Highly purified cannabidiol in the treatment of drug-resistant epilepsies: A real-life impact on seizure frequency, quality of life, behavior, and sleep patterns from a single Italian center.

Seizure frequency in treatment-resistant epilepsies seems to be decreased by cannabidiol (CBD), but contrasting data are available on its effect on sleep, behavior, and quality of life (QoL), and no data is reported on its effect on parental stress in patients with epilepsy (PWE). Thus, we conducted a retrospective study on a cohort of children and adults with drug-resistant epilepsy (DRE) who had been treated with highly purified, pharmaceutical-grade CBD to evaluate its effects on seizure frequency, QoL, behavior, parental stress, and sleep. Eighteen patients (12 adults and 6 children) were included in the cohort and followed for a median of 9 months. At the last follow-up (Tn), nine patients (50%) were considered CBD responders with at least a 50% decrease in seizure frequency. No serious adverse effects were found. No statistically significant differences were found concerning sleep, including daytime sleepiness, and no statistically significant effect was found on parental stress at Tn. An improvement was found for social interaction in quality of life (p < 0.05) for all patients. Our results demonstrate that CBD is a safe and effective antiseizure medication (ASM). CBD doesn't seem to affect sleep measures in adults and children or worsen daytime sleepiness. However, CBD improves specific QoL measures, which could indicate a possible use of CBD for other childhood disabilities. No impact of CBD was seen on parental stress, which could possibly be due to the limited follow-up or could mean that parental stress is not dependent on seizure frequency.

Filtering efficiency model that includes the statistical randomness of non-woven fiber layers in facemasks.

Facemasks have become important tools to fight virus spread during the recent COVID-19 pandemic, but their effectiveness is still under debate. We present a computational model to predict the filtering efficiency of an N95-facemask, consisting of three non-woven fiber layers with different particle capturing mechanisms. Parameters such as fiber layer thickness, diameter distribution, and packing density are used to construct two-dimensional cross-sectional geometries. An essential and novel element is that the polydisperse fibers are positioned randomly within a simulation domain, and that the simulation is repeated with different random configurations. This strategy is thought to give a more realistic view of practical facemasks compared to existing analytical models that mostly assume homogeneous fiber beds of monodisperse fibers. The incompressible Navier-Stokes and continuity equations are used to solve the velocity field for various droplet-laden air inflow velocities. Droplet diameters are ranging from 10 nm to 1.0 µm, which covers the size range from the SARS-CoV-2 virus to the large virus-laden airborne droplets. Air inflow velocities varying between 0.1 m·s-1 to 10 m·s-1 are considered, which are typically encountered during expiratory events like breathing, talking, and coughing. The presented model elucidates the different capturing efficiencies (i.e., mechanical and electrostatic filtering) of droplets as a function of their diameter and air inflow velocity. Simulation results are compared to analytical models and particularly compare well with experimental results from literature. Our numerical approach will be helpful in finding new directions for anti-viral facemask optimization.

Improving the accuracy of pancreatic cancer clinical staging by exploitation of nanoparticle-blood interactions: A pilot study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) early diagnosis is  crucial  and new, cheap and user-friendly techniques for biomarker identification  are  needed. "Protein corona" (PC) is emerging a new bio-interface potentially useful in tumor early diagnosis. In a previous investigation, we showed that relevant differences between the  protein patterns of  PCs formed on lipid NPs after exposure to PDAC and non-cancer plasma  samples exist. To extend that research, We performed this pilot study to investigate the effect of PDAC tumor size and distant metastases on PC composition. METHODS: Twenty PDACs were clinically staged according to the UICC TNM staging system 8 t h Edition. Collected plasma samples were let to interact with lipid NPs; resulting PCs were characterized by SDS-PAGE. To properly evaluate changes in the PC, the protein intensity profiles were reduced to four regions of molecular weight: < 25 kDa, 25-50 kDa, 50-120 kDa, > 120 kDa.  RESULTS: Data analysis allowed to distinguish T1-T2 cases from T3 and above all from metastatic ones (p < 0.05). Discrimination power was particularly due to a subset of plasma proteins with molecular  weight comprised between 25-50 kDa  and 50-120 kDa. CONCLUSIONS: PC composition is critically influenced by tumor size and presence of distant metastases in PDAC. If our findings will be further confirmed, we envision that future developments of cheap and user-friendly PC-based tools will allow to improve the accuracy of PDAC clinical staging, identifying among resectable  PDACs with potentially better prognosis (i.e. T1 and T2) those at higher risk of occult distant metastases.

Cascade polycyclizations in natural product synthesis.

Cascade (domino) reactions have an unparalleled ability to generate molecular complexity from relatively simple starting materials; these transformations are particularly appealing when multiple rings are forged during this process. In this tutorial review, we cover recent highlights in cascade polycyclizations as applied to natural product synthesis, including pericyclic, heteroatom-mediated, cationic, metal-catalyzed, organocatalytic, and radical sequences.

Mechanical and chemical properties of composite materials made of dredged sediments in a fly-ash based geopolymer.

Dredging activity in harbours and channels produces huge quantities of sediments, generally considered as waste soil (WS) to be disposed: the management of such sediments is a great environmental problem for many countries worldwide. Among the recycling possibilities, the use of dredged sediments for the manufacture of geopolymer-based materials seems to be an interesting alternative to disposal, due to their low cost and easy availability. In order to analyse the possibility to use these geopolymer materials as building materials - for instance as precast construction elements in maritime projects - a multi-disciplinary research activity has been developed at the Federico II University of Napoli (Italy). Some experimental tests have been carried out on different geopolymeric specimens made by mixing sediments from Napoli 'harbour and industrial fly ashes produced by a power plant in the South of Italy. A siliceous sand was used for comparison as an inert reference material. Chemical, morphological and mechanical properties of different specimens have been studied by X-ray diffraction, Scanning Electron Microscopy (SEM), Fourier transformed infrared spectroscopy (FTIR) and finally unconfined compression tests. The experimental results highlight that the use of dredged sediments in combination with fly ash can lead to geopolymeric matrices with interesting mechanical performances. Some differences in the microstructure of the geocomposite built with the siliceous sand or the dredged materials were found. In terms of environmental impacts, on the basis of standard leaching tests and according to Italian thresholds, the adopted dredged mixtures satisfy the prescribed limit for inert or non hazardous waste.

Effects of whole body vibration exercises on bone mineral density of women with postmenopausal osteoporosis without medications: novel findings and literature review.

OBJECTIVES: The aim of this study was to review the literature about the effect of whole body vibration exercise in the BMD in patients with postmenopausal osteoporosis without medications. METHODS: A systematic review was performed. RESULTS: The frequency of the mechanical vibration used in the protocols has varied from 12 to 90 Hz. The time used in the protocols varied from 2 up to 22 months. Techniques with X-rays were used in nine of the twelve publications analyzed, the Dual energy X-ray absorptiometry (DEXA) in eight studies and the High resolution peripheral quantitative computed tomography (HR-pQCT) in one publication. The concentration of some biomarkers was determined, as the sclerostin, the bone alkaline phosphatase, N-telopeptide X and 25-hydroxyvitamin D. Among the twelve articles analyzed, seven of them have shown an improvement of the BMD of some bone of postmenopausal women exposed to whole body vibration exercises not associated to medications; as well as modifications in biomarkers.

Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of multiple sclerosis patients: a longitudinal study.

Retrospective studies show that natalizumab modifies oligoclonal immunoglobulin (IgG) bands (OCBs) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. In this study, we prospectively analyzed both serum and CSF samples from 24 MS patients, before and after 2 years of natalizumab-based therapy. Our results showed complete (55%) or partial (27%) disappearance of the OCBs in CSF samples that were taken after 2 years of therapy. Intrathecal IgG production, represented by the IgG index and IgGLoc, was also quantitatively reduced. Our data showed that natalizumab substantially modulates both intrathecal polyclonal and oligoclonal IgG production: This effect was much more potent than was previously reported.

Effect of whole-body vibration stimulation on plasma soluble TNF receptors in elderly with sarcopenia: a randomized controlled trial.

Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues.

Abnormal cervical cord function contributes to fatigue in multiple sclerosis.

UNLABELLED: BACKGROUND/OBJECTIVE We aimed to investigate whether cervical cord damage and dysfunction is associated with the presence and severity of fatigue in multiple sclerosis (MS) using a multiparametric magnetic resonance (MR) approach. METHODS: Cervical cord functional magnetic resonance imaging (fMRI) during a tactile stimulation of the right hand, and structural brain and cord MRI were acquired from 20 controls, 15 MS patients without fatigue (NF) and 20 MS patients with fatigue (F). Between-group differences in the extent of focal lesions and diffusivity abnormalities in the brain and cord, cord-normalized cross-sectional area (CSAn) and fMRI activity were assessed. RESULTS: All structural MRI measures differed significantly among groups, except for cord lesion number and CSAn. Compared with controls, NF-MS patients experienced higher cord recruitment (p=0.04). Compared with F-MS, NF-MS patients had a lower brain normal-appearing white matter average fractional anisotropy (p=0.001) and increased cord recruitment (p=0.02). In patients with MS, the extent of cord recruitment was correlated with the severity of fatigue (r=-0.34, p=0.04). Compared with the other two groups, F-MS patients had a more diffuse recruitment of cord quadrants on the axial and longitudinal planes. CONCLUSIONS: Abnormalities of function, but not of structure, of the cervical cord are likely to contribute to the pathogenesis of fatigue in MS.

Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy.

BACKGROUND: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. METHODS: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. RESULTS: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. CONCLUSIONS: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

Zeolite-based monoliths for water softening by ion exchange/precipitation process.

In this work, the design of a monolithic softener obtained by geopolymer gel conversion is proposed. The softener used consists in a geopolymeric macroporous matrix functionalized by the co-crystallization of zeolite A and X in mixture. The dual nature of the proposed material promotes a softening process based on the synergistic effect of cation exchange and alkaline precipitation. A softening capacity of 90% and 54% for Ca2+ and Mg2+ respectively was attained in 24 h. In fact, the softener reported a Cation Exchange Capacity (CEC) value of 4.43 meq g-1. Technical features such as density, porosity and mechanical resistance were also measured. The use of this monolithic softener can improve performance and sustainability of hardness removal from tap water, reducing the production of sludge and adding the possibility to partially regenerate or reuse it.

Data of postoperative complications related to fibrinogen-to-albumin ratio in pancreatic resections.

Pancreatic surgery is one of the surgeries burdened with the highest mortality and morbidity rate. This is due both to the aggressive biological nature of the pathology affecting the organ and to the technical difficulties associated with surgery. A further aspect on which research is focusing is represented by inflammation related to oncological pathology. Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival (OS) in malignant tumors. Inflammatory markers had demonstrated also a role in the prediction of postoperative complication after pancreatic surgery. We speculate that FAR, as an easily available, cost-effective, and non-invasive prognostic indicator for pancreatic cancer patients, could help to identify patients at increased risk of postoperative pancreatic fistula (POPF). We therefore retrospectively analyzed the data relating to 117 pancreatic resections relating direct and indirect markers of inflammation with the incidence of post-operative complications.

Natalizumab therapy of multiple sclerosis: recommendations of the Multiple Sclerosis Study Group--Italian Neurological Society.

Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.

Effect of carbonaceous fillers on adsorption behavior of multifunctional diatomite-based foams for wastewater treatment.

Nowadays the study of the potential applications of multifunctional materials for environmental remediation is one of the main goals of the materials engineering. Multifunctional porous materials, MPMs, incorporate, all in once, different and multiple functionalities that make them suitable for several uses and can satisfy many purposes at the same time. Multifunctional diatomite-based foams with a hierarchical porosity, already produced and characterized to be applied in building as well as aerospace sectors, are proposed as adsorbents for inorganic and organic pollutants removal from wastewaters. Then, the effect of the addition of different carbonaceous nanofillers (graphite, graphene and graphene oxide) on the water purification efficiency of the adsorbent was evaluated. Firstly, pristine MPM showed the best performance in adsorbing Indigo Carmine due to its intrinsic chemism and hierarchical porosity (at macro-, micro- and nano-level), but it is not the best with respect to the Cd2+ adsorption, if compared with the nanocomposites. Among the nanocomposite products, both graphene- and graphene oxide-MPM samples showed a significantly improved adsorption capacity towards Cd2+. This behavior is due to the synergistic effect of the finer morphology, higher available foam surface, and the highly exfoliated fillers, graphene and graphene oxide, which permit a better dispersion into the matrix.

Functional tests associated with sarcopenia in moderate chronic obstructive pulmonary disease.

Objectives: To evaluate the association of physical and functional measures with sarcopenia in moderate chronic obstructive pulmonary disease (COPD) and to establish cutoff points for sarcopenia screening.Methods: The study included COPD with and without sarcopenia, of both sexes who were over 50 years old. Participants were assessed for lung function, body composition, grip strength, Short Physical Performance Battery (SPPB), 5-repetition, 10-repetition and 30-s sit-to-stand tests (5STS, 10STS, and 30STS, respectively). In addition, 6-min walking test, respiratory muscular strength, and physical activity level were tested.Results: The study had 35 participants, 24 men (68.6%) and moderate COPD (51.4%). COPD-sarcopenia showed lower values in lean mass, body fat and body mass alongside lower performance in 10 and 30 STS tests, SPPB and gait speed compared to non-sarcopenic group. The cutoff points with better sensitivity and specificity to identify sarcopenia were 10.88 and 34.14 s, 15 repetitions, and 10 points in the 5STS, 10STS, 30STS, and SPPB, respectively. The comparison of the receiver operating curves evidenced no differences between the functional tests. Only 30STS and SPPB showed acceptable discriminatory power.Conclusion: Functional tests, especially 30STS and SPPB, are simple and affordable tools for screening sarcopenia in COPD with moderate obstruction.

HLA-class I markers and multiple sclerosis susceptibility in the Italian population.

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51-0.72, P<10(-9)), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58-0.83) with a significant (P=4.94 x 10(-5)) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.

Cervical cord functional MRI changes in relapse-onset MS patients.

OBJECTIVE: To investigate whether (1) the tactile-associated cord functional MRI (fMRI) changes vary in the different clinical stages of relapse-onset multiple sclerosis (MS), and (2) the pattern of cord fMRI changes relates to severity of MS clinical disability. METHODS: Cervical cord fMRI was acquired from 49 MS patients (30 relapsing-remitting (RR), 19 secondary progressive (SP)), and 19 controls, during a tactile stimulation of the right hand. Task-related cord mean signal change and occurrence of fMRI activity at each cord quadrant and level were measured. MRI quantities were compared between groups using an univariate analysis. Between-group differences in topographical distribution of fMRI activity were evaluated using random-effect logistic regression models. RESULTS: Compared with controls, both RRMS (p=0.05) and secondary progressive multiple sclerosis (p=0.02) patients showed a higher cord fMRI activity, whereas no difference was found between patient groups. Severely disabled patients (26/49) showed a cord overactivation relative to controls (p=0.004) and patients with mild disability (p=0.04). Both controls and MS patients showed a functional lateralisation of cord activity, which was predominant in the cord side ipsilateral to the stimulus, and a more frequent activation of the posterior than of the anterior cord quadrants. DISCUSSION: This study shows that tactile-associated cervical cord fMRI activity is increased in relapse-onset MS patients. Such an overactivation is more prominent in patients with more severe locomotor disability. This suggests that an abnormality of cord functional properties may be among the factors associated with the clinical status of MS patients.

A diffusion tensor MRI study of cervical cord damage in benign and secondary progressive multiple sclerosis patients.

BACKGROUND: Diffusion tensor (DT) MRI enables quantification of the severity of brain and cervical cord pathology in multiple sclerosis (MS). OBJECTIVE: To investigate DT MRI patterns of cervical cord damage in patients with benign MS (BMS) and secondary progressive MS (SPMS), in order to achieve a better understanding of the mechanisms underlying the development of irreversible disability in MS. METHODS: Conventional and DT MRI scans of the cervical cord and brain were acquired from 40 BMS patients, 28 SPMS patients and 18 healthy individuals. Cervical cord and brain mean diffusivity (MD) and fractional anisotropy (FA) maps were created and average MD and FA were calculated. Cross sectional cord area (CSA) was also computed. RESULTS: 37 (92%) BMS patients and all (100%) SPMS patients had macroscopic cervical cord lesions. Compared with healthy individuals, BMS patients had higher average cord MD while SPMS patients had higher average cord MD, lower average cord FA and lower average CSA. Compared with BMS patients, SPMS patients had lower cord average FA and lower average CSA. In MS patients, Expanded Disability Status Scale (EDSS) was correlated with CSA (r = -0.47, p<0.0001), average cord FA (r = -0.37, p = 0.002) and brain T2 lesion volume (LV) (r = 0.34, p = 0.005). A multivariate regression model identified CSA, average cord FA and brain T2 LV as variables independently influencing the EDSS score (r = 0.58, p<0.0001). CONCLUSIONS: Cervical cord damage outside focal macroscopic lesions is limited in patients with BMS. The assessment of cord and brain pathology provides complementary information to improve the understanding of disability accumulation in MS.

Process strategy to fabricate a hierarchical porosity gradient in diatomite-based foams by 3D printing.

Motivated by the hierarchical micro and nanoscale features in terms of porosity of diatomite, the production of ceramic-graded porous foams with tailored porosity, obtained by using it as raw material, has been proposed. The main challenge during the foam-production process has been the preservation of diatomite nanometric porosity and the addition of other levels of hierarchical porosity. The coupled use of two techniques of direct foaming (chemical and mechanical), combined with the use of 3D printing inverse replica method, assured the achievement of porosity of, respectively, microscopic and macroscopic dimensions. Optical and scanning electron microscopies have been performed for an in-depth characterization of the final microstructure. XRD analysis has been carried out to check the influence of sacrificial templates on the matrix mineralogical composition. The porosity of the diatomite-based foams has been investigated by means of nitrogen-adsorption analysis and mercury-intrusion porosimetry. The experimental tests confirmed the presence of different porous architectures ranging over several orders of magnitudes, giving rise to complex systems, characterized by hierarchical levels of porosity. The presence of porosity of graded dimensions affects the final mechanical performances of the macroporous diatomite-based foams, while their mineralogical composition does not result to be affected by the addition of templates.

A longitudinal diffusion tensor MRI study of the cervical cord and brain in amyotrophic lateral sclerosis patients.

OBJECTIVE: To define the temporal evolution of intrinsic tissue damage and atrophy in the cervical cord and the brain portion of the corticospinal tracts (CST) from patients with amyotrophic lateral sclerosis (ALS). METHODS: Conventional and diffusion tensor (DT) magnetic resonance imaging (MRI) of the cervical cord and brain were obtained from 17 ALS patients and 20 controls, at baseline and after a mean follow-up of 9 months. The following measurements were assessed: (a) cervical cord cross-sectional area, average mean diffusivity (MD) and average fractional anisotropy (FA); and (b) CST T2-visible hyperintensities, average MD and FA. RESULTS: During the follow-up, ALS patients showed a significant decrease in cord area (p = 0.003) and cord average FA (p = 0.01), and a significant increase in cord average MD (p = 0.01). In ALS patients, longitudinal changes of diffusivity measurements were not associated with cord area changes. At baseline, brain CST average MD was significantly higher in ALS patients compared with controls (p = 0.001). Brain CST diffusivity measurements remained stable over time in ALS patients and did not correlate with cord damage. CONCLUSIONS: This study shows that progressive tissue loss and injury to the remaining tissue occur in the cervical cord of ALS patients and that these two features of ALS-related pathology are not strictly interrelated. Cord pathology in ALS patients is likely to be independent of brain changes, indicating that imaging the cervical cord may be a useful adjunctive tool to monitor ALS evolution.