A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living

The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities

Human NDE1 splicing and mammalian brain development.

Exploring genetic and molecular differences between humans and other close species may be the key to explain the uniqueness of our brain and the selective pressures under which it evolves. Recent discoveries unveiled the involvement of Nuclear distribution factor E-homolog 1 (NDE1) in human cerebral cortical neurogenesis and suggested a role in brain evolution; however the evolutionary changes involved have not been investigated. NDE1 has a different gene structure in human and mouse resulting in the production of diverse splicing isoforms. In particular, mouse uses the terminal exon 8 T, while Human uses terminal exon 9, which is absent in rodents. Through chimeric minigenes splicing assay we investigated the unique elements regulating NDE1 terminal exon choice. We found that selection of the terminal exon is regulated in a cell dependent manner and relies on gain/loss of splicing regulatory sequences across the exons. Our results show how evolutionary changes in cis as well as trans acting signals have played a fundamental role in determining NDE1 species specific splicing isoforms supporting the notion that alternative splicing plays a central role in human genome evolution, and possibly human cognitive predominance

Ultra-small dye-doped silica nanoparticles via modified sol-gel technique

In modern biosensing and imaging, fluorescence-based methods constitute the most diffused approach to achieve optimal detection of analytes, both in solution and on the single-particle level. Despite the huge progresses made in recent decades in the development of plasmonic biosensors and label-free sensing techniques, fluorescent molecules remain the most commonly used contrast agents to date for commercial imaging and detection methods. However, they exhibit low stability, can be difficult to functionalise, and often result in a low signal-to-noise ratio. Thus, embedding fluorescent probes into robust and bio-compatible materials, such as silica nanoparticles, can substantially enhance the detection limit and dramatically increase the sensitivity. In this work, ultra-small fluorescent silica nanoparticles (NPs) for optical biosensing applications were doped with a fluorescent dye, using simple water-based sol-gel approaches based on the classical Stober procedure. By systematically modulating reaction parameters, controllable size tuning of particle diameters as low as 10 nm was achieved. Particles morphology and optical response were evaluated showing a possible single-molecule behaviour, without employing microemulsion methods to achieve similar results

Assessment of the different types of failure on anterior cantilever resin-bonded fixed dental prostheses fabricated with three different materials: An in vitro study

background: resin-bonded fixed dental prosthesis (RBFDP) represents a highly aesthetic and conservative treatment option to replace a single tooth in a younger patient. The purpose of this in vitro study was to compare the fracture strength and the different types of failure on anterior cantilever RBFDPs fabricated using zirconia (ZR), lithium disilicate (LD), and PMMA-based material with ceramic fillers (PM) by the same standard tessellation language (STL) file. Methods: sixty extracted bovine mandibular incisives were embedded resin block; scanned to design one master model of RBFDP with a cantilevered single-retainer. Twenty cantilevered single-retainer RBFDPs were fabricated using ZR; LD; and PM. Static loading was performed using a universal testing machine. Results: the mean fracture strength for the RBFDPs was: 292.5 Newton (Standard Deviation (SD) 36.6) for ZR; 210 N (SD 37.6) for LD; and 133 N (SD 16.3) for PM. All the failures of RBFDPs in ZR were a fracture of the abutment tooth; instead; the 80% of failures of RBFDPs in LD and PM were a fracture of the connector. Conclusion: within the limitations of this in vitro study, we can conclude that the zirconia RBFDPs presented load resistance higher than the maximum anterior bite force reported in literature (270 N) and failure type analysis showed some trends among the groups

ELISA assay employing epitope-specific monoclonal antibodies to quantify circulating HER2 with potential application in monitoring cancer patients undergoing therapy with trastuzumab

Circulating HER2 extracellular domain (HER2 ECD) levels were proposed as a surrogate for HER2 tissue expression to monitor breast cancer patients for early relapse or responses to standard or HER2-targeted therapies, such as the monoclonal antibody (mAb) trastuzumab. Currently, available commercial ELISA assays for HER2 ECD rely on antibodies recognizing undisclosed or unknown epitopes. In this work, two ELISA assays employing MGR2 and MGR3 epitope-specific mAbs for HER2 ECD were developed and validated, showing good assay precision and linearity of the dose-response signal within the dynamic range of 0.19–12.50 ng mL−1 and detection limits of 0.76 and 0.75 ng mL−1 for the MGR2 and MGR3 assays, respectively. The developed assay showed a good agreement with two widely used commercial kits for HER2 ECD quantification in serum samples from breast cancer patients. A complete characterization of mAb-HER2 ECD interaction was performed by means of surface plasmon resonance using trastuzumab as control for both epitope mapping and kinetics analysis. The epitopes recognized by the two mAbs showed no overlap with trastuzumab, which was confirmed by trastuzumab interference analysis in serum samples. The method showed to be a practical approach to determine HER2 ECD with a high degree of sensitivity, reliability and recovery in samples containing mAbs-based therapies

Measuring and modelling the energy cost of reconfiguration in sensor networks [forthcoming]

As Wireless Sensor Networks (WSN) must operate for long periods on a limited power budget, estimating the energy cost of software operations is critical. Contemporary reconfiguration approaches for WSN allow for software evolution at various granularities; from reflashing of a complete software image, through replacement of complete applications, to the reconfiguration of individual software components. This paper contributes a generic model for measuring and modelling the energy cost of reconfiguration in WSN. We validate that this model is accurate in the face of different hardware platforms, software stacks and software encapsulation approaches. We have embedded this model in the LooCI middleware, resulting in the first energy aware reconfigurable component model for sensor networks. We evaluate our approach using two real-world WSN applications and demonstrate that our model predicts the energy cost of reconfiguration with 93% accuracy. Using this model we demonstrate that selecting the most appropriate software modularisation approach is key to minimising energy consumption

Energy aware software evolution for wireless sensor networks

Wireless Sensor Networks (WSNs) are subject to high levels of dynamism arising from changing environmental conditions and application requirements. Reconfiguration allows software functionality to be optimized for current environmental conditions and supports software evolution to meet variable application requirements. Contemporary software modularization approaches for WSNs allow for software evolution at various granularities; from monolithic re-flashing of OS and application functionality, through replacement of complete applications, to the reconfiguration of individual software components. As the nodes that compose a WSN must typically operate for long periods on a single battery charge, estimating the energy cost of software evolution is critical. This paper contributes a generic model for calculating the energy cost of the reconfiguration in WSN. We have embedded this model in the LooCI middleware, resulting in the first energy aware reconfigurable component model for sensor networks. We evaluate our approach using two real-world WSN applications and find that (i.) our model accurately predicts the energy cost of reconfiguration and (ii.) component-based reconfiguration has a high initial cost, but provides energy savings during software evolution

ApoE ε4 Allele Related Alterations in Hippocampal Connectivity in Early Alzheimer’s Disease Support Memory Performance

Background: Whether the presence of the Apolipoprotein E ε4 allele modulates hippocampal connectivity networks in abnormal ageing has yet to be fully clarified. Objective: Allele-dependent differences in this pattern of functional connectivity were investigated in patients with very mild neurodegeneration of the Alzheimer’s type, carriers and non-carriers of the ε4 allele. Method: A seed-based connectivity approach was used. The two groups were similar in demographics, volumetric measures of brain structure, and cognitive profiles. Results: ε4-carriers had increased connectivity between the seed area in the left hippocampus and 1) a left insular/lateral prefrontal region and 2) the contralateral right parietal cortex. Moreover, hippocampus- to-parietal connectivity in the group of ε4 carriers was positively associated with memory performance, indicating that the between-group difference reflects compensatory processes. Retrospective analyses of functional connectivity based on patients from the ADNI initiative confirmed this pattern. Conclusion: We suggest that increased connectivity with areas external to the Default Mode Network (DMN) reflects both compensatory recruitment of additional areas, and pathological interwining between the DMN and the salience network as part of a global ε4-dependent circuital disruption. These differences indicate that the ε4 allele is associated with a more profound degree of DMN network breakdown even in the prodromal stage of neurodegeneration

Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed