Introduction: Aquaporins (AQP) are a family of transmembrane proteins that transport water and small solutes such as glycerol across cell membranes. It is a mediator of transcellular water flow and plays an important role in maintaining intra/extracellular fluid homeostasis by facilitating water transport in response to changing osmotic gradients. In the skin, AQPs permit rapid, regulated, and selective water permeability and have been demonstrated to play a role in skin hydration, cell proliferation, migration, immunity, and wound healing. However, the expression of AQP-3 in the cutaneous burn wound has never been elucidated. We sought to assess the expression of AQP-3 in patients with burn wounds.Methods: A fresh full thickness biopsy sample was taken from the center of the burn wound, the burn wound edge, and the graft donor site in 7 patients (n = 21), approximately 3-7 days post injury. Fixed, paraffin embedded sections were stained using AQP-3 specific antibody and examined by immunofluorescence. Fresh samples were processed to quantify AQP-3 protein expression with Western blot analysis.Results: The central portion of the burn wound revealed destruction of the epidermis and dermis with no AQP-3 present. Along the burn wound edge where the epidermal architecture was disrupted, there was robust AQP-3 staining. Western blot analysis demonstrated deeper staining along the burn wound edge compared to unburned skin (control). Quantification of the protein shows a significant amount of AQP-3 expression along the burn wound edge (3.6 +/- 0.34) compared to unburned skin (2.1 +/- 0.28, N = 7, *p < 0.05). There is no AQP-3 expression in the burn wound center.Conclusion: AQP-3 expression is increased in the burn wound following injury. While its role in wound healing has been defined, we report for the first time the effect of cutaneous burns on AQP-3 expression. Our data provides the first step in determining its functional role in burn wounds. We hypothesize that development of AQP3 targeted therapies may improve burn wound healing. (C) 2014 Elsevier Ltd and ISBI. All rights reserved.

Acute respiratory distress syndrome (ARDS) causes significant morbidity and mortality each year. There is a paucity of information regarding the mechanisms necessary for ARDS resolution. Foxp3(+) regulatory T cells (Foxp3(+) T(reg) cells) have been shown to be an important determinant of resolution in an experimental model of lung injury. We demonstrate that intratracheal delivery of endotoxin (lipopolysaccharide) elicits alveolar epithelial damage from which the epithelium undergoes proliferation and repair. Epithelial proliferation coincided with an increase in Foxp3(+) T(reg) cells in the lung during the course of resolution. To dissect the role that Foxp3(+) T(reg) cells exert on epithelial proliferation, we depleted Foxp3(+) T(reg) cells, which led to decreased alveolar epithelial proliferation and delayed lung injury recovery. Furthermore, antibody-mediated blockade of CD103, an integrin, which binds to epithelial expressed E-cadherin decreased Foxp3(+) T(reg) numbers and decreased rates of epithelial proliferation after injury. In a non-inflammatory model of regenerative alveologenesis, left lung pneumonectomy, we found that Foxp3(+) T(reg) cells enhanced epithelial proliferation. Moreover, Foxp3(+) T(reg) cells co-cultured with primary type II alveolar cells (AT2) directly increased AT2 cell proliferation in a CD103-dependent manner. These studies provide evidence of a new and integral role for Foxp3(+) T(reg) cells in repair of the lung epithelium.

Background— Patients with heart failure are frequently hospitalized for fluid overload. A reliable method for chronic monitoring of fluid status is therefore desirable. We evaluated an implantable system capable of measuring intrathoracic impedance to identify potential fluid overload before heart failure hospitalization and to determine the correlation between intrathoracic impedance and standard measures of fluid status during hospitalization. Methods and Results— Thirty-three patients with NYHA class III and IV heart failure were implanted with a special pacemaker in the left pectoral region and a defibrillation lead in the right ventricle. Intrathoracic impedance was regularly measured and recorded between the lead and the pacemaker case. During hospitalizations, pulmonary capillary wedge pressure and fluid status were monitored. Ten patients were hospitalized for fluid overload 25 times over 20.7±8.4 months. Intrathoracic impedance decreased before each admission by an average of 12.3±5.3% ( P <0.001) over an average of 18.3±10.1 days. Impedance reduction began 15.3±10.6 days ( P <0.001) before the onset of worsening symptoms. There was an inverse correlation between intrathoracic impedance and pulmonary capillary wedge pressure ( r =−0.61, P <0.001) and between intrathoracic impedance and net fluid loss ( r =−0.70, P <0.001) during hospitalization. Automated detection of impedance decreases was 76.9% sensitive in detecting hospitalization for fluid overload, with 1.5 false-positive (threshold crossing without hospitalization) detections per patient-year of follow-up. Conclusions— Intrathoracic impedance is inversely correlated with pulmonary capillary wedge pressure and fluid balance and decreased before the onset of patient symptoms and before hospital admission for fluid overload. Regular monitoring of impedance may provide early warning of impending decompensation and diagnostic information for titration of medication.

A 65 year old woman, who was diagnosed with non-obstructive apical hypertrophic cardiomyopathy 10 years ago, presented with heart failure symptoms and incessant ventricular tachycardia despite amiodarone therapy. Coronary angiogram showed normal coronary arteries. Supplemental material showing the left ventriculography (right …

mias during long-term follow-up after ablation of ART in pts with CHD guided by 3-D mapping. Methods:Pts (n=38, age 38+14 yr.. 22 male) with drug-refractory ART and tricuspid atresia (9), transposition of the great arteries (4), atrial septal defect (9), atrio-venfricular septal defect (1). aortic valve stenosis (7), coarctatio aorta (2) and Fallot (6) were studied. Episodes of AF were documented prior to ablation in 2 pts. 3-D activation/voltage maps were constructed during ART (CL 294*79 ms) to locate target sites for ablation. Successful ablation was defined as non-inducibility of the ART after termination during ablation. Results: Successful ablation was achieved after 1 or 2 (n=7) ablation procedures in 29 (76%) pts. During follow-up (24*6 months), pts had sinus rhythm (n=27, 71%), paroxysmal AF (n=8,21%) or permanent AF (n=3,8%). Anti-arrhyihmic drugs were used by 33% of the pts with sinus rhythm. The presence of AF was associated with the no. of previous surgical procedures, interval onset arrhythmia ablation procedure, a higher degree of low voltage areas and a larger right atrial volume (p-zO.01). Conclusion: Accurate 3-D localization of target sites is crucial for successful ablation of ART in pts with surgically corrected CHD and improves both shortand long-term outcome. However, during long-term follow-up, AF developed in some pts.

Introduction: Recently, interest has focused on the presence of cell-free deoxyribonucleic acid (DNA) in the plasma of human subjects. In particular, donor-derived DNA has been detected in the plasma of recipients of liver and kidney transplantation, a phenomenon referred to as plasma DNA chimerism.

Despite current interest in the biology and diagnostic application of plasma cell-free DNA (1), there is little knowledge regarding the cellular origin of this DNA. Recently, we have used a sex-mismatched bone marrow transplantation model to study the relative contributions of hematopoietic and nonhematopoietic cells to circulating DNA (2). We have demonstrated that the predominant proportion of plasma DNA originates from the hematopoietic system (2). However, the proportions of cell-free plasma DNA originating from other organs (e.g., heart, liver, and kidneys) remain unknown. We therefore investigated the contribution of the heart, liver, and kidneys to circulating DNA with use of sex-mismatched heart, liver, and renal transplantation models, respectively. Sex-mismatched heart, liver, and renal transplantation patients were recruited for the study. Twenty-one patients who had received heart transplants were recruited from the Grantham Hospital, Hong Kong. Fourteen of these heart transplantation patients were females with male donors, whereas the remaining 7 were males with female donors. Four sex-mismatched liver transplantation patients at the Pediatric Surgical Unit of the Department of Surgery, Prince of Wales Hospital were recruited; two of these patients were females with male donors and the other two were males with female donors. Six sexmismatched renal transplantation patients were recruited from the Department of Medicine and Therapeutics of …