The Influence of Temperature on the Low-Velocity Impact Response of Polyamide 6/Basalt Plain Fabric Laminates

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Comorbidities and crash involvement among younger and older drivers

Previous studies identified comorbidities as predictors of older driver performance and driving pattern, while the direct impact of comorbidities on road crash risk in elderly drivers is still unknown. The present study is a cross-sectional aimed at investigating the association between levels of comorbidity and crash involvement in adult and elderly drivers. 327 drivers were stratified according to age range in two groups: elderly drivers (age >= 70 years old, referred as older) and adult drivers (age <70 years old, referred as younger). Driving information was obtained through a driving questionnaire. Distance traveled was categorized into low, medium and high on the basis of kilometers driven in a year. CIRS-illness severity (IS) and CIRS-comorbidity indices (CI) in all populations were calculated. Older drivers had a significantly higher crash involvements rate (p = .045) compared with the younger group based on the number of licensed drivers. Dividing comorbidity indices into tertiles among all licensed subjects, the number of current drivers significantly decreased (p < .0001) with increasing level of comorbidity. The number of current drivers among older subjects significantly decreased with increasing comorbidity level (p = .026) while no difference among younger group was found (p = .462). Among younger drivers with increasing comorbidity level, the number of road accidents significantly increased (p = .048) and the logistic regression analysis showed that comorbidity level significantly associated with crash involvement independent of gender and driving exposure. Older subjects with high level of comorbidity are able to self-regulate driving while comorbidity burden represents a significant risk factor for crash involvements among younger drivers

Extra-neural metastases in pediatric diffuse midline gliomas, H3 K27-altered: presentation of two cases and literature review

IntroductionPediatric diffuse midline gliomas (DMG), H3 K27- altered, are the most aggressive pediatric central nervous system (CNS) malignancies. Disease outcome is dismal with a median survival of less than one year. Extra-neural metastases are an unusual occurrence in DMG and have been rarely described.Methods and resultsHere, we report on two pediatric patients affected by DMG with extra-neural dissemination. Their clinical, imaging, and molecular characteristics are reported here. An 11-year-old male 5 months after the diagnosis of diffuse intrinsic pontine glioma (DIPG) developed metastatic osseous lesions confirmed with computed tomography (CT) guided biopsy of the left iliac bone. The patient died one month after the evidence of metastatic progression. Another 11-year-old female was diagnosed with a cerebellar H3K27- altered DMG. After six months, she developed diffuse sclerotic osseous lesions. A CT-guided biopsy of the right iliac bone was non-diagnostic. She further developed multifocal chest and abdominal lymphadenopathy and pleural effusions. Droplet digital polymerase chain reaction (ddPCR) on pleural effusion revealed the presence of H3.3A mutation (c.83A&gt;T, p.K28M). The patient died 24 months after the diagnosis of DMG and 3 months after the evidence of metastatic pleural effusion.DiscussionExtra-neural metastasis of DMG is a rare event and no standard therapy exists. An accurate and early diagnosis is necessary in order to develop a personalized plan of treatment. Further research is needed to gain further insights into the molecular pathology of DMG, H3K27- altered and improve the quality of life and the final outcome of patients with this deadly disease

European survey on laboratory preparedness, response and diagnostic capacity for crimean-congo haemorrhagic fever, 2012

Crimean-Congo haemorrhagic fever (CCHF) is an infectious viral disease that has (re-)emerged in the last decade in south-eastern Europe, and there is a risk for further geographical expansion to western Europe. Here we report the results of a survey covering 28 countries, conducted in 2012 among the member laboratories of the European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) to assess laboratory preparedness and response capacities for CCHF. The answers of 31 laboratories of the European region regarding CCHF case definition, training necessity, biosafety, quality assurance and diagnostic tests are presented. In addition, we identifi

Geographical Variability Affects CCHFV Detection by RT-PCR: A Tool for In-Silico Evaluation of Molecular Assays

The Crimean-Congo hemorrhagic fever virus (CCHFV) is considered to be a major emerging infectious threat, according to the WHO R&D blueprint. A wide range of CCHFV molecular assays have been developed, employing varied primer/probe combinations. The high genetic variability of CCHFV often hampers the efficacy of available molecular tests and can affect their diagnostic potential. Recently, increasing numbers of complete CCHFV genomic sequences have become available, allowing a better appreciation of the genomic evolution of this virus. We summarized the current knowledge on molecular methods and developed a new bioinformatics tool to evaluate the existing assays for CCHFV detection, with a special focus on strains c

Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation

Background: Estrogen receptors alpha (ERa) and beta (ERb) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC). The two receptors can be found co-expressed and play specific, often opposite, roles, with ERb being able to modulate the effects of ERa on gene transcription and cell proliferation. ERb is frequently lost in BC, where its presence generally correlates with a better prognosis of the disease. The identification of the genomic targets of ERb in hormone-responsive BC cells is thus a critical step to elucidate the roles of this receptor in estrogen signaling and tumor cell biology. Results: Expression of full-length ERb in hormone-responsive, ERa-positive MCF-7 cells resulted in a marked reduction in cell proliferation in response to estrogen and marked effects on the cell transcriptome. By ChIP-Seq we identified 9702 ERb and 6024 ERa binding sites in estrogen-stimulated cells, comprising sites occupied by either ERb, ERa or both ER subtypes. A search for TF binding matrices revealed that the majority of the binding sites identified comprise one or more Estrogen Response Element and the remaining show binding matrixes for other TFs known to mediate ER interaction with chromatin by tethering, including AP2, E2F and SP1. Of 921 genes differentially regulated by estrogen in ERb+ vs ERb- cells, 424 showed one or more ERb site within 10 kb. These putative primary ERb target genes control cell proliferation, death, differentiation, motility and adhesion, signal transduction and transcription, key cellular processes that might explain the biological and clinical phenotype of tumors expressing this ER subtype. ERb binding in close proximity of several miRNA genes and in the mitochondrial genome, suggests the possible involvement of this receptor in small non-coding RNA biogenesis and mitochondrial genome functions. Conclusions: Results indicate that the vast majority of the genomic targets of ERb can bind also ERa, suggesting that the overall action of ERb on the genome of hormone-responsive BC cells depends mainly on the relative concentration of both ERs in the cell

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Alzheimer's Disease from the Amyloidogenic Theory to the Puzzling Crossroads between Vascular, Metabolic and Energetic Maladaptive Plasticity

: Alzheimer's disease (AD) is a progressive and degenerative disease producing the most common type of dementia worldwide. The main pathogenetic hypothesis in recent decades has been the well-known amyloidogenic hypothesis based on the involvement of two proteins in AD pathogenesis: amyloid β (Aβ) and tau. Amyloid deposition reported in all AD patients is nowadays considered an independent risk factor for cognitive decline. Vascular damage and blood-brain barrier (BBB) failure in AD is considered a pivotal mechanism for brain injury, with increased deposition of both immunoglobulins and fibrin. Furthermore, BBB dysfunction could be an early sign of cognitive decline and the early stages of clinical AD. Vascular damage generates hypoperfusion and relative hypoxia in areas with high energy demand. Long-term hypoxia and the accumulation within the brain parenchyma of neurotoxic molecules could be seeds of a self-sustaining pathological progression. Cellular dysfunction comprises all the elements of the neurovascular unit (NVU) and neuronal loss, which could be the result of energy failure and mitochondrial impairment. Brain glucose metabolism is compromised, showing a specific region distribution. This energy deficit worsens throughout aging. Mild cognitive impairment has been reported to be associated with a glucose deficit in the entorhinal cortex and in the parietal lobes. The current aim is to understand the complex interactions between amyloid β (Aβ) and tau and elements of the BBB and NVU in the brain. This new approach aimed at the study of metabolic mechanisms and energy insufficiency due to mitochondrial impairment would allow us to define therapies aimed at predicting and slowing down the progression of AD

Fused Deposition Modelling of Polymeric Auxetic Structures: A Review

Additive Manufacturing (AM) techniques have recently attracted the attention of scientists for the development of prototypes with complex or particular geometry in a fast and cheap way. Among the different AM processes, the Fused Deposition Modelling process (FDM) offers several advantages in terms of costs, implementation features and design freedom. Recently, it has been adopted to realise auxetic structures, which are characterised by negative Poisson ratio, enhanced mechanical properties, and a higher compression resistance than conventional structures. This review outlines the use of AM processes, in particular FDM, to design and obtain auxetic structures, with the final aim to exploit their applications in different fields. The first part of this work presents a brief classification of auxetic structures and materials. Subsequently, a summary of additive manufacturing processes is presented, focusing on the use of FDM and its limitations. Finally, the studies on the use of additive manufacturing to produce auxetic structures are shown, evidencing the potential of the concurrent combination of a fast prototyping technique such as FDM and the characteristics of polymer- and/or composite-based auxetic structures. Indeed, this new technological field opens the possibility of realising novel structures with integrated smart behaviour, multifunctional properties, compression resistance, and a tailored microstructure and shape

Impact Behavior of Hybrid Basalt/Flax Twill Laminates

The purpose of hybridization is to obtain a new material preserving advantages from all of its constituents. Hybridization offers intermediate properties respect to the original materials, by creating a balance effect within the fibres incorporated in the composite materials and leading to a composite with more tailored behaviour The increasing need to mitigate the environmental impact of synthetic fibres and polymers is promoting the use and application of natural materials orienting the research toward the development of biodegradable systems. In this framework, hybrid reinforced laminates with flax and basalt twill layers alternatively stacked, were manufactured by resin infusion fabrication technology and impacted at low velocity to investigate their dynamic behaviour, in an attempt to couple the impact resistance of basalt fibres with the environmentally friendly nature of flax fibres. For comparison purposes, the same experimental characterization has been performed on laminates reinforced with only basalt or flax fibres. The experimental results confirmed the positive role played by fibre hybridization in terms of damage. The Electronic Speckle Pattern Interferometry technique was adopted to analyze the internal damage and to provide information on the shape and the extent of the delamination, that was found concentrated under the impactor-material contact point for the basalt and flax/basalt laminates