Metabolic MRI With Hyperpolarized 13 C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism.

Objectives: Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13 C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.

A Framework for Predicting X-Nuclei Transmitter Gain Using H Signal.

Commercial human MR scanners are optimised for proton imaging, containing sophisticated prescan algorithms with setting parameters such as RF transmit gain and power. These are not optimal for X-nuclear application and are challenging to apply to hyperpolarised experiments, where the non-renewable magnetisation signal changes during the experiment. We hypothesised that, despite the complex and inherently nonlinear electrodynamic physics underlying coil loading and spatial variation, simple linear regression would be sufficient to accurately predict X-nuclear transmit gain based on concomitantly acquired data from the proton body coil.

Daytime Variation in Kidney Perfusion, Oxygenation, and Sodium Concentration Assessed by Multiparametric MRI in Healthy Volunteers.

Background: MRI can provide information on kidney structure, perfusion, and oxygenation. Furthermore, it allows for the assessment of kidney sodium concentrations and handling, allowing multiparametric evaluation of kidney physiology. Multiparametric MRI is promising for establishing prognosis and monitoring treatment responses in kidney diseases, but its intraindividual variation during the day is unresolved.

Considering whole-body metabolism in hyperpolarized MRI through C breath analysis-An alternative way to quantification and normalization?

Purpose: Hyperpolarized [1- C]pyruvate MRI is an emerging clinical tool for metabolic imaging. It has the potential for absolute quantitative metabolic imaging. However, the method itself is not quantitative, limiting comparison of images across both time and between individuals.

Gadolinium-enhanced MRI visualizing backflow at increasing intra-renal pressure in a porcine model.

Introduction: Intrarenal backflow (IRB) is known to occur at increased intrarenal pressure (IRP). Irrigation during ureteroscopy increases IRP. Complications such as sepsis is more frequent after prolonged high-pressure ureteroscopy.

Fibrosis imaging with multiparametric proton and sodium MRI in pig injury models.

Chronic kidney disease (CKD) is common and has huge implications for health and mortality. It is aggravated by intrarenal fibrosis, but the assessment of fibrosis is limited to kidney biopsies, which carry a risk of complications and sampling errors. This calls for a noninvasive modality for diagnosing and staging intrarenal fibrosis.

µ-Opioid Receptor Activation Reduces Glutamate Release in the PreBötzinger Complex in Organotypic Slice Cultures.

The inspiratory rhythm generator, located in the brainstem preBötzinger complex (preBötC), is dependent on glutamatergic signaling and is affected profoundly by opioids. Here, we used organotypic slice cultures of the newborn mouse brainstem of either sex in combination with genetically encoded sensors for Ca, glutamate, and GABA to visualize Ca, glutamatergic and GABAergic signaling during spontaneous rhythm and in the presence of DAMGO. During spontaneous rhythm, the glutamate sensor SF-iGluSnFR.

Dynamics of Deep Water and N Uptake of Oilseed Rape ( L.) Under Varied N and Water Supply.

Enhanced nitrogen (N) and water uptake from deep soil layers may increase resource use efficiency while maintaining yield under stressed conditions. Winter oilseed rape ( L.) can develop deep roots and access deep-stored resources such as N and water to sustain its growth and productivity.

Lactate saturation limits bicarbonate detection in hyperpolarized C-pyruvate MRI of the brain.

Purpose: To investigate the potential effects of [1- C]lactate RF saturation pulses on [ C]bicarbonate detection in hyperpolarized [1- C]pyruvate MRI of the brain.

Methods: Thirteen healthy rats underwent MRI with hyperpolarized [1- C]pyruvate of either the brain (n = 8) or the kidneys, heart, and liver (n = 5). Dynamic, metabolite-selective imaging was used in a cross-over experiment in which [1- C]lactate was excited with either 0° or 90° flip angles.

GABAergic Inhibition of Presynaptic Ca Transients in Respiratory PreBötzinger Neurons in Organotypic Slice Cultures.

GABAergic somatodendritic inhibition in the preBötzinger complex (preBötC), a medullary site for the generation of inspiratory rhythm, is involved in respiratory rhythmogenesis and patterning. Nevertheless, whether GABA acts distally on presynaptic terminals, evoking presynaptic inhibition is unknown. Here, we begin to address this problem by measuring presynaptic Ca transients in preBötC neurons, under rhythmic and non-rhythmic conditions, with two variants of genetically encoded Ca indicators (GECIs).

Improving Inferences from Hydrological Isotope Techniques.

Plant water isotopic compositions are widely used to describe patterns of soils water uptake. Although valuable, the technique only provides relative uptake distributions, which can be misleading. Without information on total transpiration, the technique cannot address central questions on drought response, competition, and species coexistence.

Segmentation of roots in soil with U-Net.

Background: Plant root research can provide a way to attain stress-tolerant crops that produce greater yield in a diverse array of conditions. Phenotyping roots in soil is often challenging due to the roots being difficult to access and the use of time consuming manual methods. Rhizotrons allow visual inspection of root growth through transparent surfaces.

Synthesis and Structural Characterization of a Pure ZnAl(OH)(SO)·2.6HO Layered Double Hydroxide.

The phase purity of a series of ZnAl(OH)SO· nHO layered double hydroxides (ZnAl-LDH) obtained from a reaction of bayerite (Al(OH)) with an excess of zinc(II) sulfate under hydrothermal conditions was investigated as a function of the reaction temperature, the duration of the hydrothermal treatment, and the zinc(II) concentration. The product quality, i.e.

Treatment profiles in a Danish psychiatric university hospital department.

Background: Despite concerns about rising treatment of psychiatric patients with psychotropic medications and declining treatment with psychotherapy, actual treatment profiles of psychiatric patients are largely unknown.

Aims: To describe patterns in the treatment of patients in a large psychiatric university hospital department.

Methods: A descriptive mapping of treatment of in- and outpatients in a psychiatric department at Aarhus University Hospital Risskov, Denmark.

The effect of combined therapies on recovery after acquired brain injury: Systematic review of preclinical studies combining enriched environment, exercise, or task-specific training with other therapies.

Background: Acquired brain injuries (ABI) have devastating effects for the affected individual as well as society. Many studies have investigated the effect of different monotherapies. However, functional recovery is typically only partial.

Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm.

Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin producing beta cells focus on soluble molecules whereas the impact of cell-matrix interactions has been mainly unattended. In this study almost 500 different extracellular matrix protein combinations were screened to systemically identify extracellular matrix proteins that influence differentiation of human embryonic stem cells to the definitive endoderm lineage.

High intensity and reduced volume training attenuates stress and recovery levels in elite swimmers.

This study investigated the effect of increased high-intensity interval training (HIT) at the expense of total training volume on the stress and recovery levels of elite swimmers. Forty-one elite swimmers participated in the study and were randomly assigned to either a HIT or a control group (CON). Eleven swimmers did not complete the questionnaires.

Streptococcus equi subsp. zooepidemicus isolates from equine infectious endometritis belong to a distinct genetic group.

Streptococcus equi subsp. zooepidemicus is the pathogen most commonly isolated from the uterus of mares. S.

In vivo imaging of retinoic acid receptor beta2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cells.

Background: In retinoid resistant epithelial tumors, the lack of retinoic acid receptor beta2 (RARbeta2) expression due to epigenetic silencing impairs the activation of retinoid target genes including RARbeta2, and has been associated with the development of cancer. In this study we developed a strategy to monitor the re-activation of RARbeta2 by chromatin remodeling agents combined with retinoids in real time, and to correlate the RARbeta2 re-activation with anti-tumor activity.

Methods: We selected the RARbeta2-negative retinoid resistant human prostate carcinoma cell line PC3 and stably transfected it with a luciferase expression vector under the control of a functional segment of RARbeta2 promoter (pGL2-RARbeta2-PC3).

On-line monitoring of striatum glucose and lactate in the endothelin-1 rat model of transient focal cerebral ischemia using microdialysis and flow-injection analysis with biosensors.

In vivo studies on cerebral glucose and lactate metabolism following a brain insult require fast and sensitive monitoring techniques. Here we report on-line monitoring of ischemic events and metabolic changes following reperfusion in striatum of freely moving rats subjected to endothelin-1 (60-240 pmol) induced, transient focal cerebral ischemia using slow microdialysis (0.5 microl/min), fast sampling (every minute) and flow-injection analysis with biosensors for glucose and lactate.

A Phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities.

Purpose: TNFerade is a second-generation replication-deficient adenovector carrying a transgene encoding human tumor necrosis factor alpha under control of a radiation- induced promoter. The objective of this study was to assess the tolerance of combining TNFerade and radiation therapy in patients with soft tissue sarcomas of the extremity.

Experimental Design: TNFerade was administered in combination with single-daily fractionated radiation therapy in 14 patients with soft tissue sarcoma of the extremities.

TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors.

Purpose: TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy.

Patients And Methods: TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy).

VEGF gene therapy for coronary artery disease and peripheral vascular disease.

Coronary artery disease (CAD) and peripheral arterial disease (PAD) are significant medical problems worldwide. Although substantial progress has been made in prevention as well as in the treatment, particularly of CAD, there are a large number of patients, who despite maximal medical treatment have substantial symptomatology and who are not candidates for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing treatment option.

Angiogenic gene therapy strategies for the treatment of cardiovascular disease.

Coronary artery disease (CAD) and peripheral vascular disease (PVD) are significant medical problems worldwide, and arguably the biggest medical problems in the developed world. Although substantial progress has been made in prevention as well as in the treatment of these diseases, particularly of CAD, there are a large number of patients, who despite maximal medical treatment, have substantial symptomatology, and who are not candidates for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing, treatment option for these patients.

TNFerade Biologic: preclinical toxicology of a novel adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene.

TNFerade Biologic (TNFerade) is a second-generation (E1-, E3-, and E4-deleted) replication-deficient adenovector carrying the transgene encoding for human tumor necrosis factor alpha (TNFalpha), regulated by the radiation-sensitive promoter Early Growth Response (Egr-1). We hypothesized that intratumoral injection of TNFerade followed by radiation would result in potentially therapeutic levels of TNFalpha with minimal toxicity. Three preclinical studies were conducted, the purpose of which was to characterize the toxicity and pharmacokinetics of TNFerade in conjunction with radiation in nude as well as immune-competent (Balb/c) mice.