935 research outputs found
Role of Prion protein-EGFR multimolecular complex during neuronal differentiation of human dental pulp-derived stem cells
Cellular prion protein (PrPC) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrPCin human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrPCat low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrPCwith gangliosides and EGF receptor (EGF-R) during neuronal differentiation process. PrPCassociates constitutively with GM2 in control hDPSCs and with GD3 only after neuronal differentiation. Otherwise, EGF-R associates weakly in control hDPSCs and more markedly after neuronal differentiation. To analyze the functional role of PrPCin the signal pathway mediated by EGF/EGF-R, a siRNA PrP was applied to ablate PrPCand its function. The treatment with siRNA PrP significantly prevented Akt and ERK1/2 phosphorylation induced by EGF. Moreover, siRNA PrP treatment significantly prevented neuronal-specific antigens expression induced by EGF/bFGF, indicating that cellular prion protein is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that PrPCinteract with EGF-R within lipid rafts, playing a role in the multimolecular signaling complexes involved in hDPSCs neuronal differentiation
Is acting prosocially beneficial for the credit market?
This article argues that behaving prosocially implies more transparent information during the negotiation process of a financial contract and more cooperation among the parties to respect the terms of the contract. For this reason this work considers interest rate on loans and insolvency rate functions of prosocial behaviour along with the traditional socio-economic and financial collaterals. The context of study is Italy and the analysis is developed at a cross-regional level. We collect data from the two reports on “Relatives and Safety Net” produced by the Italian Centre Bureau of Statistics (ISTAT) in 1998 and 2003 and from the reports on “Regional Economics” produced by the Bank of Italy in the same years. A two-period panel model shows two interesting outcomes. Firstly, regions with a higher proportion of prosocial individuals report lower interest rates on loans and insolvency rates. Secondly, when we include the efficiency of legal enforcement, evidence supports the idea that a more efficient legal framework can act as a more reliable transmission mechanism of institutional norms and facilitate the internalisation of social norms
Do People Perceive Alexa as Gendered? A Cross-Cultural Study of People’s Perceptions, Expectations, and Desires of Alexa
Mainly, the scholarly debate on Alexa has focused on sexist/anti-woman gender representations in the everyday life of many families, on a cluster of themes such as privacy, insecurity, and trust, and on the world of education and health. This paper takes another stance and explores via online survey methodology how university student respondents in two countries (the United States, n = 333; and Italy, n = 322) perceive Alexa's image and gender, what they expect from this voice-based assistant, and how they would like Alexa to be. Results of a free association exercise showed that Alexa's image was scarcely embodied or explicitly gendered. Rather, Alexa was associated with a distinct category of being-the VBA, virtual assistant, or digital helper-with which one talks, and which possesses praiseworthy technical and social traits. Expectations of Alexa and desires regarding Alexa's ideal performance are presented and compared across the two country samples
Do People Perceive Alexa as Gendered? A Cross-Cultural Study of People’s Perceptions, Expectations, and Desires of Alexa
Mainly, the scholarly debate on Alexa has focused on sexist/anti-woman gender representations in the everyday life of many families, on a cluster of themes such as privacy, insecurity, and trust, and on the world of education and health. This paper takes another stance and explores via online survey methodology how university student respondents in two countries (the United States, n = 333; and Italy, n = 322) perceive Alexa’s image and gender, what they expect from this voice-based assistant, and how they would like Alexa to be. Results of a free association exercise showed that Alexa’s image was scarcely embodied or explicitly gendered. Rather, Alexa was associated with a distinct category of being—the VBA, virtual assistant, or digital helper—with which one talks, and which possesses praiseworthy technical and social traits. Expectations of Alexa and desires regarding Alexa’s ideal performance are presented and compared across the two country samples
Serum neurofilament light chain: a promising early diagnostic biomarker for hereditary transthyretin amyloidosis?
Background and purpose: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening disease caused by mutations in the gene encoding transthyretin (TTR). The recent therapeutic advances have underlined the importance of easily accessible, objective biomarkers of both disease onset and progression. Preliminary evidence suggests a potential role in this respect for neurofilament light chain (NfL). In this study, the aim was to determine serum NfL (sNfL) levels in a late-onset ATTRv population and evaluate whether it might represent a reliable biomarker of disease onset (i.e., 'conversion' from the asymptomatic status to symptomatic disease in TTR mutation carriers). Methods: In all, 111 individuals harbouring a pathogenic TTR variant (61 symptomatic ATTRv patients and 50 presymptomatic carriers) were consecutively enrolled. Fifty healthy volunteers were included as the control group. Ella™ apparatus was used to assess sNfL levels. Results: Serum NfL levels were increased in ATTRv patients compared to both presymptomatic carriers and healthy controls, whilst not differing between carriers and healthy controls. An sNfL cut-off of 37.10 pg/mL could discriminate between asymptomatic and symptomatic individuals with high diagnostic accuracy (area under the curve 0.958; p < 0.001), sensitivity (81.4%) and specificity (100%). Conclusions: Serum NfL seems to be a promising biomarker of peripheral nerve involvement in ATTRv amyloidosis and might become a reliable, objective measure to detect the transition from the presymptomatic stage to the onset of symptomatic disease. Further longitudinal studies are needed to confirm such a role and determine whether it could equally represent a biomarker of disease progression and response to therapy
Alteration of the late endocytic pathway in Charcot–Marie–Tooth type 2B disease
The small GTPase RAB7A regulates late stages of the endocytic pathway and plays specific roles in neurons, controlling neurotrophins trafficking and signaling, neurite outgrowth and neuronal migration. Mutations in the RAB7A gene cause the autosomal dominant Charcot–Marie–Tooth type 2B (CMT2B) disease, an axonal peripheral neuropathy. As several neurodegenerative diseases are caused by alterations of endocytosis, we investigated whether CMT2B-causing mutations correlate with changes in this process. To this purpose, we studied the endocytic pathway in skin fibroblasts from healthy and CMT2B individuals. We found higher expression of late endocytic proteins in CMT2B cells compared to control cells, as well as higher activity of cathepsins and higher receptor degradation activity. Consistently, we observed an increased number of lysosomes, accompanied by higher lysosomal degradative activity in CMT2B cells. Furthermore, we found increased migration and increased RAC1 and MMP-2 activation in CMT2B compared to control cells. To validate these data, we obtained sensory neurons from patient and control iPS cells, to confirm increased lysosomal protein expression and lysosomal activity in CMT2B-derived neurons. Altogether, these results demonstrate that in CMT2B patient-derived cells, the endocytic degradative pathway is altered, suggesting that higher lysosomal activity contributes to neurodegeneration occurring in CMT2B
Relationship between gender differences and clinical outcome in patients with the antiphospholipid syndrome
Antiphospholipid syndrome (APS), characterized by artherial and/or venous thrombosis, pregnancy morbidity and "antiphospholipid" antibodies (aPLs), is more common in women than in men, with a female to male ratio of about 3.5:1. Only few studies have investigated the clinical differences between male and female patients with APS. Therefore, this study was aimed to analyze the differences of clinical manifestations and laboratory tests, at diagnosis, between female and male APS patients and the clinical outcome. We enrolled 191 consecutive APS patients (125 with primary APS, PAPS, and 66 with secondary APS, SAPS) with a female predominant ratio of approximately 3:1 (142 vs 49). The prevalence of PAPS was higher in males than females (p<0.001). The analysis of aPL profile revealed that high IgM anti-cardiolipin (aCL) and high-medium IgG aCL titers were more frequent in males. In thrombotic APS peripheral arterial thrombosis was more common in male than female patients (p=0.049), as well as myocardial infarction (p=0.031). Multivariate analysis to correct for cardiovascular risk factors, high titer of aPLs and triple positivity for aPLs, revealed that the odds ratio for myocardial infarction in male was 3.77. Thus, APS may be considered as a disease in which serological (IgM titer) and clinical profiles are influenced by gender
Machine Learning for Early Diagnosis of ATTRv Amyloidosis in Non-Endemic Areas: A Multicenter Study from Italy
Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is an adult-onset multisystemic disease, affecting the peripheral nerves, heart, gastrointestinal tract, eyes, and kidneys. Nowadays, several treatment options are available; thus, avoiding misdiagnosis is crucial to starting therapy in early disease stages. However, clinical diagnosis may be difficult, as the disease may present with unspecific symptoms and signs. We hypothesize that the diagnostic process may benefit from the use of machine learning (ML). Methods: 397 patients referring to neuromuscular clinics in 4 centers from the south of Italy with neuropathy and at least 1 more red flag, as well as undergoing genetic testing for ATTRv, were considered. Then, only probands were considered for analysis. Hence, a cohort of 184 patients, 93 with positive and 91 (age- and sex-matched) with negative genetics, was considered for the classification task. The XGBoost (XGB) algorithm was trained to classify positive and negative TTR mutation patients. The SHAP method was used as an explainable artificial intelligence algorithm to interpret the model findings. Results: diabetes, gender, unexplained weight loss, cardiomyopathy, bilateral carpal tunnel syndrome (CTS), ocular symptoms, autonomic symptoms, ataxia, renal dysfunction, lumbar canal stenosis, and history of autoimmunity were used for the model training. The XGB model showed an accuracy of 0.707 ± 0.101, a sensitivity of 0.712 ± 0.147, a specificity of 0.704 ± 0.150, and an AUC-ROC of 0.752 ± 0.107. Using the SHAP explanation, it was confirmed that unexplained weight loss, gastrointestinal symptoms, and cardiomyopathy showed a significant association with the genetic diagnosis of ATTRv, while bilateral CTS, diabetes, autoimmunity, and ocular and renal involvement were associated with a negative genetic test. Conclusions: Our data show that ML might potentially be a useful instrument to identify patients with neuropathy that should undergo genetic testing for ATTRv. Unexplained weight loss and cardiomyopathy are relevant red flags in ATTRv in the south of Italy. Further studies are needed to confirm these findings
Anxiety and depression in Charcot-Marie-Tooth disease: data from the Italian CMT national registry
Background There is little information about neuropsychiatric comorbidities in Charcot-Marie-Tooth disease (CMT). We assessed frequency of anxiety, depression, and general distress in CMT.Methods We administered online the Hospital Anxiety-Depression Scale (HADS) to CMT patients of the Italian registry and controls. HADS-A and HADS-D scores >= 11 defined the presence of anxiety/depression and HADS total score (HADS-T) >= 22 of general distress. We analysed correlation with disease severity and clinical characteristics, use of anxiolytics/antidepressants and analgesic/anti-inflammatory drugs.Results We collected data from 252 CMT patients (137 females) and 56 controls. CMT patient scores for anxiety (mean +/- standard deviation, 6.7 +/- 4.8), depression (4.5 +/- 4.0), and general distress (11.5 +/- 8.1) did not differ from controls and the Italian population. However, compared to controls, the percentages of subjects with depression (10% vs 2%) and general distress (14% vs 4%) were significantly higher in CMT patients. We found no association between HADS scores and disease duration or CMT type. Patients with general distress showed more severe disease and higher rate of positive sensory symptoms. Depressed patients also had more severe disease. Nineteen percent of CMT patients took antidepressants/anxiolytics (12% daily) and 70% analgesic/anti-inflammatory drugs. Patients with anxiety, depression, and distress reported higher consumption of anxiolytics/antidepressants. About 50% of patients with depression and/or general distress did not receive any specific pharmacological treatment.Conclusions An appreciable proportion of CMT patients shows general distress and depression. Both correlated with disease severity and consumption of antidepressants/anxiolytics, suggesting that the disease itself is contributing to general distress and depression
Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy
Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient's functional autonomy negatively affects the patient's quality of life and requires increasing involvement of relatives in the patient's daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients' and relatives' socio-demographic variables, patients' clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives
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