Primary Xenografts of Human Prostate Tissue as a Model to Study Angiogenesis Induced by Reactive Stroma

Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6–14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6–10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts

Nonzero-sum Stochastic Games

This paper treats of stochastic games. We focus on nonzero-sum games and provide a detailed survey of selected recent results. In Section 1, we consider stochastic Markov games. A correlation of strategies of the players, involving ``public signals'', is described, and a correlated equilibrium theorem proved recently by Nowak and Raghavan for discounted stochastic games with general state space is presented. We also report an extension of this result to a class of undiscounted stochastic games, satisfying some uniform ergodicity condition. Stopping games are related to stochastic Markov games. In Section 2, we describe a version of Dynkin's game related to observation of a Markov process with random assignment mechanism of states to the players. Some recent contributions of the second author in this area are reported. The paper also contains a brief overview of the theory of nonzero-sum stochastic games and stopping games which is very far from being complete

18F-Fluoro-2-Deoxyglucose Positron Emission Tomography in delirium.

Delirium is a common, serious, yet poorly understood syndrome. Growing evidence suggests cerebral metabolismis fundamentally disturbed; however, it has not been investigated using 2-18F-fluoro-2-deoxyglucose (FDG) positronemission tomography (PET) in delirium. This prospective study thus explored FDG PET patterns of cerebral glucosemetabolism in older inpatients with delirium. A particular emphasis was on the posterior cingulate cortex (PCC), a keyregion for attention, which is a central feature of delirium. Delirium scans were compared with post-delirium scans usingvisual analysis and semi-quantitative analysis with NeuroQ; 13 participants (8 female, median 84 y) were scanned duringdelirium, and 6 scanned again after resolution. On visual analysis, cortical hypometabolism was evident in all participantsduring delirium (13/13), and improved with delirium resolution (6/6). Using NeuroQ, glucose metabolism was higherpost-delirium in the whole brain and bilateral PCC compared to during delirium (p<0.05). Greater metabolism in bothPCCs correlated with better performance on a neuropsychological test of attention, the WAIS-IV Digit Span Testforwards, and with shorter delirium duration. This research found widespread, reversible cortical hypometabolismduring delirium and PCC hypometabolism was associated with inattention during delirium

Load on osseointegrated fixation of a transfemoral amputee during a fall: Loading, descent, impact and recovery analysis

Falling represents a health risk for lower limb amputees fitted with an osseointegrated fixation mainly because of the potential damage to the fixation. The purpose of this study was to characterise a real forward fall that occurred inadvertently to a transfemoral amputee fitted with an osseointegrated fixation while attending a gait measurement session to assess the load applied on the residuum. The objective was to analyse the load applied on the fixation with an emphasis on the sequence of events, the pattern and the magnitude of the forces and moments. The load was measured directly at 200 Hz using a six-channel transducer. Complementary video footage was also studied. The fall was divided into four phases: loading (240 ms), descent (620 ms), impact (365 ms) and recovery (2495 ms). The main impact forces and moments occurred 870 ms and 915 ms after the heel contact, and corresponded to 133 %BW and 17 %BWm, or 1.2 and 11.2 times the maximum forces and moments applied during the previous steps of the participant, respectively. This study provided key information to engineers and clinicians facing the challenge to design equipment, and rehabilitation and exercise programs to restore safely the locomotion of lower limb amputees

Echocardiographic parameters in 14 healthy English Bull Terriers

Objective To determine the range of various cardiac parameters using echocardiography in apparently normal, healthy English Bull Terriers. Design Fourteen English Bull Terriers were selected for study. Cardiac auscultation of the parents of these dogs was normal. Echocardiographic examination of one parent of each animal showed: no mitral or aortic valve abnormalities; no myocardial lesions; no two dimensional evidence of fixed or dynamic left ventricular outflow tract obstruction; and no systolic aortic or left ventricular outflow tract turbulence on colour flow Doppler examination. The 14 selected dogs did not have arrhythmias or murmurs, and on echocardiographic examination had similar findings to their parents. Systolic blood pressure was measured in all dogs and they had no clinical evidence of Bull Terrier polycystic kidney disease or Bull Terrier hereditary nephritis. Procedure All dogs were auscultated and subjected to a sequential global echocardiographic assessment of the heart, including two dimensional long and short axis, and colour flow Doppler interrogation of the mitral and aortic valves. Dimensional measurements, including those from the left atrium, aortic annulus and left ventricle, were taken from a right parasternal window, and derived values such as fractional shortening, stroke volume and left atrial to aortic annulus ratio were calculated. Peak systolic aortic velocity was measured from the left parasternal window using two dimensional-guided pulsed wave Doppler with angle correction. Systolic blood pressure was measured using a Doppler monitor. The absence of Bull Terrier polycystic kidney disease was determined using renal ultrasonography, and of Bull Terrier hereditary nephritis using urinary protein to creatinine ratio. Results These 14 dogs had greater left ventricular wall thickness and smaller aortic root diameters than those reported as normal for other breeds of comparable body size. Left atrial dimensions were also larger, however this may have been due to the maximising method of measurement. These apparently normal English Bull Terriers also had higher aortic velocities than those reported for other breeds, possibly due to a smaller aortic root diameter or other anatomic substrate of the left ventricular outflow tract, lower systemic vascular resistance, or breed-specific normal left ventricular hypertrophy. While these dogs were selected to be as close to normal as possible, the breed may have a particular anatomy that produces abnormal left ventricular echocardiographic parameters. Conclusion These echocardiographic parameters may be used to diagnose left ventricular outflow tract obstruction and left ventricular hypertrophy, and inaccurate diagnoses may result if breed-specific values are not used