Non-invasive positive pressure ventilation in acute hypercapnic respiratory failure: clinical experience of a respiratory ward

Background: Although a controlled trial demonstrated that non-invasive positive pressure ventilation (NIV) can be successfully applied to a respiratory ward (RW) for selected cases of acute hypercapnic respiratory failure (AHRF), clinical practice data about NIV use in this setting are limited. The aim of this observational study is to assess the feasibility and efficacy of NIV applied to AHRF in a RW in everyday practice. Methods: Twenty-two percent (216/984) of patients consecutively admitted for AHRF to our RW in Arezzo (years: 1996-2003) received NIV in addition to standard therapy, according to pre-defined routinely used criteria. Tolerance, effects upon arterial blood gases (ABG), success rate (avoidance a priori criteria for intubation) and predictors of failure of NIV were analysed. Results: Nine patients (4.2%) were found to be intolerant to NIV, while the remaining 207 (M: 157, F: 50; mean (SD) age: 73.2 (8.9) yrs; COPD: 71.5%) were ventilated for >1 hour. ABG significantly improved after two hours of NIV (pH: 7.32 (0.06) versus median (Interquartiles) 7.28 (7.24-7.31), p<0.0001; PaCO2: 71.9 (13.5) mmHg versus 80.0 (15.2) mmHg, p<0.0001; PaO2/FiO2: 212 (66) versus 184 (150-221), p<0.0001). NIV succeeded in avoiding intubation in 169/207 patients (81.6%) with hospital mortality of 15.5%. NIV failure was independently predicted by Activity of Daily Living score, pneumonia as cause of AHRF and Acute Physiology and Chronic Health Evaluation III score. Conclusions: In clinical practice NIV is feasible, effective in improving ABG and useful in avoiding intubation in most AHRF episodes that do not respond to the standard therapy managed in an RW adequately trained in NIV

Climate change effects on bread wheat phenology and grain quality: A case study in the north of Italy

Increasing temperatures, heat waves, and reduction of annual precipitation are all the expressions of climate change (CC), strongly affecting bread wheat (Triticum aestivum L.) grain yield in Southern Europe. Being temperature the major driving force of plants' phenological development, these variations also have effects on wheat phenology, with possible consequences on grain quality, and gluten protein accumulation. Here, through a case study in the Bolognese Plain (North of Italy), we assessed the effects of CC in the area, the impacts on bread wheat phenological development, and the consequences on grain gluten quality. The increasing trend in mean annual air temperature in the area since 1952 was significant, with a breakpoint identified in 1989, rising from 12.7 to 14.1°C, accompanied by the signals of increasing aridity, i.e., increase in water table depth. Bread wheat phenological development was compared in two 15-year periods before and after the breakpoint, i.e., 1952-1966 (past period), and 2006-2020 (present period), the latest characterized by aridity and increased temperatures. A significant shortening of the chronological time necessary to reach the main phenological phases was observed for the present period compared to the past period, finally shortening the whole life cycle. This reduction, as well as the higher temperature regime, affected gluten accumulation during the grain-filling process, as emerged analyzing gluten composition in grain samples of the same variety harvested in the area both before and after the breakpoint in temperature. In particular, the proportion of gluten polymers (i.e., gliadins, high and low molecular weight glutenins, and their ratio) showed a strong and significant correlation with cumulative growing degree days (CGDDs) accumulated during the grain filling. Higher CGDD values during the period, typical of CC in Southern Europe, accounting for higher temperature and faster grain filling, correlated with gliadins, high molecular weight glutenins, and their proportion with low molecular weight glutenins. In summary, herein reported, data might contribute to assessing the effects of CC on wheat phenology and quality, representing a tool for both predictive purposes and decision supporting systems for farmers, as well as can guide future breeding choices for varietal innovation

Reliability and inter-observer agreement of dermoscopic diagnosis of melanoma and melanocytic naevi

The aim of this study was to analyse the reliability and the inter- observer agreement of dermoscopy in the diagnosis of melanocytic skin lesions. Nine dermatologists, with a different training experience and who routinely used dermoscopy in different hospitals in Italy, evaluated clinical and dermoscopy photographs of 15 melanocytic lesions (four invasive melanomas, four histologically common naevi, and seven naevi with histological atypia). A further series of dermoscopic photographs of 40 melanocytic lesions was evaluated to quantify inter-observer concordance in recognizing dermoscopic criteria. Compared to the true (histological) diagnosis, clinical diagnosis (categories: melanoma, common naevus, atypical naevus) was correct in 40% of cases (range, 27-53%). The percentage raised to 55% (40-73%) by the use of dermoscopy, with an average improvement of 15.6%. Concerning melanoma, clinical diagnosis resulted in a sensitivity of 41.9%, specificity of 77.8%, positive predictive value (PPV) of 36.1%, negative predictive value (NPV) of 81.8%. By using dermoscopy, an improvement of diagnostic performance was found (sensitivity 75%, specificity 88.8%, VPP 71.0%, VPN 90.7%). The inter-observer agreement in melanoma diagnosis, by using dermoscopy, was similar to that obtained by clinical examination (k statistics = 0.54 and 0.52, respectively). Concerning dermoscopic criteria, the best agreement among observers was found for pseudopods, a dermoscopic parameter related to the radial growth phase of melanoma. We conclude that dermoscopy is an useful tool for a non-invasive diagnosis of melanocytic skin lesions, improving the diagnostic performance compared to clinical examination

Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer's Disease

With innumerable clinical failures of target-specific drug candidates for multifactorial diseases, such as Alzheimer's disease (AD), which remains inefficiently treated, the advent of multitarget drug discovery has brought a new breath of hope. Here, we disclose a class of 6-chlorotacrine (huprine)‒TPPU hybrids as dual inhibitors of the enzymes soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), a multitarget profile to provide cumulative effects against neuroinflammation and memory impairment. Computational studies confirmed the gorge-wide occupancy of both enzymes, from the main site to a secondary site, including a so far non-described AChE cryptic pocket. The lead compound displayed in vitro dual nanomolar potencies, adequate brain permeability, aqueous solubility, and human microsomal stability and lack of neurotoxicity, and rescued memory, synaptic plasticity and neuroinflammation in an AD mouse model, after low dose chronic oral administration

Estimation of traffic matrices for LRD traffic

The estimation of traffic matrices in a communications network on the basis of a set of traffic measurements on the network links is a well known problem, for which a number of solutions have been proposed when the traffic does not show dependence over time, as in the case of the Poisson process. However, extensive measurements campaigns conducted on IP networks have shown that the traffic exhibits long range dependence. Here two methods are proposed for the estimation of traffic matrices in the case of long range dependence, their asymptotic properties are studied, and their relative merits are compared

Definition and diagnostic criteria of sleep-related hypermotor epilepsy.

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis

Definition and diagnostic criteria of sleep-related hypermotor epilepsy

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis

Cooperative development of logical modelling standards and tools with CoLoMoTo.

The identification of large regulatory and signalling networks involved in the control of crucial cellular processes calls for proper modelling approaches. Indeed, models can help elucidate properties of these networks, understand their behaviour and provide (testable) predictions by performing in silico experiments. In this context, qualitative, logical frameworks have emerged as relevant approaches, as demonstrated by a growing number of published models, along with new methodologies and software tools. This productive activity now requires a concerted effort to ensure model reusability and interoperability between tools. Following an outline of the logical modelling framework, we present the most important achievements of the Consortium for Logical Models and Tools, along with future objectives. Our aim is to advertise this open community, which welcomes contributions from all researchers interested in logical modelling or in related mathematical and computational developments

In vivo myelin water quantification using diffusion–relaxation correlation MRI: A comparison of 1D and 2D methods

Multidimensional Magnetic Resonance Imaging (MRI) is a versatile tool for microstructure mapping. We use a diffusion weighted inversion recovery spin echo (DW-IR-SE) sequence with spiral readouts at ultra-strong gradients to acquire a rich diffusion–relaxation data set with sensitivity to myelin water. We reconstruct 1D and 2D spectra with a two-step convex optimization approach and investigate a variety of multidimensional MRI methods, including 1D multi-component relaxometry, 1D multi-component diffusometry, 2D relaxation correlation imaging, and 2D diffusion-relaxation correlation spectroscopic imaging (DR-CSI), in terms of their potential to quantify tissue microstructure, including the myelin water fraction (MWF). We observe a distinct spectral peak that we attribute to myelin water in multi-component T1 relaxometry, T1-T2 correlation, T1-D correlation, and T2-D correlation imaging. Due to lower achievable echo times compared to diffusometry, MWF maps from relaxometry have higher quality. Whilst 1D multi-component T1 data allows much faster myelin mapping, 2D approaches could offer unique insights into tissue microstructure and especially myelin diffusion