Virginia Commonwealth University

About: Virginia Commonwealth University is a education organization based out in Richmond, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23822 authors who have published 49587 publications receiving 1787046 citations. The organization is also known as: VCU.

Ductal Carcinoma In situ and the Emergence of Diversity during Breast Cancer Evolution

Abstract: Purpose: Human invasive breast cancers (IBC) show enormous histologic and biological diversity. This study comprehensively evaluated diversity in ductal carcinoma in situ (DCIS), the immediate precursors of IBCs. Experimental Design: The extent of diversity for conventional histologic grade and standard prognostic biomarkers assessed by immunohistochemistry was evaluated in a series of pure DCIS ( n = 200) compared with a contemporaneous series of IBCs ( n = 200). A subset of the DCIS ( n = 25) was evaluated by DNA microarrays for the presence of luminal, basal, and erbB2 intrinsic subtypes. The extent of diversity within individual cases of DCIS ( n = 120) was determined by assessing multiple regions independently for histologic (nuclear) grade and several biomarkers by immunohistochemistry, which approximate microarrays in determining intrinsic subtypes. Results: DCIS showed a broad distribution of conventional histologic grades and standard biomarkers ranging from well to poorly differentiated, nearly identical to IBCs. Microarrays showed the same intrinsic subtypes in DCIS as in IBCs. However, higher resolution analysis showed that multiple histologic grades, biomarker phenotypes, and intrinsic subtypes often coexist within the same DCIS, and these diverse regions probably compete for dominance. Diversity within cases of DCIS was highly correlated with mutated p53 ( P = 0.0007). Conclusions: These results support the hypothesis that poorly differentiated DCIS gradually evolve from well-differentiated DCIS by randomly acquiring genetic defects resulting in increasingly abnormal cellular features. This diversity is amplified by defects resulting in genetic instability (e.g., p53 mutation), and the alterations are propagated to IBC in a manner independent of progression to invasion.

Guidelines for Perioperative Care in Esophagectomy: Enhanced Recovery After Surgery (ERAS ® ) Society Recommendations.

Abstract: Enhanced recovery after surgery (ERAS) programs provide a format for multidisciplinary care and has been shown to predictably improve short term outcomes associated with surgical procedures. Esophagectomy has historically been associated with significant levels of morbidity and mortality and as a result routine application and audit of ERAS guidelines specifically designed for esophageal resection has significant potential to improve outcomes associated with this complex procedure. A team of international experts in the surgical management of esophageal cancer was assembled and the existing literature was identified and reviewed prior to the production of the guidelines. Well established procedure specific components of ERAS were reviewed and updated with changes relevant to esophagectomy. Procedure specific, operative and technical sections were produced utilizing the best current level of evidence. All sections were rated regarding the level of evidence and overall recommendation according to the evaluation (GRADE) system. Thirty-nine sections were ultimately produced and assessed for quality of evidence and recommendations. Some sections were completely new to ERAS programs due to the fact that esophagectomy is the first guideline with a thoracic component to the procedure. The current ERAS society guidelines should be reviewed and applied in all centers looking to improve outcomes and quality associated with esophageal resection.

Diesel Exhaust Activates and Primes Microglia: Air Pollution, Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity

Abstract: Background: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood. Objectives: Here, we sought to address the brain-region–specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity. Methods: Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron–glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms. Results: Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity. Conclusions: Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity.

Toward Pervasive Gait Analysis With Wearable Sensors: A Systematic Review

Abstract: After decades of evolution, measuring instruments for quantitative gait analysis have become an important clinical tool for assessing pathologies manifested by gait abnormalities. However, such instruments tend to be expensive and require expert operation and maintenance besides their high cost, thus limiting them to only a small number of specialized centers. Consequently, gait analysis in most clinics today still relies on observation-based assessment. Recent advances in wearable sensors, especially inertial body sensors, have opened up a promising future for gait analysis. Not only can these sensors be more easily adopted in clinical diagnosis and treatment procedures than their current counterparts, but they can also monitor gait continuously outside clinics – hence providing seamless patient analysis from clinics to free-living environments. The purpose of this paper is to provide a systematic review of current techniques for quantitative gait analysis and to propose key metrics for evaluating both existing and emerging methods for qualifying the gait features extracted from wearable sensors. It aims to highlight key advances in this rapidly evolving research field and outline potential future directions for both research and clinical applications.

Prevalence and costs of co-occurring traumatic brain injury with and without psychiatric disturbance and pain among Afghanistan and Iraq war veteran VA users

Abstract: BACKGROUND:: Traumatic brain injury (TBI) is the "signature injury" in the Afghanistan and Iraq wars [Operation Enduring Freedom in Afghanistan (OEF)/Operation Iraqi Freedom (OIF)]. Patients with combat-related TBI also have high rates of psychiatric disturbances and pain. OBJECTIVES:: To determine the prevalence of TBI alone and TBI with other conditions and the average cost of medical care for veterans with these diagnoses. METHODS:: Observational study using national inpatient, outpatient, and pharmacy data from Veterans Health Administration (VHA) datasets. Costs are estimated from utilization related to care within the VHA system. Participants were all OEF/OIF VHA users in 2009. RESULTS:: Among 327,388 OEF/OIF veterans using VHA services in 2009, 6.7% were diagnosed with TBI. Among those with TBI diagnoses, 89% were diagnosed with a psychiatric diagnosis [the most frequent being posttraumatic stress disorder (PTSD) at 73%], and 70% had a diagnosis of head, back, or neck pain. The rate of comorbid PTSD and pain among those with and without TBI was 54% and 11%, respectively. The median annual cost per patient was nearly 4-times higher for TBI-diagnosed veterans as compared with those without TBI ($5831 vs. $1547). Within the TBI group, cost increased as diagnostic complexity increased, such that those with TBI, pain, and PTSD demonstrated the highest median cost per patient ($7974). CONCLUSIONS:: The vast majority of VHA patients diagnosed with TBI also have a diagnosed mental disorder and more than half have both PTSD and pain. Patients with these comorbidities incur substantial medical costs and represent a target population for future research aimed at improving health care efficiency. Language: en