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Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

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The term "neurodegenerative diseases" (NDs) identifies a group of heterogeneous diseases characterized by progressive loss of selectively vulnerable populations of neurons, which progressively deteriorates over time, leading to neuronal dysfunction. Protein aggregation and neuronal loss have been considered the most characteristic hallmarks of NDs, but growing evidence confirms that significant dysregulation of innate immune pathways plays a crucial role as well. NDs vary from multiple sclerosis, in which the autoimmune inflammatory component is predominant, to more "classical" NDs, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. Of interest, many of the clinical differences reported in NDs seem to be closely linked to sex, which may be justified by the significant changes in immune mechanisms between affected females and males. In this review, we examined some of the most studied NDs by looking at their pathogenic and phenotypical features to highlight sex-related discrepancies, if any, with particular interest in the individuals' responses to treatment. We believe that pointing out these differences in clinical practice may help achieve more successful precision and personalized care. [ABSTRACT FROM AUTHOR]

Background: In previous investigations of combined miRNAs/mRNAs expressions in neurodegenerative diseases like Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) we have targeted some interesting genes and molecular pathways that needed further confirmation. Methods: By nanofluidic qPCR analysis, we aimed to verify the expression of genes that resulted differentially expressed in the previous analyses. Data from MS patients -- either the pediatric and the adult occurrence of the disease (adMS and pedMS, respectively) -- was compared to age-matched healthy groups. As neurological controls we recruited a cohort of ALS subjects, considering published searches of possible genetic similarities between the two diseases. Results: The main results confirmed the involvement of most of the investigated genes in pedMS and adMS, like BACH2 and MICAL3. On the other hand, suggestive MS candidate genes like TNFSF13B showed an interesting trend possibly influenced by interfering factors, such as concomitant disease-modifying treatments; it is worth noting that TNFSF13B was one of the genes upregulated in ALS compared to age-matched adMS patients, together with the transcription factor TFDP1. Conclusions: Although with caution due to the small sample size, this study confirms the interest in transcriptomic analysis supported by integrated and educated bioinformatics evaluations, to shed further light in complex neurological diseases. [ABSTRACT FROM AUTHOR]

Syncope is a frequent cause of access to emergency departments. Recurrent syncope may be associated with a transient lock of consciousness. When neurological or cardiological common causes of syncope are excluded, rare causes of syncope, such as solid carotid tumors, should be considered. In this study, we report a rare case of left carotid chemodectoma in a patient with frequent access to the emergency room for syncope in which a thorough differential diagnosis has been performed. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs), a class of non-coding RNAs, seem to play a key role in complex diseases like multiple sclerosis (MS), as well as in many cognitive functions associated with the disease. In a previous cross-sectional evaluation on pediatric MS (PedMS) patients, the expression of some miRNAs and their target genes were found to be associated with the scores of some neuropsychiatric tests, thus suggesting that they may be involved in early processes of cognitive impairment. To verify these data, we asked the same patients to be re-evaluated after a 1-year interval; unfortunately, only nine of them agreed to this further clinical and molecular analysis. The main results showed that 13 differentially expressed miRNAs discriminated the two time-points. Among them, the expression of miR-182-5p, miR-320a-3p, miR-744-5p and miR-192-5p significantly correlated with the attention and information processing speed performances, whereas the expression of miR-182-5p, miR-451a, miR-4742-3p and miR-320a-3p correlated with the expressive language performances. The analysis of mRNA expression uncovered 58 predicted and/or validated miRNA-target pairs, including 23 target genes, some of them already associated with cognitive impairment, such as the transducing beta like 1 X-linked receptor-1 gene (TBL1XR1), correlated to disorders of neurodevelopment; the Snf2 related CREBBP activator protein gene (SRCAP) that was found implicated in a rare form of dementia; and the glia maturation factor beta gene (GMFB), which has been reported to be implicated in neurodegeneration and neuroinflammation. No molecular pathways involving the most targeted genes survived the adjustment for multiple data. Although preliminary, these findings showed the feasibility of the methods also applied to longitudinal investigations, as well as the reliability of the obtained results. These findings should be confirmed in larger PedMS cohorts in order to identify early markers of cognitive impairment, towards which more efficient therapeutic efforts can be addressed. [ABSTRACT FROM AUTHOR]

Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and effcacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. While genetics and other factors contribute to ALS pathogenesis, critical knowledge is still missing and validated biomarkers for monitoring the disease activity have not yet been identified. To address those aspects we carried out this study with the primary aim of identifying possible miRNAs/mRNAs dysregulation associated with the sporadic form of the disease (sALS). Additionally, we explored miRNAs as modulating factors of the observed clinical features. Study included 56 sALS and 20 healthy controls (HCs). We analyzed the peripheral blood samples of sALS patients and HCs with a high-throughput next-generation sequencing followed by an integrated bioinformatics/biostatistics analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p, miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR-151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584-5p, miR-93-5p) were significantly downregulated in sALS. We also found that different miRNAs profiles characterized the bulbar/spinal onset and the progression rate. This observation supports the hypothesis that miRNAs may impact the phenotypic expression of the disease. Genes known to be associated with ALS (e.g., PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed to be dysregulated in our study. We also identified other potential candidate genes like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in mitochondrial-induced apoptosis). Some of the downregulated genes are involved in molecular bindings to ions (i.e., metals, zinc, magnesium) and in ions-related functions. The genes that we found upregulated were involved in the immune response, oxidation–reduction, and apoptosis. These findings may have important implication for the monitoring, e.g., of sALS progression and therefore represent a significant advance in the elucidation of the disease’s underlying molecular mechanisms. The extensive multidisciplinary approach we applied in this study was critically important for its success, especially in complex disorders such as sALS, wherein access to genetic background is a major limitation. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs), nanoparticles originated from different cell types, seem to be implicated in several cellular activities. In the Central Nervous System (CNS), glia and neurons secrete EVs and recent studies have demonstrated that the intercellular communication mediated by EVs has versatile functional impact in the cerebral homeostasis. This essential role may be due to their proteins and RNAs cargo that possibly modify the phenotypes of the targeted cells. Despite the increasing importance of EVs, little is known about their fluctuations in physiological as well as in pathological conditions. Furthermore, only few studies have investigated the contents of contemporary EVs subgroups (microvesicles, MVs and exosomes, EXOs) with the purpose of discriminating between their features and functional roles. In order to possibly shed light on these issues, we performed a pilot study in which MVs and EXOs extracted from serum samples of a little cohort of subjects (patients with the first clinical evidence of CNS demyelination, also known as Clinically Isolated Syndrome and Healthy Controls) were submitted to deep small-RNA sequencing. Data were analysed by an in-home bioinformatics platform. In line with previous reports, distinct classes of non-coding RNAs have been detected in both the EVs subsets, offering interesting suggestions on their origins and functions. We also verified the feasibility of this extensive molecular approach, thus supporting its valuable use for the analysis of circulating biomarkers (e.g., microRNAs) in order to investigate and monitor specific diseases. [ABSTRACT FROM AUTHOR]

Differential gene expression analyses to investigate multiple sclerosis (MS) molecular pathogenesis cannot detect genes harboring genetic and/or epigenetic modifications that change the gene functions without affecting their expression. Differential co-expression network approaches may capture changes in functional interactions resulting from these alterations. We re-analyzed 595 mRNA arrays from publicly available datasets by studying changes in gene co-expression networks in MS and in response to interferon (IFN)-β treatment. Interestingly, MS networks show a reduced connectivity relative to the healthy condition, and the treatment activates the transcription of genes and increases their connectivity in MS patients. Importantly, the analysis of changes in gene connectivity in MS patients provides new evidence of association for genes already implicated in MS by single-nucleotide polymorphism studies and that do not show differential expression. This is the case of amiloride-sensitive cation channel 1 neuronal (ACCN1) that shows a reduced number of interacting partners in MS networks, and it is known for its role in synaptic transmission and central nervous system (CNS) development. Furthermore, our study confirms a deregulation of the vitamin D system: among the transcription factors that potentially regulate the deregulated genes, we find TCF3 and SP1 that are both involved in vitamin D3-induced p27Kip1 expression. Unveiling differential network properties allows us to gain systems-level insights into disease mechanisms and may suggest putative targets for the treatment. [ABSTRACT FROM AUTHOR]

Meningioma is a common intracranial tumor involving the meninges. The localization of this type of tumor is rarely extracranial due to its typically low invasive properties. Furthermore, invasion of the middle ear is exceptional. The present study reported a case of meningioma extending into the middle ear from the middle cranial fossa through the tegmen tympani. The clinical and pathological characteristics, as well as the outcome of the patient, were described. [ABSTRACT FROM AUTHOR]

The valorisation of the Italian cultural hotspots to enhance the tourism industry has always been at the heart of the local policies. Advanced computer applications can crucially contribute to this aim. In such a conceptual framework, an apparently "endless" series of ICT applications, sharing 3D assets, sprang into life in Bologna thanks to an Open Source background. The sequence of projects, that are going to be presented in the article, was initiated by the creation of the stereoscopic 3D medium-length movie "Apa the Etruscan". As an immediate consequence, four other projects have started, re-using some of the 3D models from "Apa ", and more are following. Our experience proves that a non possessive stance towards ones own products, speeds up and optimises time and costs, improving different end-products. The continuous transfer of models, adapted to new requirements, speeds up the productions, allowing to focus more on aesthetics, without damaging neither the source project nor the recipient, and reaching the widest audience possible. The multiplication of references can be seen even in the short term as much more fruitful than creating expensive projects closed in themselves. The rapidity of development and the increasing quality of the final product allows, hence, a distribution able to reach an increasingly wider audience, bringing the promotion of cultural heritage to a newer and higher awareness. [ABSTRACT FROM AUTHOR]

The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000–25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS. [ABSTRACT FROM AUTHOR]

Background: The adherence to the Mediterranean Diet (Med Diet) seems to reduce the incidence of metabolic syndrome. The present study aimed to explore whether the adherence to the overall Med Diet pattern and to specific Med Diet items is associated with the presence of metabolic syndrome, impaired fasting glucose (IFG), insulin resistance (IR), and microinflammation in subjects free of diabetes and cardiovascular diseases. Measurements: Each patient underwent clinical assessment. Adherence to the Med Diet was measured by a previously validated 14-item questionnaire. Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria; IR was defined by homeostasis model assessment of insulin resistance (HOMA-IR); inflammation was assessed through a high-sensitivity C-reactive protein (hsCRP) assay. Results: A total of 120 subjects (64.2% women, mean age 59.8±10.2 years) were enrolled at this study. Subjects with lower Med Diet pattern adherence exhibited higher occurrence of metabolic syndrome and all its components and higher HOMA-IR and hsCRP values ( P for all <0.0001). Subjects with metabolic syndrome were less likely to consume olive oil ( P=0.002) and vegetables ( P=0.023). By multivariable analyses, the overall Med Diet score was found to be strongly and inversely associated with the presence of metabolic syndrome [B=−0.066; 95% confidence interval (CI) −0.105 to −0.028; P=0.001], IFG (B=−0.076; 95% CI −0.114 to −0.038; p<0.0001), high HOMA-IR (B=−0.071; 95% CI −0.108 to −0.034; P<0.0001) and high hsCRP (B=−0.082; 95% CI −0.125 to −0.045; P<0.0001). None of specific Med Diet items independently predicted metabolic syndrome, IFG, and high HOMA-IR. Instead, the consumption of white meat over red meat (B=−0.324; 95% CI −0.467 to −0.178; P<0.0001) was found to be inversely associated with increased hsCRP. Conclusions: The inverse associations between adherence to Med Diet and the prevalence of metabolic syndrome and prediabetes may be due more to the effects of the entire dietary pattern rather than to individual food components. Metabolic syndrome-related microinflammation may further be linked to specific Med Diet components. [ABSTRACT FROM AUTHOR]

Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val66Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val66Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val66 allele, relative to Met66 carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met66 carriers relative to Val66 homozygous during retrieval (but not encoding) while, again, the reverse was true for healthy controls. The Val66Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical management of memory deficits in patients with Multiple Sclerosis. [ABSTRACT FROM AUTHOR]