Observations about subcalcaneal adventitial bursitis (heel fat pad inflammatory lesion) in rheumatoid arthritis. Comment on the article of Suzuki and Shirai.

Not available.

Transverse Single-Spin Asymmetry for Very Forward Neutral Pion Production in Polarized p+p Collisions at sqrt[s]=510 GeV.

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}<1 GeV/c for the first time, at this collision energy. The asymmetries show an approximate x_{F} scaling in the p_{T} region where nonperturbative processes are expected to dominate. A non-negligible contribution from soft processes may be necessary to explain the nonzero neutral pion asymmetries.

Applications of muon absorption radiography to the fields of archaeology and civil engineering.

Muon radiography, also known as muography, is an imaging technique that provides information on the mass density distribution inside large objects. Muons are naturally produced in the interactions of cosmic rays in the Earth's atmosphere. The physical process exploited by muography is the attenuation of the muon flux, that depends on the thickness and density of matter that muons cross in the course of their trajectory. A particle detector with tracking capability allows the measurement of the muons flux as a function of the muon direction. The comparison of the measured muon flux with the expected one gives information on the distribution of the density of matter, in particular, on the presence of cavities. In this article, the measurement performed at Mt. Echia in Naples (Saracino 2017 Sci. Rep. 7, 1181. (doi:10.1038/s41598-017-01277-3)), will be discussed as a practical example of the possible application of muography in archaeology and civil engineering.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Tests of a novel imaging algorithm to localize hidden objects or cavities with muon radiography.

A novel algorithm developed within muon radiography to localize objects or cavities hidden inside large material volumes was recently proposed by some of the authors (Bonechi et al. 2015 J. Instrum. 10, P02003 (doi:10.1088/1748-0221/10/02/P02003)). The algorithm, based on muon back projection, helps to estimate the three-dimensional position and the transverse extension of detected objects without the need for measurements from different points of view, which would be required to make a triangulation. This algorithm can now be tested owing to the availability of real data collected both in laboratory tests and from real-world measurements. The methodology and some test results are presented in this paper.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Imaging the dome of Santa Maria del Fiore using cosmic rays.

The dome of Santa Maria del Fiore, Florence Cathedral, was built between 1420 and 1436 by architect Filippo Brunelleschi and it is now cracking under its own weight. Engineering efforts are under way to model the dome's structure and reinforce it against further deterioration. According to some scholars, Brunelleschi might have built reinforcement structures into the dome itself; however, the only known reinforcement is a wood chain 7.75 m above the springing of the Cupola. Multiple scattering muon radiography is a non-destructive imaging method that can be used to image the interior of the dome's wall and therefore ascertain the layout and status of any iron substructure in it. A demonstration measurement was performed at the Los Alamos National Laboratory on a mock-up wall to show the feasibility of the work proposed, and a lightweight and modular imaging system is currently under construction. We will discuss here the results of the demonstration measurement and the potential of the proposed technique, describe the imaging system under construction and outline the plans for the measurement.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Effect of organizational features on patient satisfaction with care in Italian multiple sclerosis centres.

BACKGROUND AND PURPOSE: Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients' satisfaction with healthcare. METHODS: Eighty-one centres and 707 patients (502 women, mean age 40.5 years, SD 10.2; mean education 12.2 years, SD 3.6; time since diagnosis 5.9 years, SD 1.5) were included in the analysis. The care organization and service provided by each centre were evaluated in comparison with the National Institute for Health and Care Excellence (NICE) guidelines on management of MS. Patients' satisfaction with care was measured using the patient self-assessed questionnaire 'Comunicazione medico-paziente nella Sclerosi Multipla, revised' section 2 (COSM-R section 2). RESULTS: The clinical characteristics of patients significantly affected their satisfaction. A multivariate regression model showed that higher patients' satisfaction (COSM-R score) was inversely associated with hospital size (number of patients under care) (ß = -0.21, 95% confidence interval -0.35; -0.07) and directly associated with psychological interventions (ß = 2.44, 95% confidence interval 0.29; 4.59). CONCLUSIONS: Multiple sclerosis patients from larger hospitals are less satisfied with the information received and the relationship with HPs. Building an individualized relationship between patients and HPs and tailoring the communication of information improve patients' satisfaction. Such a goal is probably less likely to be accomplished in larger centres with many incoming patients. Moreover, when the centres also provide structured psychological interventions, the patients are more satisfied.

Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies.

BACKGROUND: Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. AIM: The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. METHODS: We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. RESULTS: From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18-4.41; I (2 )= 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52-1.43; I (2 )= 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64-1.26), and the second one suggested an increased risk of 2.51 (1.10-5.71). In this case, because of the high degree of heterogeneity, results were not pooled. CONCLUSIONS: To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.

Use of Rasch analysis to refine a patient-reported questionnaire on satisfaction with communication of the multiple sclerosis diagnosis.

BACKGROUND: The Comunicazione medico-paziente nella Sclerosi Multipla - Revised (COSM-R) is a patient self-assessed questionnaire probing the moment of multiple sclerosis (MS) diagnosis disclosure (section 1, five items) and following period (section 2, 15 items). OBJECTIVES: This study examined COSM-R dimensionality and measurement properties through Rasch analysis (partial-credit model) and proposed a revised questionnaire. METHODS: Cross-sectional COSM-R data were obtained from 1068 people with MS (PwMS, 1065 questionnaires) participating in four studies (102 centres). Mean age was 40 years (range 17-73); 70% were women; 53% were from Northern, 25% from Central, and 21% from Southern Italy. RESULTS: Unidimensionality was not confirmed for COSM-R section 1, but was for section 2 after removal of three items. The revised instrument (COSM-S, Shortened) consisted of the original five-item checklist (section 1), modified by removing the table grouping of three items, and 12 of the original 15 section 2 items, which could now be summed and transformed into an interval scale. Scores were higher for items assessing emotional satisfaction than for those assessing informational satisfaction. CONCLUSIONS: The proposed COSM-S is a composite measure of satisfaction with MS diagnosis communication with improved metric properties over the original COSM-R, and whose section 2 satisfies Rasch model expectations.

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

Heart failure: molecular, genetic and epigenetic features of the disease.

Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

Development of a disability scale for myotonic dystrophy type 1.

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests in the literature have evaluated single aspects of DM1 patients, mainly focusing on muscular impairment, without an overall quantification of the different disease-specific neurological features. We developed and validated a new functional scale for DM1 patients based on neuromuscular impairment (NI) and disability. MATERIALS AND METHODS: Thirty-three patients were tested in basal condition, 18 were re-evaluated after therapeutic intervention with mexiletine, and 13 at one year follow-up without treatment. The scale includes 21 ordinal items in four areas: neuropsychology, motricity, myotonia and daily life activities. We evaluated inter- and intra-observer reliability (intraclass correlation coefficient, ICC and Spearman correlations, respectively), internal consistency (Cronbach's alpha), external validity (Spearman correlations between each area and other clinical and objective measurements and scales), and sensitivity to clinical changes after treatment or at follow-up. RESULTS: Our analysis provided good results for inter-observer agreement (ICC = 0.72-0.97), intra-observer reliability, and internal consistency for all areas (Cronbach's α > 0.73). Total score and single area subscores were significantly correlated to objective measurements, disease duration and multisystem involvement. Finally, the scale was sensitive to clinical changes disclosing a significant improvement after treatment in the items assessing myotonia, and also to disease progression showing a significant worsening in all areas but myotonia in untreated patients. DISCUSSION: Our scale provides a new practical measure to evaluate NI and disability of DM1 patients. Further longitudinal studies are warranted to confirm its reliability in tracking disease progression and severity over a longer period of time.

Incidence and predictors of acute symptomatic seizures after stroke.

OBJECTIVE: To assess incidence and predictors of acute symptomatic seizures in a prospective cohort of patients with first stroke. METHODS: Patients with first stroke hospitalized in 31 Italian centers were recruited. Relevant demographic data, disease characteristics, and risk factors were collected. Acute symptomatic seizures (≤7 days) were recorded and correlated to age, gender, family history of epilepsy, and vascular risk factors. RESULTS: A total of 714 patients (315 women, 399 men; age 27-97 years) were enrolled. A total of 609 (85.3%) had cerebral infarction (32 cerebral infarction with hemorrhagic transformation [CIHT]) and 105 (14.7%) primary intracerebral hemorrhage (PIH). A total of 141 (19.7%) had a large lesion (>3 cm) and 296 (41.5%) cortical involvement. Twelve patients reported family history of seizures. Forty-five patients (6.3%) presented acute symptomatic seizures, 24 with cerebral infarction (4.2%), 4 with CIHT (12.5%), and 17 (16.2%) with PIH. In multivariate analysis, compared to cerebral infarction, PIH carried the highest risk (odds ratio [OR] 7.2; 95% confidence interval [CI] 3.5-14.9) followed by CIHT (OR 2.7; 95% CI 0.8-9.6). Cortical involvement was a risk factor for PIH (OR 6.0; 95% CI 1.8-20.8) and for CI (OR 3.1; 95% CI 1.3-7.8). Hyperlipidemia (OR 0.2; 95% CI 0.03-0.8) was a protective factor for IPH. CONCLUSION: The incidence of acute symptomatic seizures is the highest reported in patients with first stroke with prospective follow-up. Hemorrhagic stroke and cortical lesion were independent predictors of acute symptomatic seizures. Hyperlipidemia was a protective factor for hemorrhagic stroke.

Chronic acquired hepatocerebral degeneration: effects of liver transplantation on neurological manifestations.

Three cirrhotic patients with chronic acquired hepatocerebral degeneration (CAHD) received neurologic, neuropsychologic and neuroimaging assessment before and after liver transplantation (LT). Before transplantation, neurologic dysfunction consisted in severe bradykinesia, dystonia, dyskinesia, ataxia and dysarthria. Cognitive impairment affected mainly attentional and executive domains. Brain MRI showed bilateral hyperintensities of the basal ganglia on T1-weighted images. After transplantation, motor manifestations promptly resolved. Cognitive testing showed a major improvement in two patients, whereas cognitive performances were slightly worsened in the third, reasonably due to the effects of a head injury before LT and a tacrolimus-related encephalopathy arising early after LT. MRI images 12 months later showed a slight reduction of the previously disclosed abnormalities in all three patients. None of them experienced recurrence of CAHD. Our observation reinforces the assumption that surgery is the best treatment option for CAHD and that severe neurological impairment in CAHD should not be considered a contraindication for LT.

Three years of experience: the Italian registry and safety data update.

At the end of 2006, a pharmacovigilance program on natalizumab was settled by the Italian Pharmaceutical Agency, and on January 2007, multiple sclerosis patients poorly responding to the immunomodulating therapies or with an aggressive clinical form of disease from onset initiated to be registered and to receive the medication. On February 2010, almost 3,000 cases have been treated with natalizumab. The drop-out rate is 10%. Almost 800 cases received cycles of natalizumab for more than 18 months. One case of PML was reported and other adverse events are similar to those described in phase III studies. The majority of cases remained stable, while in 25% of cases, an improvement of disability was documented.

Development and validation of a patient self-assessed questionnaire on satisfaction with communication of the multiple sclerosis diagnosis.

BACKGROUND: We describe the development and clinical validation of a patient self-administered tool assessing the quality of multiple sclerosis diagnosis disclosure. METHOD: A multiple sclerosis expert panel generated questionnaire items from the Doctor's Interpersonal Skills Questionnaire, literature review, and interviews with neurology inpatients. The resulting 19-item Comunicazione medico-paziente nella Sclerosi Multipla (COSM) was pilot tested/debriefed on seven patients with multiple sclerosis and administered to 80 patients newly diagnosed with multiple sclerosis. The resulting revised 20-item version (COSM-R) was debriefed on five patients with multiple sclerosis, field tested/debriefed on multiple sclerosis patients, and field tested on 105 patients newly diagnosed with multiple sclerosis participating in a clinical trial on an information aid. The hypothesized monofactorial structure of COSM-R section 2 was tested on the latter two groups. RESULTS: The questionnaire was well accepted. Scaling assumptions were satisfactory in terms of score distributions, item-total correlations and internal consistency. Factor analysis confirmed section 2's monofactorial structure, which was also test-retest reliable (intraclass correlation coefficient [ICC] 0.73; 95% CI 0.54-0.85). Section 1 had only fair test-retest reliability (ICC 0.45; 95% CI 0.12-0.69), and three items had 8-21% missed responses. CONCLUSIONS: COSM-R is a brief, easy-to-interpret MS-specific questionnaire for use as a health care indicator.

An information aid for newly diagnosed multiple sclerosis patients improves disease knowledge and satisfaction with care.

BACKGROUND: Patients report information deficits in the period surrounding diagnosis of multiple sclerosis (MS). We assessed the effectiveness of an add-on information aid for newly diagnosed MS patients. METHODS: We randomly assigned 120 newly diagnosed MS patients from five Italian centres to diagnosis disclosure (current practice at the centre) or current practice plus information aid (ISRCTN81072971). The information aid consisted of a personal interview with a physician using a navigable compact disc and a take-home booklet. The primary composite endpoint was score in the highest tertile of MS knowledge and satisfaction with care questionnaires. Other endpoints were safety; treatment adherence; extra contacts/consultations; switching of care centre; and changes in Hospital Anxiety and Depression Scale and Control Preference Scale scores. RESULTS: At 1 month, 30/60 intervention and 8/60 control patients achieved the primary endpoint (odds ratio [OR] 6.5, 95% CI 2.6-16.0; p < 0.001; number needed to treat [NNT] 3). Figures at 6 months were 26/60 intervention and 11/60 control patients (OR 3.4, 95% CI 1.5-7.8; p = 0.04; NNT 4). There were no adverse events. No significant treatment effects were seen on secondary outcomes. CONCLUSION: The information aid was safe and significantly associated with attainment of the primary outcome at 1 and 6 months.

Differential repression by the transcription factor REST/NRSF of the various Ca2+ signalling mechanisms in pheochromocytoma PC12 cells.

Expression of the nerve cell phenotype is orchestrated by the REST/NRSF transcription repressor, working on hundreds of genes recognized at a specific regulatory binding sequence. Most PC12 clones, the most frequently employed neuronal model, maintain low levels of REST; however a few, defective of neurosecretion, express high levels. To investigate the role of REST in Ca2+ signalling we studied the [Ca2+](i) changes in single cells of four clones, two wild-type and two defective, pre-treated for 5 days with NGF. We focused on Ca2+ influxes induced by depolarization and ATP. Only a subpopulation ( approximately 15%) of the defective, high REST cells responded to depolarization (Ca(V) expression approximately 10%). The ATP-induced intracellular Ca2+ release was little changed, whereas influx via ionotropic P2X receptors was decreased, in agreement with the decreased expression of P2X2 receptors. The percentage of defective cells expressing store-operated calcium entry (SOCE) following ATP stimulation was also lower. The responses of the defective clones were little affected by their differentiated state. In conclusion, our results revealed important new aspects of REST control of Ca2+ homeostasis, of potential physiological importance. The mechanisms of this control remain to be investigated.

The pharmacovigilance program on natalizumab in Italy: 2 years of experience.

At the end of 2006 a country-based surveillance program on natalizumab therapy in multiple sclerosis was settled in Italy by a collaborative effort of the Italian Drug Agency (AIFA) and a group of experts and neurologists appointed by the National Society of Neurology (SIN). After 2 years, 1,818 patients are registered in the database. The majority of cases (88.6%) failed the therapy with beta interferon or glatiramer acetate and had relapses or accumulated disability during immunomodulating treatment, while 11.4% of patients enrolled in the surveillance study were not previously treated with immunomodulating therapies and had a rapidly evolving clinical course. Almost 10% of the patients treated with natalizumab interrupted, for various different reasons, the therapy. Treatment was well tolerated and side effects were similar to those reported in the registrative studies. The majority of treated cases are stable or ameliorated.