Veterans Health Administration

About: Veterans Health Administration is a government organization based out in Washington D.C., District of Columbia, United States. It is known for research contribution in the topics: Population & Veterans Affairs. The organization has 63820 authors who have published 98417 publications receiving 4835425 citations. The organization is also known as: VHA.

Activators of the nuclear receptor ppargamma enhance colon polyp formation

Abstract: A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene expression in response to fatty acids, lipid-derived metabolites and antidiabetic drugs. To explore the role of the PPARs in diet-induced carcinogenesis, we treated mice predisposed to intestinal neoplasia with a synthetic PPARgamma ligand. Reflecting the pattern of expression of PPARgamma in the gastrointestinal tract, treated mice developed a considerably greater number of polyps in the colon but not in the small intestine, indicating that PPARgamma activation may provide a molecular link between a high-fat diet and increased risk of colorectal cancer.

Distinct basal ganglia territories are engaged in early and advanced motor sequence learning

Abstract: In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Ultrasound Assessment of Flow-Mediated Dilation

Abstract: Developed in 1992, the flow-mediated dilation test is now the most commonly used noninvasive assessment of vascular endothelial function in humans Since its inception, scientists have refined their understanding of the physiology, analysis, and interpretation of this measurement Recently, a significant growth of knowledge has added to our understanding and implementation of this clinically relevant research methodology Therefore, this tutorial provides timely insight into recent advances and practical information related to the ultrasonic assessment of vascular endothelial function in humans

Improvements in Speed-Based Gait Classifications Are Meaningful

Abstract: Background and Purpose—Gait velocity is a powerful indicator of function and prognosis after stroke. Gait velocity can be stratified into clinically meaningful functional ambulation classes, such as household ambulation (0.4 m/s), limited community ambulation (0.4 to 0.8 m/s), and full community ambulation (0.8 m/s). The purpose of the current study was to determine whether changes in velocity-based community ambulation classification were related to clinically meaningful changes in stroke-related function and quality of life. Methods—In subacute stroke survivors with mild to moderate deficits who participated in a randomized clinical trial of stroke rehabilitation and had a baseline gait velocity of 0.8 m/s or less, we assessed the effect of success versus failure to achieve a transition to the next class on function and quality of life according to domains of the Stroke Impact Scale (SIS). Results—Of 64 eligible participants, 19 were initially household ambulators, and 12 of them (68%) transitioned to limited community ambulation, whereas of 45 initially limited community ambulators, 17 (38%) became full community ambulators. Function and quality-of-life SIS scores after treatment were significantly higher among survivors who achieved a favorable transition compared with those who did not. Among household ambulators, those who transitioned to limited or full community ambulation had significantly better SIS scores in mobility (P0.0299) and participation (P0.0277). Among limited community ambulators, those who achieved the transition to full community ambulatory status had significantly better scores in SIS participation (P0.0085). Conclusions—A gait velocity gain that results in a transition to a higher class of ambulation results in better function and quality of life, especially for household ambulators. Household ambulators possibly had more severe stroke deficits, reducing the risk of “ceiling” effects in SIS-measured activities of daily living and instrumental activities of daily living. Outcome assessment based on transitions within a mobility classification scheme that is rooted in gait velocity yields potentially meaningful indicators of clinical benefit. Outcomes should be selected that are clinically meaningful for all levels of severity. (Stroke. 2007;38:2096-2100.)

KIT Gene Mutations and Copy Number in Melanoma Subtypes

Abstract: Purpose: We recently identified a KIT exon 11 mutation in an anorectal melanoma of a patient who had an excellent response to treatment with imatinib. To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors. Experimental Design: One hundred eighty-nine melanomas were screened for mutations in KIT exons 11, 13, and 17. KIT copy number was assessed by quantitative PCR. A subset of cases was evaluated for BRAF and NRAS mutations. Immunohistochemistry was done to assess KIT (CD117) expression. Results: KIT mutations were detected in 23% (3 of 13) of acral melanomas, 15.6% (7 of 45) of mucosal melanomas, 7.7% (1 of 13) of conjunctival melanomas, 1.7% (1 of 58) of cutaneous melanomas, and 0% (0 of 60) of choroidal melanomas. Almost all the KIT mutations were of the type predicted to be imatinib sensitive. There was no overlap with NRAS mutations (11.1% of acral and 24.3% of mucosal tumors) or with BRAF mutations (absent in mucosal tumors). Increased KIT copy number was detected in 27.3% (3 of 11) of acral and 26.3% (10 of 38) of mucosal melanomas, but was less common among cutaneous (6.7%; 3 of 45), conjunctival (7.1%; 1 of 14), and choroidal melanomas (0 of 28). CD117 expression, present in 39% of 105 tumors representing all melanoma types, did not correlate with either KIT mutation status or KIT copy number. Conclusions: Our findings confirm that KIT mutations are most common in acral and mucosal melanomas but do not necessarily correlate with KIT copy number or CD117 expression. Screening for KIT mutations may open up new treatment options for melanoma patients.