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Summary Background The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. Methods EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov , NCT02069509 . Findings Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich's ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included. Interpretation Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich's ataxia. Funding European Commission, Voyager Therapeutics, and EuroAtaxia.

The morphological arrangement of scaffold is fundamental to drive cell growth and regeneration of collagen extracellular matrix. Electrospinning is a very promising technique to produce nanofibrous scaffolds able to guide cells in the regeneration of injured tissues. We developed a resorbable electrospun scaffold mimicking the hierarchical structure of tendons and ligaments. The aim of the present study was to investigate if hierarchically structured poly(L-lactic acid) (PLLA) and collagen (Coll) electrospun scaffolds can induce morphological modifications in human fibroblasts, while cultured in static and dynamic conditions. Different imaging techniques such as high-resolution x-ray computed tomography (XCT), scanning electron microscopy (SEM), fluorescence microscopy and histology were combined to assess the potential of such scaffolds.

Frataxin deficiency, responsible for Friedreich’s ataxia (FRDA), is crucial for cell survival since it critically affects viability of neurons, pancreatic beta cells and cardiomyocytes. In FRDA, the heart is frequently affected with typical manifestation of hypertrophic cardiomyopathy, which can progress to heart failure and cause premature death. A microarray analysis performed on FRDA patient’s lymphoblastoid cells stably reconstituted with frataxin, indicated HS-1-associated protein X-1 (HAX-1) as the most significantly upregulated transcript (FC = +2, P

Parkinson’s disease is a common neurodegenerative disease that can be treated with pharmacological or surgical therapy. Subthalamic nucleus (STN) deep brain stimulation is a commonly used surgical option. A reported side effect of STN-DBS is weight gain: the aim of our study was to find those factors that determine weight gain, through one year-long observation of 32 patients that underwent surgery in our centre. During the follow-up, we considered: anthropometric features, hormonal levels, motor outcome, neuropsychological and quality of life outcomes, therapeutic parameters and electrodes position. The majority (84%) of our patients gained weight (6.7 kg in 12 months); more than a half of the cohort became overweight. At 12th month, weight gain showed a correlation with dyskinesias reduction, electrodes voltage and distance on the lateral axis. In the multivariate regression analysis, the determinants of weight gain were dyskinesias reduction and electrodes position. In this study, we identified dyskinesias reduction and distance between the active electrodes and the third ventricle as determining factors of weight gain after STN-DBS implantation in PD patients. The first finding could be linked to a decrease in energy consumption, while the second one could be due to a lower stimulation of the lateral hypothalamic area, known for its important role in metabolism and body weight control. Weight gain is a common finding after STN-DBS implantation, and it should be carefully monitored given the potential harmful consequences of overweight.

Background Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. Objective To evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. Methods Twenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. Results No drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P Conclusions High-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

The complex multiple melting behavior of poly(thiodiethylene terephthalate) (PSDET) was investigated by means of differential scanning calorimetry, X-ray diffraction and hot-stage optical microscopy. The phenomenon was ascribed to the existence of two different crystal structures (a and b), each of them being able to melt and recrystallize under the experimental conditions adopted. Linear and nonlinear treatments were applied in order to estimate the equilibrium melting temperature for a PSDET, by using the corrected values of Tm. The nonlinear estimation led to a higher value by about 25 8C. Isothermal crystallization kinetics of each crystalline form were analyzed according to Avrami’s treatment. In both cases, values of Avrami’s exponent, n, close to 3 were obtained, in agreement with a crystallization process originating from predeterminated nuclei and characterized by three dimensional spherulitic growth. The rate of crystallization of each crystalline structure was found to become lower as the crystallization temperature is increased, as usual at low undercooling, where the crystallization process is controlled by nucleation.

Functional disorders-FD account for major disability and impairment. As multidisciplinary approach appears to be the most effective treatment, placebo can effectively relieve symptoms in some cases. Our aim was to assess FD outcome after sham rTMS and to identify response predictors. Sixteen consecutive patients (13 females, age 29.9 ± 11.2 years, disease duration-DD 3.8 years, range 0–26) underwent multiple sessions (5.4 + 4.5) of sham rTMS with H-coil as symptomatic treatment for FD. Global Clinical Impression of Improvement (CGI-I) was collected from the treating physician and correlated with clinical-demographical data using Spearman test. A coexisting neurological disease was diagnosed in 4 patients, while 8 had a psychiatric disorder; 8 patients presented with either sensitive or motor deficits, 7 had hyperkinetic movement disorders and 3 a mixture of both. Twelve patients improved following treatment (CGI-I 2.9 + 1.0) with only 1 patient with psychogenic tremor showing a mild and transitory feeling of postural instability. A greater CGI-I was found for shorter disease duration (r − 0.871, p

Objective repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for the treatment of post-stroke motor deficits. Since the crucial role of non-primary motor cortices and contralesional brain areas is emerging for motor recovery in chronic stroke; we assessed safety and efficacy of bilateral rTMS over the motor areas associated to physical training (PT) on upper extremity (UE) motor function. Methods double-blind, placebo-controlled trial on 20 patients with chronic stroke conditioning moderate to mild upper limb motor impairment. Eleven sessions of high frequency rTMS were delivered with the H-coil over the motor areas bilaterally. Subjects were randomly allocated to the real rTMS plus PT or the placebo (sham) rTMS plus PT. UE impairment was evaluated by the Fugl-Meyer assessment for UE (FM-UE), Modified Ashworth Scale (MAS) and hand grip strength at baseline (T0), after treatment (T1) and one-month follow-up (T2). Results no serious adverse events were reported. At T1 FM-UE significantly improved in both groups, while at T2 the improvement was significant only for the real group. The improvement was significantly higher in the real compared with the sham group. In the real group, greater improvement in FM-UE was found in patients moderately impaired compared with less impaired at baseline. Spasticity and hand grip strength also significantly improved in the real group at T1 and amelioration of spasticity persisted also at T2. Conclusion bilateral high-frequency rTMS with H-coil associated with PT is safe and enhances the effect of PT alone. Although plegic patients were not included, subjects with moderate rather than mild motor impairment may mainly benefit from this stimulation protocol.

A 76-year-old woman had progressive memory loss for 2 years. Neurologic examination confirmed the memory deficit and also demonstrated ideative-ideomotor apraxia and visuospatial disturbances (Mini-Mental State Examination 17/30). A diagnosis of probable Alzheimer disease dementia (AD) was formulated. She showed us notebooks filled with drawings she had completed as a hobby, covering a period form before the illness (figure 1) to the present (figure 2). These sketches provide an inside into AD-related changes in creativity and visuospatial skills.1 Drawing performance is related to perceptual and executive dysfunctions in the visuospatial domain.

The full-profile refinement of X-ray diffraction patterns was used to investigate two poly(thiodiethylene terephthalate) (PSDET) samples with different thermal history in order to thoroughly analyze their polymorphic aspects. In each sample, a crystalline (a or b) and a microcrystalline (a0 or b0) phase were identified together with an amorphous component. The crystal structures of all the ordered phases were determined. The data indicated an appreciable difference between the two crystalline forms, while the microcrystalline were rather similar. The results reported in this paper agree with the hypothesis that the polymorphic and morphological aspects of PSDET have to be correlated with the order degree and reorganization of crystallites and microcrystallites.

Background In Italy, the autosomal recessive diseases beta-thalassaemia and sickle cell anaemia are so widespread that in some regions they can be defined as 'social diseases'. In this study, nine clinical applications of preimplantation genetic diagnosis (PGD) were performed for beta-thalassaemia and sickle cell anaemia on seven Sicilian couples and carriers of beta-globin gene mutations. Methods and results The studied mutations were: Cd39, HbS, IVS1 nt1, IVS1 nt6 and IVS1 nt110. ICSI was performed with partner's sperm on 131 out of 147 retrieved oocytes, and this resulted in 72 zygotes; 32 embryos were successfully biopsied on day 3. The biopsied blastomeres were lysed and the beta-globin alleles amplified by nested PCR. The mutation diagnosis was performed by restriction enzyme digestion and reverse dot-blot. The amplification efficacy was 97.2%. The genotype study of non-transferred and surplus embryos showed that the allele drop-out rate was 8.6%. Seventeen embryos were transferred in utero on day 4. All couples received an embryo transfer; of the four pregnancies obtained, three resulted in live births and one miscarried at 11 weeks. Prenatal diagnosis at the 11th week and miscarriage material analysis confirmed the PGD results. Conclusions These studies represent the first successful application of PGD for beta-thalassaemia and sickle cell anaemia in Italy.

Our aim is to investigate intra-session reliability of lower limbs (LL) motor evoked potentials (MEPs) amplitudes elicited by Transcranial Magnetic Stimulation (TMS) and measured from Tibialis-Anterior (TA) and Abductor-Hallucis (AH), comparing double cone and circular coil. TMS was used in healthy subjects (HS) (n = 7) to elicit MEPs in TA and AH of both LL, at rest and during low level muscle contraction. Double cone and circular coil were used. Two sets of eight responses were recorded for each coil in a random order, using a stimulation intensity of 100% of the maximum stimulator output. Intra-session reliability was calculated using Intraclass correlation coefficients (ICC). Double cone and circular coil showed excellent intra-session reliability in TA and AH of both LL, at rest and during low level muscle contraction (ICC ⩾ 0.75 in all experimental conditions). Interestingly, circular coil failed to elicit measurable MEPs at rest in non-dominant limb in 3 out of 7 HS. Double cone coil is an efficient alternative to circular coil in order to measure LL MEPs amplitudes in HS. Since circular coil did not elicit MEPs in all HS, double cone coil could be more useful in neurological patients to better detect MEPs in cortico-spinal tract pathological conditions.

Among postural abnormalities in Parkinson’s disease (PD), striatal hand (SH) is a particularly underexplored phenomenon. It leads to extreme abnormalities of hand posture, causing altered dexterity, pain and disfigurement. In our study, three blinded investigators examined several pictures of the hands of individuals with PD (N = 40) and controls (N = 15). The investigators quantified postural alterations using the Striatal Hand Score. Demographic and clinical data were also collected. As no differences were detected among investigators agreement, a final Hand Score (HS, range 0–4) was obtained for each hand. The Striatal Hand Score in both the left and right hand was significantly different in PD compared to controls (p

Differential scanning calorimetry and high angle X-ray diffraction analyses were performed on gelatin films, air dried at different values of constant elongation, crosslinked with glutaraldehyde and examined at constant relative humidity of 75%. Drawing induces a preferential orientation of the chain segments of gelatin parallel to the stretching direction, and a linear increase of the renaturation level, calculated as the ratio between the denaturation enthalpy of gelatin films and that of tendon collagen. The comparison with the results previously obtained on the mechanical properties of the films, puts into evidence the different contributions of orientation and renaturation on the improvement of the mechanical parameters on drawing. The results offer important information on the role of glutaraldehyde (GTA) crosslinking on the stability of collagenous materials.

Repetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for treatment of post-stroke deficits. We evaluated the feasibility, safety and efficacy of excitatory Hz rTMS with H-coil over the leg motor areas combined with active cycling on paretic lower limb motor function in chronic post-stroke. rTMS was delivered with the H-coil targeting the lower limbs (real or sham for 11 sessions over 3weeks, with cross-over after 4weeks wash-out, in 12 subjects with first stroke more than 6months before. Lower limb function was assessed with the Fugl-Meyer lower limb scale (FM-LL), with additional timed measures (10-m and 6min walking tests) and modified ashworth scale to the lower limb. No participant reported adverse effects. Real rTMS treatment was associated with a significant improvement in FM-LL scores ( p p =0.007 chi square). The 10min test did not significantly improve and the 6min test improved after both treatments ( p

The voltammetric response and the π → π * absorption band of poly(4,4′-dipentoxy-2,2′-bithiophene) clearly depend on the supporting electrolyte used in the electrochemical preparation. The X-ray diffraction experiments showed a more extended crystal phase in the polymer prepared with tetrabutylammonium tetrafluoroborate as electrolyte, while the same polymer prepared with tetrabutylammonium perchlorate is practically amorphous.

X-ray diffraction and polarized optical microscopy investigations were carried out on thin sections of rabbit tibia in order to study the morphological organization of the structural components of this tissue, which often is utilized to test bone response to implants. In the optical microscope, the lateral face as well as the lateral portion of the caudal face exhibit a lamellar structure with an alternation of dark and bright lamellae running parallel to the long axis of the tibia. In contrast, both in the medial face and in the medial portion of the caudal face there are numerous osteonic structures. In spite of the complexity of this morphological organization, the results of small- and high-angle X-ray diffraction analyses indicate that the structural relationship between collagen fibrils and inorganic crystals is quite similar to that observed in single osteons and allows evaluation of the orientation of the two main structural components. Both collagen fibrils and apatitic crystallites are preferentially oriented parallel to the long axis of the tibia. The degree of orientation is greater in the thickness than in the plane of the lamellae, suggesting that collagen fibrils and inorganic crystallites lie preferentially in the plane of the lamellae, where they follow an oblique course. The degree of orientation of the apatitic crystallites is higher in the lateral face than in the medial and caudal faces, in agreement with the optical microscopic images. The results provide information that must be taken into account when evaluating the structural modifications of bone due to the insertion of a prosthetic device.

Menopause is a physiological event of women's life that is the end of menstrual cycles and the end of the fertile period. Normally the age at which women reach menopause is between 50 and 52 years, as the world average. Menopause occurs when the functional ovarian reserve is exhausted or can be induced by surgical removal of the ovaries. What follows, however, is the establishment of a state of hypoestrogenism, which potentially affects various organs and systems (genito-urinary system, cardiovascular system, skeleton, skin, brain) and quality of life of women (varying degrees of vasomotor symptoms, vaginal atrophy, osteoporosis). Hormone replacement therapy (HRT), it is based on estrogen or estrogen and progesterone, can be used to compensate for estrogen deficiency and to prevent or limit the damages that may result. During the years, there have been several observational studies designed to identify the risks and benefits arising from the use of postmenopausal hormone replacement therapy, in spontaneous and surgical menopause. In fact, although several studies have shown that women treated with estrogen enjoyed a better overall level of health, over the last decade have raised doubts about the safety of hormone replacement therapy long term. In our study we try to discuss, based on a review of the literature and evidence available to date, what are the present indications and controindications to the use of hormone replacement therapy.

Walking impairment has a strong impact on quality of life of multiple sclerosis (MS) patients. Excitatory Transcranial-Repetitive-Magnetic-Stimulation (rTMS) enhances corticospinal excitability and plasticity, potentially favouring the effects of neurorehabilitation. The aim of this study is to explore the impact of neurophysiological and clinical features on rTMS efficacy on walking in progressive MS patients undergoing neurorehabilitation. 42 progressive MS patients, randomized into real and sham-placebo rTMS, underwent 11 rTMS sessions during neurorehabilitation. Motor-threshold (RMT), duration of disease progression, walking speed (10mt-walking-test) and endurance (2 and 6 mwt) were assessed at baseline and at the end of treatment, as well as Modified-Ashworth-Scale (MAS), pain and spasticity VAS, Fatigue-Severity-Scale, EDSS, MS-walking-scale-12, PASAT and nine-hole-peg-test. Real rTMS patients showed greater improvement both in 10mt (p = 0.007) and 6mwt (p = 0.04). Greater disability was associated with greater 6mwt improvement in all patients (p = 0.01) and in the real-rTMS subgroup (p = 0.04), not in sham. In real-rTMS group, RMT negatively correlated with 6mwt improvement (p = 0.003). The potential for improvement, greater in more disabled patients after rTMS, can be exploited using this treatment associated with neurorehabilitation. RMT, resulting from combination of corticospinal excitability and of corticomotor fibres available for conduction, could be considered a predictive marker of therapeutic response to rTMS neuromodulation.

In the last few years Multifocal Vibration (MFV) has been evaluated as a tool to modify posture and to speed recovery after physical exercise. The aim of this study is to assess whether MFV can also modify resting state EEG. Eleven healthy subjects were included in this study. All subjects underwent a resting state EEG recording of six minutes (three with eyes closed and three minutes with eyes open) for evaluation of resting cortical rhythms, before and after one session of MFV with KEOPE-GPR. Data obtained were collapsed in four region of interest (ROIs): frontal, central, temporal and occipital. Frequency bands of interest were δ (0.5–3.5 Hz), θ (4–7.5 Hz), α 1 (8–10.5 Hz), α 2 (11–12.5 Hz), β 1 (13–19.5 Hz), and β 2 (20–30 Hz). The ratio between slow (delta + theta) and faster (alpha1 + alpha2) rhythms was evaluated using paired t -test. Subsequent statistical analysis was carried on using repeated measures ANOVA (RM-ANOVA) using time (2-levels), side (2-levels) and rhythm (6-levels) as within-subjects factors for each ROI. No statistically significant variations were observed on qEEG with eyes closed. The analysis of ratios between slow and faster frequencies after MFV identified significant variations following MFV ( p MFV can modulate oscillatory activity as observed by qEEG. The increase in alpha band observed in central regions could be related to an enhancement in mu rhythm.

Progressive supranuclear palsy-PSP is the second most common parkinsonian syndrome after Parkinson’s disease-PD, with some overlapping clinical features in the early phases. Non-invasive neurophysiological techniques, such as transcranial magnetic stimulation-TMS, could be useful for the differential diagnosis. Seventeen PD, 13 PSP and 11 healthy controls-HC subjects were included in this study. TMS evaluation included resting motor threshold-RMT, motor evoked potentials-MEP amplitude and latency, response to inhibitory-SICI and facilitating-ICF conditioned stimuli, cortical silent period-CSP, and ipsilateral silent period-iSP. Statistical analysis was performed using either parametric or non-parametric ANOVA according to data distribution. PSP and PD groups did not significantly differ in UPDRS. TMS assessment showed different distribution of RMT across the groups (p.008), with PSP patients showing the highest values and PD the lowest (PSP vs PD p.002). Group also affected iSP duration (p.016), being longest in PSP and lowest in HC (PSP vs HC p.005). On paired-pulse inhibition and facilitation, a significant effect for ISI ( p

Objective Progressive Supranuclear Palsy-PSP is the second most common parkinsonian syndrome after Parkinson’s disease-PD. Non-invasive neurophysiological techniques, such as transcranial magnetic stimulation-TMS, could prove useful to gain insight into these pathologies and for differential diagnosis. Methods Seventeen PD, 13 PSP and 11 healthy controls-CT were included in this study. TMS evaluation included resting motor threshold-RMT, motor evoked potentials-MEP amplitude, response to inhibitory-SICI and facilitating-ICF conditioning stimuli, cortical-CSP and ipsilateral silent period-iSP. Statistical analysis was performed using either parametric or non-parametric ANOVA and post-hoc tests according to data distribution. Results PSP and PD groups did not significantly differ in UPDRS. RMT distributed differently across groups (p.008), with PSP patients showing highest values and PD lowest (PSPvs.PD p.002). Group also affected iSP duration (p.016), being longest in PSP and lowest in HC (PSPvs.CT p.005). On paired-pulse inhibition and facilitation, a significant effect for inter-stimulus interval-ISI ( p Conclusions This study suggests that TMS can help differentiate PD and PSP. PSP patients displayed different response to the perturbation induced by conditioning stimuli and iSP elongation, probably due to impairment of GABA-mediated neurotransmission.

Background: Parkinson's disease (PD) is characterized by various changes in motor excitability. Objective: To examine through Transcranial Magnetic Stimulation (TMS) cortical excitability, specifically addressing interhemispheric connections in PD. Methods: Nineteen PD patients with a predominant involvement of the left hemibody (7 females, age 61.7 years,) and 13 controls (6 females, age 61.5 years) entered the study. Patients were subdivided into two groups (early and advanced) according to the time from PD diagnosis. Participants underwent evaluation of Resting Motor Threshold (RMT) and ipsilateral Silent Period (iSP), induced by suprathreshold TMS on the ipsilateral-M1, measured as suppression of voluntary EMG activity. Mirror Movements (MM) were EMG-recorded and scored, in three upper limb muscles, during unilateral voluntary hand movement. Patients were studied at baseline (OFF drug) and after acute levodopa challenge (ON). Results: PD patients showed a general reduction in RMT vs controls (P

A new series of poly(ether-alkyl)oxadiazoles of general formula: with m = 3, 4, and 5 has been obtained from the corresponding polyhydrazides through thermal cyclization reaction. The polymers were characterized by infrared spectroscopy, differential scanning calorimetry, wide-angle x-ray analysis, and optical microscopy. The polymers were crystalline, with a crystalline texture and structural parameters strongly dependent on the value of m. The Tm's and Tg's value decreased with increasing number of CH2. © 1994 John Wiley & Sons, Inc.

La gestione di un processo di donazione e trapianto di organi coinvolge numerose figure professionali aventi diverse competenze (cliniche, chirurgiche, immunologiche, tecniche e logistiche), che devono integrarsi le une alle altre in perfetta sintonia.

The peculiar structural modifications of Nylons 8, 10 and 12 prepared by crystallization from solutions and reported as α*, were studied by differential scanning calorimetry (DSC) and thermomicroscopy, supported also by some X-ray diffraction (XRD) measurements. The results indicate that the phase transition shown by the α*-forms of the Nylon 8–12 series exhibits the characteristics of a melting immediately followed by crystallization into γ-form, rather than of a α* γ solid-solid transition. When the γ-crystallization is concluded, the melting of this form takes place. DSC and XRD data demonstrate that the α* γ transition is irreversible. The changes in the DSC traces of the Nylon 8 – 12 series were interpreted as indicative of a gradual stability increase of the α-form in comparison with the corresponding α*-form, depending on the increase of the number of methylene groups in the repeating unit.

The recognition abilities of biological molecules and their specificity are object of increasing interest by the scientific community, also for their potential use in biosensors fully integrated in microelectronic chips. Aim of this work was the optimization of an immobilization protocol of biomolecules on silicon dioxide (SiO2) surfaces to build a biosensor, which has electrical transducer. We chose to use the Glucose oxidase (GOx) protein as bioreceptor and a SiO2 layer as immobilization surface, which is possible to integrate into a microelectronic device. To test the protocol validity and the uniformity of the organic layer obtained, we used X-ray Photoelectron Spectroscopy (XPS) [1]. In particular, we demonstrated the enzyme presence monitoring both the C1s and N1s signals; while the XPS Si2p signal, monitored during the various immobilization steps, allowed us to verify the layer uniformity. We demonstrated that the glucose oxidase activity was maintained after immobilization by using spectrophotometric measurements. Finally, to demonstrate that is possible use electrical transduction, we carried out the electrical characterization of biological molecules immobilized on the dielectric of a MOSlike structure.

High frequency transcranial repetitive magnetic stimulation (rTMS) enhances corticospinal excitability and plasticity, potentially favouring the effects of neurorehabilitation, as in a preliminary study by our group. We aimed at replicating our previous study and at combining results exploring baseline features. Twenty subjects with progressive MS, randomized in real and sham-placebo H-coil rTMS targeting lower limbs, underwent 11 sessions following intensive rehabilitation. Walking speed (10MWT), endurance (6 min test), modified Ashworth Scale-MAS, numeric rating scale-NRS for spasticity and pain, EDSS, PASAT, NHPT, Fatigue Severity Scale, MS walking scale-12, were assessed at baseline and end of treatment. Real rTMS had significant improvement in 10MWT and MAS vs sham, confirming data from a previous pilot study on 21 participants. Pooling data with the latter study, a correlation between resting motor threshold to the lower limb and walking improvement was found exclusively in the real rTMS group. The improvement in walking speed observed after real rTMS with the H-coil is consistent with data from our previous pilot study. Resting motor threshold could be considered as a specific therapeutic reserve index for rTMS, being predictive of therapeutic response to corticospinal neuromodulation.

To evaluate the effect of repetitive deep transcranial magnetic stimulation—rDTMS on motor symptoms in Parkinson’s Disease—PD in a randomized, placebo controlled study. Sixty patients underwent 12 sessions (3 sessions/week) of 10 Hz rDTMS, after randomization into 3 groups: Group 1 (real rDTMS on primary motor—M1 and prefrontal—PF areas); Group 2 (M1-real/PF-sham), Group 3 (M1-sham/PF-sham). Primary outcome was percent reduction of Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, OFF therapy. Secondary outcomes were: changes in UPDRSIII sub-scores; improvement in timed tests (Hand Tapping—HT, Foot Tapping—FT, Walking Time—WT, Nine Hole Peg Test—NHPT). Statistical analysis was performed using Mann–Whitney or t-test. Outcomes were tested in hierarchical order, by comparing the two real groups (1–2) only if their pooled data significantly differed from sham. No drop-outs or serious adverse effects were recorded. Both real groups improved significantly more than sham in UPDRSIII (p = .010 and p = .045, respectively), while they did not significantly differ between them. Pooled real groups showed a significant improvement vs sham in UPDRSIII (p = .007), tremor (p = .011) and lateralized sub-scores (p = .042 and p = .012 for worse and better side, respectively). Timed tests significantly improved more in the real group vs sham on the worse side (HT p = .041, FT p = .012, NHPT p = .003). rDTMS with H-coil appeared safe and effective on motor symptoms as add-on treatment in PD.

Accurate air temperature measurements made by surface meteorological stations are demanded by climate research programs for various uses. Heating of the temperature sensor due to inadequate coupling with the environment can lead to significant errors. Therefore, accurate in-situ temperature measurements require shielding the sensor from exposure to direct and reflected solar radiation, while also allowing the sensor to be brought into contact with atmospheric air at the ambient temperature. The difficulty in designing a radiation shield for such a temperature sensor lies in satisfying these two conditions simultaneously. In this paper, we perform a computational fluid dynamics analysis of mechanically aspirated radiation shields (MARS) to study the effect of geometry, wind speed, and interplay of multiple heat transfer processes. Finally, an artificial neural network model is developed to learn the relationship between the temperature error and specified input variables. The model is then used to perform a sensitivity analysis and design optimization.

A multivariate insight into the in vitro antitumour screen database of the NCI by means of the SIMCA package allows to propose hypotheses on the mechanism of action of novel anticancer compounds. As an example, the application of multivariate analysis to the NCI standard database provided clues to the classification of drugs whose mechanism is either unknown or controversial. Moreover, the influence of intrinsic biochemical cell line properties (molecular targets) on the sensitivity to drug treatment could be evaluated simultaneously for classes of compounds which act by the same mechanism. Interestingly, the present approach can also provide a correlation between the molecular targets and the therapeutical fingerprint of novel active compounds thus suggesting specific biochemical studies for the investigation of new mechanisms of drug action and resistance. The statistical approach reported here represents a valuable tool for handling theenormous data sets deriving from recent genome-wide investigations of gene expression in the NCI cell lines.

The occurrence of Hb CS is usually limited to the geographic area which includes Southern China and South East Asia. In 1968 Hb CS was also found to occur in the Mediterranean area where it was originally described as Hb Athens. We investigated the independent origin of these termination codon mutations of the alpha 2-globin gene by determining the alpha-cluster haplotype and comparing the hematologic data from Hb CS-Hb H patients and their family members.We studied one Hb CS-Hb H patient of Greek origin and a Sicilian family in which one individual was affected by Hb CS-Hb H. The haplotype of the Hb CS allele was determined and compared to the haplotype of an Hb CS-Hb H individual of Chinese origin.The haplotype found for the Greek and Sicilian Hb CS was the same but differed significantly from the Asiatic Hb CS mutation.The Hb CS mutation found in both Mediterranean patients arose independently in the Mediterranean area. The difference in clinical manifestation of the Hb CS-Hb H disease in both patients is less common but consistent with similar variation in the clinical expression of analogous Hb Icaria-Hb H disease patients.

The molecular causes of ATR-X syndrome reside in mutations involving the XNP/ATR-X gene, which maps in the Xq13.3 region. Mutational analysis of this gene in two unrelated affected patients allowed us to identify two new molecular defects in two distinct regions of the gene. The first is a A--G splice mutation in the acceptor site of the intron 11 that removes most of the 3' part of the protein, including the helicase domains and the glutamic acid stretch. Three cryptic acceptor splice sites are activated by this point mutation with consequent production of three types of abnormal mRNA: two with intronic insertions and a smaller one, approximately 10% of the total transcript, which is shorter than normal mRNA by one amino acid residue (E). Since the physiopathological characteristics of the patient carrying the splice mutation do not exhibit severe urogential abnormalities despite the lack of the -COOH end of the protein, a residual function of this third transcript is to be suspected. The second encountered nucleotide change (G--T) leads to an R246L amino acid substitution in the putative zinc finger DNA-binding domain in the -NH2 terminal part of the protein.