Reconstruction and Simulation of Neocortical Microcircuitry.

Unlabelled: We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.

Aberrant cell cycle reentry in human and experimental inclusion body myositis and polymyositis.

Inclusion body myositis (IBM), a degenerative and inflammatory disorder of skeletal muscle, and Alzheimer's disease share protein derangements and attrition of postmitotic cells. Overexpression of cyclins and proliferating cell nuclear antigen (PCNA) and evidence for DNA replication is reported in Alzheimer's disease brain, possibly contributing to neuronal death. It is unknown whether aberrant cell cycle reentry also occurs in IBM.

Synaptic and cellular organization of layer 1 of the developing rat somatosensory cortex.

Layer 1 of the neocortex is sparsely populated with neurons and heavily innervated by fibers from lower layers and proximal and distal brain regions. Understanding the potential functions of this layer requires a comprehensive understanding of its cellular and synaptic organization. We therefore performed a quantitative study of the microcircuitry of neocortical layer 1 (L1) in the somatosensory cortex in juvenile rats (P13-P16) using multi-neuron patch-clamp and 3D morphology reconstructions.

Endothelial dysfunction and systemic hypertension by selective cGMP-dependent protein kinase I inhibition using novel cell-penetrating peptide delivered in vivo.

Background And Objective: Nitric oxide (NO) and related nitrovasodilators regulate blood pressure by activation of soluble guanylate cyclase, elevation of cyclic guanosine monophosphate (cGMP), and activation of cGMP-dependent protein kinase (cGPK). Despite the progress of our understanding of the NO/cGMP mediated vasorelaxation, partly through conventional cGPK knock-out mice, the role of cGPK remains unclear. In particular, the downstream target(s) of the kinase are not well defined.

Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy.

Rationale: Bone marrow (BM)-derived mesenchymal stem cells (MSCs) hold great promise for cardiovascular cell therapy owing to their multipotency and culture expandability.

Objective: The aim of the study was to investigate whether MSCs can treat experimental acute myocardial infarction (MI) and diabetic neuropathy.

Methods And Results: We isolated mononuclear cells from mouse BM and cultured MSCs in a conventional manner.

Patients' perspectives on fecal incontinence after brachytherapy for localized prostate cancer.

Background: When a patient is deciding between treatment options for localized prostate cancer, brachytherapy is commonly chosen for its perceived low complication profile. Brachytherapy can frequently be complicated by the development of fecal incontinence. The potential long-term impact of this dysfunction on a patient's life should be discussed.

Improving murine embryonic stem cell differentiation into cardiomyocytes with neuregulin-1: differential expression of microRNA.

Identification of factors that direct embryonic stem (ES) cell (ESC) differentiation into functional cardiomyocytes is essential for successful use of ESC-based therapy for cardiac repair. Neuregulin-1 (NRG1) and microRNA play important roles in the cardiac differentiation of ESCs. Understanding how NRG1 regulates microRNA will provide new mechanistic insights into the role of NRG1 on ESCs.

Renal acidification responses to respiratory acid-base disorders.

Respiratory acid-base disorders are those abnormalities in acid-base equilibrium that are expressed as primary changes in the arterial carbon dioxide tension (PaCO2). An increase in PaCO2 (hypercapnia) acidifies body fluids and initiates the acid-base disturbance known as respiratory acidosis. By contrast, a decrease in PaCO2 (hypocapnia) alkalinizes body fluids and initiates the acid-base disturbance known as respiratory alkalosis.

Accuracy and stability of measuring GABA, glutamate, and glutamine by proton magnetic resonance spectroscopy: a phantom study at 4 Tesla.

Proton magnetic resonance spectroscopy has the potential to provide valuable information about alterations in gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln) in psychiatric and neurological disorders. In order to use this technique effectively, it is important to establish the accuracy and reproducibility of the methodology. In this study, phantoms with known metabolite concentrations were used to compare the accuracy of 2D J-resolved MRS, single-echo 30 ms PRESS, and GABA-edited MEGA-PRESS for measuring all three aforementioned neurochemicals simultaneously.

The acute and late CNS glutamine response to benzodiazepine challenge: a pilot pharmacokinetic study using proton magnetic resonance spectroscopy.

Benzodiazepines (BZs), which are typically used as anxiolytics, act by modulating inhibitory signaling through gamma-aminobutyric acid A (GABA)(A) receptors. Functionally, the inhibitory effects of GABA may be counterbalanced by the excitatory effects of glutamate (Glu) as the two neurotransmitter systems are metabolically linked through their synthetic intermediate glutamine (Gln). The primary aim of this study was to determine whether the effects of different BZs on the GABA and Glu/Gln systems would vary according to the pharmacokinetics of the different drugs.

Whole blood transcriptomics in cardiac surgery identifies a gene regulatory network connecting ischemia reperfusion with systemic inflammation.

Background: Cardiac surgery with cardiopulmonary bypass (CS/CPB) is associated with increased risk for postoperative complications causing substantial morbidity and mortality. To identify the molecular mechanisms underlying CS/CPB-induced pathophysiology we employed an integrative systems biology approach using the whole blood transcriptome as the sentinel organ.

Methodology/principal Findings: Total RNA was isolated and globin mRNA depleted from whole blood samples prospectively collected from 10 patients at time points prior (0), 2 and 24 hours following CS/CPB.

Significance of prostate weight on peri and postoperative outcomes of robot assisted laparoscopic extraperitoneal radical prostatectomy.

Introduction: To determine the significance of prostate weight (PW) on clinical and pathological outcomes in patients undergoing da Vinci robot assisted laparoscopic extraperitoneal radical prostatectomy (EP-RARP).

Methods: From November 2008 to January 2010, 295 men underwent EP-RARP at our institution. We retrospectively reviewed our database and stratified patients into four groups based on pathologic PW: Group 1, less than 30 g; Group 2, 30 g to less than 50 g; Group 3, 50 g to less than 80 g; and Group 4, 80 g or larger.

Staphylococcus intermedius is not only a zoonotic pathogen, but may also cause skin abscesses in humans after exposure to saliva.

Background: Staphylococcus intermedius is a very rare human pathogen. There are only 16 cases in the literature that have described S. intermedius as a cause of infection in humans.

The promoting role of a tumour-secreted chemorepellent in self-metastatic tumour progression.

It has been proposed that cancer cells, in particular glioma tumour cells, secrete a chemorepellent factor that guides cell migration away from the tumour, facilitating migration and invasion. We present a hybrid continuous-discrete mathematical model of tumour growth and the chemotropism phenomenon to show that such a chemorepellent factor can also act as a promoter of self-metastases, a mechanism for tumour expansion we have previously shown can explain several essential kinetic dependencies of tumour growth. A sufficient criterion for this expansion was found to be the passive migration of peripheral cancer stem and non-stem cells away from the main tumour mass, where migrating cancer stem cells form new clusters.

First experience with rotational angiography of the right ventricle to guide ventricular tachycardia ablation.

Background: Rotational angiography with three-dimensional reconstruction (3DRA) is a new imaging tool recently introduced to guide mapping and ablation of the left atrium.

Objective: The purpose of this study was to determine the utility of 3DRA for imaging the ventricles and guiding ventricular tachycardia (VT) ablation.

Methods: Using the Philips Allura Xper FD10 system, 3DRA was performed in eight patients referred for right ventricular outflow tract (RVOT) VT ablation.

Acquired hemophilia as the cause of life-threatening hemorrhage in a 94-year-old man: a case report.

Introduction: Acquired factor VIII deficiency is a rare entity that can lead to severe and life-threatening bleeding. We describe a case of severe bleeding from the tongue secondary to acquired hemophilia and discuss treatment options, including aminocaproic acid and recombinant factor VIII, which have not been widely reported in the literature for the management of such patients.

Case Presentation: A 94-year-old Caucasian man presented to our institution with diffuse bruising and extensive bleeding from the tongue secondary to mechanical trauma.

Quantitative modeling of tumor dynamics and radiotherapy.

Cancer is a complex disease, necessitating research on many different levels; at the subcellular level to identify genes, proteins and signaling pathways associated with the disease; at the cellular level to identify, for example, cell-cell adhesion and communication mechanisms; at the tissue level to investigate disruption of homeostasis and interaction with the tissue of origin or settlement of metastasis; and finally at the systems level to explore its global impact, e.g. through the mechanism of cachexia.

Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with overactive bladder.

Background: Muscarinic receptors in the brain play an important role in cognitive function, especially memory, and there is growing awareness that specific antimuscarinic drugs for overactive bladder (OAB) may have adverse central nervous system (CNS) effects. Selection of an antimuscarinic OAB drug with reduced potential for CNS effects could be especially beneficial in the elderly people, in whom even the modest cognitive impairment may negatively affect independence.

Purpose: The purpose of the study is to determine if trospium chloride is assay detectable in the CNS of older adults with OAB and to assess whether deterioration of memory occurs in these individuals.

An unusual foreign body as cause of chronic sinusitis: a case report.

Introduction: The presence of a foreign body in the nose is a relatively uncommon occurrence. Many unusual foreign bodies in the nose have been reported in the literature, but no case of a nasal packing occurring as a foreign body in the nasal cavity for a prolonged time has been found.

Case Presentation: We describe a unique case of the largest foreign body left in situ in the nasal cavity for over 10 years.

Autologous transplantation of endothelial progenitor cells genetically modified by adeno-associated viral vector delivering insulin-like growth factor-1 gene after myocardial infarction.

The regenerative potential of bone marrow-derived endothelial progenitor cells (EPCs) has been adapted for the treatment of myocardial and limb ischemia via ex vivo expansion. We sought to enhance EPC function by the efficient genetic modification of EPCs in a rat model of myocardial infarction. Peripheral blood EPCs were expanded and transduced, using adeno-associated virus (AAV).

Electrotonic coupling between pyramidal neurons in the neocortex.

Electrotonic couplings (i.e., electrical synapses or gap junctions) are fundamental to neuronal synchronization, and thus essential for many physiological functions and pathological disorders.

Female pelvic surgical devices and techniques need better evidence-based medicine.

The adoption of evidence-based medicine (EBM) recommendations in female pelvic surgical technique and surgical device intervention is contingent upon the availability of EBM and the willingness and ability of practitioners to accept and implement the recommendations. It can be assumed that there is virtually no disagreement among either the practitioners or the experts who practice the craft with regard to the benefits of applying scientific and clinical data that can be obtained from prior and ongoing experience to the selection of current treatments. However, there is significant controversy regarding the existence of adequate "evidence" and the mechanism for developing and applying the recommendations that can be distilled from the available data.

Anaphylactoid reaction considered ciprofloxacin related: a case report and literature review.

Background: Although ciprofloxacin is a generally well-tolerated fluoroquinolone antibiotic, serious and life-threatening adverse events such as anaphylaxis and pulmonary edema have been described with its use. However, there is a lack of data in the scientific literature regarding these events.

Objectives: This report describes a case of an anaphylactoid reaction, considered probably ciprofloxacin related, that manifested as angioedema and later as pulmonary edema.