Speech Communication

Contains research objectives and reports on three research projects.U. S. Air Force (Electronic Systems Division) under Contract AF19(628)-5661National Institutes of Health (Grant 5 RO1 NB-04332-04

Speech Communication

Contains research objectives and reports on four research projects.U.S. Air Force (Electronic Systems Division) under Contract AF 19(628)-3325National Institutes of Health (Grant NB-04332-03

A role of mitochondrial complex II defects in genetic models of Huntington's disease expressing N-terminal fragments of mutant huntingtin.

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of a CAG repeat encoding a polyglutamine tract in the huntingtin (Htt) protein. The mutation leads to neuronal death through mechanisms which are still unknown. One hypothesis is that mitochondrial defects may play a key role. In support of this, the activity of mitochondrial complex II (C-II) is preferentially reduced in the striatum of HD patients. Here, we studied C-II expression in different genetic models of HD expressing N-terminal fragments of mutant Htt (mHtt). Western blot analysis showed that the expression of the 30 kDa Iron-Sulfur (Ip) subunit of C-II was significantly reduced in the striatum of the R6/1 transgenic mice, while the levels of the FAD containing catalytic 70 kDa subunit (Fp) were not significantly changed. Blue native gel analysis showed that the assembly of C-II in mitochondria was altered early in N171-82Q transgenic mice. Early loco-regional reduction in C-II activity and Ip protein expression was also demonstrated in a rat model of HD using intrastriatal injection of lentiviral vectors encoding mHtt. Infection of the rat striatum with a lentiviral vector coding the C-II Ip or Fp subunits induced a significant overexpression of these proteins that led to significant neuroprotection of striatal neurons against mHtt neurotoxicity. These results obtained in vivo support the hypothesis that structural and functional alterations of C-II induced by mHtt may play a critical role in the degeneration of striatal neurons in HD and that mitochondrial-targeted therapies may be useful in its treatment

Prognostic Value of Fusobacterium nucleatum after Abdominoperineal Resection for Anal Squamous Cell Carcinoma

International audienceMain prognostic factors of anal squamous cell carcinoma (ASCC) are tumor size, differ-entiation, lymph node involvement, and male gender. However, they are insufficient to predict relapses after exclusive radiotherapy (RT) or chemoradiotherapy (CRT). Fusobacterium nucleatum has been associated with poor prognosis in several digestive cancers. In this study, we assessed the association between intratumoral F. nucleatum load and clinico-pathological features, relapse, and survival in patients with ASCC who underwent abdominoperineal resection (APR) after RT/CRT. We retrospectively analyzed surgical samples from a cohort of 166 patients with ASCC who underwent APR. F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. We associated F. nucleatum load with classical clinicopathological features, overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) using Cox regression univariate and multivariate analyses. Tumors harboring high loads of F. nucleatum (highest tercile) showed longer OS and DFS (median: not reached vs. 50.1 months, p = 0.01, and median: not reached vs. 18.3 months, p = 0.007, respectively). High F. nucleatum load was a predictor of longer OS (HR = 0.55, p = 0.04) and DFS (HR = 0.50, p = 0.02) in multivariate analysis. High F. nucleatum load is an independent favorable prognostic factor in patients with ASCC who underwent APR. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Laparoscopic versus open surgery for gastric gastrointestinal stromal tumors: what is the impact on postoperative outcome and oncologic results?

Objectives: The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs). Background: The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5cm, remains unknown. Methods: Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20cm (N=666), by either laparoscopy (group L, n=282) or open surgery (group O, n=384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. Results: In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P=0.086) and 11.3% vs 19.5% (P=0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P=0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P=0.103). After 1:1 propensity score matching (n=224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P=0.005), surgical morbidity (4.9% vs 9.8%; P=0.048), and medical morbidity (6.2% vs 13.4%; P=0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P=0.011). In tumors greater than 5cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P=0.255 and P=0.423, respectively). Conclusions: Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results