirrel monkey SI, VSD reveals clear focal digit topography consistent with previous electrophysiological and intrinsic signal imaging studies. VSD also reveals interactions in SI in response to multidigit stimulation.

Novel compounds targeting the enterohemorrhagic Escherichia coli type three secretion system reveal insights into mechanisms of secretion inhibition.

Anti-virulence (AV) compounds are a promising alternative to traditional antibiotics for fighting bacterial infections. The Type Three Secretion System (T3SS) is a well-studied and attractive AV target, given that it is widespread in more than 25 species of Gram-negative bacteria, including enterohemorrhagic E. coli (EHEC), and as it is essential for host colonization by many pathogens.

Compensatory and decompensatory alterations in cardiomyocyte Ca dynamics in hearts with diastolic dysfunction following aortic banding.

Key Points: At the cellular level cardiac hypertrophy causes remodelling, leading to changes in ionic channel, pump and exchanger densities and kinetics. Previous studies have focused on quantifying changes in channels, pumps and exchangers without quantitatively linking these changes with emergent cellular scale functionality. Two biophysical cardiac cell models were created, parameterized and validated and are able to simulate electrophysiology and calcium dynamics in myocytes from control sham operated rats and aortic-banded rats exhibiting diastolic dysfunction.

Characterization of TauC3 antibody and demonstration of its potential to block tau propagation.

The spread of neurofibrillary tangle (NFT) pathology through the human brain is a hallmark of Alzheimer's disease (AD), which is thought to be caused by the propagation of "seeding" competent soluble misfolded tau. "TauC3", a C-terminally truncated form of tau that is generated by caspase-3 cleavage at D421, has previously been observed in NFTs and has been implicated in tau toxicity. Here we show that TauC3 is found in the seeding competent high molecular weight (HMW) protein fraction of human AD brain.

Enhanced Tau Aggregation in the Presence of Amyloid β.

Amyloid plaques and neurofibrillary tangles co-occur in Alzheimer disease, but with different topological and temporal patterns. Whether these two lesions are independent or pathobiologically related is uncertain. For example, amyloid deposition in the neocortex precedes the spread of tau neurofibrillary tangles from the limbic areas to the cortex.

Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy.

Aims: Concentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload.

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

Study Design: A multicenter, retrospective review of C5 palsy after cervical spine surgery.

Objective: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery.

Intraoperative Death During Cervical Spinal Surgery: A Retrospective Multicenter Study.

Study Design: A retrospective multicenter study.

Objective: Routine cervical spine surgeries are typically associated with low complication rates, but serious complications can occur. Intraoperative death is a very rare complication and there is no literature on its incidence.

Epidural Hematoma Following Cervical Spine Surgery.

Study Design: A multicentered retrospective case series.

Objective: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine.

Methods: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified.

Disarming the enemy: targeting bacterial toxins with small molecules.

The rapid emergence of antibiotic-resistant bacterial strains has prompted efforts to find new and more efficacious treatment strategies. Targeting virulence factors produced by pathogenic bacteria has gained particular attention in the last few years. One of the inherent advantages of this approach is that it provides less selective pressure for the development of resistance mechanisms.

Tau Antibody Targeting Pathological Species Blocks Neuronal Uptake and Interneuron Propagation of Tau in Vitro.

The clinical progression of Alzheimer disease (AD) is associated with the accumulation of tau neurofibrillary tangles, which may spread throughout the cortex by interneuronal tau transfer. If so, targeting extracellular tau species may slow the spreading of tau pathology and possibly cognitive decline. To identify suitable target epitopes, we tested the effects of a panel of tau antibodies on neuronal uptake and aggregation in vitro.

When and where? Pathogenic differentially sense host D-serine using a universal transporter system to monitor their environment.

Sensing environmental stimuli is critically important for bacteria when faced with the multitude of adversities presented within the host. Responding appropriately to these signals and in turn integrating these responses into the regulatory network of the cell allows bacteria to control precisely when and where they should establish colonization. D-serine is an abundant metabolite of the human urinary tract but is a toxic metabolite for that lack a D-serine tolerance locus.

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults.

There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology. A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain ( = 296; mean ± SD age: 73 ± 8.

Genetic and genomic evidence of niche partitioning and adaptive radiation in mountain pine beetle fungal symbionts.

Bark beetles form multipartite symbiotic associations with blue stain fungi (Ophiostomatales, Ascomycota). These fungal symbionts play an important role during the beetle's life cycle by providing nutritional supplementation, overcoming tree defences and modifying host tissues to favour brood development. The maintenance of stable multipartite symbioses with seemingly less competitive symbionts in similar habitats is of fundamental interest to ecology and evolution.

Intrinsic signal optical imaging of visual brain activity: Tracking of fast cortical dynamics.

Hemodynamic-based brain imaging techniques are typically incapable of monitoring brain activity with both high spatial and high temporal resolutions. In this study, we have used intrinsic signal optical imaging (ISOI), a relatively high spatial resolution imaging technique, to examine the temporal resolution of the hemodynamic signal. We imaged V1 responses in anesthetized monkey to a moving light spot.

Spatial Distribution of Attentional Modulation at Columnar Resolution in Macaque Area V4.

Attention to a location in a visual scene affects neuronal responses in visual cortical areas in a retinotopically specific manner. Optical imaging studies have revealed that cortical responses consist of two components of different sizes: the stimulus-nonspecific global signal and the stimulus-specific mapping signal (domain activity). It remains unclear whether either or both of these components are modulated by spatial attention.

Identification and Characterization of Novel Compounds Blocking Shiga Toxin Expression in O157:H7.

Infections caused by Shiga toxin (Stx)-producing strains constitute a health problem, as they are problematic to treat. Stx production is a key virulence factor associated with the pathogenicity of enterohaemorrhagic (EHEC) and can result in the development of haemolytic uremic syndrome in infected patients. The genes encoding Stx are located on temperate lysogenic phages integrated into the bacterial chromosome and expression of the toxin is generally coupled to phage induction through the SOS response.

The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline.

The increasing consumption of amino acids from a wide variety of sources, including dietary supplements, natural health products, medical foods, infant formulas, athletic and work-out products, herbal medicines, and other national and international categories of nutritional and functional food products, increases the exposure to amino acids to amounts far beyond those normally obtained from the diet, thereby necessitating appropriate and robust safety assessments of these ingredients. Safety assessments of amino acids, similar to all food constituents, largely rely on the establishment of an upper limit [Tolerable Upper Intake Level (UL)] considered to be a guide for avoiding high intake, above which adverse or toxic effects might occur. However, reliable ULs have been difficult or impossible to define for amino acids because of inadequate toxicity studies in animals and scarce or missing clinical data, as well as a paucity or absence of adverse event reporting data.

Contraceptive choices and preferences in a cohort of women with cystic fibrosis.

Objectives: As life expectancy for women with cystic fibrosis (CF) improves, reproductive decision-making is becoming increasingly relevant. We sought to characterize fertility intentions, contraceptive use, and preferences among adult females with CF.

Study Design: We conducted a cross-sectional survey of contraceptive use and preferences in reproductive-aged women with CF.

Intracellular d-Serine Accumulation Promotes Genetic Diversity via Modulated Induction of RecA in Enterohemorrhagic Escherichia coli.

Unlabelled: We recently discovered that exposure of enterohemorrhagic Escherichia coli (EHEC) to d-serine resulted in accumulation of this unusual amino acid, induction of the SOS regulon, and downregulation of the type III secretion system that is essential for efficient colonization of the host. Here, we have investigated the physiological relevance of this elevated SOS response, which is of particular interest given the presence of Stx toxin-carrying lysogenic prophages on the EHEC chromosome that are activated during the SOS response. We found that RecA elevation in response to d-serine, while being significant, was heterogeneous and not capable of activating stx expression or stx phage transduction to a nonlysogenic recipient.

Dynamic Evaluation of the Cervical Spine and the Spinal Cord of Symptomatic Patients Using a Kinetic Magnetic Resonance Imaging Technique.

Purpose: The purpose of this study was to examine the movement of the spinal cord and its relationship to the spinal canal in patients with mild spondylosis using kinetic magnetic resonance imaging (kMRI).

Methods: Weight-bearing, multiposition kMRI was performed on symptomatic patients through a full range of flexion-extension. A total of 52 study patients were selected based on the C2-C7 Cobb angle of sagittal alignment: lordotic (from 30 to 45 degrees).