From scan-to-BIM to a structural finite elements model of built heritage for dynamic simulation

The progress in information technology allows an innovative transformation of practices commonly involved in the engineering and construction field, especially in relation to the existing architectural heritage’s control and management activities. The proposed methodology takes advantage of an integrated 3D metric survey as a basis for an HBIM (Historic Building Information Modelling) model to be exploited for the definition of a Finite Elements Model (FEM). This paper aims to show the applicability of a digital process, stemmed from the integration in Rhinoceros 3D of a BIM structural model, leading to the dynamic simulation of the analytical FEM through PRO_SAP® (a PROfessional Structural Analysis Program). The described workflow investigates the interoperability issues, along with the difficulties in the Scan-to-HBIM processes, demonstrating how HBIM models can anyhow support operations aimed at maintaining and preserving existing historical assets, also from a structural point of view, even if with still persistent criticalities

Enhanced Glutathione Levels and Oxidoresistance Mediated by Increased Glucose-6-phosphate Dehydrogenase Expression *

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway that is responsible for the generation of NADPH, which is required in many detoxifying reactions. We have recently demonstrated that G6PD expression is induced by a variety of chemical agents acting at different steps in the biochemical pathway controlling the intracellular redox status. Although we obtained evidence that the oxidative stress-mediated enhancement of G6PD expression is a general phenomenon, the functional significance of such G6PD induction after oxidant insult is still poorly understood. In this report, we used a GSH-depleting drug that determines a marked decrease in the intracellular pool of reduced glutathione and a gradual but notable increase in G6PD expression. Both effects are seen soon after drug addition. Once G6PD activity has reached the maximum, the GSH pool is restored. We suggest and also provide the first direct evidence that G6PD induction serves to maintain and regenerate the intracellular GSH pool. We used HeLa cell clones stably transfected with the human G6PD gene that display higher G6PD activity than the parent HeLa cells. Although the activities of glutathione peroxidase, glutathione reductase, and catalase were comparable in all strains, the concentrations of GSH were significantly higher in G6PD-overexpressing clones. A direct consequence of GSH increase in these cells is a decreased reactive oxygen species production, which makes these cells less sensitive to the oxidative burst produced by external stimuli. Indeed, all clones that constitutively overexpress G6PD exhibited strong protection against oxidants-mediated cell killing. We also observe that NF-kappa B activation, in response to tumor necrosis factor-alpha treatment, is strongly reduced in human HeLa cells overexpressing G6PD

Nonconvulsive Seizures and Dementia: A Case Report

Nonconvulsive status epilepticus (NCSE) is a severe medical condition that shows increased incidence in the elderly and is frequently underdiagnosed because of its pleomorphic presentation. We report an NCSE in a 76-year-old woman affected by dementia with acute change of cognitive status and behavior. Intravenous diazepam solved clinical and electroencephalographic manifestations. Neuropsychological assessment after NCSE conclusion showed impairment of several fields that remained unchanged at 3-month followup. NCSE should be considered when sudden and transient cognitive fluctuations appear in the elderly. Epileptic events in dementia occur frequently and are often underrecognized; this could be a misleading factor when considering a quick progression of mnesic performances. Moreover, recent findings both in animal models and in humans demonstrated the deep link between epilepsy and dementia, also supporting the hypothesis that epileptiform activity could contribute to cognitive impairment

Transcranial Magnetic Stimulation Studies in Alzheimer's Disease

Although motor deficits affect patients with Alzheimer's disease (AD) only at later stages, recent studies demonstrated that primary motor cortex is precociously affected by neuronal degeneration. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries, thereby maintaining motor performances in daily living. Effectively several transcranial magnetic stimulation (TMS) studies have demonstrated that cortical excitability is enhanced in AD and primary motor cortex presents functional reorganization. Although the best hypothesis for the pathogenesis of AD remains the degeneration of cholinergic neurons in specific regions of the basal forebrain, the application of specific TMS protocols pointed out a role of other neurotransmitters. The present paper provides a perspective of the TMS techniques used to study neurophysiological aspects of AD showing also that, based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological and pathological brain aging at least at the group level. Moreover repetitive TMS might become useful in the rehabilitation of AD patients. Finally integrated approaches utilizing TMS together with others neuro-physiological techniques, such as high-density EEG, and structural and functional imaging as well as biological markers are proposed as promising tool for large-scale, low-cost, and noninvasive evaluation of at-risk populations

Where are Compton-thick radio galaxies? A hard X-ray view of three candidates

We present a broad-band X-ray spectral analysis of the radio-loud active galactic nuclei NGC 612, 4C 73.08 and 3C 452, exploiting archival data from NuSTAR, XMM-Newton, Swift and INTEGRAL. These Compton-thick candidates are the most absorbed sources among the hard X-ray selected radio galaxies studied in Panessa et al. We find an X-ray absorbing column density in every case below 1.5 × 1024 cm-2, and no evidence for a strong reflection continuum or iron K α line. Therefore, none of these sources is properly Compton-thick. We review other Compton-thick radio galaxies reported in the literature, arguing that we currently lack strong evidences for heavily absorbed radio-loud AGNs

Study of Cytotoxic and Genotoxic Effects of Hydroxyl-Functionalized Multiwalled Carbon Nanotubes on Human Pulmonary Cells

Chemical functionalization of multiwalled carbon nanotubes (MWCNTs) increases their solubility, dispersion, and biological applications. Since there are only a few studies on the toxicity of functionalized MWCNTs, we investigated the cytotoxic and genotoxic-oxidative effects of OH-functionalized MWCNTs on human lung epithelial cells (A549) in order to obtain information on their biological effects. We exposed the cells to 10, 20, 40, and 100 μg/mL of commercial MWCNT-OH for 24 h. Cytotoxicity was then evaluated as the reduction in cell viability, membrane damage, and apoptosis, assessed by MTT and LDH assays and fluorescence microscopic analysis, respectively. The Fpg-modified comet assay was used to assess direct/oxidative DNA damage. We found a concentration-dependent reduction in cell viability and an increase of percentage of apoptotic cells, with no significant cellular LDH release. There was also concentration-dependent direct DNA damage but no oxidative DNA damage. These findings demonstrate the cytotoxicity of MWCNT-OH, through reduction of cell viability and induction of apoptosis without cell membrane damage, and the genotoxicity, by direct DNA damage induction, suggesting that the MWCNTs enter the cell without damaging its membrane and directly interact with the nucleus. This preliminary study highlights the need for further research to examine the potential toxicity of functionalized MWCNTs before starting to use them in biological applications

Hard X-ray selected giant radio galaxies - II. Morphological evidence of restarted radio activity

About 6 per cent of radio galaxies (RGs) can reach linear sizes larger than 0.7 Mpc, and are then classified as giant radio galaxies (GRGs). The conditions that make possible the formation of such big structures are still not clear - either core accretion properties or environmental factors. Recent studies have shown that GRGs can be up to four times more abundant in hard X-ray selected (I.e. from INTEGRAL/IBIS and Swift/BAT at >20 keV) RG samples. Moreover, a high fraction of young radio sources found in their cores suggest a recently restarted activity, as suggested from the discrepancy between the measured jet and lobes power, with respect to the one expected from core X-ray luminosity. Here, we present a radio morphological study of a sample of 15 hard X-ray selected GRGs, discussing low-frequency images from our GMRT campaign complemented with others from the literature: among them, 7/15 show evidence of restarted radio activity either in the form of double-double/X-shaped morphology, or as a cocoon emission embedding more recent jets. This, together with the objects from this sample already found hosting a young radio source in their core, suggests that at least 13 over 15 of these hard X-ray selected GRGs show features that are consistent with the possibility of restarted radio activity

A pathogenic variant in the FLCN gene presenting with pure dementia: is autophagy at the intersection between neurodegeneration and cancer?

IntroductionFolliculin, encoded by FLCN gene, plays a role in the mTORC1 autophagy cascade and its alterations are responsible for the Birt–Hogg–Dubé (BHD) syndrome, characterized by follicle hamartomas, kidney tumors and pneumothorax.Patient and resultsWe report a 74-years-old woman diagnosed with dementia and carrying a FLCN alteration in absence of any sign of BHD. She also carried an alteration of MAT1A gene, which is also implicated in the regulation of mTORC1.DiscussionThe MAT1A variant could have prevented the development of a FLCN-related oncological phenotype. Conversely, our patient presented with dementia that, to date, has yet to be documented in BHD. Folliculin belongs to the DENN family proteins, which includes C9orf72 whose alteration has been associated to neurodegeneration. The folliculin perturbation could affect the C9orf72 activity and our patient could represent the first human model of a relationship between FLCN and C9orf72 across the path of autophagy

Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells.

Metabolic reprogramming of cancer cells provides energy and multiple intermediates critical for cell growth. Hypoxia in tumors represents a hostile environment that can encourage these transformations. We report that glycogen metabolism is upregulated in tumors in vivo and in cancer cells in vitro in response to hypoxia. In vitro, hypoxia induced an early accumulation of glycogen, followed by a gradual decline. Concordantly, glycogen synthase (GYS1) showed a rapid induction, followed by a later increase of glycogen phosphorylase (PYGL). PYGL depletion and the consequent glycogen accumulation led to increased reactive oxygen species (ROS) levels that contributed to a p53-dependent induction of senescence and markedly impaired tumorigenesis in vivo. Metabolic analyses indicated that glycogen degradation by PYGL is important for the optimal function of the pentose phosphate pathway. Thus, glycogen metabolism is a key pathway induced by hypoxia, necessary for optimal glucose utilization, which represents a targetable mechanism of metabolic adaptation

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine