Advancing Thrombosis Research: A Novel Device for Measuring Clot Permeability

Thromboembolism, a global leading cause of mortality, needs accurate risk assessment for effective prophylaxis and treatment. Current stratification methods fall short in predicting thrombotic events, emphasizing the need for a deeper understanding of clot properties. Fibrin clot permeability, a crucial parameter in hypercoagulable states, impacts clot structure and resistance to lysis. Current clot permeability measurement limitations propel the need for standardized methods. Prior findings underscore the importance of clot permeability in various thrombotic conditions but call for improvements and more precise, repeatable, and standardized methods. Addressing these challenges, our study presents an upgraded, portable, and cost-effective system for measuring blood clot permeability, which utilizes a pressure-based approach that adheres to Darcy's law. By enhancing precision and sensitivity in discerning clot characteristics, this innovation provides a valuable tool for assessing thrombotic risk and associated pathological conditions. In this paper, the authors present a device that is able to automatically perform the permeability measurements on plasma or fibrinogen in vitro-induced clots on specific holders (filters). The proposed device has been tailored to distinguish clot permeability, with high precision and sensitivity, between healthy subjects and high cardiovascular-risk patients. The precise measure of clot permeability represents an excellent indicator of thrombotic risk, thus allowing the clinician, also on the basis of other anamnestic and laboratory data, to attribute a risk score to the subject. The proposed instrument was characterized by performing permeability measurements in plasma and purified fibrinogen clots derived from 17 Behcet patients and 15 sex- and age-matched controls. As expected, our results clearly indicate a significant difference in plasma clot permeability in Behcet patients with respect to controls (0.0533 +/- 0.0199 d vs. 0.0976 +/- 0.0160 d, p < 0.001). This difference was confirmed in the patient's vs. control fibrin clots (0.0487 +/- 0.0170 d vs. 0.1167 +/- 0.0487 d, p < 0.001). In conclusion, our study demonstrates the feasibility, efficacy, portability, and cost-effectiveness of a novel device for measuring clot permeability, allowing healthcare providers to better stratify thrombotic risk and tailor interventions, thereby improving patient outcomes and reducing healthcare costs, which could significantly improve the management of thromboembolic diseases

Amino grafted MCM-41 as highly efficient and reversible ecofriendly adsorbent material for the Direct Blue removal from wastewater

The very high adsorption efficiency of Direct Blue (DB), an anionic toxic azo dye, onto amino grafted mesoporous silica nanoparticles (MCM-41), was studied in this paper, for possible industrial applications. Interesting challenges and advances are proposed in this field, presenting an adsorbent able to efficiently and rapidly remove the anionic dye from water. The important added value of this work regards the system recycle, which allows both the DB and adsorbent material recover, with a global reduction of the environmental impact, in the viewpoint of the green economy. Indeed, this paper is the first example of very fast removal and recycle of great amounts of DB with adsorbent materials characterized by impressive adsorption/desorption capacities, at least of around 300mg/g for each adsorption cycle, potentially increasable by performing consecutive cycles of DB adsorption/desorption. In detail, the MCM-41 amino functionalization (MCM-41-NH2) was obtained after (MCM- 41-POST) and during (MCM-41-PRE) the synthesis of MCM-41, obtaining materials with different behavior towards the DB adsorption. The MCM-41-NH2 surface features and porous structure, before and after the dye adsorption, were carefully characterized. Considering the adsorption process, for investigating the nature of the DB/MCM-41-NH2 interaction, several parameters were studied: the contact time, the DB solutions pH values, adsorbent material and dye amount, with the additional analysis of how the adsorption process was influenced by the presence of electrolytes. The isotherms of adsorption were also considered. Although MCM-41-PRE exhibited a higher affinity towards DB molecules, the MCM-41-POST were able to rapidly desorb it, thus recycling both DB and the adsorbent material

CSF heavy neurofilament may discriminate and predict motor neuron diseases with upper motor neuron involvement

Objective: To assess whether phosphorylated neurofilament heavy chain (pNfH) can discriminate different upper motor neuron (UMN) syndromes, namely, ALS, UMN-predominant ALS, primary lateral sclerosis (PLS) and hereditary spastic paraparesis (hSP) and to test the prognostic value of pNfH in UMN diseases. Methods: CSF and serum pNfH were measured in 143 patients presenting with signs of UMN and later diagnosed with classic/bulbar ALS, UMNp-ALS, hSP, and PLS. Between-group comparisons were drawn by ANOVA and receiver operating characteristic (ROC) analysis was performed. The prognostic value of pNfH was tested by the Cox regression model. Results: ALS and UMNp-ALS patients had higher CSF pNfH compared to PLS and hSP (p < 0.001). ROC analysis showed that CSF pNfH could differentiate ALS, UMNp-ALS included, from PLS and hSP (AUC = 0.75 and 0.95, respectively), while serum did not perform as well. In multivariable survival analysis among the totality of UMN patients and classic/bulbar ALS, CSF pNfH independently predicted survival. Among UMNp-ALS patients, only the progression rate (HR4.71, p = 0.01) and presence of multifocal fasciculations (HR 15.69, p = 0.02) were independent prognostic factors. Conclusions: CSF pNfH is significantly higher in classic and UMNp-ALS compared to UMN diseases with a better prognosis such as PLS and hSP. Its prognostic role is confirmed in classic and bulbar ALS, but not among UMNp, where clinical signs remained the only independent prognostic factors

Mechanical and in vitro biological properties of uniform and graded Cobalt-chrome lattice structures in orthopedic implants

Human bones are biological examples of functionally graded lattice capable to withstand large in vivo loading and allowing optimal stress distribution. Disruption of bone integrity may require biocompatible implants capable to restore the original bone structure and properties. This study aimed at comparing mechanical properties and biological behavior in vitro of uniform (POR-FIX) and graded (POR-VAR) Cobalt-chrome alloy lattice structures manufactured via Selective Laser Melting. In compression, the POR-VAR equivalent maximum stress was about 2.5 times lower than that of the POR-FIX. According to the DIC analysis, the graded lattice structures showed a stratified deformation associated to unit cells variation. At each timepoint, osteoblast cells were observed to colonize the surface and the first layer of both scaffolds. Cell activity was always significantly higher in the POR-VAR (p < 0.0005). In terms of gene expression, the OPG/RANKL ratio increased significantly over time (p < 0.0005) whereas IL1β and COX2 significantly decreased (7 day vs 1 day; p < 0.0005) in both scaffolds. Both uniform- and graded-porosity scaffolds provided a suitable environment for osteoblasts colonization and proliferation, but graded structures seem to represent a better solution to improve stress distribution between implant and bone of orthopedic implants

A Variant in TBCD Associated with Motoneuronopathy and Corpus Callosum Hypoplasia: A Case Report

Mutations in the tubulin-specific chaperon D (TBCD) gene, involved in the assembly and disassembly of the α/β-tubulin heterodimers, have been reported in early-onset progressive neurodevelopment regression, with epilepsy and mental retardation. We describe a rare homozygous variant in TBCD, namely c.881G>A/p.Arg294Gln, in a young woman with a phenotype dominated by distal motorneuronopathy and mild mental retardation, with neuroimaging evidence of corpus callosum hypoplasia. The peculiar phenotype is discussed in light of the molecular interpretation, enriching the literature data on tubulinopathies generated from TBCD mutations