223 research outputs found
Amyotrophic Lateral Sclerosis and Air Pollutants in the Province of Ferrara, Northern Italy: An Ecological Study
The etiopathogenesis of amyotrophic lateral sclerosis (ALS) is still largely unknown, but likely depends on gene-environment interactions. Among the putative sources of environmental exposure are air pollutants and especially heavy metals. We aimed to investigate the relationship between ALS density and the concentration of air pollution heavy metals in Ferrara, northern Italy. An ecological study was designed to correlate the map of ALS distribution and that of air pollutants. All ALS cases diagnosed between 2000 and 2017 (Ferrara University Hospital administrative data) were plotted by residency in 100 sub-areas, and grouped in 4 sectors: urban, rural, northwestern and along the motorway. The concentrations of silver, aluminium, cadmium, chrome, copper, iron, manganese, lead, and selenium in moss and lichens were measured and monitored in 2006 and 2011. Based on 62 ALS patients, a strong and direct correlation of ALS density was observed only with copper concentrations in all sectors and in both sexes (Pearson coefficient (Ï) = 0.758; p = 0.000002). The correlation was higher in the urban sector (Ï = 0.767; p = 0.000128), in women for the overall population (Ï = 0.782, p = 0.000028) and in the urban (Ï = 0.872, p = 0.000047) population, and for the older cohort of diagnosed patients (2000-2009) the assessment correlated with the first assessment of air pollutants in 2006 (Ï = 0.724, p = 0.008). Our data is, in part, consistent with a hypothesis linking copper pollution to ALS
Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study
To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS).We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes.The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB.Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS
An Extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the <i>HLA-DRB1</i> locus
Multiple sclerosis (MS) is a common inflammatory disease of the
central nervous system unsurpassed for variability in disease outcome.
A cohort of sporadic MS cases (n=63), taken from opposite
extremes of the distribution of long-term outcome, was used to
determine the role of the HLA-DRB1 locus on MS disease severity.
Genotyping sets of benign and malignant MS patients showed that
HLA-DRB1*01 was significantly underrepresented in malignant
compared with benign cases. This allele appears to attenuate the
progressive disability that characterizes MS in the long term. The
observation was doubly replicated in (i) Sardinian benign and
malignant patients and (ii) a cohort of affected sibling pairs
discordant for HLA-DRB1*01. Among the latter, mean disability
progression indices were significantly lower in those carrying the
HLA-DRB1*01 allele compared with their disease-concordant siblings
who did not. The findings were additionally supported by
similar transmission distortion of HLA-DRB1*04 subtypes closely
related to HLA-DRB1*01. The protective effect of HLA-DRB1*01 in
sibling pairs may result from a specific epistatic interaction with the
susceptibility allele HLA-DRB1*1501. A high-density (>700) SNP
examination of the MHC region in the benign and malignant
patients could not identify variants differing significantly between
the two groups, suggesting that HLA-DRB1 may itself be the
disease-modifying locus. We conclude that HLA-DRB1*01, previously
implicated in disease resistance, acts as an independent
modifier of disease progression. These results closely link susceptibility
to long-term outcome in MS, suggesting that shared quantitative
MHC-based mechanisms are common to both, emphasizing
the central role of this region in pathogenesis
Measurement of the atmospheric muon depth intensity relation with the NEMO Phase-2 tower
The results of the analysis of the data collected with the NEMO Phase-2
tower, deployed at 3500 m depth about 80 km off-shore Capo Passero (Italy), are
presented. Cherenkov photons detected with the photomultipliers tubes were used
to reconstruct the tracks of atmospheric muons. Their zenith-angle distribution
was measured and the results compared with Monte Carlo simulations. An
evaluation of the systematic effects due to uncertainties on environmental and
detector parameters is also included. The associated depth intensity relation
was evaluated and compared with previous measurements and theoretical
predictions. With the present analysis, the muon depth intensity relation has
been measured up to 13 km of water equivalent.Comment: submitted to Astroparticle Physic
The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis.
Synthetic glycopeptides have the potential to detect antibodies in multiple
sclerosis (MS). In the present study, we analyzed the antibodies (IgM class, IgG
class and IgG subclasses) to the synthetic glycopeptide CSF114(Glc) in the serum
of 186 MS patients, 166 blood donors (BDs), 25 patients affected by
meningitis/encephalitis, 41 affected by systemic lupus erythematosus (SLE) and 49
affected by rheumatoid arthritis (RA). The IgM antibody level to CSF114(Glc) was
significantly increased in MS patients versus BDs (p<0.001) or versus other
autoimmune diseases (SLE or RA, p<0.001). The IgG response was restricted to the
subclass IgG2. IgM antibodies to CSF114(Glc) were found in 30% of
relapsing/remitting MS patients and, at lower levels, in subjects affected by
meningitis/encephalitis. The study of antibodies to CSF114(Glc) is a new,
potential immunological marker of MS
Development of a Real-Time, Large Area, High Spatial Resolution Particle Tracker Based on Scintillating Fibers
The design of a detector for tracking charged particles is presented together with the characterization techniques developed to extract the main design specifications. The goals for the final detector are to achieve real-time imaging performances, a large detection area, and a high spatial resolution, particularly suitable for medical imaging applications. This paper describes the prototype of the tracker plane, which has a 20 Ă 20âcm2 sensitive area consisting of two crossed ribbons of 500âÎŒm square scintillating fibers. The information about the hit position extracted real-time tracker in an innovative way, using a reduced number of the read-out channels to obtain a very large detection area but with moderate costs and complexity. The performances of the tracker have been investigated using ÎČ sources, cosmic rays, and a 62âMeV proton beam
Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study
Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patientâs prognosis, it should be more extensively applied to this fragile group of patients
Patient expression of emotions and neurologist responses in first multiple sclerosis consultations
Background: Anxiety and depression are common in people with multiple sclerosis (MS), but data on emotional communication during MS consultations are lacking. We assessed patient expressions of emotion and neurologist responses during first-ever MS consultations using the Verona Coding Definitions of Emotional Sequences (VR-CoDES). Methods: We applied VR-CoDES to recordings/transcripts of 88 outpatient consultations (10 neurologists, four MS Italian centers). Before consultation, patients completed the Hospital Anxiety and Depression Scale (HADS). Multilevel sequential analysis was performed on the number of cues/concerns expressed by patients, and the proportion of reduce space responses by neurologists. Results: Patients expressed 492 cues and 45 concerns (median 4 cues and 1 concern per consultation). The commonest cues were verbal hints of hidden worries (cue type b, 41%) and references to stressful life events (type d, 26%). Variables independently associated with number of cues/concerns were: anxiety (HADS-Anxiety score >8) (incidence risk ratio, IRR 1.08, 95% CI 1.06-1.09; p<0.001); patient age (IRR 0.98, 95% CI 0.98-0.99; p<0.001); neurologist age (IRR 0.94, 95% CI 0.92-0.96; p=0.03); and second opinion consultation (IRR 0.72, 95% CI 0.60-0.86; p=0.007). Neurologists reacted to patient emotions by reducing space (changing subject, taking no notice, giving medical advice) for 58% of cues and 76% of concerns. Anxiety was the only variable significantly associated with 'reduce space' responses (odds ratio 2.17, 95% CI 1.32-3.57; p=0.003). Conclusions: Patient emotional expressions varied widely, but VR-CoDES cues b and d were expressed most often. Patient anxiety was directly associated with emotional expressions; older age of patients and neurologists, and second opinion consultations were inversely associated with patient emotional expression. In over 50% of instances, neurologists responded to these expressions by reducing space, more so in anxious patients. These findings suggest that neurologists need to improve their skills in dealing with patient emotions
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