Drosophila estrogen-related receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis.

Metabolism and development must be closely coupled to meet the changing physiological needs of each stage in the life cycle. The molecular mechanisms that link these pathways, however, remain poorly understood. Here we show that the Drosophila estrogen-related receptor (dERR) directs a transcriptional switch in mid-pupae that promotes glucose oxidation and lipogenesis in young adults. dERR mutant adults are viable but display reduced locomotor activity, susceptibility to starvation, elevated glucose, and an almost complete lack of stored triglycerides. Molecular profiling by RNA-seq, ChIP-seq, and metabolomics revealed that glycolytic and pentose phosphate pathway genes are induced by dERR, and their reduced expression in mutants is accompanied by elevated glycolytic intermediates, reduced TCA cycle intermediates, and reduced levels of long chain fatty acids. Unexpectedly, we found that the central pathways of energy metabolism, including glycolysis, the tricarboxylic acid cycle, and electron transport chain, are coordinately induced at the transcriptional level in mid-pupae and maintained into adulthood, and this response is partially dependent on dERR, leading to the metabolic defects observed in mutants. Our data support the model that dERR contributes to a transcriptional switch during pupal development that establishes the metabolic state of the adult fly.

Overground and Virtual Reality Gait Speed Are Associated With Atypical Symptom Reporting in Active Duty Service Members With a History of Mild to Moderate Traumatic Brain Injury.

OBJECTIVE: Physical therapy following traumatic brain injury (TBI) can be negatively impacted by psychological symptoms, atypical symptom reporting, and response bias. We examined rates of Symptom Validity Test (SVT) failure in active duty military service members with a history of mild-moderate TBI and its impact on gait speed. SETTING: Intensive Outpatient Program at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. PARTICIPANTS: Participants were 84 active duty service members with a history of mild-moderate TBI classified as SVT pass ( n = 49) or SVT fail ( n = 35). DESIGN: Retrospective study. MAIN MEASURES: Overground preferred and fast walking speed as well as Computer Assisted Rehabilitation Environment (CAREN) gait speed were recorded. Participants completed the Neurobehavioral Symptom Inventory and the Validity-10 was used to assign patients into the SVT pass and SVT fail groups. Gait speed metrics were compared across these groups and test operating characteristics were calculated. RESULTS: Approximately 42% of the sample was classified into the SVT fail group. All 3 gait speed measures were significantly slower in the SVT fail group than in the SVT pass group ( P s < .001, d s = 0.60-0.80). Gait speed cutoffs for screeners or indicators of atypical reporting were identified. CONCLUSIONS: The potential for response bias is a critical area for the clinician to consider when conducting physical therapy evaluations. Participants in the SVT fail group had slower walking speed on all 3 measures assessed. Several useful cutoffs were identified to serve as screeners or indicators of SVT failure, though these preliminary findings have limitations and need to be replicated.

The Community Balance and Mobility Scale: A Pilot Study Detecting Impairments in Military Service Members With Comorbid Mild TBI and Psychological Health Conditions.

OBJECTIVE: To compare the capacity of the Community Balance and Mobility Scale (CB&M) to identify balance and mobility deficits in Service Members (SMs) with mild traumatic brain injury and comorbid psychological health conditions (mTBI/PH) to other commonly used balance assessments. SETTING: A clinical research institute that provides a 4-week, outpatient, interdisciplinary program for active-duty SMs with mTBI/PH. DESIGN: A nonrandomized, cross-sectional design that compared multiple measures between 2 groups-active duty SMs with (n = 8) and without (n = 8) the dual diagnosis of mTBI/PH. MAIN MEASURES: Gait speed, Activities-specific Balance Confidence scale (ABC), Functional Gait Assessment (FGA), and CB&M to assess functional balance among the community-dwelling, TBI population. RESULTS: Across all measures, the mTBI/PH group performed significantly worse (P ≤ .01) with the exception of the FGA. The abilities of all objective measures to distinguish participants with mTBI/PH from healthy controls ranged from fair to excellent (area under the curve [AUC] = 0.66-0.94). However, the CB&M showed the largest group differences in effect size (d = 2.6) and had the highest discriminate ability (AUC = 0.98; sensitivity 100%; specificity 88%). CONCLUSION: The CB&M appears to have higher sensitivity and specificity than other measures of balance in SMs with mTBI/PH. A higher cut score for the CB&M is needed for this population.

Prognostic factors in 401 elderly women with metastatic breast cancer.

BACKGROUND: Elderly patients with metastatic breast cancer have a prognosis and outcome that may be dependent on a host of factors. PATIENTS AND METHODS: We retrospectively analyzed 401 female breast cancer patients who developed metastatic disease after the age of 70 years in order to define potential prognostic factors for specific survival at the time of first recurrence. RESULTS: With a median follow-up of 60 months from the time of recurrence, the median specific survival was 21.0 months (95% CI 17.0-23.0). In multivariate analysis we demonstrated that negative hormonal receptor status (p = 0.002), presence of positive lymph nodes at initial cancer diagnosis (hazard ratio, HR = 1.37; 95% CI 1.07-1.75; p = 0.01), site of metastasis (p < 10(-4)) and metastasis-free interval (HR = 0.99; 95% CI 0.95-0.99; p = 0.008) constituted unfavorable independent prognostic factors able to predict specific survival from the time of metastatic occurrence. Age at initial diagnosis, Scarff-Bloom Richardson grade and adjuvant treatments were significant only in univariate analysis. CONCLUSION: These survival prognostic factors associated with the use of a specific geriatric questionnaire to assess frailty may assist physicians in evaluating the patient's survival potential and choose a tailored treatment to this cancer population.

[Head to head comparison of two currently used nomograms predicting the risk of side specific extra capsular extension to indicate nerve sparing during radical prostatectomy for treatment of prostate cancer]. / Validation externe des nomogrammes de prédiction de l'extension extra-prostatique spécifiquement au côté pour des patients atteints de cancer de prostate traités par prostatectomie totale.

OBJECTIVE: To perform a head to head comparison of these two nomograms by an external validation combined with an identification of probability cut-offs when to indicate NS. METHODS: The full models of the nomograms of Ohori et al. and Steuber et al. were used to calculate the risk of ECE based on PSA and side specific information on clinical stage, biopsy Gleason score, % positive cores, and % cancer in cores. A dataset of 968 prostate half lobes was used retrospectively for analysis. All patients underwent laparoscopic robot-assisted or open radical prostatectomy for localized prostate cancer. RESULTS: The predictive accuracy of the Ohori nomogram was at 0.80 and for the Steuber Nomogram at 0.78 (comparison P > 0.05). In the calibration plot, the Ohori nomogram showed less departures from ideal predictions than the Steuber nomogram. The best probability cut-off to allow NS for the Ohori nomogram seemed to be ≤ 10%, permitting NS in 59.7% of all cases and being associated with a false negative rate of 10%. The best cut-off for the Steuber nomogram seemed to be ≤ 8%, permitting NS in 44% and associated with a false negative rate 12.5%. CONCLUSIONS: The Ohori et al. and the Steuber et al. nomograms allow highly accurate and comparable predictions of the risk of side specific ECE. LEVEL OF EVIDENCE: 4.

Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

BACKGROUND: Sunitinib is a standard of care for metastatic renal cell carcinoma (mRCC). Hypothyroidism is frequently observed under sunitinib therapy. This study was conducted to prospectively determine the correlation between thyroid function and progression-free survival (PFS) in this population. PATIENTS AND METHODS: One hundred and eleven mRCC patients treated with sunitinib were evaluated for serum thyroid-stimulating hormone (TSH) and T4 levels before treatment and every 6 weeks during treatment. Survival was analysed according to a landmark method with a cut-off of 6 months, excluding early progressive or early-censored patients. RESULTS: Out of the 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction, including 95% hypothyroidisms out of which 90.9% received L-thyroxine replacement. Median time to TSH alteration was 5.4 months. Median PFS was 11.7 months for the entire population. Median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months, respectively, log-rank P = 0.94, hazard ratio = 1.02, 95% confidence interval = 0.54-1.93). There was no difference even after adjustment for Memorial Sloan-Kettering Cancer Centre classification and therapy line. CONCLUSIONS: Abnormal thyroid function with hormonal substitution did not increase survival in our population, independent of initial prognosis and previous treatments. Larger comparative studies are deserved to validate these conclusions.

[Real time elastography in the diagnosis of prostate cancer: comparison of preoperative imaging and histology after radical prostatectomy]. / Élastographie en temps réel pour l'identification du cancer de prostate : comparaison d'imagerie préopératoire avec l'anatomopathologie après prostatectomie totale.

INTRODUCTION: Conventional grey scale ultrasound has only limited sensitivity and specificity in the detection of prostate cancer. Real time elastography is a promising modality to overcome this problem. The goal of the current study was an evaluation of real time elastography for the correct detection of prostate cancer lesions in prostatectomy specimens. PATIENTS AND METHODS: Between 11/2008 and 05/2009, 28 patients diagnosed with prostate cancer and scheduled for radical prostatectomy underwent real time elastography before radical prostatectomy. Elastography was performed using a Hitachi(®) EUB 7500 ultrasound machine with a V53W rectal probe at 7,5MHz by one operator. During the exam, each prostate was partitioned into 12 sectors (anterior, posterior, left, right, base, middle gland, apex). Suspect zones were identified and filed depending on their localization. The prostatectomy specimens were processed according to the Stanford protocol in 3-5mm step sections. The preoperative and postoperative results regarding tumor localization were compared. RESULTS: In total, 88 cancer lesions could be identified in the prostatectomy specimen, where 125 sectors were positive for a total of 336 sectors evaluated. Based on elastography 134 suspicious sectors were identified. For real time elastography, the sensitivity and specificity for correct cancer identification were 73.4 and 79.0 %, respectively. The negative and positive predictive value was 83.4 and 67.4 %, respectively. Accuracy for correct identification of the tumor lesion was 76.5 %. CONCLUSION: In this study, real time elastography showed high accuracy in the identification of prostate cancer lesions in the prostate. Routine use of elastography could improve the diagnosis of prostate cancer, as well as the therapeutic management.

Examining the Relationship Between Conventional Outcomes and Immersive Balance Task Performance in Service Members With Mild Traumatic Brain Injury.

INTRODUCTION: Mild traumatic brain injury (mTBI) is associated with significant financial cost and reduced military readiness and impacts quality of life for active duty service members (SMs). Post-concussive symptoms can include vestibular impairments, such as chronic dizziness and postural instability, which can be compounded by psychological comorbidities like PTSD. Comprehensive vestibular evaluations are required to assess symptoms and guide clinical decision-making. At the National Intrepid Center of Excellence (NICoE), in addition to traditional vestibular assessments, clinicians can also leverage virtual environments (VEs) in the Computer-Assisted Rehabilitation Environment (CAREN) to further evaluate balance. The objective of this study was to examine the relationship between conventional outcomes and VE performance on immersive balance tasks in the CAREN, determine whether VE performance could predict conventional outcomes, and explore the impact of PTSD. MATERIALS AND METHODS: This retrospective analysis included 112 SMs from the NICoE Intensive Outpatient Program who provided informed consent for their clinical data to be used for research purposes. All had a history of mTBI, underwent vestibular evaluations, and completed immersive balance tasks on the CAREN. Conventional outcomes included the Sensory Organization Test (SOT), Functional Gait Assessment (FGA), Activities Balance Confidence (ABC) Scale, and Dizziness Handicap Inventory (DHI). The PTSD Checklist-Military Version was added to account for behavioral symptoms. Computer-Assisted Rehabilitation Environment outcomes included total time to complete the Balance Cubes VE, with the platform static (BC-Static) and with random platform motion (BC-PM) as well as composite scores for the Shark Hunt VE, with (SH-Recall) and without a recall task (SH-Standard). Statistical analyses included independent t-tests to determine group differences, Pearson's correlations to examine relationships between conventional outcomes and VE performance, and binary logistic regressions to determine if VE performance predicted conventional outcomes based on clinically relevant cutoffs. RESULTS: SMs who took less time to complete BC-Static had better overall balance, indicated by higher ABC, SOT, and FGA scores (P <.001). Those with greater self-reported dizziness, higher DHI scores, took longer to complete BC-Static (P < .05). FGA and SOT, objective gait and balance, were similarly correlated to BC-PM performance (P <.001). SMs with higher SOT scores, better balance, also tended to have higher SH-Standard scores (P <.1). SMs, who were above normative SOT, FGA, and ABC cutoffs, completed BC-Static significantly faster than those below (P <.05). This remained true for BC-PM but was only significant for SOT (P = .004). Performance on BC-Static, BC-PM, and SH-Standard was significant predictors of SOT score. For SMs with comorbid mTBI and PTSD, increased functional disability was observed in conventional outcomes and diminished VE performance was noted. CONCLUSION: Objective balance and gait, SOT and FGA, demonstrated the strongest relationships to immersive VE performance in the CAREN. Our findings suggest that these immersive balance tasks may be effective as an adjunct assessment to examine balance. Future work will focus on moving these VEs from the CAREN to a portable system, which could be more readily utilized in a variety of clinical settings, increasing accessibility.

Dietary conjugated linoleic acid supplementation alters skeletal muscle mitochondria and antioxidant status in young horses.

Conjugated linoleic acid (CLA) improves oxidative stress and mitochondrial biogenesis in various species but has not been thoroughly investigated in horses. We collected blood and muscle samples from lightly exercising horses before and 6 and 12 wk after receiving either soybean oil (CON; n = 5) or CLA (CLA; n = 5) supplementation. Samples were analyzed for markers of mitochondrial characteristics, antioxidant status, oxidative stress, and muscle damage. Data were analyzed using a linear model with repeated measures. In the triceps brachii (TB), citrate synthase (CS) activity was higher in CON than CLA horses (P = 0.003) but was unaffected by diet in the gluteus medius (GM). Integrative (relative to mg protein) cytochrome c oxidase (CCO) activity was higher in TB than the GM (P < 0.0001), while intrinsic (relative to CS) CCO was lower in the TB than the GM (P = 0.02) and tended to be lower in CON than CLA horses (P = 0.06). Neither CS nor integrative CCO activities were affected by time. In the GM, superoxide dismutase activity tended to increase in CON through week 12 (P = 0.10). Over both muscle groups, glutathione peroxidase activity tended to be higher in CON compared with CLA at week 12 (P = 0.06). Malondialdehyde was higher in the TB than the GM (P = 0.0004) but was unaffected by diet, while serum creatine kinase activity tended to be lower in CLA than CON horses (P = 0.07). These results suggest that CLA supplementation may lead to mitochondrial adaptations and prevent myofiber perturbation in skeletal muscle of young, lightly exercised horses.

Tumor protein p53-induced nuclear protein (TP53INP1) expression in medullary thyroid carcinoma: a molecular guide to the optimal extent of surgery?

BACKGROUND: Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent. METHODS: Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears. RESULTS: TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts. CONCLUSIONS: TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.

[Robot-assisted radical prostatectomy: Perioperative complications, pathological results and functional results during the learning curve]. / La prostatectomie totale robot-assistée : complications périopératoires, résultats anatomopathologiques et fonctionnels pendant la période d'initiation.

OBJECTIVE: We report our experiences regarding the peri- and postoperative complications as well as pathological and functional results of robot-assisted radical prostatectomy during the implementation phase and the learning curve of the technique. MATERIAL: All clinical, paraclinical, as well as peri- and postoperative events of the first 102 patients were filed. Postoperative complications were classified according to the Clavien classification. Regarding functional results, continence was defined as the use of 0 pads or one pad for security reasons. Erectile function was classified into absence of spontaneous erections, erections insufficient for sexual intercourse and erections sufficient for sexual intercourse. RESULTS: Median procedure time was 240min, blood-loss 400mL and transfusion rate 2%. Overall, 7.8% of all patients had perioperative complications, 13.7% had minor and 4.9% had mayor post operative complications. The overall positive surgical margin rate was 16.0%. At 12month, 87% of all patients were continent and 21.1% had spontaneous erections and 47.4% had sexual intercourse. CONCLUSION: Patients treated during the implementation phase of robot-assisted radical prostatectomy show rates of peri- and postoperative complications, as well as pathological and functional results comparable to the results of centers of excellence published in the literature.

The Community Balance and Mobility Scale: Detecting Impairments in Military Service Members With Mild Traumatic Brain Injury.

INTRODUCTION: The objective of this study was to determine the utility of the Community Balance and Mobility scale (CB&M) among service members presenting with mild traumatic brain injury (mTBI), to compare the results against well-established balance assessments, and to find a new military-specific CB&M cut score to help differentiate those with and without mTBI. MATERIALS AND METHODS: The setting was a 4-week, intensive-outpatient, interdisciplinary program for active duty service members with mTBI. This was a nonrandomized, cross-sectional design that compared multiple measures between two groups: active duty service members with (n = 45) and without (n = 45) mTBI. The assessments, including the Activities-Specific Balance Confidence Scale, gait speed (comfortable and fast), the Functional Gait Assessment, and the CB&M, were provided to both sample groups. RESULTS: The mTBI group performed significantly worse (P ≤ 0.01) across all measures. A higher cut score for the CB&M of 81.5 is suggested. The CB&M demonstrated the best sensitivity (78%) and specificity (91%) ratio, as well as the largest effect size and area under the curve(0.92). CONCLUSION: All objective measures distinguish participants with mTBI from controls, ranging from fair to excellent. The recommended CB&M cut score of 81.5 allows for good variance, standard deviation, and reduced risk of ceiling or floor effects. Further examination of the recommended CB&M cut score is warranted for use in the mTBI civilian populations.

Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer.

BACKGROUND: Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer. PATIENTS AND METHODS: This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other. RESULTS: Median age was 69 years (range 51-77 years), and median PSA 102 ng/ml (range 3-1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the >or=20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients. CONCLUSION: Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.

Vestibular Test Patterns in the NICoE Intensive Outpatient Program Patient Population.

The National Intrepid Center of Excellence (NICoE), on the campus of Walter Reed National Military Medical Center, was developed to help improve the lives of active duty service members (SMs) with traumatic brain injury (TBI) and comorbid behavioral health (BH) conditions. During the NICoE intensive outpatient program, SM who have all been identified as having some degree of TBI, undergo extensive interdisciplinary evaluations, including comprehensive vestibular assessment. These SMs sometimes present with vestibular symptoms ranging from lightheadedness to vertigo associated with the dual TBI/BH diagnoses, and vestibular testing results reported elsewhere have varied among this population. The study's purpose was to collate the vestibular test results obtained from a sample of the NICoE patients to determine if specific tests have a tendency to be abnormal in these SMs. Results indicate that oculomotor tests, particularly pursuit and saccade, were most often abnormal. The vertical subtests of the pursuit and saccade tests were abnormal more frequently than the horizontal subtests, suggesting that the vertical subtests should be utilized when evaluating the TBI population. Overall, oculomotor tests of vertical pursuit and saccades, as well as tests of central vestibular function, appear useful for detecting neurologic changes in active duty SMs with chronic symptoms after TBI.

Development of a Physical Education-Related State Policy Classification System (PERSPCS).

BACKGROUND: As policy-based approaches are increasingly proposed to address childhood obesity, this paper seeks to: (1) present the development of a system to systematically and reliably assess the nature and extent of state physical education (PE) and recess-related policies; (2) determine the inter-rater agreement in using the system; and (3) report on the variability in state policies using a December 31, 2003 baseline. METHODS: The PE and Recess State Policy Classification System (PERSPCS) was developed from a conceptual framework and was informed by reviewing the scientific and gray literatures and through consultations with an expert panel and key experts. Statutes and regulations enacted as of December 31, 2003 were retrieved from Westlaw (data retrieved and analyzed in 2004-2005). RESULTS: PERSPCS addresses five areas: PE time requirements, staffing requirements for PE, curriculum standards for PE, assessment of health-related fitness, and recess time (elementary schools only). The inter-rater agreement ranged from 0.876 (PE staffing requirements) to perfect agreement (recess time). Staffing requirements had more restrictive policies, followed in decreasing order by time requirements, curriculum standards, assessment, and recess time. Overall, state policies met minimal requirements across areas and grade levels as of December 2003. CONCLUSIONS: Extending PERSPCS to address other aspects of childhood obesity is a critical first step in understanding the range of state policy approaches in this area and their impact. PERSPCS should be examined in conjunction with school district-level policies to determine the overall effects of policies on school environmental and behavioral outcomes. PERSPCS is not designed to set policy guidelines.

Development of a School Nutrition-Environment State Policy Classification System (SNESPCS).

BACKGROUND: As policy strategies are rapidly being developed to address childhood overweight, a system was developed to systematically and reliably classify state policies related to the school nutrition environment. This study describes the development process, the inter-rater reliability to code state policies enacted as of December 2003, and the variability in state policies related to the school nutrition environment. METHODS: The development of the School Nutrition Environment State Policy Classification System (SNESPCS) included a comprehensive review of published literature, reports from government and nongovernmental sources, input from an expert panel, and select experts. Baseline statutes and regulations for each of the 50 states and the District of Columbia were retrieved from Westlaw (data retrieved in 2005-2006 and analyzed in 2006) and pilot testing of the system was conducted. RESULTS: SNESPCS included 11 policy areas that relate to a range of environmental and surveillance domains. At baseline, states had no (advertising/promotion and preferential pricing) or modest (school meal environment, reimbursable school meals, coordinating or advisory councils, body mass index screening) activities in many of the policy areas. As of 2003, 60% of the states had policies related to the sale of foods in school that compete with the school meal program. CONCLUSIONS: Evaluation of policies that affect the school-nutrition environment is in its earliest stage. SNESPCS provides a mechanism for assessing variation in state policies that can be incorporated in an evaluation framework aimed at elucidating the impact of state policies on the school environment, social norms, and children's dietary behaviors in schools.

Expanding Clinical Assessment for Traumatic Brain Injury and Comorbid Post-Traumatic Stress Disorder: A Retrospective Analysis of Virtual Environment Tasks in the Computer-Assisted Rehabilitation Environment.

The objective of this study was to determine whether physical performance during virtual environment (VE) tasks in the Computer-Assisted Rehabilitation Environment (CAREN) could differentiate between service members (SMs) with a history of traumatic brain injury (TBI) with and without comorbid post-traumatic stress disorder (PTSD). Data were obtained by independent review of clinical notes, objective outcomes, and validated questionnaires from 214 SMs (208 males) with a history of TBI assessed in the CAREN from 2010 to 2015. Three preliminary VEs acclimatized patients to the CAREN: Balance Balls, weight shifting on a static platform (timed); Balance Cubes, step shifting with and without platform motion (timed); and Continuous Road, flat ambulation (self-selected speed). Multiple regression analyses revealed that patients with comorbid TBI-PTSD were significantly slower in completing the VE tasks than patients without PTSD. Logistic regression showed that the Balance Cubes VE without platform motion significantly predicted diagnostic category (i.e., no PTSD vs. comorbid PTSD). In conclusion, in SMs with a history of TBI, physical performance on the CAREN effectively distinguished those with comorbid PTSD, as their performance was significantly slower than SMs without PTSD. These results portray the potential of the CAREN as a novel assessment tool in SMs with a history of TBI.

Expression of tpo mRNA in thyroid tumors: quantitative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes.

Immunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0.0001; R = 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0.05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar gamma1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0.01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.

ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients.

Like children exposed to Chernobyl fallout, the workers who cleaned up after the accident, also known as liquidators, have exhibited an increased incidence of thyroid cancer. A high prevalence of ret/PTC3 rearrangement has been found in pediatric post-Chernobyl thyroid tumors, but this feature has not been investigated in liquidator thyroid tumors. In this study we analyzed the prevalence of ret/PTC1 and ret/PTC3 in thyroid tumors from 21 liquidators, 31 nonirradiated adult Ukrainian patients, and 34 nonirradiated adult French patients. ret rearrangements in carcinomas were found in 83.3% of liquidators, 64.7% of Ukrainian patients, and 42.9% of French patients. The prevalence of ret/PTC1 was statistically similar in the three groups. The prevalence of ret/PTC3 was significantly higher in liquidators than in French patients (P = 0.03) but it was also high in nonirradiated Ukrainian patients who exhibited values intermediate between liquidators and French patients. In adenomas the prevalence of rearrangement was significantly higher in all Ukrainians than in French patients (P = 0.004). Like children exposed to Chernobyl fallout, liquidators showed a high prevalence of ret/PTC3. This finding suggests that irradiation had the same effect regardless of age. However, given the high rate of ret/PTC3 in nonirradiated adult Ukrainians, the possibility of genetic susceptibility or low-level exposure to radiation in that group cannot be excluded.

Hepatitis Bx antigen stimulates expression of a novel cellular gene, URG4, that promotes hepatocellular growth and survival.

Hepatitis B virus encoded X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) by up- or downregulating the expression of cellular genes that promote cell growth and survival. To test this hypothesis, HBxAg-positive and -negative HepG2 cells were constructed, and the patterns of cellular gene expression compared by polymerase chain reaction select cDNA subtraction. The full-length clone of one of these upregulated genes (URG), URG4, encoded a protein of about 104 kDa. URG4 was strongly expressed in hepatitis B-infected liver and in HCC cells, where it costained with HBxAg, and was weakly expressed in uninfected liver, suggesting URG4 was an effector of HBxAg in vivo. Overexpression of URG4 in HepG2 cells promoted hepatocellular growth and survival in tissue culture and in soft agar, and accelerated tumor development in nude mice. Hence, URG4 may be a natural effector of HBxAg that contributes importantly to multistep hepatocarcinogenesis.