Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance.

Purpose: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer.

Materials And Methods: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density.

Co-Occurrence of Asthma and Nephrolithiasis in Children.

It has been proposed that epithelial dysfunction and inflammation may predispose patients to kidney stone formation. Asthma is another chronic condition related to epithelial dysfunction and inflammation. We hypothesized that pediatric patients with asthma would have an increased prevalence of nephrolithiasis.

Long-term Survival From Muscleinvasive Bladder Cancer With Initial Presentation of Symptomatic Cerebellar Lesion: The Role of Selective Surgical Extirpation of the Primary and Metastatic Lesion.

A 59-year-old man was diagnosed with urothelial carcinoma involving an isolated cerebellar metastasis after presenting to the emergency department for headache complaints. After selective surgical excision of the symptomatic brain lesion and delayed cystectomy due to intractable hematuria, he survived 11 years without evidence of recurrence or subsequent systemic chemotherapy. He eventually expired after delayed recurrence in the lung, supraclavicular lymph node, and brain.

Clinical phenotyping of urologic pain patients.

Purpose Of Review: Urologic pain conditions such as chronic prostatitis/chronic pelvic pain syndrome, interstitial cystitis/bladder pain syndrome and chronic orchialgia are common, yet diagnosis and treatment are challenging. Current therapies often fail to show efficacy in randomized controlled studies. Lack of efficacy may be due to multifactorial causes and heterogeneity of patient presentation.

Renal mitochondrial damage and protein modification in type-2 diabetes.

Although mitochondrial reduction-oxidation (redox) stress and increase in membrane permeability play an important role in diabetic-associated renal microvasculopathies, it is unclear whether the intra-renal mitochondrial oxidative stress induces mitochondrial protein modifications, leading to increase mitochondrial membrane permeability. The hypothesis is that mitochondrial oxidative stress induces mitochondrial protein modification and leakage in the mitochondrial membrane in type-2 diabetes. The present study was conducted to determine the involvement of intra-renal mitochondrial oxidative stress in mitochondrial protein modifications and modulation of membrane permeability in the setting of type-2 diabetes.

Cardiac dys-synchronization and arrhythmia in hyperhomocysteinemia.

Although cardiac synchronization is important in maintaining myocardial performance, the mechanism of dys-synchronization in ailing to failing myocardium is unclear. It is known that the cardiac myocyte contracts and relaxes individually; however, it synchronizes only when connected to one another by low resistance communications called gap junction protein (connexins) and extra cellular matrix (ECM). Therefore, the remodeling of connexins and ECM in heart failure plays an important role in cardiac conduction, synchronization and arrhythmias.

Reversal of systemic hypertension-associated cardiac remodeling in chronic pressure overload myocardium by ciglitazone.

Elevated oxidative stress has been characterized in numerous disorders including systemic hypertension, arterial stiffness, left ventricular hypertrophy (LVH) and heart failure. The peroxisome proliferator activated receptor gamma (PPARgamma) ameliorates oxidative stress and LVH. To test the hypothesis that PPARgamma decreased LVH and cardiac fibrosis in chronic pressure overload, in part, by increasing SOD, eNOS and elastin and decreasing NOX4, MMP and collagen synthesis and degradation, chronic pressure overload analogous to systemic hypertension was created in C57BL/6J mice by occluding the abdominal aorta above the kidneys (aortic stenosis-AS).

Cardiac synchronous and dys-synchronous remodeling in diabetes mellitus.

Glucose-mediated impairment of homocysteine (Hcy) metabolism and decrease in renal clearance contribute to hyperhomocysteinemia (HHcy) in diabetes. The Hcy induces oxidative stress, inversely relates to the expression of peroxisome proliferators activated receptor (PPAR), and contributes to diabetic complications. Extracellular matrix (ECM) functionally links the endothelium to the myocyte and is important for cardiac synchronization.

Oxidative remodeling in pressure overload induced chronic heart failure.

Despite extensive strides in understanding pressure overload induced heart failure, there is very little known about oxidative stress induced matrix metalloproteinase (MMP) activation, collagen degradation and remodeling in pressure overload heart failure. We hypothesize that pressure overload leads to redox imbalance causing increased expression/activity of MMP-2/9 producing collagen degradation and heart failure. To test this hypothesis, we created pressure overload heart failure by abdominal aortic stenosis (AS) in wild-type C57BL/6J and collagen mutant (Col1a1 with 129 s background) mice.

Arrhythmia and neuronal/endothelial myocyte uncoupling in hyperhomocysteinemia.

Elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are associated with arrhythmogenesis and sudden cardiac death (SCD). Hcy decreases constitutive neuronal and endothelial nitric oxide (NO), and cardiac diastolic relaxation. Hcy increases the iNOS/NO, peroxynitrite, mitochondrial NADPH oxidase, and suppresses superoxide dismutase (SOD) and redoxins.

Homocysteine-induced myofibroblast differentiation in mouse aortic endothelial cells.

Differentiation of myofibroblast, as evidenced by alpha-smooth muscle actin (alpha-SMA) expression, is largely mediated by transforming growth factor-beta1 (TGF-beta1). This mechanism often follows inflammatory events such as endothelial damage due to oxidative stress, which can further leads to vascular thickening, stiffness, and fibrosis. We hypothesized that hyperhomocysteinemia (HHcy)-induced oxidative stress lead to vascular stiffness, in part due to endothelial-myofibroblast differentiation and alteration of collagen homeostasis in the extracellular matrix (ECM).