Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 \ub1 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30) and High (H = 27 subjects with AHI >30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications

Mechanical behavior of a sandwich with corrugated GRP core: numerical modeling and experimental validation

In this work the mechanical behaviour of a core reinforced composite sandwich structure isstudied. The sandwich employs a Glass Reinforced Polymer (GRP) orthotropic material for both the twoexternal skins and the inner core web. In particular, the core is designed in order to cooperate with the GRPskins in membrane and flexural properties by means of the addition of a corrugated laminate into the foamcore. An analytical model has been developed to replace a unit cell of this structure with an orthotropicequivalent thick plate that reproduces the in plane and out of plane behaviour of the original geometry.Different validation procedures have been implemented to verify the quality of the proposed method. At first acomparison has been performed between the analytical model and the original unit cell modelled with a FiniteElement mesh. Elementary loading conditions are reproduced and results are compared. Once the reliability ofthe analytical model was assessed, this homogenised model was implemented within the formulation of a shellfinite element. The goal of this step is to simplify the FE analysis of complex structures made of corrugatedcore sandwiches; in fact, by using the homogenised element, the global response of a real structure can beinvestigated only with the discretization of its mid-surface. Advantages are mainly in terms of time to solutionsaving and CAD modelling simplification. Last step is then the comparison between this FE model andexperiments made on sandwich beams and panels whose skins and corrugated cores are made of orthotropiccross-ply GRP laminates. Good agreement between experimental and numerical results confirms the validity ofthe proposed model

Autonomic nervous system responses to strength training in top-level weight lifters

In athletes, spectral analysis of HR variability (HRV) has been shown capable to detect the adaptational changes in sympatho-vagal control attending physical training. So far, studies investigated autonomic nervous system (ANS) changes occurring with endurance training, whereas adaptations to markedly different exercise modes, for example, strength training, have never been investigated. We assessed the changes in cardiac ANS parameters during long-term training in weight lifters of the Italian team preparing for the European Championship, where athletes competed for obtaining the pass for Olympic Games. We investigated nine athletes. Subject trained 3 sessions/day, 6 days a week. The intensity of strength exercises varied from 70% to 95% 1 RM. Training load (TL) was calculated as: volume (min)  7 intensity (%1RM).All ANS parameters were significantly and highly correlated on an individual basis to the dose of exercise with a second-order regression model (r2 ranged from 0.96 to 0.99; P < 0.001). The low-frequency (LF) component of HRV and LF/HF ratio showed an initial increase with the progression of TL and then a decrease, resembling a bell-shaped curve with a minimum at the highest TL. The high-frequency (HF) component of HRV and R-R interval showed a reciprocal pattern, with an initial decrease with progression of TL followed by an increase, resembling an U-shaped curve with a maximum at the highest TL. These adaptations were at the opposite to those previously reported in endurance athletes. These results suggest that in Olympic weight lifters, ANS adaptations to training are dose-related on individual basis and that ANS adaptations are mainly sport-specific

Dreaming Characteristics in Non-Rapid Eye Movement Parasomnia and Idiopathic Rapid Eye Movement Sleep Behaviour Disorder: Similarities and Differences

Background: Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). Methods: A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Results: Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. Conclusion: The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications

A digital shadow cloud-based application to enhance quality control in manufacturing

In Industry 4.0 era, rapid changes to the global landscape of manufacturing are transforming industrial plants in increasingly more complex digital systems. One of the most impactful innovations generated in this context is the "Digital Twin", a digital copy of a physical asset, which is used to perform simulations, health predictions and life cycle management through the use of a synchronized data flow in the manufacturing plant. In this paper, an innovative approach is proposed in order to contribute to the current collection of applications of Digital Twin in manufacturing: a Digital Shadow cloud-based application to enhance quality control in the manufacturing process. In particular, the proposal comprises a Digital Shadow updated on high performance computing cloud infrastructure in order to recompute the performance prediction adopting a variation of the computer-aided engineering model shaped like the actual manufactured part. Thus, this methodology could make possible the qualification of even not compliant parts, and so shift the focus from the compliance to tolerance requirements to the compliance to usage requirements. The process is demonstrated adopting two examples: the structural assessment of the geometry of a shaft and the one of a simplified turbine blade. Moreover, the paper presents a discussion about the implications of the use of such a technology in the manufacturing context in terms of real-time implementation in a manufacturing line and lifecycle management. Copyright (C) 2020 The Authors

De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2 weeks letrozole: results of the PerELISA neoadjuvant study

BACKGROUND: In HER2+ breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive vs negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-weeks letrozole. PATIENTS AND METHODS: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-weeks letrozole, then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for 5 cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a 2-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. RESULTS: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95%CI 11.1%-34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched vs other subtypes (45.5% vs 13.8%, p=0.042). CONCLUSIONS: The primary endpoint of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared

NEMO: A Project for a km3^3 Underwater Detector for Astrophysical Neutrinos in the Mediterranean Sea

The status of the project is described: the activity on long term characterization of water optical and oceanographic parameters at the Capo Passero site candidate for the Mediterranean km$^3$ neutrino telescope; the feasibility study; the physics performances and underwater technology for the km$^3$; the activity on NEMO Phase 1, a technological demonstrator that has been deployed at 2000 m depth 25 km offshore Catania; the realization of an underwater infrastructure at 3500 m depth at the candidate site (NEMO Phase 2).Comment: Proceeding of ISCRA 2006, Erice 20-27 June 200

Measurement of the atmospheric muon flux with the NEMO Phase-1 detector

The NEMO Collaboration installed and operated an underwater detector including prototypes of the critical elements of a possible underwater km3 neutrino telescope: a four-floor tower (called Mini-Tower) and a Junction Box. The detector was developed to test some of the main systems of the km3 detector, including the data transmission, the power distribution, the timing calibration and the acoustic positioning systems as well as to verify the capabilities of a single tridimensional detection structure to reconstruct muon tracks. We present results of the analysis of the data collected with the NEMO Mini-Tower. The position of photomultiplier tubes (PMTs) is determined through the acoustic position system. Signals detected with PMTs are used to reconstruct the tracks of atmospheric muons. The angular distribution of atmospheric muons was measured and results compared with Monte Carlo simulations.Comment: Astrop. Phys., accepte

Direct RNA Nanopore Sequencing of SARS-CoV-2 Extracted from Critical Material from Swabs

In consideration of the increasing prevalence of COVID-19 cases in several countries and the resulting demand for unbiased sequencing approaches, we performed a direct RNA sequencing (direct RNA seq.) experiment using critical oropharyngeal swab samples collected from Italian pa-tients infected with SARS-CoV-2 from the Palermo region in Sicily. Here, we identified the sequences SARS-CoV-2 directly in RNA extracted from critical samples using the Oxford Nanopore MinION technology without prior cDNA retrotranscription. Using an appropriate bioinformatics pipeline, we could identify mutations in the nucleocapsid (N) gene, which have been reported previously in studies conducted in other countries. In conclusion, to the best of our knowledge, the technique used in this study has not been used for SARS-CoV-2 detection previously owing to the difficulties in the extraction of RNA of sufficient quantity and quality from routine oropharyngeal swabs. Despite these limitations, this approach provides the advantages of true native RNA sequencing and does not include amplification steps that could introduce systematic errors. This study can provide novel information relevant to the current strategies adopted in SARS-CoV-2 next-generation sequencing