The electrophysiologic effects of KCNQ1 extend beyond expression of IKs: evidence from genetic and pharmacologic block.

Aims: While variants in KCNQ1 are the commonest cause of the congenital long QT syndrome, we and others find only a small IKs in cardiomyocytes from human-induced pluripotent stem cells (iPSC-CMs) or human ventricular myocytes.

Methods And Results: We studied population control iPSC-CMs and iPSC-CMs from a patient with Jervell and Lange-Nielsen (JLN) syndrome due to compound heterozygous loss-of-function (LOF) KCNQ1 variants. We compared the effects of pharmacologic IKs block to those of genetic KCNQ1 ablation, using JLN cells, cells homozygous for the KCNQ1 LOF allele G643S, or siRNAs reducing KCNQ1 expression.

Clinical, Radiologic, and Histopathologic Features that Distinguish a Pigmented Plexiform Neurofibroma from a Congenital Melanocytic Nevus.

A 13-year-old Hispanic boy with no significant medical etymology presented with a chief complaint of widespread brown macules and patches. He had a large and evenly pigmented brown patch, with a centrally located 2.2 cm × 1.

Functional Assays Reclassify Suspected Splice-Altering Variants of Uncertain Significance in Mendelian Channelopathies.

Background: Rare protein-altering variants in , , and are major causes of Brugada syndrome and the congenital long QT syndrome. While splice-altering variants lying outside 2-bp canonical splice sites can cause these diseases, their role remains poorly described. We implemented 2 functional assays to assess 12 recently reported putative splice-altering variants of uncertain significance and 1 likely pathogenic variant without functional data observed in Brugada syndrome and long QT syndrome probands.

Differentiating Pemphigus Foliaceus From Pemphigus Vulgaris in Clinical Practice.

Pemphigus is a skin condition that causes intraepidermal separation of keratinocytes. Multiple types of pemphigus exist, including pemphigus vulgaris and pemphigus foliaceus. These can be differentiated by histopathology, clinical presentation, appearance of lesions, and antibodies, among other factors.

A recurrent melanocytic nevus phenomenon in the setting of Hailey-Hailey disease.

Atypical acquired melanocytic nevi in patients with epidermolysis bullosa (EB) have been referred to as EB nevi and are considered to be a type of recurrent nevus with atypical but distinctive histopathologic findings. Herein, we describe an atypical nevus in a patient with Hailey-Hailey disease with different histopathologic findings from EB nevi because of presumably different pathogenesis. It is important to be aware that the recurrent nevi phenomenon can be seen in acantholytic conditions as well as blistering disorders, given these lesions may clinically resemble melanoma.

Epstein-Barr virus: dermatologic associations and implications: part II. Associated lymphoproliferative disorders and solid tumors.

Epstein-Barr virus (EBV) was the first human virus to be associated with oncogenesis. Over the past few decades, cumulative research has revealed that latent EBV infection may be implicated in the pathogenesis of a heterogeneous group of lymphoproliferative disorders and malignancies occurring in both immunocompetent and immunocompromised hosts. Many of these diseases have either primary or secondary cutaneous manifestations.

Epstein-Barr virus: dermatologic associations and implications: part I. Mucocutaneous manifestations of Epstein-Barr virus and nonmalignant disorders.

Epstein-Barr virus (EBV) is a ubiquitous virus that has been implicated in a wide range of human diseases, many of which have mucocutaneous manifestations. As a member of the herpesviridae family, EBV causes lifelong infection by establishing latency in B lymphocytes. An intact immune response is critical in preventing progression of EBV disease, and the clinical manifestations of infection are dependent on the intricate relationship between virus and host immune system.

Defining the role of CD2 in disease progression and overall survival among patients with completely resected stage-II to -III cutaneous melanoma.

Background: Accurate assessment of prognosis remains clinically challenging in stage II to III cutaneous melanoma. Studies have implicated CD2 in immune surveillance, T-cell activation, and antitumor immunity, but its role in melanoma progression warrants further investigation.

Objective: We sought to investigate the prognostic role of CD2 in primary cutaneous melanoma.

Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.

Re-examination of features to distinguish polyarteritis nodosa from superficial thrombophlebitis.

The correct identification of vessel type is crucial in distinguishing cutaneous polyarteritis nodosa from superficial thrombophlebitis. As the treatment and prognosis of these conditions are very different, correct diagnosis is critical, but they have overlapping clinical and histopathologic features, which can sometimes make the distinction difficult. Features commonly used to distinguish an artery from vein include vessel shape and diameter, the presence or absence of an internal elastic lamina, smooth muscle pattern, and the presence or absence of valves.

Endovascular treatment of a congenital thoracic aortic aneurysm in a premature newborn.

Congenital aortic aneurysms are a rare, life-threatening disorder that present complex treatment challenges. The authors describe a congenital thoracic aortic aneurysm treated by endovascular means with stent-assisted coil deployment. Because of rapid in utero aneurysm growth and cardiac dysfunction, a 2.

Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I predisposes children to increased pulmonary artery pressure following surgical repair of congenital heart defects: a validated genetic association study.

Increased pulmonary artery pressure (PAP) can complicate the postoperative care of children undergoing surgical repair of congenital heart defects. Endogenous NO regulates PAP and is derived from arginine supplied by the urea cycle. The rate-limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl-phosphate synthetase I (CPSI).

The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency.

CPSI deficiency is an inborn error of metabolism caused by mutations in the first, rate-determining enzyme of the urea cycle. Our mutation detection data from this disorder suggest that a significant number of mutant alleles cause RNA instability, most likely through the nonsense-mediated decay pathway. We identified 26 non-consanguinous CPSID patients with an available RNA source (liver tissue or cell line) and screened both genomic DNA and RNA for the identification and classification of mutations.

Intentional retrieval of viabil stent-grafts from the biliary system.

The present report describes the intentional retrieval of six Viabil stent-grafts from the biliary system. The six stent-grafts were successfully removed from five patients with a mean time from placement to retrieval of 38 days. Successful retrieval was independent of underlying disease etiology and included strictures associated with benign disease, malignant disease, disease of unknown etiology, and stent-graft misplacement.

Combination of NMR and MRI quantitation of moisture and structure changes for convection cooking of fresh chicken meat.

This study demonstrates that a combination of bulk NMR and magnetic resonance imaging measurements of the T(2)-values of water protons can be used to determine the heat-induced changes in the structure and moisture content of fresh chicken meat which had been cooked in a convection oven at 200°C for a range of times. The gravimetric moisture content was also determined for both the raw and cooked meat. Multi-exponential fitting of the bulk NMR T(2) relaxation time data demonstrated three distinct water populations T(21) (39-43ms), T(22) (82-99ms) and T(23) (2-3ms) for raw meat which changed to 18-31ms (T(21)), 61-208ms (T(22)) and 3-7ms (T(23)) after the meat had been cooked.

Mapping of the cerebral response to acetazolamide using graded asymmetric spin echo EPI.

Cerebral vascular reactivity in different regions of the rat brain was quantitatively characterized by spatial and temporal measurements of blood oxygenation level-dependent (BOLD)-fMRI signals following intravenous administration of the carbonic anhydrase inhibitor acetazolamide: this causes cerebral vasodilatation through a cerebral extracellular acidosis that spares neuronal metabolism and vascular smooth muscle function, thus separating vascular and cerebral metabolic events. An asymmetric spin echo-echo planar imaging (ASE-EPI) pulse sequence sensitised images selectively to oxygenation changes in the microvasculature; use of a surface coil receiver enhanced image signal-to-noise ratios (SNRs). Image SNRs and hardware integrity were verified by incorporating quality assurance procedures; cardiorespiratory stability in the physiological preparations were monitored and maintained through the duration of the experiments.

Simultaneous measurement of blood and myocardial velocity in the rat heart by phase contrast MRI using sparse q-space sampling.

Purpose: To measure cardiac blood flow patterns and ventricular wall velocities through the cardiac cycle in anesthetized Wistar Kyoto (WKY) rats.

Materials And Methods: A gradient-echo cine pulse sequence incorporating pulsed field gradients (PFGs) provided phase contrast (PC) motion encoding. We achieved a range of velocity sensitivity that was sufficient to measure simultaneously the large flow velocities within the cardiac chambers and aortic outflow tract (up to 70 cm s(-1) during systole), and the comparatively small velocities of the cardiac wall (0-3 cm s(-1)).

Placement of the Essure permanent birth control device with fluoroscopic guidance: a novel method for tubal sterilization.

An effective transcervical method for fluoroscopically guided fallopian tube occlusion has long been sought for female sterilization. The Essure permanent birth control device was approved by the Food and Drug Administration in November 2002 and is currently indicated for hysteroscopic placement. In a series of eight patients, bilateral Essure microcoils were placed with fluoroscopic guidance in seven patients for a success rate of 87.

A novel non line-of-sight method for coating hydroxyapatite onto the surfaces of support materials by biomineralization.

A novel method is described for the non line-of-sight coating of hydroxyapatite onto polyurethane reticulated foam and titanium discs. This utilises a biofilm of Serratia sp. NCIMB 40259 which, when challenged with a solution containing calcium chloride and phosphatase substrate, manufactures biofilm-bound material identified as hydroxyapatite by X-ray powder diffraction analysis.