Early and intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): description of the intervention.

STUDY DESIGN: Descriptive. OBJECTIVES: The primary objective is to describe the intervention that will be provided in a large multi-centre randomised controlled trial titled: Early and Intensive Motor Training for people with Spinal Cord Injuries (the SCI-MT Trial). The secondary objective is to describe the strategies that will be used to operationalise and standardise the Motor Training provided to participants while keeping the intervention person-centred. METHODS: The paper focuses on the rationale and principles of Motor Training for people with spinal cord injuries (SCI). The description of the intervention is based on the Template for Intervention Description and Replication (TIDieR) checklist. Specifically, it addresses the following 6 criteria of the TIDieR checklist: why the effectiveness of Motor Training is being examined; what, how, where and when the Motor Training will be administered; and how much Motor Training will be provided. RESULTS: A detailed intervention manual has been developed to help standardise the delivery of the intervention. CONCLUSIONS: This paper describes the details of a complex intervention administered as part of a large randomised controlled trial. It will facilitate the subsequent interpretation of the trial results and enable the intervention to be reproduced in clinical practice and future trials.

The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer.

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.

A rare case of necrotic thymoma.

The Authors report the case of a patient who underwent resection of a huge anterior mediastinal mass, revealing to be a necrotic thymoma. The patient had been previously submitted to surgical biopsies of the mass yielding non-diagnostic results due to extensive necrosis. A sternotomy was then performed to resect the mediastinal mass originating from the thymus, en-bloc with the mediastinal fat and the apparently infiltrated lung. Histopathology showed a possible cyst/thymoma in massive necrosis, not further definable; revision by a specialized experienced pathologist (J. Rosai) confirmed total mass necrosis and no lung infiltration, thus orientating diagnosis towards a necrotic thymoma and excluding a lymphoblastic lymphoma, with similar histopathological features but more frequent in children or characterized by neoplastic infiltration of surrounding lung. Total body computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/CT, show neither local recurrence, nor distant metastases two years after surgery. In case of anterior mediastinal mass with difficult histopathological diagnosis due to massive necrosis, the hypothesis of a necrotic thymoma should be considered. After radical removal prognosis is generally favourable and no adjuvant treatment is required.

Biomechanics of Exoskeleton-Assisted Treadmill Walking.

To exploit the benefits of treadmill-based exoskeletons, it is crucial to assess possible deviations from natural walking depending on assistive parameters. This study evaluated the biomechanics of exoskeleton-assisted treadmill walking by comparing it with free gait. Five healthy participants walked freely on a treadmill and with the assistance of the Lokomat gait trainer, while changing Body Weight Support (BWS), Gait Speed (GS), and Guidance Force (GF). Results showed that the hip and knee joint kinematics depended on BWS and GS, while changes due to GF were limited. Moreover, joint kinematics and the activity of related muscles were altered with respect to free gait, for any combination of robot parameters in the case of the ankle, and especially for low GS and with BWS in the case of hip and knee. Overall, walking with the Lokomat can mostly resemble free gait at high speed and without BWS.

Relationship between oxidative stress and "burning mouth syndrome" in female patients: a scientific hypothesis.

INTRODUCTION: Burning Mouth Syndrome (BMS) is characterized by burning sensation and pain in the mouth with or without inflammatory signs and specific lesions. MATERIALS AND METHODS: Aim of the present study was to investigate about a possible correlation between the Burning Mouth Syndrome and oxidative stress. We recruited 18 healthy female patients between 54 and 68 years of age with a diagnosis of Burning Mouth Syndrome. Oxidative stress assessment was performed by means of an integrated analytical system composed of a photometer and a mini-centrifuge (FRAS4, H and D s.r.l., Parma, Italy). Samples of whole capillary blood were taken by a finger puncture in a heparinized tube and immediately centrifuged; a small amount of samples plasma (10 microL) were thereafter tested for total oxidant capacity (d-ROMs test) and biological antioxidant potential as iron-reducing activity (BAP test) (Diacron International s.r.l., Grosseto, Italy). RESULTS: Our results indicate that female patients affected by Burning Mouth Syndrome show significantly different d-ROMs and BAP levels, similar to those present in oxidative stress condition with respect to the general population. It was also emphasized that, after the most painful phase, the levels representing the present oxidative stress, progressively return to normal, even if still significantly higher 7 days after, with respect to the normal population. No similar study was performed up to now. CONCLUSIONS: This study confirms the effectiveness of antioxidant treatments in the patients affected by BMS, in order to prevent or decrease the onset of oxidative stress and the consequent increased risk of oxidative-related systemic diseases.

A cultural effect on brain function.

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.

Association of short-term memory with a variant within DYX1C1 in developmental dyslexia.

A substantial genetic contribution in the etiology of developmental dyslexia (DD) has been well documented with independent groups reporting a susceptibility locus on chromosome 15q. After the identification of the DYX1C1 gene as a potential candidate for DD, several independent association studies reported controversial results. We performed a family-based association study to determine whether the DYX1C1 single nucleotide polymorphisms (SNPs) that have been associated with DD before, that is SNPs '-3GA' and '1249GT', influence a broader phenotypic definition of DD. A significant linkage disequilibrium was observed with 'Single Letter Backward Span' (SLBS) in both single-marker and haplotype analyses. These results provide further support to the association between DD and DYX1C1 and it suggests that the linkage disequilibrium with DYX1C1 is more saliently explained in Italian dyslexics by short-term memory, as measured by 'SLBS', than by the categorical diagnosis of DD or other related phenotypes.

Evaluation of narrative abilities in patients suffering from Duchenne Muscular Dystrophy.

The present work investigated cognitive, linguistic and narrative abilities in a group of children suffering from Duchenne Muscular Dystrophy, an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. The patients showed mildly reduced IQ with lower Verbal than Performance Intelligence Quotient and were mildly affected in visual attention and short-term memory processing. At the linguistic assessment, neither receptive (word comprehension) nor expressive (naming tasks and fluency) lexical abilities were impaired. However, their narratives were qualitatively inferior with respect to those produced by a group of typically developing children. Their speech samples were characterized by the presence of fewer verbs and complete sentences. It is suggested that the reduced production of complete sentences is due to a selective problem in verb argument structure generation. Since the lack of dystrophin is assumed to produce effects on the maturation of the cerebellum, whose involvement has been recently suggested in verb and syntactic processing, these findings may lend indirect support to the hypothesis of a cerebellar-cortical circuit specialized in verb and sentence production.

Towards localization of malignant sites of asymmetry across bilateral mammograms.

BACKGROUND AND OBJECTIVES: The analysis of patterns of asymmetry between the left and right mammograms of a patient can provide meaningful insights into the presence of an underlying tumor in its early stage. However, the identification of breast cancer by investigating bilateral asymmetry is difficult to perform due to the indistinct and borderline nature of the asymmetric signs as they appear on mammograms. METHODS: In this study, to increase the positive-predictive value of asymmetry in mammographic screening, a novel computerized approach for the automatic localization of malignant sites of asymmetry in mammograms is proposed. The sites of anatomical correspondence between the right and left regions of each radiographic projection were extracted by means of two bilateral masking procedures, inspired by radiologists' criteria in interpreting mammograms and based on the use of detected landmarking structures. Relative variations of spatial patterns of intensity values and of orientations of directional components within each site were quantified by combining multidirectional Gabor filters and indices of structural similarity. The localization of the sites of malignant asymmetry was performed by coupling two quadratic discriminant analysis classifiers, one for each masking procedure, that assigned the likelihood of malignancy to each site of correspondence. RESULTS: The performance of the proposed method was assessed on 94 mammographic images from two publicly available databases and containing at least one asymmetric site. Sensitivity, specificity and balanced accuracy levels of 0.83 (0.09), 0.75 (0.06), and 0.79 (0.04), respectively were obtained in the classification of malignant asymmetric sites vs benign/normal sites using cross-validation. In addition, a further blind test on a dataset of Full Field Digital Mammograms achieved levels of sensitivity, specificity, and balanced accuracy of 0.86, 0.65, and 0.75, respectively. CONCLUSIONS: The achieved performance indicates that the proposed system is effective in localizing sites of malignant asymmetry and it is expected to improve computer-aided diagnosis of breast cancer.

[A randomized study comparing amoxicillin-clavulanic acid with cefazolin as antimicrobial prophylaxis in laparotomic gynecologic surgery]. / Studio randomizzato che paragona l'acido amoxicillino-clavulanico alla cefazolina come profilassi antimicrobica nella chirurgia ginecologica per via laparotomica.

AIM: The aim of this paper was to compare amoxicillin-clavulanic acid with cefazolin as ultra-short term prophylaxis in laparotomic gynecologic surgery. METHODS: A prospective randomized study was conducted to compare 2 antimicrobial regimens in the surgical prophylaxis of laparotomic surgery. Patients were randomly allocated to receive amoxicillin-clavulanic acid (2.2 g, group A) or cefazolin (2 g, group B) as a single dose 30 min before surgery. Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site, urinary tract and respiratory tract. RESULTS: In the amoxicillin-clavulanic acid (group A) and cefazolin (group B) groups, overall 346 and 352 patients, respectively, were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both arms. Febrile morbidity occurred in 21 (6.1%) and 26 (7.4%) patients respectively in the amoxicillin-clavulanic acid and cefazolin groups. Wound infection and urinary tract infection were also higher, but not significantly in the cefazolin group (1.1% versus 0.5% and 2.5% versus 2%, respectively). There was one respiratory tract infection (0.2%) in group B and no septic death in either groups. CONCLUSIONS: Ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe in elective laparotomic gynecologic surgery.

Proton-cation translocation in tumor cell mitochondria.

The capacity of mitochondria isolated from tumor cells to conserve the transmembrane electrochemical proton gradient set up by respiration has been studied. In a K+ medium, mitochondria from Ehrlich ascites tumor cells exhibit a capacity to conserve aerobic delta microH comparable to that displayed by normal rat liver mitochondria. Mitochondria from Morris hepatoma 3924A show a decreased capacity to store delta microH+, which is principally due to lowering of delta pH. In a Na+ medium, both species of tumor mitochondria show a significant decrease of aerobic delta pH, while delta psi is the same, with respect to rat liver mitochondria. Experiments on passive swelling show that mitochondria from ascites tumor cells have an enhanced permeability to chloride salts of monovalent cations and increased activity of the Na+ (K+)-H+ exchange system of the mitochondrial membrane with respect to normal mitochondria. The enhanced activity of this system in ascites cells is also shown by the characteristics of respiration-linked proton translocation in submitochondrial particles and subsequent anaerobic proton diffusion. It is concluded that the decreased capacity of mitochondria from tumor cells to conserve aerobic delta pH is due to enhanced cyclic flow of Na+ across the membrane.

Mechanism of respiration-driven proton translocation in the inner mitochondrial membrane. Analysis of proton translocation associated with oxidation of endogenous ubiquinol.

A study is presented of the kinetics and stoichiometry of fast proton translocation associated to aerobic oxidation of components of the mitochondrial respiratory chain. 1. Aerobic oxidation of ubiquinol and b cytochromes is accompanied in EDTA particles, obtained by sonication of beef-heart mitochondria, by synchronous proton uptake. 2. The rapid proton uptake associated to oxidation and b cytochromes is greatly stimulated by valinomycin plus K+, but is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 3. 4 gion H+ are taken up per mol ubiquinol oxidized by oxygen. This H+/2e- ratio, measured in the rapid anaerobic-aerobic transition of the particles is unaffected by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. 4. Intact mitochondria aerobic oxidation of oxygen-terminal electron carriers is accompanied by antimycin-insensitive synchronous proton release, oxidation of ubiquinol and reduction of b cytochromes. The amount of protons released is in excess with respect to the amount of ubiquinol oxidized. 5. It is concluded that electron flow along complex III, from ubiquinol to cytochrome c, is directly coupled to vectorial proton translocation. The present data suggest that there exist(s) between ubiquinol and cytochrome c one (or two) respiratory carrier(s), whose oxido-reduction is directly linked to effective transmembrane proton translocation.

Characterization of the iron-sulfur protein of the mitochondrial outer membrane partially purified from beef kidney cortex.

The iron-sulfur protein present in the mitochondrial outer membrane has been partially purified from beef kidney cortex mitochondria by means of selective solubilization followed by DEAE-cellulose chromatography. The EPR spectrum of the iron-sulfur protein with g-values at 2.01, 1.94 and 1.89 was well resolved up to 200 K which is unusual for an iron-sulfur protein. Analyses confirmed a center with two iron and two labile sulfur atoms in the protein. By measuring the effect of oxidation-reduction potential on the EPR signal amplitude, midpoint potentials at pH 7.2 were determined both for the purified iron-sulfur protein, +75 (+/- 5) mV, and in prepared mitochondrial outer membrane, +62 (+/- 6) mV. At pH 8.2 slightly lower values were indicated, +62 and 52 mV, respectively. The oxidation-reduction equilibrium involved a one electron transfer. A functional relationship to the rotenone-insensitive NADH-cytochrome c oxidoreductase in the mitochondrial outer membrane is suggested. Both this activity and the iron-sulfur center were sensitive to acidities slightly below pH 7 in contrast to the iron-sulfur centers of the inner membrane.

Effect of papain digestion on redox-linked proton translocation in b-c1 complex from beef heart reconstituted into liposomes.

Papain treatment of the cytochrome b-c1 complex from beef heart results in partial proteolysis of core protein II, the iron-sulphur protein and the 15-kDa subunit. Under these conditions a significant inhibition of electron flow and complete suppression of proton translocation in the complex reconstituted into liposomes are observed. Kinetic experiments indicate a correlation between the digestion of core protein II and 15-kDa subunit and the suppression of proton translocation. The results suggest an active involvement of polypeptides of the complex in stabilizing the semiquinone species and/or providing pathways to exchange protons between bound quinone systems and aqueous phases.

Effect of ATP on the activity of bovine heart mitochondrial b-c1 complex.

The effect of ATP on the reductase activity of purified bovine heart b-c1 complex was studied. ATP stimulates the steady-state activity and the antimycin-insensitive pre-steady-state reduction of b and c1 cytochromes, also causing changes of kinetic properties of the enzyme. There is no absolute specificity for ATP since other polyvalent anions such as EDTA and EGTA produce similar effects in the micromolar range. It is proposed that ATP stimulates the activity of the b-c1 complex, chelating inhibitory cation(s), exerting a modulatory action on the enzyme.

Effect of 2,4-dinitrofluorobenzene on the enzymatic properties of the b-c1 complex isolated from beef heart mitochondria.

A study is presented on the effect of 2,4-dinitrofluorobenzene (DFNB) on the enzymatic properties of mitochondrial b-c1 complex. The chemical modification by DNFB strongly inhibits the reductase activity of the complex, this being accompanied by labelling by [3H]DNFB of core protein I, the apoprotein of b cytochromes and the 12 kDa subunit. Chemical modification by DNFB appears to alter, in particular, the domain of heme b-562.

Characteristics of redox-linked proton ejection in cytochrome c oxidase reconstituted in phospholipid vesicles. New observations support mechanisms different from proton pumping.

Experimental observations reveal a number of characteristics of the redox-linked proton ejection from cytochrome c oxidase vesicles, which apparently cannot be explained by a proton pumping activity of the oxidase. These observations seem, on the other hand, to provide useful elements for alternative explanation(s) of the proton ejection. It is proposed here that the process is scalar and not vectorial and can derive from redox-linked rupture of protonated salt-bridges in the oxidase-lipid complex.

Localization of acidic residues involved in the proton pumping activity of the bovine heart mitochondrial bc1 complex.

Chemical modification of carboxyl residues in polypeptide subunits of the mitochondrial bc1 complex causes a decoupling effect, that is inhibition of the proton pumping activity, without affecting the rate of electron transfer to ferricytochrome c. The study presented here is aimed at localizing and identifying the residues whose modification results in decoupling of the complex. Glutamate-53 in subunit IX (the DCCD-binding protein) and aspartate-166 in the Rieske iron-sulfur protein are the residues modified by N,N'-dicyclohexylcarbodiimide (DCCD) and N-(ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ), respectively. The results obtained also suggest that the carboxy-terminal sequence of the Core protein II, which is fairly rich in acidic residues, may also play a role in the vectorial proton translocation activity of the complex.

Arachidonic acid interaction with the mitochondrial electron transport chain promotes reactive oxygen species generation.

A study has been carried out on the interaction of arachidonic acid and other long chain free fatty acids with bovine heart mitochondria. It is shown that arachidonic acid causes an uncoupling effect under state 4 respiration of intact mitochondria as well as a marked inhibition of uncoupled respiration. While, under our conditions, the uncoupling effect is independent of the fatty acid species considered, the inhibition is stronger for unsaturated acids. Experiments carried out with mitochondrial particles indicated that the arachidonic acid dependent decrease of the respiratory activity is caused by a selective inhibition of Complex I and III. It is also shown that arachidonic acid causes a remarkable increase of hydrogen peroxide production when added to mitochondria respiring with either pyruvate+malate or succinate as substrate. The production of reactive oxygen species (ROS) at the coupling site II was almost double than that at site I. The results obtained are discussed with regard to the impairment of the mitochondrial respiratory activity as occurring during the heart ischemia/reperfusion process.