Quantitatively distinct requirements for signaling-competent cell spreading on engineered versus natural adhesion ligands.

To design synthetic microenvironments that elicit desired cell behaviors, we must better understand the molecular mechanisms by which cells interact with candidate biomaterials. Using cell lines with distinct alpha5beta1 integrin expression profiles, we demonstrate that this integrin mediates cell spreading on substrata coated with genetically engineered artificial extracellular matrix (aECM) proteins containing the RGD sequence (RGD-containing aECM protein [aRGD]) but lacking the PHSRN synergy site. Furthermore, aRGD-mediated adhesion stimulates an intracellular focal adhesion kinase (FAK) signal that is indicative of integrin tethering. Although both aRGD and the natural ECM protein fibronectin (FN) support alpha5beta1 integrin-mediated cell spreading, quantitative single-cell analysis revealed that aRGD-mediated spreading requires ten-fold greater threshold amount of integrin expression than FN-mediated spreading. Our analysis demonstrates that aRGD-based substrata mediate both biophysical (cell spreading) and biochemical (FAK signaling) events via the alpha5beta1 integrin, albeit with efficacy quantitatively distinct from that of natural ECM proteins that possess the full spectrum of adhesion and synergy domains.     

Insular carcinomas of the thyroid exhibit poor prognosis and long-term survival in comparison to follicular and papillary T4 carcinomas

Background Insular thyroid carcinoma was described as a tumor with aggressive behavior, and patients usually present themselves with an advanced tumor stage. Whether the insular component is an independent factor for poor prognosis remains unclear. Therefore, in the present study, we compared the survival of patients with advanced insular, follicular, and papillary thyroid cancer. Materials and methods The clinical behavior of tumors in three groups of patients with T4 thyroid carcinoma—8 patients with insular, 11 patients with follicular, and 21 patients with papillary thyroid carcinomas—was compared. Disease-free survival and disease-specific death were analyzed statistically. Cox regression analysis was used to evaluate the influence of histotype and other prognostic factors. Results At 3 years, survival was 37.5% (mean 26 months) among patients with insular thyroid carcinoma, 80% (mean 59 months) among those with follicular, and 89% (mean 126 months) among those with papillary thyroid carcinomas (p = 0.007). Disease-free survival in patients without initial distant metastasis was worst in patients with insular thyroid carcinoma (20%) compared to those with follicular (75%) and those with papillary thyroid carcinomas (71%). Conclusion Patients with advanced insular thyroid carcinoma have a poorer outcome in comparison to patients with similar advanced stage who have follicular or papillary thyroid carcinoma.     

Fatty acids platelets and oxidative markers following intravenous n-3 fatty acids administration in cystic fibrosis: An open pilot observational study.

BACKGROUND: An imbalance in the ratio of arachidonic acid and docosahexaenoic acid (DHA) was found in cystic fibrosis (CF) affected tissues and was suggested to promote inflammation. Several studies have shown that the long chain n-3 fatty acids reduced inflammatory activity while others have highlighted prooxidant activity of DHA at high concentrations. The aim of our study was to evaluate the effects of an intravenous fish-oil emulsion enriched with n-3 FA in patients with CF on plasma and platelet FA composition and peroxidation markers. METHODS: 13 patients with CF received one IV emulsion per week of 2 mL/kg fish-oil n-3 emulsion for 12 weeks. RESULTS: There was a significant increase in 20:5 n-3 and 22:6 n-3 platelet FA composition, no variation in 20:4 n-6, a decrease in n-9. There was no variation in plasma FA composition. Specific urinary markers of lipid peroxidation derived from n-3 and n-6 showed a very high level before infusion compared with usual values in healthy subjects which was not affected by treatment. A significant weight loss and a decrease in reduced glutathione were observed in adult patients. CONCLUSIONS: The intravenous administration of n-3 FA in CF patients induced a significant modification in platelet FA composition but no modification of oxidative markers. However, the weight loss and the decreased level in reduced glutathione observed in adult patients may suggest a potential deleterious activity for some patients. Further studies are necessary to determine the optimal dose and route for long chain FA administration required to reach a potential beneficial effect.     

Motor and non-motor sequence learning in children and adolescents with cerebellar damage.

Cerebellar involvement in motor and non-motor sequence learning was examined with serial reaction time tasks (SRT). Our sample consisted of 8 children and adolescents who had undergone surgical removal of a benign posterior fossa tumor (PFT) during childhood. None of them had undergone chemotherapy or cranial radiation therapy (CRT). Ages ranged from 1-11 years at surgery and 9-17 years at testing. The children were tested not earlier than 2.5 years after surgery (M = 5.9 years), enabling brain plasticity and recovery of functions. Their performance was compared with a matched control sample. The PFT group was not impaired in the implicit learning of sequences, as reflected in their performance in blocks with a repeated sequence, both before and after a random block. However, in the perceptual task, their performance deteriorated more than that of the control group when a random block was introduced, suggesting that it was more difficult for the patients to respond flexibly or change their response set when encountering changing task demands. These results are in line with another study by our group on task switching with the same patients.     

Long-term Doppler echocardiographic evaluation of the right heart after major lung resections.

OBJECTIVE: The effects of major lung resections on cardiac function in the medium and long term have not been thoroughly evaluated. We have studied right heart function with serial Doppler echocardiography in patients undergoing lobectomy and pneumonectomy during 4 years of follow-up after surgery. METHODS: Thirty-six patients undergoing lobectomy and 15 receiving pneumonectomy were evaluated with one- and two-dimensional Doppler standard transthoracic echocardiography before surgery and 1 week, 3 months, 6 months, 1 year, and 4 years postoperatively. We have studied the right midventricular diastolic diameter (RVDD), the right ventricle free wall thickness, the tricuspid valve insufficiency (TVI) and regurgitation jet (TRJ), and the pulmonary artery systolic pressure (PASP). RESULTS: None of the patients died within the first postoperative year. After lobectomy there were no significant modifications of any variable at any time. RVDD progressively increased after pneumonectomy (26.5+/-2.2mm preoperatively vs 34.3+/-7.6 at 4 years; p<0.001). Four years after surgery all patients undergoing pneumonectomy had moderate TVI while only 55% of patients receiving lobectomy showed it (low grade in 50% and moderate in 5%). In this group of patients PASP increased from 26.1+/-2.6 mmHg preoperatively to 34.3+/-7.6 mmHg at 4 years (p<0.00001). CONCLUSIONS: Right ventricle modifications are clearly evident after pneumonectomy and even if they do not show a clear clinical impact they should not be neglected.     

Awake one stage bilateral thoracoscopic sympathectomy for palmar hyperhidrosis: a safe outpatient procedure.

OBJECTIVE: To verify the feasibility and compare the results of thoracoscopic sympathectomy under local anaesthesia (LA) and spontaneous breathing vs. general anaesthesia (GA) with one-lung ventilation. METHODS: Two groups of consecutive patients underwent one stage bilateral T2-T3 thoracoscopic sympathectomy under LA (n=15) and GA (n=30) by the same surgical team for treatment of primary palmar hyperhidrosis. The groups were homogeneous for relevant demographic, physiological and clinical data, including pulmonary function. In both groups, patient's satisfaction was evaluated 24h after surgery by a simple interview and scored into five grades (1=very poor to 5=excellent), while quality of life (QOL) was evaluated by SF-36 and Nottingham's Health Profile questionnaires before and 6 months after surgery. A cost comparison between groups concerning devices, drugs, global in operating room time, medical personnel and hospital stay was also carried out. RESULTS: No operative mortality was recorded. The overall in operating room time for the whole bilateral procedure under LA was 63.55+/-10.58 vs. 86.05+/-5.75 under GA (P<0.01) and temperature increased in all patients from a baseline of 25.42+/-0.56 up to 32.15+/-0.84 degrees C. All patients undergone LA were discharged the same day after a chest roentgenogram and a short stay in the outpatient clinic. Among them three patients (20%) experienced a minimal (<30%) pneumothorax that required no treatment, while five (33.3%) had a trunk compensatory sweating that spontaneously resolved on the long run. Patients undergoing GA were discharged after a mean stay of 1.38+/-0.6 days. Among these, eight (26.6%) had prolonged trunk compensatory sweating that did not persist longer than 3 months. At a follow-up of 7.16+/-2.97 months, QOL was significantly improved with no difference between groups. The overall rate of satisfaction was greater in the LA group (P<0.05). CONCLUSIONS: In our study, awake one stage bilateral thoracoscopic sympathectomy for palmar hyperhidrosis could be safely and effectively performed as an outpatient procedure in patients refusing GA. Postoperative quality of life was equal to that in patients undergone the same procedure under GA, while patient satisfaction was better and cost were significantly reduced.