High Expression of Glycolytic Genes in Clinical Glioblastoma Patients Correlates With Lower Survival

Glioblastoma (GBM), the most aggressive brain tumor, is associated with a median survival at diagnosis of 16–20 months and limited treatment options. The key hallmark of GBM is altered tumor metabolism and marked increase in the rate of glycolysis. Aerobic glycolysis along with elevated glucose consumption and lactate production supports rapid cell proliferation and GBM growth. In this study, we examined the gene expression profile of metabolic targets in GBM samples from patients with lower grade glioma (LGG) and GBM. We found that gene expression of glycolytic enzymes is up-regulated in GBM samples and significantly associated with an elevated risk for developing GBM. Our findings of clinical outcomes showed that GBM patients with high expression of HK2 and PKM2 in the glycolysis related genes and low expression of genes involved in mitochondrial metabolism-SDHB and COX5A related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), respectively, was associated with poor patient overall survival. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in GBM compared to LGG but was lower compared to normal brain. The fact that in GBM the expression levels of TCA cycle and OXPHOS-related genes are higher than those in LGG patients suggests the metabolic shift in GBM cells when progressing from LGG to GBM. These results are an important step forward in our understanding of the role of metabolic reprogramming in glioma as drivers of the tumor and could be potential prognostic targets in GBM therapies

Does bracing affect bone health in women with adolescent idiopathic scoliosis?

Purpose: Adolescent idiopathic scoliosis (AIS) is often associated with low bone mineral content and density (BMC, BMD). Bracing, used to manage spine curvature, may interfere with the growth-related BMC accrual, resulting in reduced bone strength into adulthood. The purpose of this study was to assess the effects of brace treatment on BMC in adult women, diagnosed with AIS and braced in early adolescence. Methods: Participants included women with AIS who: (i) underwent brace treatment (AIS-B, n = 15, 25.6 ± 5.8 yrs), (ii) underwent no treatment (AIS, n = 15, 24.0 ± 4.0 yrs), and (iii) a healthy comparison group (CON, n = 19, 23.5 ± 3.8 yrs). BMC and body composition were assessed using dual-energy X-ray absorptiometry. Differences between groups were examined using a oneway ANOVA or ANCOVA, as appropriate. Results: AIS-B underwent brace treatment 27.9 ± 21.6 months, for 18.0 ± 5.4 h/d. Femoral neck BMC was lower (p = 0.06) in AIS-B (4.54 ± 0.10 g) compared with AIS (4.89 ± 0.61 g) and CON (5.07 ± 0.58 g). Controlling for lean body mass, calcium and vitamin D daily intake, and strenuous physical activity, femoral neck BMC was statistically different (p = 0.02) between groups. A similar pattern was observed at other lower extremity sites (p < 0.05), but not in the spine or upper extremities. BMC and BMD did not correlate with duration of brace treatment, duration of daily brace wear, or overall physical activity. Conclusion: Young women with AIS, especially those who were treated with a brace, have significantly lower BMC in their lower limbs compared to women without AIS. However, the lack of a relationship between brace treatment duration during adolescence and BMC during young adulthood, suggests that the brace treatment is not the likely mechanism of the low BMC

The Cost to Successfully Apply for Level 3 Medical Home Recognition

The NCQA Patient Centered Medical Home (PCMH) recognition program provides practices an opportunity to implement Medical home activities. Understanding the costs to apply for recognition may enable practices to plan their work

Gender-specific effects of HIV protease inhibitors on body mass in mice

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p \u3c 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p \u3c 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p \u3c 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol

The 2005 Nevada Rangeland Vegetation Survey General Public Questionnaire and Survey of Responses

The 2005 Nevada Rangeland Vegetation Survey was conducted as a collaborative effort between the University of Nevada, Reno (UNR) Department of Resource Economics and the University of Nevada Cooperative Extension (UNCE) Natural Resources Program to fulfill two roles

Discerning Applicants\u27 Interests in Rural Medicine: A Textual Analysis of Admission Essays

BACKGROUND: Despite efforts to construct targeted medical school admission processes using applicant-level correlates of future practice location, accurately gauging applicants\u27 interests in rural medicine remains an imperfect science. This study explores the usefulness of textual analysis to identify rural-oriented themes and values underlying applicants\u27 open-ended responses to admission essays. METHODS: The study population consisted of 75 applicants to the Rural Physician Leadership Program (RPLP) at the University of Kentucky College of Medicine. Using WordStat, a proprietary text analysis program, applicants\u27 American Medical College Application Service personal statement and an admission essay written at the time of interview were searched for predefined keywords and phrases reflecting rural medical values. From these text searches, derived scores were then examined relative to interviewers\u27 subjective ratings of applicants\u27 overall acceptability for admission to the RPLP program and likelihood of practicing in a rural area. RESULTS: The two interviewer-assigned ratings of likelihood of rural practice and overall acceptability were significantly related. A statistically significant relationship was also found between the rural medical values scores and estimated likelihood of rural practice. However, there was no association between rural medical values scores and subjective ratings of applicant acceptability. CONCLUSIONS: That applicants\u27 rural values in admission essays were not related to interviewers\u27 overall acceptability ratings indicates that other factors played a role in the interviewers\u27 assessments of applicants\u27 acceptability for admission

Selection of patients for heart transplantationin the current era of heart failure therapy

AbstractObjectivesWe sought to assess the relationship between survival, peak exercise oxygen consumption (Vo2), and heart failure survival score (HFSS) in the current era of heart failure (HF) therapy.BackgroundBased on predicted survival, HF patients with peak Vo2<14 ml/min/kg or medium- to high-risk HFSS are currently considered eligible for heart transplantation. However, these criteria were developed before the widespread use of beta-blockers, spironolactone, and defibrillators—interventions known to improve the survival of HF patients.MethodsPeak Vo2and HFSS were assessed in 320 patients followed from 1994 to 1997 (past era) and in 187 patients followed from 1999 to 2001 (current era). Outcomes were compared between these two groups of patients and those who underwent heart transplantation from 1993 to 2000.ResultsSurvival in the past era was 78% at one year and 67% at two years, as compared with 88% and 79%, respectively, in the current era (both p < 0.01). One-year event-free survival (without urgent transplantation or left ventricular assist device) was improved in the current era, regardless of initial peak Vo2: 64% vs. 48% for peak Vo2<10 ml/min/kg (p = 0.09), 81% vs. 70% for 10 to 14 ml/min/kg (p = 0.05), and 93% vs. 82% for >14 ml/min/kg (p = 0.04). Of the patients with peak Vo2of 10 to 14 ml/min/kg, 55% had low-risk HFSS and exhibited 88% one-year event-free survival. One-year survival after transplantation was 88%, which is similar to the 85% rate reported by the United Network for Organ Sharing for 1999 to 2000.ConclusionsSurvival for HF patients in the current era has improved significantly, necessitating re-evaluation of the listing criteria for heart transplantation

An Assessment of Oral Health on the Pine Ridge Indian Reservation

An assessment on the oral health of 292 Oglala Lakota residents of the Pine Ridge Indian Reservation in South Dakota looks at dental issues, periodontal disease, oral lesions and need for dental care. The research was conducted by the University of Colorado, Center for Native Oral Health Research and funded by the W.K. Kellogg Foundation

of Green Tea Extracts on Gene Expression in HepG2 and Cal-27 Cells

Abstract: Green tea extract is known to contain compounds that are able to produce antioxidant effects in many types of living cells. Treatment of cultured human hepatoma (HepG2) cells with green tea extract resulted in dramatically increased expression of at least 15 genes that are present on a commercial human drug metabolism gene array. RT-PCR was used to confirm the microarray results, and analysis of the 5&apos;-flanking region of each of these genes revealed potential electrophile/antioxidant response elements. Members of the acetyl transferase, epoxide hydrolase, sulfotransferase and glutathione transferase gene families were strongly induced. In addition, the human tongue carcinoma cell line Cal-27 did not respond to green tea extract in the same way, as none of the induced genes in the HepG2 cells were induced in the Cal-27 cells. The lack of induction of detoxification enzymes in the Cal-27 cell line may help to explain the previously observed increased cytotoxicity of green tea catechins on this cell line