Leukocyte Derived Microvesicles as Disease Progression Biomarkers in Slow Progressing Amyotrophic Lateral Sclerosis Patients

The lack of biomarkers in Amyotrophic Lateral Sclerosis (ALS) makes it difficult to determine the stage of the disease in patients and, therefore, it delays therapeutic trials. Microvesicles (MVs) are possible biomarkers implicated in physiological and pathological functions, however, their role in ALS remains unclear. We investigated whether plasma derived microvesicles could be overrepresented in a group of 40 patients affected by ALS compared to 28 Alzheimer’s Disease (AD) patients and 36 healthy volunteers. Leukocyte derived MVs (LMVs) compared to endothelial, platelet, erythrocyte derived MVs, were mostly present in ALS patients compared to AD patients and healthy donors. Correlation analysis corrected for the presence of confounding variables (riluzole, age at onset, site of onset, gender) was tested between PRL (Progression Rate at the Last visit) and LMVs, and a statistically significant value was found (Pearson partial correlation r = 0.407, p = 0.006). We also investigated SOD1, TDP-43 intravesicular protein level in LMVs. Misfolded SOD1 was selectively transported by LMVs and its protein level was associated with the percentage of LMVs in slow progressing patients (r = 0.545, p = 0.033). Our preliminary findings suggest that LMVs are upregulated in ALS patients and they can be considered possible markers of disease progression

Core–shell silica–rhodamine B nanosphere for synthetic opals: from fluorescence spectral redistribution to sensing

Silica nanospheres were functionalized with rhodamine B and self-assembled into opals. Photoluminescence redistribution and pollutant responsivity were also investigated

Evaluation of an integrated system of wearable physiological sensors for stress monitoring in working environments by using biological markers

Objective: The objectives of this paper are to develop and test the ability of a wearable physiological sensors system, based on ECG, EDA, and EEG, to capture human stress and to assess whether the detected changes in physiological signals correlate with changes in salivary cortisol level, which is a reliable, objective biomarker of stress. Methods: 15 healthy participants, eight males and seven females, mean age 40.8 ± 9.5 years, wore a set of three commercial sensors to record physiological signals during the Maastricht Acute Stress Test, an experimental protocol known to elicit robust physical and mental stress in humans. Salivary samples were collected throughout the different phases of the test. Statistical analysis was performed using a support vector machine (SVM) classification algorithm. A correlation analysis between extracted physiological features and salivary cortisol levels was also performed. Results: 15 features extracted from heart rate variability, electrodermal, and electroencephalography signals showed a high degree of significance in disentangling stress from a relaxed state. The classification algorithm, based on significant features, provided satisfactory outcomes with 86% accuracy. Furthermore, correlation analysis showed that the observed changes in physiological features were consistent with the trend of salivary cortisol levels (R2 = 0.714). Conclusion: The tested set of wearable sensors was able to successfully capture human stress and quantify stress level. Significance: The results of this pilot study may be useful in designing portable and remote control systems, such as medical devices used to turn on interventions and prevent stress consequences

Pain in Postsurgical Orthopedic Rehabilitation: A Multicenter Study

Objective.\u2002 The aim of this study was to quantify and characterize pain in patients undergoing lower limb postsurgical orthopedic rehabilitation and to investigate the impact of pain in slowing or interrupting their rehabilitation. Design.\u2002 The study was designed as a multicenter cross-sectional study. Setting.\u2002 The study was set in rehabilitation departments of the Don Gnocchi Foundation. Subjects.\u2002 The study subjects were the inpatients attending rehabilitation. Interventions.\u2002 There were no interventions used in the study. Outcome Measures.\u2002 Pain intensity was measured with a numeric rating scale (NRS); pain characteristics were assessed with the McGill Pain Questionnaire and the ID Pain (able to discriminate nociceptive from neuropathic pain). Quality of life (QoL) was measured with the Short Form 36 Health Status Survey. A semi-structured questionnaire on pain occurrence, impact, and management was administered by the physiotherapist in charge of the patients and by the physician. Results.\u2002 We studied 139 patients, 82% of whom complained of at least moderate pain (NRS 65 3). According to ID pain, 45.6% patients complained of probable (33.8%) or highly probable (11.8%) neuropathic pain. A higher pain intensity was significantly related to the probability of having neuropathic pain (P < 0.001). Patients with more severe pain reported lower physical and mental QoL scores. In 38.6% of cases, pain interfered with the rehabilitation process, and in 18.5% it was the cause of physical therapy discontinuation. Conclusions.\u2002 In light of the high occurrence and intensity of pain in the sample, and of the significant impact on the rehabilitation program, clinicians should pay more attention to pain, especially neuropathic pain, in postsurgical patients. Tailored pain pharmacological therapy could possibly improve patient compliance during the rehabilitation process and enhance long-term outcomes

«Un tesoro infinito inveduto». Erudizione e archivi a Milano tra XVII e XIX secolo. Atti della giornata di studio Milano, Archivio di Stato di Milano

Atti di un convegno dedicato al rapporto tra archivi ed erudizione a Milano tra antico regime e XIX secolo

Air pollution as a contributor to the inflammatory activity of multiple sclerosis

Objective: Air pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclerosis (MS) METHODS: Daily recording of PM10 was obtained by monitors depending on the residence of subjects. Expression of molecules involved in activation, adhesion, and migration of T lymphocytes were tested by flow cytometry in 57 MS patients and 19 healthy controls. We next assessed in vitro the effect of PM10 on expression of C-C chemokine receptors 6 (CCR6) by peripheral blood mononuclear cells (PBMCs), on cytokine production by monocyte-derived dendritic cells (mdDC), and on T cell polarization in PBMC/mdDC mixed cultures. Results: We identified a significant correlation between mean PM10 levels and expression of CCR6 CD4+ T circulating cells in MS patients. This was paralleled by the observation in vitro of a higher level of CCR6 expression on PBMC following treatment with increased doses of particulate matter. Moreover, in mdDC cultures, particulate matter induced the secretion by mdDC of Th17 polarizing IL1 beta, IL6, and IL23 and, in mdDC/PBMC mixed cultures, enhanced generation of IL17-producing T cells. Conclusions: Ex vivo and in vitro studies support the pro-inflammatory role of PM in MS, by upregulating expression of CCR6 on circulating CD4+ T cells and inducing in innate immune cells the production of Th17 polarizing cytokines. Therefore, we speculate that in MS respiratory exposure to PM10 may induce the production in the lung of autoreactive Th17 lymphocytes and boost their migratory properties through the blood-brain barrier

Pain in patients attending outpatient rehabilitation: results of a pilot study.

The aim of the study was to investigate pain occurrence, characteristics and correlations in an outpatient rehabilitation setting. This was an observational pilot study. The setting was an outpatient rehabilitation facility. The subjects included all patients attending physiotherapy in the week 25th to 29th September 2010 and the interventions were made using self-administered questionnaire. Ongoing pain was assessed by a yes–no question, pain intensity by a numeric rating scale (NRS) ranging 0–10. Pain-related medication was investigated, along with pain characteristics, patient treatment expectations, life satisfaction, and catastrophism. Of the 201 patients, 12 were excluded and 189 enrolled (age 63.6 ± 15.6; 70.4 % women). Pain (mean NRS = 5.6 ± 2.4) was reported by 60.9 % patients (66 % orthopedic and 40 % neurological). In 87.8 % cases, pain was chronic (>6 months). According to patients reporting pain, the main objectives of treatment were both pain relief and functional recovery for 51 %; pain relief for 24.9 %; functional recovery for 22.8 %. Low treatment expectations were reported by 15.3 % patients; catastrophism by 40.7 %; 28.6 % patients were on pain medication: use of drugs was related to age (p = 0.005), pain intensity (p = 0.009) and catastrophism (p = 0.0003). In a multivariate analysis, pain was independently correlated with an orthopedic versus neurological diagnosis (p = 0.000), and with reduced treatment expectations (p = 0.020), while independent of age (p = 0.74) gender (p = 0.22), and catastrophism (0.17). A high prevalence of pain was observed in outpatients undergoing rehabilitation. Pain was chronic in most cases. Pain relief was the most desired treatment outcome by patients reporting pain. Pain complaint was independently correlated to orthopedic vs neurological diagnosis and to reduced treatment expectations