Real estate appraisals with Bayesian approach and Markov Chain Hybrid Monte Carlo Method: An application to a central urban area of Naples

This paper experiments an artificial neural networks model with Bayesian approach on a small real estate sample. The output distribution has been calculated operating a numerical integration on the weights space with the Markov Chain Hybrid Monte Carlo Method (MCHMCM). On the same real estate sample, MCHMCM has been compared with a neural networks model (NNs), traditional multiple regression analysis (MRA) and the Penalized Spline Semiparametric Method (PSSM). All four methods have been developed for testing the forecasting capacity and reliability of MCHMCM in the real estate field. The Markov Chain Hybrid Monte Carlo Method has proved to be the best model with an absolute average percentage error of 6.61%

Autonomic dysfunction is associated with disease progression and survival in amyotrophic lateral sclerosis: a prospective longitudinal cohort study

Background: Among non-motor symptoms, autonomic disturbances have been described in amyotrophic lateral sclerosis (ALS) and reported as mild to moderate in up to 75% of patients. However, no study has systematically investigated autonomic symptoms as prognostic factors. Objectives: The main aim of this longitudinal study was to examine the association of autonomic dysfunction with disease progression and survival in ALS. Methods: We enrolled newly diagnosed ALS patients and a healthy control group (HC). Time from disease onset to disease milestone (King’s stage 4) and death were calculated to assess disease progression and survival. Autonomic symptoms were assessed by a dedicated questionnaire. Longitudinal evaluation of parasympathetic cardiovascular activity was performed by the heart rate variability (HRV). Multivariable Cox proportional hazards regression models on the risk of the disease milestone and death were used. A mixed-effect linear regression model was used to compare autonomic dysfunction with a HC group as well as its impairment over time. Results: A total of 102 patients and 41 HC were studied. ALS patients, compared with HC, complained of more autonomic symptoms, especially in bulbar onset patients. Autonomic symptoms occurred in 69 (68%) patients at diagnosis and progressed over time (post-6: p = 0.015 and post-12: p < 0.001). A higher autonomic symptom burden was an independent marker of faster development of King’s stage 4 (HR 1.05; 95% CI 1.00–1.11; p = 0.022); whereas, urinary complaints were independent factors of a shorter survival (HR 3.12; 95% CI 1.22–7.97; p = 0.018). Moreover, HRV in ALS patients was lower than in HC (p = 0.018) and further decreased over time (p = 0.003), implying a parasympathetic hypofunction that progressed over time. Conclusion: Autonomic symptoms occur in most of the ALS patients at diagnosis and progress over time, implying that autonomic dysfunction represents an intrinsic non-motor feature of the disease. A higher autonomic burden is a poor prognostic factor, associated with a more rapid development of disease milestones and shorter survival

Targeting lipid rafts as a strategy against coronavirus

Lipid rafts are functional membrane microdomains containing sphingolipids, including gangliosides, and cholesterol. These regions are characterized by highly ordered and tightly packed lipid molecules. Several studies revealed that lipid rafts are involved in life cycle of different viruses, including coronaviruses. Among these recently emerged the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The main receptor for SARS-CoV-2 is represented by the angiotensin-converting enzyme-2 (ACE-2), although it also binds to sialic acids linked to host cell surface gangliosides. A new type of ganglioside-binding domain within the N-terminal portion of the SARS-CoV-2 spike protein was identified. Lipid rafts provide a suitable platform able to concentrate ACE-2 receptor on host cell membranes where they may interact with the spike protein on viral envelope. This review is focused on selective targeting lipid rafts components as a strategy against coronavirus. Indeed, cholesterol-binding agents, including statins or methyl-β-cyclodextrin (MβCD), can affect cholesterol, causing disruption of lipid rafts, consequently impairing coronavirus adhesion and binding. Moreover, these compounds can block downstream key molecules in virus infectivity, reducing the levels of proinflammatory molecules [tumor necrosis factor alpha (TNF-α), interleukin (IL)-6], and/or affecting the autophagic process involved in both viral replication and clearance. Furthermore, cyclodextrins can assemble into complexes with various drugs to form host–guest inclusions and may be used as pharmaceutical excipients of antiviral compounds, such as lopinavir and remdesivir, by improving bioavailability and solubility. In conclusion, the role of lipid rafts-affecting drugs in the process of coronavirus entry into the host cells prompts to introduce a new potential task in the pharmacological approach against coronavirus

The role of cardiolipin as a scaffold mitochondrial phospholipid in autophagosome formation: In vitro evidence

Cardiolipin (CL) is a hallmark phospholipid localized within the inner mitochondrial membrane. Upon several mitochondrial stress conditions, CL is translocated to specialized plat-forms, where it may play a role in signaling events to promote mitophagy and apoptosis. Recent studies characterized the molecular composition of MAM-associated lipid microdomains and their implications in regulating the autophagic process. In this study we analyzed the presence of CL within MAMs following autophagic stimulus and the possible implication of raft-like microdomains enriched in CL as a signaling platform in autophagosome formation. Human 2FTGH fibroblasts and SKNB-E-2 cells were stimulated under nutrient deprivation with HBSS. MAM fraction was obtained by an ultracentrifugation procedure and analyzed by HPTLC immunostaining. CL interactions with mitofusin2 (MFN2), calnexin (CANX) and AMBRA1 were analyzed by scanning confocal microscopy and coimmunoprecipitation. The analysis revealed that CL accumulates in MAMs fractions following autophagic stimulus, where it interacts with MFN2 and CANX. It associates with AMBRA1, which in turn interacts with BECN1 and WIPI1. This study demonstrates that CL is present in MAM fractions following autophagy triggering and interacts with the multimolecular complex (AMBRA1/BECN1/WIPI1) involved in autophagosome formation. It may have both structural and functional implications in the pathophysiology of neurodegenerative disease(s)

Combined Collection and Analysis of Inorganic and Organic Gunshot Residues.

Gunshot residue (GSR) analysis and their interpretation provide crucial information on a criminal investigation involving the use of firearms. To date, several approaches have been proposed for the implementation of a combined sampling and analysis of inorganic (IGSR) and organic GSR (OGSR). However, it is not clear at this stage if concurrent analyses of both types of residue might be detrimental to the analysis of IGSR currently applied in forensic laboratories. Thus, this work aims to compare and evaluate three different protocols for the combined collection and analysis of IGSR and OGSR. These methods, respectively, involve the use of a modified stub (with two halves, one for the detection of IGSR and the other for the analysis of OGSR); the sequential recovery of GSR with two stubs mounted with different adhesives (double-sided carbon tape and Tesa® TACK) and the sequential analysis of IGSR and OGSR from a single carbon stub following carbon deposition. The detection of IGSR was carried out using SEM-EDX, while OGSR analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Obtained results for experiments performed using Geco Sinoxid &lt;sup&gt;®&lt;/sup&gt; ammunition indicated that sequential analysis was the most suitable protocol for the combined collection and analysis of both IGSR and OGSR. A higher number of inorganic (characteristic and consistent) particles and higher concentrations of ethylcentralite, N-nitrosodiphenylamine, diphenylamine, and nitroglycerin were recovered with this method

Advances in the Pathophysiology of Thrombosis in Antiphospholipid Syndrome. Molecular Mechanisms and Signaling through Lipid Rafts

The pathological features of antiphospholipid syndrome (APS) are related to the activity of circulating antiphospholipid antibodies (aPLs) associated with vascular thrombosis and obstetric complications. Indeed, aPLs are not only disease markers, but also play a determining pathogenetic role in APS and exert their effects through the activation of cells and coagulation factors and inflammatory mediators for the materialization of the thromboinflammatory pathogenetic mechanism. Cellular activation in APS necessarily involves the interaction of aPLs with target receptors on the cell membrane, capable of triggering the signal transduction pathway(s). This interaction occurs at specific microdomains of the cell plasma membrane called lipid rafts. In this review, we focus on the key role of lipid rafts as signaling platforms in the pathogenesis of APS, and propose this pathogenetic step as a strategic target of new therapies in order to improve classical anti-thrombotic approaches with "new " immunomodulatory drugs

Antiphospholipid reactivity against cardiolipin metabolites occurring during endothelial cell apoptosis.

We have recently shown that cardiolipin (CL) and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. In this study, we investigate the immunoreactivity to CL derivatives occurring during endothelial apoptosis in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We compared the serum immunoreactivity to CL with that of its derivatives monolysocardiolipin (MCL), dilysocardiolipin (DCL), and hydrocardiolipin (HCL) by means of both enzyme-linked immunosorbent assay and thin-layer chromatography (TLC) immunostaining. In addition, we investigated the composition of phospholipid extracts from the plasma membrane of apoptotic endothelial cells and the binding of patients' sera to the surface of the same cells by using high-performance TLC and immunofluorescence analysis. The average reactivity to MCL was comparable with that of CL and significantly higher than that for DCL and HCL in patients studied, both in the presence or in the absence of beta2-glycoprotein I. Of relevance for the pathogenic role of these autoantibodies, immunoglobulin G from patients' sera showed an increased focal reactivity with the plasma membrane of endothelial cells undergoing apoptosis. Interestingly, the phospholipid analysis of these light membrane fractions showed an accumulation of both CL and MCL. Our results demonstrated that a critical number of acyl chains in CL derivatives is important for the binding of antiphospholipid antibodies and that MCL is an antigenic target with immunoreactivity comparable with CL in APS and SLE. Our finding also suggests a link between apoptotic perturbation of CL metabolism and the production of these antibodies

Role of a Novel Heparanase Inhibitor on the Balance between Apoptosis and Autophagy in U87 Human Glioblastoma Cells

Background: Heparanase (HPSE) is an endo-&amp; beta;-glucuronidase that cleaves heparan sulfate side chains, leading to the disassembly of the extracellular matrix, facilitating cell invasion and metastasis dissemination. In this research, we investigated the role of a new HPSE inhibitor, RDS 3337, in the regulation of the autophagic process and the balance between apoptosis and autophagy in U87 glioblastoma cells. Methods: After treatment with RDS 3337, cell lysates were analyzed for autophagy and apoptosis-related proteins by Western blot. Results: We observed, firstly, that LC3II expression increased in U87 cells incubated with RDS 3337, together with a significant increase of p62/SQSTM1 levels, indicating that RDS 3337 could act through the inhibition of autophagic-lysosomal flux of LC3-II, thereby leading to accumulation of lipidated LC3-II form. Conversely, the suppression of autophagic flux could activate apoptosis mechanisms, as revealed by the activation of caspase 3, the increased level of cleaved Parp1, and DNA fragmentation. Conclusions: These findings support the notion that HPSE promotes autophagy, providing evidence that RDS 3337 blocks autophagic flux. It indicates a role for HPSE inhibitors in the balance between apoptosis and autophagy in U87 human glioblastoma cells, suggesting a potential role for this new class of compounds in the control of tumor growth progression

Poliomyelitis surveillance report number 18, May 20, 1955

Dr. Edwin Lennette, Virus Laboratory, California Department of Public Health, reports isolation of type 1 virus from the stool of case PSU No. Cal-21. He also reports isolation of type 1 virus from the stool of a third \uc2\ub0th contact of non-paralytic case PSU No. Cal-14. Isolations from 2 other contacts of this case were previously reported.Dr. Werner Henle, Children\ue2\u20ac\u2122s Hospital, Philadelphia, reports isolation of type 1 poliomyelitis virus from Case PSU No. Pa-2. This is the first isolation from a case receiving Wyeth Vaccine. This case had first paralysis at the same site as inoculation.One new case was accepted today from West Virginia. This seven-year-old female developed bulbar signs 26 days after inoculation with Lilly Vaccine. Vaccinated cases total 79 at 12:00 noon 5-20-55 (Table l)