University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Pregnancy. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness.

Abstract: Decreased elasticity of the cardiovascular system is one of the hallmarks of the normal aging process of mammals. A potential explanation for this decreased elasticity is that glucose can react nonenzymatically with long-lived proteins, such as collagen and lens crystallin, and link them together, producing advanced glycation endproducts (AGEs). Previous studies have shown that aminoguanidine, an AGE inhibitor, can prevent glucose cross-linking of proteins and the loss of elasticity associated with aging and diabetes. Recently, an AGE cross-link breaker (ALT-711) has been described, which we have evaluated in aged dogs. After 1 month of administration of ALT-711, a significant reduction ( approximately 40%) in age-related left ventricular stiffness was observed [(57.1 +/- 6.8 mmHg x m(2)/ml pretreatment and 33.1 +/- 4.6 mmHg x m(2)/ml posttreatment (1 mmHg = 133 Pa)]. This decrease was accompanied by improvement in cardiac function.

Virtual Reality for Gait Training: Can It Induce Motor Learning to Enhance Complex Walking and Reduce Fall Risk in Patients With Parkinson's Disease?

Abstract: Background Gait and cognitive disturbances are common in Parkinson's disease (PD). These deficits exacerbate fall risk and difficulties with mobility, especially during complex or dual-task walking. Traditional gait training generally fails to fully address these complex gait activities. Virtual reality (VR) incorporates principles of motor learning while delivering engaging and challenging training in complex environments. We hypothesized that VR may be applied to address the multifaceted deficits associated with fall risk in PD. Methods Twenty patients received 18 sessions (3 per week) of progressive intensive treadmill training with virtual obstacles (TT + VR). Outcome measures included gait under usual-walking and dual-task conditions and while negotiating physical obstacles. Cognitive function and functional performance were also assessed. Results Patients were 67.1 ± 6.5 years and had a mean disease duration of 9.8 ± 5.6 years. Posttraining, gait speed significantly improved during usual walking, during dual task, and while negotiating overground obstacles. Dual-task gait variability decreased (ie, improved) and Trail Making Test times (parts A and B) improved. Gains in functional performance measures and retention effects, 1 month later, were also observed. Conclusions To our knowledge, this is the first time that TT + VR has been used for gait training in PD. The results indicate that TT + VR is viable in PD and may significantly improve physical performance, gait during complex challenging conditions, and even certain aspects of cognitive function. These findings have important implications for understanding motor learning in the presence of PD and for treating fall risk in PD, aging, and others who share a heightened risk of falls.

A novel single nucleotide polymorphism within the 5' tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity.

Abstract: Thymidylate synthase (TS) gene expression is modulated by a polymorphism in the 5' regulatory region of the gene. The polymorphism consists mainly of either two repeats (2R) or three repeats (3R) of a 28-bp sequence, yielding greater TS gene expression and protein levels with a 3R genotype. Two USF family E-box consensus elements are found within the tandem repeats of the 3R genotype, and one is found within the 2R genotype. These elements bind USF proteins in vitro by electrophoretic mobility shift analysis and in vivo by chromatin immunoprecipitation assay. We show that the additional USF consensus element within the 3R construct confers greater transcriptional activity relative to the 2R construct. Mutagenesis of the USF sites shows that the transcriptional regulation of TS is dependent, in part, on USF proteins binding within the tandem repeats. In addition, we identified a novel G-->C single nucleotide polymorphism in the second repeat of 3R alleles within the USF consensus element that alters the ability of USF proteins to bind and thus alters the transcriptional activation of TS gene constructs bearing this genotype. Through RFLP analysis, we determined the respective frequencies of the C allele (3RC) among all 3R alleles in non-Hispanic whites, Hispanic whites, African Americans, and Singapore Chinese to be 56%, 47%, 28%, and 37%, respectively. Based on our findings, this novel single nucleotide polymorphism should be considered when the 5' tandem repeat polymorphism is being used as a predictor of clinical outcome to TS inhibitors.

J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial.

Abstract: Aim In patients with coronary artery disease (CAD), a J-curve relationship has been reported between blood pressure (BP) and future cardiovascular events. However, this is controversial. The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD. Methods and results We evaluated 10 001 patients with CAD and a low-density lipoprotein (LDL) cholesterol level <130 mg/dL, randomized to atorvastatin 80 vs. 10 mg, enroled in the TNT trial. The post-baseline, time-dependent BPs [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were categorized into 10 mmHg increments. The primary outcome was a composite of death from coronary disease, non-fatal myocardial infarction (MI), resuscitated cardiac arrest, and fatal or non-fatal stroke. Among the 10 001 patients, 982 (9.82%) experienced a primary outcome at 4.9 years (median) of follow-up. The relationship between SBP or DBP and primary outcome followed a J-curve with increased event rates above and below the reference BP range, both unadjusted and adjusted (for baseline covariates, treatment effect, and LDL levels). A time-dependent, non-linear, multivariate Cox proportional hazard model identified a nadir of 146.3/81.4 mmHg where the event rate was lowest. A similar non-linear relationship with a higher risk of events at lower pressures was found for most of the secondary outcomes of all-cause mortality, cardiovascular mortality, non-fatal MI, or angina. However, for the outcome of stroke, lower was better for SBP. Conclusion In patients with CAD, a low BP (<110–120/<60–70 mmHg) portends an increased risk of future cardiovascular events (except stroke).

Tissue Levels of Bone Resorptive Cytokines in Periodontal Disease

Abstract: The levels of 3 bone resorptive cytokines, interleukin 1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor alpha (TNF alpha), were assessed in tissues from sites of periodontal disease. As determined by ELISA of tissue extracts, IL-1 beta and TNF alpha were detected in all diseased sites, whereas IL-1 alpha was present in 8/22 sites, IL-1 beta was present in highest concentration (mean +/- SEM: 11,695 +/- 2,888 pg/ml; 672 pM), followed by TNF alpha (434 +/- 135 pg/ml; 26 pM), and IL-1 alpha (342 +/- 160 pg/ml; 20 pM). The levels of all 3 mediators were significantly lower in clinically healthy tissues. There was a highly significant correlation between levels of IL-1 beta and TNF alpha (rs = 0.61, P less than 0.001), suggesting coordinated expression of these 2 mediators. The numbers of cells containing each mediator was also determined by indirect immunofluorescence on frozen tissue sections. Consistent with findings from tissue extracts, IL-1 beta-containing cells were present in approximately 5-fold higher numbers than TNF alpha-containing cells, and 40-fold higher numbers than IL-1-alpha-containing cells. Taken together with previous findings, these results indicate that IL-1 beta is likely to be an important mediator in the pathogenesis of periodontal disease.