COMPARISON OF MULTI-SOURCE DATA, INTEGRATED SURVEY FOR COMPLEX ARCHITECTURE DOCUMENTATION

The metric documentation of architectural complexes requires today the use of several integrated survey methodologies. This need is an answer to the morphology of the object such as dimension, geometry, inaccessible areas and urban context. These properties inhibit the use of single surveying techniques and force the integration of Geomatics tools. In addition, the metric documentation of Cultural heritage objects not always requires uniform accuracy and resolution, therefore the integration of different surveying methodologies and techniques become the only effective solution both from a technical and economic point of view. The integration, that is today adopted as normal strategy, allows also the better understanding of the benefits which can arise to speed up the metric documentation of Cultural Heritage objects and the benefits that each of the possible surveying techniques can have thanks to the integration of the different potentialities. This study starting from an integrated survey, performed whit a combined use of Mobile Mapping System (MMS), Unmanned Aerial Vehicles (UAV) and Terrestrial Laser Scanner (TLS) and show the results of the comparisons between the possible achievable accuracies by using a correct integration between the different used technologies and the ones achievable by using the same techniques as independent tools. The case study is the architectural complex of the Ducal Palace in Gubbio (Italy), located upstream of the most important town square facing the cathedral in a very complex but realistic urban context

Surveillance of Multidrug-Resistant Pathogens in Neonatal Intensive Care Units of Palermo, Italy, during SARS-CoV-2 Pandemic

Background: Antimicrobial resistance (AMR) is a topic of concern, especially in high-level care departments like neonatal intensive care units (NICUs). The systematic use of an “active” epidemiological surveillance system allows us to observe and analyze any changes in microbial distribution, limiting the risk of healthcare-associated infection (HAI) development. Methods: We have conducted a longitudinal observational study in the five NICUs of Palermo, comparing the “pre-pandemic period” (March 2014–February 2020) with the “pandemic” one (March 2020–February 2022). The primary aim of the study was to evaluate the cumulative prevalence of carriage from multi-drug resistant (MDR) bacteria in the cumulative NICUs (NICU C). Results: During the “pre-pandemic period”, 9407 swabs were collected (4707 rectal, 4700 nasal); on the contrary, during the “pandemic period”, a total of 2687 swabs were collected (1345 rectal, 1342 nasal). A statistically significant decrease in MDR-Gram-negative bacteria (GNB) carriage prevalence was detected during the pandemic. At the same time, there was a general worsening of the carriage of carbapenemase-forming MDR-GNB (CARBA-R+) and methicillin-resistant Staphylococcus aureus (MRSA) during the pandemic period. A significant reduction in methicillin-susceptible Staphylococcus aureus (MSSA) carriage was detected too. Conclusions: The surveillance of MDRO carriage in NICUs is fundamental for limiting the social and economic burden of HAIs

Nuclear localization of the mitochondrial factor HIGD1A during metabolic stress.

Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo

FROM DATA TO TANGIBLE MODELS: CASE STUDY OF A VAULT IN THE ROYAL RESIDENCE OF VENARIA REALE

Framed on a wider research project that investigates Geometry as a cultural substrate and shared language for the comprehension of Architecture and its shapes, the presented research focuses on the geometric analysis and dissemination actions of a vault of the Royal Residence of Venaria Reale, designed by Benedetto Alfieri in the XVIII century. The vault is the only one offering to visitors’ sight both its intrados and extrados surfaces. We propose an interdisciplinary approach that uses Geometry both as qualifying intangible heritage of the built shapes and as a language transversal to observation and survey, return of data and their interpretation from a dissemination point of view. To achieve this, we propose an innovative use of physical models, both in their meaning of object to be explored and in that of their design, between prototyping and seriality. Interaction between public and physical models becomes a way to promote critical shape-reading activities and to enhance spatial visualization abilities by their haptic/visual exploration, to recognize 3D built geometry and to explore architecture from different a point of view, getting closer to its shapes

Protein carbonylation and aggregation precede neuronal apoptosis induced by partial glutathione depletion

While the build-up of oxidized proteins within cells is believed to be toxic, there is currently no evidence linking protein carbonylation and cell death. In the present study, we show that incubation of nPC12 (neuron-like PC12) cells with 50 μM DEM (diethyl maleate) leads to a partial and transient depletion of glutathione (GSH). Concomitant with GSH disappearance there is increased accumulation of PCOs (protein carbonyls) and cell death (both by necrosis and apoptosis). Immunocytochemical studies also revealed a temporal/spatial relationship between carbonylation and cellular apoptosis. In addition, the extent of all three, PCO accumulation, protein aggregation and cell death, augments if oxidized proteins are not removed by proteasomal degradation. Furthermore, the effectiveness of the carbonyl scavengers hydralazine, histidine hydrazide and methoxylamine at preventing cell death identifies PCOs as the toxic species. Experiments using well-characterized apoptosis inhibitors place protein carbonylation downstream of the mitochondrial transition pore opening and upstream of caspase activation. While the study focused mostly on nPC12 cells, experiments in primary neuronal cultures yielded the same results. The findings are also not restricted to DEM-induced cell death, since a similar relationship between carbonylation and apoptosis was found in staurosporine- and buthionine sulfoximine-treated nPC12 cells. In sum, the above results show for the first time a causal relationship between carbonylation, protein aggregation and apoptosis of neurons undergoing oxidative damage. To the best of our knowledge, this is the first study to place direct (oxidative) protein carbonylation within the apoptotic pathway

Efficacy of a coordinated strategy for containment of multidrug-resistant Gram-negative bacteria carriage in a Neonatal Intensive Care Unit in the context of an active surveillance program

Background: Antimicrobial resistance in neonatal intensive care unit (NICU) patients is a threat, due to the frequent use of antimicrobial treatment and invasive devices in fragile babies. Since 2014 an active surveillance program of multidrug-resistant Gram-negative bacteria (MDR-GNB) carriage has been in place in the five NICUs of Palermo, Italy. In 2017 an increase in the prevalence of MDR-GNB, and in particular of extended-spectrum β-lactamases-producing Klebsiella pneumoniae (ESBL-KP), was observed in “Civico” hospital NICU. Aim: To assess the impact of a coordinated intervention strategy in achieving long-lasting reduction of MDR-GNB prevalence in the NICU. Methods: Rectal swabs were obtained monthly and processed to detect MDR-GNB using standard methods. MDR-GNB were characterized by pulsed-field gel electrophoresis (PFGE). Since November 2017 the following intervention measures were applied: (a) two-months intensification of sample collection; (b) stakeholders meetings; (c) improvement of prevention measures and antimicrobial policies. Findings: During the intensified microbiological surveillance MDR-GNB and ESBL-KP were detected in rectal swabs (34.8%; 23.2%), nasal swabs (24.6%; 14.5%), oral swabs (14.5%; 5.4%), milk samples (32.1%; 17.9%), pacifiers swabs (30.8%; 17.9%) and from sub-intensive room surfaces. Thirteen ESBL-KP strains isolated from clinical and environmental samples showed identical PFGE patterns. The prevalence of MDR-GNB and ESBL-KP carriage significantly decreased in the year after intervention compared to the previous year (20.6% vs 62.2%; p < 0.001 and 11.1% vs 57.8%; p < 0.001). MDR-GNB were not detected at all for three months and ESBL-KP for five months. Multivariate analysis of the principal exposure variables showed that admission in the post-intervention period significantly reduced the risk of MDR-GNB carriage (adj-OR = 0.21, 95% CI = 0.076–0.629; p < 0.001). Conclusions: MDR-GNB broadly circulate in NICU setting, they can colonize different body sites and spread through various vehicles. A coordinated strategy of multiple interventions with active cooperation between epidemiologists and clinicians in the NICU can effectively reduce their circulation and in particular the carriage of the most dangerous ESBL-KP strains

A Snapshot on MRSA epidemiology in a neonatal intensive care unit network, Palermo, Italy

Objectives: We performed a 1-year prospective surveillance study on MRSA colonization within the five NICUs of the metropolitan area of Palermo, Italy. The purpose of the study was to assess epidemiology of MRSA in NICU from a network perspective. Methods: Transfer of patients between NICUs during 2014 was traced based on the annual hospital discharge records. In the period February 2014-January 2015, in the NICU B, at the University teaching hospital, nasal swabs from all infants were collected weekly, whereas in the other four NICUs (A, C, D, E) at 4 week-intervals of time. MRSA isolates were submitted to antibiotic susceptibility testing, SCCmec typing, PCR to detect lukS-PV and lukF-PV (lukS/F-PV) genes and the gene encoding the toxic shock syndrome toxin (TSST-1), multilocus variable number tandem repeat fingerprinting (MLVF), and multilocus sequence typing (MLST). Results: In the period under study, 587 nasal swabs were obtained from NICU B, whereas 218, 180, 157, and 95 from NICUs A, C, D, and E, respectively. Two groups of NICUs at high prevalence and low prevalence of MRSA colonization were recognized. Overall, 113 isolates of MRSA were identified from 102 infants. Six MLVF types (A-F) were detected, with type C being subdivided into five subtypes. Five sequence types (STs) were found with ST22-IVa being the most frequent type in all NICUs. All the MRSA molecular subtypes, except for ST1-IVa, were identified in NICU B. Conclusions: Our findings support the need to approach surveillance and infection control in NICU in a network perspective, prioritizing referral healthcare facilities

Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study

Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients

Passive immunotherapy for N-truncated tau ameliorates the cognitive deficits in two mouse AD models

Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer\u2019s disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26\u201336aa of tau protein) could improve the Alzheimer\u2019s disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloid\u3b2 metabolisms involved in early disease-associated synaptic deterioration; (iii) improves episodic-like type of learning/memory skills in hippocampal-based novel object recognition and object place recognition behavioural tasks; (iv) restores the specific up-regulation of the activity-regulated cytoskeleton-associated protein involved in consolidation of experience-dependent synaptic plasticity; (v) relieves the loss of dendritic spine connectivity in pyramidal hippocampal CA1 neurons; (vi) rescues the Alzheimer\u2019s disease-related electrophysiological deficits in hippocampal long-term potentiation at the CA3-CA1 synapses; and (vii) mitigates the neuroinflammatory response (reactive gliosis). These findings indicate that the 20\u201322 kDa NH2-terminal tau fragment is crucial target for Alzheimer\u2019s disease therapy and prospect immunotherapy with 12A12 monoclonal antibody as safe (normal tau-preserving), beneficial approach in contrasting the early Amyloid\u3b2-dependent and independent neuropathological and cognitive alterations in affected subject

Plasma BDNF levels following transcranial direct current stimulation allow prediction of synaptic plasticity and memory deficits in 3 7Tg-AD mice.

Early diagnosis of Alzheimer\u2019s disease (AD) supposedly increases the effectiveness of therapeutic interventions. However, presently available diagnostic procedures are either invasive or require complex and expensive technologies, which cannot be applied at a larger scale to screen populations at risk of AD.We were looking for a biomarker allowing to unveil a dysfunction of molecular mechanisms, which underly synaptic plasticity and memory, before the AD phenotype is manifested and investigated the effects of transcranial direct current stimulation (tDCS) in 3 x Tg-AD mice, an experimental model of AD which does not exhibit any long-term potentiation (LTP) and memory deficits at the age of 3 months (3 x Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3 x Tg-AD-3M and age-matched wild-type (WT) mice. While tDCS increased LTP at CA3-CA1 synapses and memory in WT mice, it failed to elicit these effects in 3 x Tg-AD-3M mice. Remarkably, 3 x Tg-AD-3M mice did not show the tDCS-dependent increases in pCREBSer133 and pCaMKIIThr286, which were found in WT mice. Of relevance, tDCS induced a significant increase of plasma BDNF levels in WT mice, which was not found in 3 x Tg-AD-3M mice. Collectively, our results showed that plasticity mechanisms are resistant to tDCS effects in the pre-AD stage. In particular, the lack of BDNF responsiveness to tDCS in 3 x Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-todetect and low-cost biomarker of covert impairment of synaptic plasticity mechanisms underlying memory, which could be clinically applicable. Testing proposed here might be useful to identify AD in its preclinical stage, allowing timely and, hopefully, more effective disease-modifying interventions