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.

Gamow-Teller Strength in

We develop a fully self-consistent subtracted second random-phase approximation for charge-exchange processes with Skyrme energy-density functionals. As a first application, we study Gamow-Teller excitations in the doubly magic nucleus ^{48}Ca, the lightest double-ß emitter that could be used in an experiment, and in ^{78}Ni, the single-beta-decay rate of which is known. The amount of Gamow-Teller strength below 20 or 30 MeV is considerably smaller than in other energy-density-functional calculations and agrees better with experiment in ^{48}Ca, as does the beta-decay rate in ^{78}Ni. These important results, obtained without ad hoc quenching factors, are due to the presence of two-particle-two-hole configurations. Their density progressively increases with excitation energy, leading to a long high-energy tail in the spectrum, a fact that may have implications for the computation of nuclear matrix elements for neutrinoless double-ß decay in the same framework.

Effectiveness of a sensor-based technology in upper limb motor recovery in post-acute stroke neurorehabilitation: a randomized controlled trial.

Sensor-based technological therapy devices could be a possible neurorehabilitation strategy for motor rehabilitation in patients with stroke during the post-acute hospitalization, especially for treating upper extremities function limitations. The audio-visual feedback devices are characterized by interactive therapy games that allow training the movement of shoulders, elbows, and wrist, measuring the strength and the active range of motion of upper limb, registering data in an electronic database to quantitatively monitoring measures and therapy progress. This study aimed to investigate the effects of sensor-based motor rehabilitation in add-on to the conventional neurorehabilitation for improving the upper limb functions in patients with subacute stroke. Thirty-seven patients were enrolled in the study and randomly assigned to the experimental group and the control group. The training consisting of twelve sessions of upper limb training compared with twelve sessions of upper limb sensory-motor training, without robotic support. Both rehabilitation programs were performed for 40 minutes three times a week, for 4 weeks, in addition to conventional therapy. All patients were evaluated at the baseline (T0) and after 4 weeks of training (T1). The within-subject analysis showed a statistically significant improvement in both groups in all clinical scales. The analysis of effectiveness revealed that, compared with baseline (T0), the improvement percentage in the Modified Barthel Index was greater in the experimental group than the control group. The use of a sensor-based training with audio-video-feedback could be a useful complementary strategy for improving upper limb motor functions in patients with stroke during post-acute neurorehabilitation.

CO2 reactivity with Mg2NiH4 synthesized by in situ monitoring of mechanical milling.

CO2 capture and conversion are a key research field for the transition towards an economy only based on renewable energy sources. In this regard, hydride materials are a potential option for CO2 methanation since they can provide hydrogen and act as a catalytic species. In this work, Mg2NiH4 complex hydride is synthesized by in situ monitoring of mechanical milling under a hydrogen atmosphere from a 2MgH2:Ni stoichiometric mixture. Temperature and pressure evolution is monitored, and the material is characterized, during milling in situ, thus providing a good insight into the synthesis process. The cubic polymorph of Mg2NiH4 (S.G. Fm3[combining macron]m) starts to be formed in the early beginning of the mechanical treatment due to the mechanical stress induced by the milling process. Then, after 25 hours of milling, Mg2NiH4 with a monoclinic (S.G. C12/c1) structure appears. The formation of the monoclinic polymorph is most likely related to the stress release that follows the continuous refinement of the material's microstructure. At the end of the milling process, after 60 hours, the as-milled material is composed of 90.8 wt% cubic Mg2NiH4, 5.7 wt% monoclinic Mg2NiH4, and 3.5 wt% remnant Ni. The as-milled Mg2NiH4 shows high reactivity for CO2 conversion into CH4. Under static conditions at 400 °C for 5 hours, the interactions between as-milled Mg2NiH4 and CO2 result in total CO2 consumption and in the formation of the catalytic system Ni-MgNi2-Mg2Ni/MgO. Experimental evidence and thermodynamic equilibrium calculations suggest that the global methanation mechanism takes place through the adsorption of C and the direct solid gasification towards CH4 formation.

Prevalence of dysphagia in a consecutive cohort of subjects with MS using fibre-optic endoscopy.

INTRODUCTION: Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Dysphagia is a symptom that represents challenges in clinical practice. The aim of the present study was to evaluate the prevalence of dysphagia in an Italian cohort of subjects with MS using the Dysphagia Outcome Severity Score (DOSS), based on fibre-optic endoscopy, and determine factors that correlate with the presence of swallowing problems. MATHERIALS AND METHODS: Data were collected in a multicentre study from a consecutive sample of MS patients, irrespective of self-reported dysphagia. The study included 215 subjects. Possible scores for DOSS range from 7 to 1, with 7 indicating normal swallowing. RESULTS: One hundred twenty-four (57.7%) subjects demonstrated abnormal swallowing and 57 (26.5%) of these had swallowing problems that required nutrition/diet modifications when evaluated objectively with fibre-optic endoscopy. Subjects with dysphagia were more severely disabled and more often had a progressive form of MS, compared to MS subjects with normal swallowing. In subjects with EDSS, < 4, 8 (13.3%), had a DOSS < 4. Seventy-five percent of subjects older than 60 years of age had dysphagia. CONCLUSION: In this sample of MS patients, more nearly 60% showed swallowing problems.

Evaluation of the formation and carbon dioxide capture by Li4SiO4 using in situ synchrotron powder X-ray diffraction studies.

Carbon capture and storage using regenerable sorbents are an effective approach to reduce CO2 emissions from stationary sources. In this work, lithium orthosilicate (Li4SiO4) was studied as a carbon dioxide sorbent. For a deeper understanding of the synthesis and carbonation mechanism of Li4SiO4, an in situ synchrotron radiation powder X-ray diffraction technique was used. The Li4SiO4 powders were synthesized by a combination of ball milling of a Li2CO3 and SiO2 mixture followed by a thermal treatment process at low temperature. In situ studies showed that formation of Li4SiO4 from the as-milled 2Li2CO3-SiO2 mixture involves decomposition of Li2CO3 by reaction with SiO2via Li2SiO3 as an intermediate compound. No evidence of Li2Si2O5 formation was obtained, in spite of thermodynamic predictions. The CO2 capture by Li4SiO4 was evaluated dynamically over a wide temperature range, reaching a maximum weight increase of 34 wt% and good cyclability after about 10 cycles. By thermogravimetric and microstructural analyses in combination with ex situ and in situ measurements, a two step carbonation mechanism and its influence on the final CO2 capture was clearly elucidated. Under dynamical conditions up to 700 °C, the lower number of Li2CO3 nuclei initially formed retards the double shell formation and the nucleation and growth of the Li2CO3 particles remains the controlling step up to higher CO2 capture capacity. Isothermal carbonation at 700 °C favours the formation of a higher number of Li2CO3 nuclei that creates a thin carbonate shell. The CO2 diffusion through this shell is the limiting step from the beginning and further carbonation is hindered as the reaction progresses.

SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.

Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome.

Individualized quality of life of severely affected multiple sclerosis patients: practicability and value in comparison with standard inventories.

PURPOSE: Individualized quality of life (QoL) measures differ from traditional inventories in that QoL domains/weights are not predetermined, but identified by the individual. We assessed practicability of the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW) interview in severely affected multiple sclerosis (MS) patients; the key QoL dimensions identified; and the correlation of the SEIQoL-DW index score with standard patient-reported outcome measures (PROMs). METHODS: Participants were people with severe MS who performed the baseline visit of the PeNSAMI trial (ISRCTN73082124). The SEIQoL-DW was administered at the patient's home by a trained examiner. Patients then received the following PROMs: the Core-Palliative care Outcome Scale (Core-POS), the Palliative care Outcome Scale-Symptoms-MS (POS-S-MS), the European Quality of Life Five Dimensions-3L (EQ-5D-3L), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Of 59 enrolled patients, 11 (19 %) did not receive the SEIQoL-DW (and the other PROMs) because of severe cognitive compromise or inability to communicate. SEIQoL-DW administration was completed and deemed valid in all 48 cases (mean age 60 years, 58 % women, median Expanded Disability Status Scale score 8.5). Mean SEIQoL-DW index score was 59.1 (SD 25.5). The most commonly nominated SEIQoL-DW areas were family (94 % of the patients), relationships, and leisure activities (both 65 %). Core-POS and POS-S-MS contained 70 % of the SEIQoL-DW-nominated areas. Nevertheless, correlations between SEIQoL-DW index, Core-POS, and POS-S-MS (and the other PROMs) were negligible. CONCLUSIONS: Individualized QoL can be assessed in severely affected MS patients, providing information that is not tracked by the standard inventories Core-POS, POS-S-MS, EQ-5D-3L, and HADS.

Ureteroscopy and laser lithotripsy: technologic advancements.

Ureteroscopic lithotripsy has evolved since the first reported cases employing rigid rod-lens endoscopes and stiff ultrasonic lithotrites. Fiber optics facilitated rigid endoscope miniaturization and the development of a steerable, deflectable flexible ureteroscopes. Over 30 years of technical innovations culminating in digital imagers and powerful, precise laser lithotrites, complimented by progressive endoscopic techniques have produced efficient endoscopic therapies with minimal morbidity and commonly performed in an outpatient setting.

Use of cidofovir in HPV patients with recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is a viral-induced disease, associated with exophytic epithelial lesions affecting the upper airways. Problem of treatment is the high recurrence of papilloma growth after surgical removal; therefore, adjuvant therapy schemes have been established. We used cidofovir, 7.5 mg/ml, in adjuvant therapy in the past years. Out of 31 adult patients treated with the drug, 26 (83.9 %) are at the moment in complete response. 19 (73 % of pts with CR) of those 26 patients were cured with a number of injections between 1 and 4 (mean 2.5). We did not see any clinical manifestation of renal toxicity or neutropenia (superinfection) necessitating a blood test. Six patients presented dysplasia during the treatment with the drug, while six patients had dysplasia prior to cidofovir injection. Due to recurrent nature of the disease and the high number of mechanical and laser surgeries required we treated one tracheal stenosis, two scarred larynx, and two glottic synechiaes. There is still an ongoing discussion within the European Laryngological Society about the effectiveness and possible side effects of this drug. Results show promising long-term effects of adjuvant use of cidofovir, without any relevant side effects.

Mutations in GDI1 are responsible for X-linked non-specific mental retardation.

Rab GDP-dissociation inhibitors (GDI) are evolutionarily conserved proteins that play an essential role in the recycling of Rab GTPases required for vesicular transport through the secretory pathway. We have found mutations in the GDI1 gene (which encodes uGDI) in two families affected with X-linked non-specific mental retardation. One of the mutations caused a non-conservative substitution (L92P) which reduced binding and recycling of RAB3A, the second was a null mutation. Our results show that both functional and developmental alterations in the neuron may account for the severe impairment of learning abilities as a consequence of mutations in GDI1, emphasizing its critical role in development of human intellectual and learning abilities.

The new Ghent criteria for Marfan syndrome: what do they change?

The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.

Beyond mean-field theories with zero-range effective interactions: a way to handle the ultraviolet divergence.

Zero-range effective interactions are commonly used in nuclear physics and in other domains to describe many-body systems within the mean-field model. If they are used within a beyond-mean-field framework, contributions to the total energy that display an ultraviolet divergence are found. We propose a general strategy to regularize this divergence and we illustrate it in the case of the second-order corrections to the equation of state (EOS) of uniform symmetric matter. By setting a momentum cutoff Λ, we show that for every (physically meaningful) value of Λ it is possible to determine a new interaction such that the EOS with the second-order corrections reproduces the empirical EOS, with a fit of the same quality as that obtained at the mean-field level.

Infratentorial lesion volume correlates with sensory functional system in multiple sclerosis patients: a 3.0-Tesla MRI study.

PURPOSE: This study sought to correlate lesion volume in infratentorial areas using 3.0-T proton-density (PD)-weighted images with disability scales and appropriate functional system scores in patients with multiple sclerosis (MS). MATERIALS AND METHODS: We examined 20 consecutive patients (13 women and 7 men) with a median age of 47 years (range 26-70). Neurological examination included the Expanded Disability Status Scale and its functional systems, the Barthel Index (BI) and the Rivermead Mobility Index (RMI). MRI scans were performed on a system operating at 3.0 T using a quadrature birdcage head coil. Acquired images imported as Digital Imaging and Communication in Medicine (DICOM) files, and the region of interest (ROI) files were converted to Neuroimaging Informatics Technology Initiative (NIfTI) format and normalised to the Montreal Neurological Institute (MNI) standard template. An automated segmentation algorithm was used to distinguish between supratentorial and infratentorial areas. Normalisation to the magnetisation-prepared rapid acquisition with gradient echo (MPRAGE) T1-weighted sequence allowed lesion volume estimation in the different anatomical areas. RESULTS: A significant correlation was found between infratentorial lesion volume and the sensory functional system score (rho=0.76, p=0.002). No significant correlation was found between supratentorial lesion volume and Expanded Disability Status Scale (EDSS), RMI and BI scores. CONCLUSIONS: The described method, by means of anatomical assignment of MS lesions, allows detection of significant correlation coefficients between clinical and MRI lesion burden in MS patients at the infratentorial level.

The role of cytokines in head and neck squamous cell carcinoma: A review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for approximately 6% of all cancer cases and responsible for an estimated 1-2% of all cancer deaths. Much research evidence has accumulated in the recent years on the changes in the expression of pro-inflammatory and, to a lesser extent, anti-inflammatory cytokines, that (i) may have a role in the malignant transformation of HNSCC, (ii) may be used as diagnostic markers in the sera of patients because of their excessive production by the tumor cells and (iii) may act as possible immunotherapeutic targets. Among pro-inflammatory cytokines, interleukin-8 (IL--8) has been reported to have an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL--8 in patients with HNSCC and a positive association with lymph node metastasis and tumor classification, although IL--8 was not significantly associated with shorter overall survival and cancer progression-free survival. Additional evidence on the pathological mechanism of origin, invasion, and metastasis of HNSCC, as well as a better understanding of the implications of cytokines, chemokines and growth factors, are of paramount importance for the advancement of research in head and neck oncology.

Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature.

Mowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, and characterized by typical face, moderate-to-severe mental retardation, epilepsy, Hirschsprung disease, and multiple congenital anomalies, including genital anomalies (particularly hypospadias in males), congenital heart defects, agenesis of the corpus callosum, and eye defects. Since the first delineation by Mowat et al. [Mowat et al. (1998); J Med Genet 35:617-623], approximately 179 patients with ZEB2 mutations, deletions or cytogenetic abnormalities have been reported primarily from Europe, Australia and the United States. Genetic defects include chromosome 2q21-q23 microdeletions (or different chromosome rearrangements) in few patients, and ZEB2 mutations in most. We report on clinical and genetic data from 19 Italian patients, diagnosed within the last 5 years, including six previously published, and compare them with patients already reported. The main purpose of this review is to underline a highly consistent phenotype and to highlight the phenotypic evolution occurring with age, particularly of the facial characteristics. The prevalence of MWS is likely to be underestimated. Knowledge of the phenotypic spectrum of MWS and of its changing phenotype with age can improve the detection rate of this condition.

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion.

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.