Learning models for classifying Raman spectra of genomic DNA from tumor subtypes

An early and accurate detection of different subtypes of tumors is crucial for an effective guidance to personalized therapy and in predicting the ability of tumor to metastasize. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated silicon nanowires (Ag/SiNWs), to efficiently discriminate genomic DNA of different subtypes of melanoma and colon tumors. The diagnostic information is obtained by performing label free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat and leveraging the classification ability of learning models to reveal the specific and distinct physico-chemical interaction of tumor DNA molecules with the Ag/NW, here supposed to be partly caused by a different DNA methylation degree

Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies

Abstract : To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs. The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively). Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB-patients and between patients with high (> 200 t1/10) and low (£ 200 t1/10) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manne

Learning models for classifying Raman spectra of genomic DNA from tumor subtypes

An early detection of different tumor subtypes is crucial for an effective guidance to personalized therapy. While much efforts focus on decoding the sequence of DNA basis to detect the genetic mutations related to cancer, it is becoming clear that physical properties, including structural conformation, stiffness, and shape, as well as biological processes, such as methylation, can be pivotal to recognize DNA modifications. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated--silicon nanowires, to investigate genomic DNA from subtypes of melanoma and colon cancers and to efficiently discriminate tumor and healthy cells, as well as the different tumor subtypes. The diagnostic information is obtained by performing label--free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat, and leveraging the classification ability of learning models to reveal the specific and distinct interaction of healthy and tumor DNA molecules with nanowires

MEMORY ARTS CAFÉ

La demenza è una malattia cronico-degenerativa caratterizzata dalla progressione più o meno rapida di sintomi con progressiva perdita dell’autonomia. La forma più frequente è la malattia di Alzheimer, caratterizzata da una fase preclinica asintomatica e una fase clinica con comparsa dei sintomi caratteristici. “The World Alzheimer Report 2019” evidenzia che finora non esiste una terapia farmacologica in grado di contrastare la malattia. Le cure mediche trattano sostanzialmente i sintomi, ma non sono risolutive. La ricerca è perciò diretta a migliorare la qualità della vita degli interessati e delle persone coinvolte, focalizzandosi su prevenzione, sostegno e inclusione. L’arteterapia, insieme alla psicoterapia tradizionale ed ai farmaci, viene proposta nell’ambito della prevenzione e cura dei malati di Alzheimer per migliorare funzioni cognitive, capacità mnemonica (soprattutto a breve termine) e coordinamento motorio. Gli obiettivi dello studio comprendono anche la riduzione di depressione, stress e difficoltà relazionali al fine di guadagnare una “ri-socializzazione” del malato. Durante le sedute di trattamento riabilitativo si osserva che la ripetizione di esercizi legati all’arte promuove l’orientamento nella realtà, il recupero delle potenzialità residue e delle funzioni mnesiche e la possibilità di riottenere in parte l’autonomia nelle attività di vita quotidiana. A partire da questi presupposti, il progetto Memory Arts Café si propone di strutturare percorsi guidati di fruizione museale per pazienti affetti da demenza, allo scopo di innescare sovrapposizioni mnesiche che contrastino la perdita della memoria, favorendo il recupero del benessere emotivo-relazionale dei pazienti

An observational study on electrolyte disorders in the acute phase of ischemic stroke and their prognostic value

Data on electrolyte disorders in neurological conditions and in acute stroke are somewhat scanty and not easily compared. In our Stroke Unit we studied patients hospitalized within six hours of the onset of an acute ischemic stroke and recorded their demographic and clinical data. Blood test results were recorded before any pharmacological therapy. A total of 475 individuals (256 males, 219 females; age range: 14-96 years) treated over a period of 18 consecutive months, were selected. According to a multiple logistic regression analysis, the baseline National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.22-1.44) and alterations in serum sodium (OR = 6.89; 95% CI = 1.94-24.40) were associated with higher odds of death. Based on an ordinal logistic regression analysis, the baseline NIHSS score (OR = 1.07; 95% CI = 1.03-1.10) and baseline hypernatremia (OR = 9.69; 95% CI = 1.55-60.69) were related to early neurological worsening. Our work suggests an association between serum sodium alterations and mortality, and between high sodium levels and neurological clinical impairment, in the acute phase of an ischemic stroke. (C) 2011 Elsevier Ltd. All rights reserved

Duloxetine for the Treatment of Overactive Bladder Syndrome in Multiple Sclerosis: A Pilot Study

OBJECTIVES: Overactive bladder (OAB) syndrome represents one of the main urinary disorders associated with multiple sclerosis (MS). At present, no widely accepted effective treatment is available. Duloxetine, an antidepressant acting as a selective serotonin-norepinephrine reuptake inhibitor, has been shown to be effective in the treatment of some symptoms of stress urinary incontinence and OAB because of etiology other than MS.The present study aims at establishing the efficacy and tolerability of duloxetine in the treatment of OAB in patients affected by remitting-relapsing MS and secondary progressive MS. MATERIALS AND METHODS: Twenty-three patients with MS, 13 of which with remitting-relapsing MS and 10 with secondary progressive MS, have been treated with duloxetine and placebo for a total period of 8 weeks during a single-blinded cross-over trial. At each programmed visit, patients have been screened for the following: (1) quantitative evaluation of maximal bladder capacity and postmicturition residual volume; (2) questionnaire administration to evaluate bladder disorder-Overactive Bladder Questionnaire, quality of life-Visual Analogue Scale-Quality of life, fatigue-Fatigue Severity Scale, and depression-Beck Depression Inventory. RESULTS: Three patients did not complete the study because of duloxetine-related adverse events. A statistically significant improvement in bladder disorder, as measured by OAB-Q, has been observed after duloxetine treatment compared with both basal levels and placebo with values of 21.8 ± 1.1 versus 34.2 ± 1.2 (P < 0.0001) and 21.8 ± 1.1 versus 30.1 ± 1.7 (P < 0.003), respectively.In addition, a decrease in postmicturition residual volume has also been observed compared with basal level (6.8 ± 3.2 ml vs 38.1 ± 12.2 ml, P = 0.06) together with an improvement in quality of life (7.1 ± 0.5 vs 6.3 ± 0.4, P = 0.07). Both these changes were close to being statistically significant. CONCLUSIONS: It emerges from this study that duloxetine might become an effective therapeutic alternative to be investigated in a larger number of MS patients for the treatment of OAB. Duloxetine should be considered a first-choice drug in the treatment of MS patients presenting both depression and OAB; in addition, it should also be considered as a suitable alternative or as concomitant treatment in MS patients with OAB but not experiencing depression Copyright © 2012 by Lippincott Williams & Wilkins

Mitochondrial Genome Profile in Demyelinating Diseases

Multiple sclerosis and neuromyelitis optica are chronic inflammatory diseases of the central nervous system. These pathologies share clinical similarities with Leber hereditary optic neuropathy, which is primarily due to mutations of mitochondrial DNA. Mitochondrial genetic variations may influence susceptibility to develop multiple sclerosis and neuromyelitis optica. In order to explore the possible correlation between mitochondrial DNA specific patterns and demyelinating diseases involving central nervous system, mitochondrial DNA from 13 patients with relapsing-remitting multiple sclerosis, 4 patients with neuromyelitis optica, 1 patient with myelitis, 2 patient with optic neuritis, and 7 healthy controls were analyzed by sequencing the full length 16 Kbs of the mitochondrial DNA genome. Common variants presence in healthy controls and patients showing no clinical impact on diseases development were not further explored. Analyzing 414 patient specific variants, six nonsense mutations, causing early stop-codon formation, and nine previously described variants, associated with demyelinating/degenerative disease of central nervous system were identified. Some of these variants are linked to disease development through known and previously described mechanisms. We report for the first time other truncating mutations leading to incomplete proteins involved in Oxidative Phosporilation complexes and we speculate their role in demyelinating diseases developmen

Statistical Classification for Raman Spectra of Tumoral Genomic DNA

We exploit Surface-Enhanced Raman Scattering (SERS) to investigate aqueous droplets of genomic DNA deposited onto silver-coated silicon nanowires, and we show that it is possible to efficiently discriminate between spectra of tumoral and healthy cells. To assess the robustness of the proposed technique, we develop two different statistical approaches, one based on the Principal Components Analysis of spectral data and one based on the computation of the ℓ2 distance between spectra. Both methods prove to be highly efficient, and we test their accuracy via the Cohen’s κ statistics. We show that the synergistic combination of the SERS spectroscopy and the statistical analysis methods leads to efficient and fast cancer diagnostic applications allowing rapid and unexpansive discrimination between healthy and tumoral genomic DNA alternative to the more complex and expensive DNA sequencing

Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies

To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs. The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively). Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB-patients and between patients with high (> 200 t(1/10)) and low (<= 200 t(1/10)) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manner

Neopterin production and tryptophan degradation during 24-months therapy with interferon beta-1a in multiple sclerosis patients

<p/> <p>Background</p> <p>Increased synthesis of neopterin and degradation of tryptophan to kynurenine, measured as kynurenine/tryptophan ratio (kyn/trp ratio), are considered <it>in vitro </it>markers of interferon beta-1a (IFNβ-1a) activity. The aim of the study was to investigate the dynamic profile of neopterin and kyn/trp ratio in patients with relapsing remitting multiple sclerosis (RRMS) treated with two different doses of IFNβ-1a over a period of 24 months.</p> <p>Methods</p> <p>RRMS patients (n = 101) received open-label IFNβ-1a 22 mcg (low dose, LD) or 44 mcg (high dose, HD) subcutaneously (sc), three times weekly for 24 months. Serum measurements of neopterin, kyn/trp ratio and neutralizing antibodies (NAbs) were obtained before treatment (i.e., at baseline) and 48 hours post-injection every 3 months thereafter. Clinical assessments were performed at baseline and every 6 months. Changes in biomarkers over time were compared between LD- and HD-group as well as between patients with/without relapses and with/without NAbs using Analysis of Variance and Mann-Whitney tests.</p> <p>Results</p> <p>Neopterin (p < 0.001) and kyn/trp ratio (p = 0.0013) values increased over time vs baseline in both treatment groups. Neopterin values were higher (p = 0.046) in the HD-compared to the LD-group at every time point with the exclusion of months 21 and 24 of therapy. Conversely, there were no differences between the two doses groups in the kyn/trp ratio with the exclusion of month 6 of therapy (p < 0.05). Neopterin levels were significantly reduced in NAb-positive patients starting from month 9 of therapy (p < 0.05); the same result was observed for kyn/trp ratio but only at month 9 (p = 0.02). Clinical status did not significantly affect neopterin production and tryptophan degradation.</p> <p>Conclusions</p> <p>Although differences in serum markers concentration were found following IFNβ administration the clinical relevance of these findings needs to be confirmed with more detailed studies.</p