Effect of Exoskeleton-Assisted Rehabilitation Over Prefrontal Cortex in Multiple Sclerosis Patients: A Neuroimaging Pilot Study.

Application of a passive and fully articulated exoskeleton, called Human Body Posturizer (HBP), has been demonstrated to improve mobility, response accuracy and ambulation in multiple sclerosis (MS) patients. By using functional magnetic imaging (fMRI) during a visuomotor discrimination task, we performed a pilot study to evaluate the effect of HBP over the neural correlates of motor and cognitive functions which are typically impaired in MS patients. Specifically, we tested the effect of a 6-week multidisciplinary rehabilitation intervention on two groups of MS patients: a control group who followed a standard physiotherapeutic rehabilitation protocol, and an experimental group who used the HBP during physical exercises in addition to the standard protocol. We found that, after treatment, the experimental group exhibited a significant lower activity (as compared to the control group) in the inferior frontal gyrus. This post-treatment activity reduction can be explained as a retour to a normal range, being the amount of iFg activity observed in the experimental patients very similar to that observed in healthy subjects. These findings indicate that the use of HBP during rehabilitation intervention normalizes the prefrontal activity, mitigating the cortical hyperactivity associated to MS.

Final Results of the OPERA Experiment on ν_{τ} Appearance in the CNGS Neutrino Beam.

The OPERA experiment was designed to study ν_{µ}→ν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target. Selection criteria looser than in previous analyses have produced ten ν_{τ} candidate events, thus reducing the statistical uncertainty in the measurement of the oscillation parameters and of ν_{τ} properties. A multivariate approach for event identification has been applied to the candidate events and the discovery of ν_{τ} appearance is confirmed with an improved significance level of 6.1σ. |Δm_{32}^{2}| has been measured, in appearance mode, with an accuracy of 20%. The measurement of the ν_{τ} charged-current cross section, for the first time with a negligible contamination from ν[over ¯]_{τ}, and the first direct evidence for the ν_{τ} lepton number are also reported.

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{µ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{µ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{µ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.

Frequency and clinical relevance of MOG-antibodies in CSF in pediatric patients with MOG antibody-associated diseases.

OBJECTIVE: This retrospective study aimed to describe a cohort of 38 pediatric patients with MOGAD and to investigate the clinical differences between patients with CSF-negativity and CSF-positivity for MOG-abs. METHODS: The clinical and laboratory characteristics of pediatric patients with MOGAD were retrospectively studied. Demographics, clinical characteristics, CSF analysis, treatments and prognosis of patients were recorded. All patients' serums and CSF were tested for MOG-IgG by live cell-based assays (CBA). The data were statistically analysed. RESULTS: A total of 38 pediatric MOGAD patients were enrolled in the study, including 22 (57.9 %) females and 16 male (42.1 %) with a mean age of 8.4 ± 4.0 years at disease onset. Twenty-seven (71.7 %) patients were CSF-positive for MOG-abs while 11 (28.9 %) patients were CSF-negative for MOG-abs. The median follow-up was 25.5 months (IQR 5.5-73.25). Seventeen (44.7 %) patients presented a relapsing disease course, and the majority of these patients was CSF positive with a significant difference between the two groups (p = 0.038) in terms of recurrent diseases. CSF-positive patients presented more often an increased white cell count (p = 0.043), and in this cohort clinical phenotypes with spinal involvement were more frequent while encephalitis-like phenotypes were more frequent in the CSF negative cohort (p = 0.019). CONCLUSIONS: CSF-status appears to identify two subgroups in this pediatric MOGAD population; thus, CSF-status requires further studies in pediatric patients with MOGAD.

The human homologue of macaque area V6A.

In macaque monkeys, V6A is a visuomotor area located in the anterior bank of the POs, dorsal and anterior to retinotopically-organized extrastriate area V6 (Galletti et al., 1996). Unlike V6, V6A represents both contra- and ipsilateral visual fields and is broadly retinotopically organized (Galletti et al., 1999b). The contralateral lower visual field is over-represented in V6A. The central 20°-30° of the visual field is mainly represented dorsally (V6Ad) and the periphery ventrally (V6Av), at the border with V6. Both sectors of area V6A contain arm movement-related cells, active during spatially-directed reaching movements (Gamberini et al., 2011). In humans, we previously mapped the retinotopic organization of area V6 (Pitzalis et al., 2006). Here, using phase-encoded fMRI, cortical surface-based analysis and wide-field retinotopic mapping, we define a new cortical region that borders V6 anteriorly and shows a clear over-representation of the contralateral lower visual field and the periphery. As with macaque V6A, the eccentricity increases moving ventrally within the area. The new region contains a non-mirror-image representation of the visual field. Functional mapping reveals that, as in macaque V6A, the new region, but not the nearby area V6, responds during finger pointing and reaching movements. Based on similarity in position, retinotopic properties, functional organization and relationship with the neighboring extrastriate visual areas, we propose that the new cortical region is the human homologue of macaque area V6A.

Distortion-product otoacoustic emissions: a useful test for monitoring ototoxicity induced by pegylated interferon and ribavirin treatment in patients with chronic hepatitis C.

Pegylated-interferon (peg-IFN) and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) infection is well known to be associated with significant adverse effects. Several studies have investigated a possible auditory pathway involvement during IFN therapy, but a method to monitor the potential auditory involvement during treatment has not yet been described. The aim of this study is to evaluate possible modifications of the outer hair cell (OHC) function in HCV patients receiving peg-IFN and ribavirin combination therapy. Thirteen adult HCV patients (8 F/5 M, mean age 52∓12 years) treated with peg-IFN and ribavirin combination therapy underwent Pure Tone Audiogram and Distortion Product Otoacoustic Emission (DPOAE) tests. We compared mean auditory thresholds (PTA) and mean DPOAE amplitude before, at month 3 during, and at the end of treatment (T0, T3, and Tend, respectively), and 3 months after treatment discontinuation (Tfu). No significant differences were found in hearing levels at the different time points analyzed. During treatment, three patients developed tinnitus, which in 2 cases resolved spontaneously after the end of therapy. Compared to T0 (19.5±0.83), a statistically significant DPOAE increase at T3 (30±1,26) and Tend (28.6±2.16) was found (p<0.05 at both time points), while DPOAEs returned to pre-treatment levels at Tfu (19.3±1.3). In our group, none of the patients reported a permanent auditory impairment, excluding one patient with persistent tinnitus. Peg-IFN could produce an increase of motility of the OHCs by means of intracellular pathways. DPOAE test could be considered a new method for monitoring ototoxicity induced by IFN. On the basis of recent literature and our audiological results, physicians should be aware of the possible ototoxic effects of peg-IFN, requiring appropriate surveillance, and the patient should be informed of the potential side effects of IFN therapy on the auditory pathway.

Prospective comparative analysis of colour-Doppler ultrasound, contrast-enhanced ultrasound, computed tomography and magnetic resonance in detecting endoleak after endovascular abdominal aortic aneurysm repair.

OBJECTIVES: To assess the accuracy of colour-Doppler ultrasound (CDUS), contrast-enhanced ultrasonography (CEUS), computed tomography angiography (CTA) and magnetic resonance angiography (MRA) in detecting endoleaks after endovascular abdominal aortic aneurysm repair (EVAR). DESIGN: Prospective, observational study. MATERIALS AND METHODS: From December 2007 to April 2009, 108 consecutive patients who underwent EVAR were evaluated with CDUS, CEUS, CTA and MRA as well as angiography, if further treatment was necessary. Sensitivity, specificity, accuracy and negative predictive value of ultrasound examinations were compared with CTA and MRA as the reference standards, or with angiography when available. RESULTS: Twenty-four endoleaks (22%, type II: 22 cases, type III: two cases) were documented. Sensitivity and specificity of CDUS, CEUS, CTA, and MRA were 58% and 93%, 96% and 100%, 83% and 100% and 96% and 100% respectively. CEUS allowed better classification of endoleaks in 10, two and one patients compared with CDUS, CTA and MRA, respectively. CONCLUSIONS: The accuracy of CEUS in detecting endoleaks after EVAR is markedly better than CDUS and is similar to CTA and MRA. CEUS seems to be a feasible tool in the long-term surveillance after EVAR, and it may better classify endoleaks missed by other imaging techniques.

Human v6: the medial motion area.

Cortical-surface-based functional Magnetic Resonance Imaging mapping techniques and wide-field retinotopic stimulation were used to verify the presence of pattern motion sensitivity in human area V6. Area V6 is highly selective for coherently moving fields of dots, both at individual and group levels and even with a visual stimulus of standard size. This stimulus is a functional localizer for V6. The wide retinotopic stimuli used here also revealed a retinotopic map in the middle temporal cortex (area MT/V5) surrounded by several polar-angle maps that resemble the mosaic of small areas found around macaque MT/V5. Our results suggest that the MT complex (MT+) may be specialized for the analysis of motion signals, whereas area V6 may be more involved in distinguishing object and self-motion.

OPERA tau neutrino charged current interactions.

The OPERA experiment was designed to discover the vτ appearance in a vµ beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors. It was exposed from 2008 to 2012 to the CNGS beam: an almost pure vµ beam with a baseline of 730 km, collecting a total of 1.8·1020 protons on target. The OPERA Collaboration eventually assessed the discovery of vµâ†’vτ oscillations with a statistical significance of 6.1 σ by observing ten vτ CC interaction candidates. These events have been published on the Open Data Portal at CERN. This paper provides a detailed description of the vτ data sample to make it usable by the whole community.

Locoregional IL-2 therapy in the treatment of colon cancer. Cell-induced lesions of a murine model.

BACKGROUND: Local therapy with IL-2 may be very effective in the treatment of different forms of cancer. The aim of this study was to determine the effectiveness of IL-2 locoregional application in the treatment of colon cancer. MATERIALS AND METHODS: Twenty eight syngenic BDIX rats were utilized in this study. The rats were divided into two groups of fourteen animals: group T (treatment) and group C (control). All rats of both groups were injected, under the splenic capsule, with T 10(7) DHD/K2/ TRb neoplastic cells. Then, within and around the site of the previous inoculation, the T group was injected with 1 ml of glucosate solutions + 0.1% albumin (BSA) containing 2.5 x 10(6) IU of IL-2 ( Proleukin-Chiron), whereas the C group was injected with 1 ml of BSA alone. After three weeks, rats were sacrificed and the liver and spleen were removed. The following parameters were considered: volume and weight, neoplastic-non neoplastic tissue index of the spleen, mitotic index and vascular density of splenic and hepatic lesions. RESULTS: All the studied parameters showed statistically significant differences in treated and untreated animals. CONCLUSION: This study of a murine model demonstrated that IL-2 locoregional therapy may be effective in the treatment of colon cancer.

Reduction of cell proliferation induced by PD166866: an inhibitor of the basic fibroblast growth factor.

UNLABELLED: Cell proliferation control plays a key role in tumor development. The basic Fibroblast Growth Factor (bFGF), as well as other growth factors, is involved in several pathologies characterized by dysregulation of cell proliferation. In the present work the effects of PD166866, a very potent and selective tyrosine kinase inhibitor were evaluated. Cultured murine fibroblasts (the cell line 3T6) were used to assess the FGFR-1 inhibition mediated by PD166866. Evaluation of cell viability and molecular biology techniques were adopted. PD166866 controls negatively the bFGF/FGFR-1 system thus promoting a significant reduction of cell proliferation and loss of viability in 3T6 cells. The drug possibly controls proliferation via induction of apoptosis as evidenced by a relevant chromatin degradation. CONCLUSION: This study demonstrated that PD166866 might be used in the control of fibrotic proliferative diseases, as well as in other tumor pathologies.

Mesenteric fibromatosis. Case report.

Deep fibromatosis is a rare locally aggressive but not metastasizing proliferation. Intra-abdominal fibromatosis (IAF) occurs either in association with Gardner's syndrome or as a sporadic event and presents in most cases differential diagnostic problems with myofibroblastic or fibroblastic tumors, characterized by a more aggressive biological behaviour such as gastrointestinal stromal tumors (GISTs). In absence of loco-regional and/or distant metastasis differential diagnosis may be difficult and represents a topical issue, since it influences treatment choice. We describe the case of a patient with sporadic IAF in which the tumor locally involved the mesentery and presented no loco-regional and distant spread. On histology, some morphological features of the neoplasm were in common with a GIST. Definitive diagnosis was made, postoperatively, on the basis of immunohistochemical findings.

Hepatic complications of bariatric surgery : the reverse side of the coin.

BACKGROUND: Even if the jejunoileal bypass has been definitely abandoned due to the high rate of hepatic complications, cases of liver injury after the new bariatric procedures are still reported. We aimed to review the available literature concerning liver damage associated with the older and newer types of bariatric surgeries. METHODS: An extensive literature search of MEDLINE was performed using different combinations of the following terms: "bariatric surgery OR biliopancreatic diversion OR jejunoileal bypass OR roux-en-y gastric bypass OR vertical banded gastroplasty OR laparoscopic adjustable gastric banding" AND "hepatic/liver damage OR hepatic/liver impairment OR hepatic/liver failure". RESULTS: Although weight loss after bariatric surgery frequently induces an improvement of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, and even the regression of hepatic fibrosis, bariatric procedures have been also associated with cases of acute liver failure or of chronic liver disease evolving until cirrhosis. After the jejunoileal bypass has been definitely abandoned, most of the recently described cases concern biliopancreatic diversion with/without duodenal switch, but liver damage has been reported after almost all types of bariatric surgeries. Protein-calorie malnutrition, bacterial overgrowth, lipotoxicity and genetic background are likely to play a central role in the physiopathology of hepatic injury. CONCLUSIONS: Understanding the inner mechanisms underlying acute or chronic liver injury after bariatric surgery can help in the prevention, early recognition and treatment of these rare but concrete cases.

Clinical and biological features of an intranodal palisaded myofibroblastoma.

Intranodal palisaded myofibroblastoma (IPM) is a rare benign tumor of the lymph nodes probably arising from smooth muscle-like cells. The tumor is characterized by intranodal proliferation of spindle cells. Neoplastic spindle-cell proliferation is most often of metastatic repetition which is very important in the recognition of IPM, because it may be mistaken for metastasis or other tumors such as Kaposi's sarcoma. We report a novel case of IPM that confirms the myofibroblastic differentiation of the tumor. The onset of IPM has been associated with Epstein-Barr virus (EBV). In addition, recently reported cases of IPM have been seen with cyclin 1 overexpression and also with human herpes virus (HHV)-8 and EBV DNA sequences. In our case, there was no evidence of HHV-8 and EBV DNA sequences and we were not able to find cyclin 1 overexpression.

Surgical complications after resection of adrenal carcinoma.

A 76-year-old woman with a history of dyspnoea, weight loss and abdominal pain, was admitted to our Hospital. Sonographic and tomographic examinations showed the presence of a large adrenal gland tumor and the promptly performed adrenalectomy and splenectomy proved that the lesion was an adrenal gland carcinoma infiltrating the spleen. One month after surgical treatment, the patient's general condition dramatically worsened due to development of perirenal abscess and renal infarction; finally, the patient died. In accordance with literature, we decided to only perform adrenalectomy and splenectomy that are the treatment of choice in these cases. In fact, complications are unforeseeable and avoiding the resection of the kidney surely offered the patient a better life quality.

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease.

BACKGROUND: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. AIM: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. METHODS: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. RESULTS: Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 showed significant negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = -0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment. CONCLUSIONS: Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin-like growth factor-1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.

The diimide drug PIPER has a cytotoxic dose-dependent effect in vitro and inhibits telomere elongation in HELA cells.

It is known that, in vitro, PIPER (N,N'-bis [2-(1-piperidino)ethyl]-3,4,9,10-tetracarboxylic diimide) induces the formation of the Hoogsteen quadruplex structure in telomere DNA, thus inhibiting the polymerisation of telomeric repeats. Since the action of PIPER in vivo has been scarcely investigated, this study was addressed to gain some insight into the effects of this drug on cultured HeLa cells. Vital staining with erythrosine, performed on cells exposed to different PIPER concentrations (from 1 to 50 microM), showed that the drug exerts a dose-dependent cytotoxic effect, clearly evident after a short-term (24 h) treatment. This early cytotoxic effect of PIPER on cultured HeLa cells was confirmed by a spectrophotometric/colorimetric method employing methylthiazoletetrazolium (Mossmann assay). Hematoxylin/eosin staining of cells treated with PIPER for 24 h showed a nuclear condensation and a cytoplasmic vacuolisation, very pronounced at higher drug concentrations. These pictures suggest that PIPER-induced cell death might be of the apoptotic type. Finally, the anti-telomerase activity of PIPER was monitored by TRAP assay, performed on HeLa cell nuclear extracts treated with increasing drug concentrations. It was found that some inhibition of telomerase is apparent even at low concentrations, while at the highest concentration the enzyme is completely inhibited. These results indicate that the cytotoxic power of PIPER is possibly related to its antitelomeric effect.

Presence and incidence of DNA sequences of human polyomaviruses BKV and JCV in colorectal tumor tissues.

The human polyomaviruses JCV and BKV are widespread within population, as shown by serological studies. However, exposure to these viruses does not seem to have pathological consequences in immunocompetent individuals, while in immunocompromised or immunosuppressed patients, polyomaviruses can be activated, giving rise to serious pathologies. Viral DNA sequences were also found in cells from a number of human tumors of mesothelial origin, suggesting that activation of BKV and JCV, taking place in genetically predisposed and/or in immunodepressed individuals, might be involved in the mechanisms of tumor transformation. In this study, samples obtained from 18 patients with colon rectal carcinoma were probed for the presence of JCV and BKV by three different techniques: Southern blot, PCR and in situ hybridization. Our results demonstrate that viral DNA sequences were present in 16 out of the 18 cases considered (88.9%). In the large majority of cases, viruses were detected both in the tumor mass and in the surrounding healthy tissues. Lymphocytes in the investigated areas were also found to be infected by polyomaviruses. These data indicate, for the first time, a possible involvement of polyomaviruses in the pathogenesis of tumors of endothelial origin, like the human colon rectal carcinoma.