Post‐earthquake estimates of different ground motion intensity measures for the 2012 Emilia earthquake

Estimates of the earthquake ground motion intensity over a geographical area have multiple uses, that is, emergency management, civil protection and seismic fragility assessment. In particular, with reference to fragility assessment, it is of interest to have estimates of the values of different ground-motion intensity measures in order to correlate them with the observed damage. To this purpose, the present paper uses a procedure recently proposed in the literature to estimate the ground-motion intensity for the 2012 Emilia mainshocks, considering different groundmotion intensity measures and directionality effects. Groundmotion prediction equations based on different site effect models, and spatial correlation models are calibrated for the Emilia earthquakes. The paper discusses the accuracy of the shakemaps obtained using the different soil effect models considered and presents the obtained shakemaps as supplementary material. The procedure presented in the paper is aimed at providing ground motion intensity values for seismic fragility assessment and is not intended as a tool to estimate shakemaps for rapid emergency assessment

Tenebrio molitor as a Simple and Cheap Preclinical Pharmacokinetic and Toxicity Model

The progression of drugs into clinical phases requires proper toxicity assessment in animals and the correct identification of possible metabolites. Accordingly, different animal models are used to preliminarily evaluate toxicity and biotransformations. Rodents are the most common models used to preliminarily evaluate the safety of drugs; however, their use is subject to ethical consideration and elevated costs, and strictly regulated by national legislations. Herein, we developed a novel, cheap and convenient toxicity model using Tenebrio molitor coleoptera (TMC). A panel of 15 drugs-including antivirals and antibacterials-with different therapeutic applications was administered to TMC and the LD50 was determined. The values are comparable with those already determined in mice and rats. In addition, a TMC model was used to determine the presence of the main metabolites and in vivo pharmacokinetics (PK), and results were compared with those available from in vitro assays and the literature. Taken together, our results demonstrate that TMC can be used as a novel and convenient preliminary toxicity model to preliminarily evaluate the safety of experimental compounds and the formation of main metabolites, and to reduce the costs and number of rodents, according to 3R principles

Biomarkers of Alzheimer's Disease: From Central Nervous System to Periphery?

Alzheimer's Disease (AD) is the most frequent form of dementia and represents one of the main causes of disability among older subjects. Up to now, the diagnosis of AD has been made according to clinical criteria. However, the use of such criteria does not allow an early diagnosis, as pathological alterations may be apparent many years before the clear-cut clinical picture. An early diagnosis is even more valuable to develop new treatments, potentially interfering with the pathogenetic process. During the last decade, several neuroimaging and cerebrospinal fluid (CSF) parameters have been introduced to allow an early and accurate detection of AD patients, and, recently, they have been included among research criteria for AD diagnosis. However, their use in clinical practice suffers from limitations both in accuracy and availability. The increasing amount of knowledge about peripheral biomarkers will possibly allow the future identification of reliable and easily available diagnostic tests

Use and Propensity to Use Substances as Cognitive Enhancers in Italian Medical Students

International media has paid attention to the use of substances by healthy subjects to enhance cognitive performance. Medical students are liable to use cognitive enhancers (CE) with the aim of improving academic performance. The study explored use and attitudes toward the use of CE in Italian medical students. The authors anonymously surveyed 433 medical students of the University of Modena and Reggio Emilia with an ad hoc 36-items questionnaire. CE were broadly defined as any substance taken with the purpose of improving cognitive functions, from readily available beverages and substances, such as coffee, tea, energy drinks, and supplements to prescription only medication, such as psychostimulants and modafinil. Response rate was 83.8% (n = 363). While the majority of the students (74.7%; n = 271) said that they had used substances to improvecognitivefunctions,only2students(0.6%)reportedtheuseofprescription-onlymedications in the last 30 days. Main reasons for not taking prescription-only drugs were concerns about safety and side effects, reported by 83.3% of students (n = 295). A positive attitude toward use was held by 60.3% (n = 219) subjects. The surveyed Italian medical students used many substances as CE, but this did not seem to apply significantly to psychostimulants. A multivariable analysis showed that the followingvariableswererelatedtothepropensitytousesubstancesasCE:malegender,self-reported memory impairment, concerns about worsening of cognitive performance, lifetime use of at least one illegal substance, use of any substance (both legal or illegal) in the last 30 days

Soil ecosystem functions in a high-density olive orchard managed by different soil conservation practices

The long-term effects of two different soil management practices, natural grass cover (NC) and conservation tillage (CT), on soil functions (carbon sequestration, habitat for organisms, and water movement and retention) were determined in a high-density, mature olive orchard (Olea europaea L. cv. Frantoio) growing in a sandy loam soil (Typic Haploxeralf) in a Mediterranean environment. Ten years after the beginning of the different soil management, soil samples were collected at 0–10 and 10–20 cm depth and at two distances from the trunk, underneath the olive canopy (UC) and in the inter-row (IR). There were no differences in fruit yield, oil yield, and yield efficiency between the two soil management systems during the 2011–2013 period. CT negatively affected soil organic carbon pools (total and humified), but only at the IR position. The distance from the plant did not significantly influence soil structure and hydrological properties, while NC treatment increased water movement and retention. Tillage reduced the microarthropod abundance, in particular Collembola and eu-edaphic forms, which were the most sensitive groups to soil perturbation. We conclude that natural grass cover was more effective than conservation tillage in maintaining or improving elements of soil functionality

Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation

Background: Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active players of the disease. Besides the cholinesterase mainstay, the multifaceted interplay between nicotinic receptors and amyloid is actually considered to have a central role in neuroprotection. Thus, the multitarget drug-design strategy has emerged as a chance to face the disease network. Results: By exploiting the multitarget approach, the present study provides new molecules able to target the cholinergic pathway, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit Aβ aggregation. Conclusions: These new compounds emerged as a suitable starting point for a further optimization process

Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD

Short-Term Exposure to Bisphenol A Does Not Impact Gonadal Cell Steroidogenesis In Vitro

: Bisphenol A (BPA) is a ubiquitous, synthetic chemical proven to induce reproductive disorders in both men and women. The available studies investigated the effects of BPA on male and female steroidogenesis following long-term exposure to the compound at relatively high environmental concentrations. However, the impact of short-term exposure to BPA on reproduction is poorly studied. We evaluated if 8 and 24 h exposure to 1 nM and 1 µM BPA perturbs luteinizing hormone/choriogonadotropin (LH/hCG)-mediated signalling in two steroidogenic cell models, i.e., the mouse tumour Leydig cell line mLTC1, and human primary granulosa lutein cells (hGLC). Cell signalling studies were performed using a homogeneous time-resolved fluorescence (HTRF) assay and Western blotting, while gene expression analysis was carried out using real-time PCR. Immunostainings and an immunoassay were used for intracellular protein expression and steroidogenesis analyses, respectively. The presence of BPA leads to no significant changes in gonadotropin-induced cAMP accumulation, alongside phosphorylation of downstream molecules, such as ERK1/2, CREB and p38 MAPK, in both the cell models. BPA did not impact STARD1, CYP11A1 and CYP19A1 gene expression in hGLC, nor Stard1 and Cyp17a1 expression in mLTC1 treated with LH/hCG. Additionally, the StAR protein expression was unchanged upon exposure to BPA. Progesterone and oestradiol levels in the culture medium, measured by hGLC, as well as the testosterone and progesterone levels in the culture medium, measured by mLTC1, did not change in the presence of BPA combined with LH/hCG. These data suggest that short-term exposure to environmental concentrations of BPA does not compromise the LH/hCG-induced steroidogenic potential of either human granulosa or mouse Leydig cells

Benralizumab in Patients With Severe Eosinophilic Asthma With and Without Chronic Rhinosinusitis With Nasal Polyps: An ANANKE Study post-hoc Analysis

Background: Severe eosinophilic asthma (SEA) in the presence of chronic rhinosinusitis with nasal polyps (CRSwNP) indicates the presence of a more extensive eosinophilic inflammation. Post-hoc analyses from a pivotal clinical trial have demonstrated the enhanced efficacy of benralizumab on asthma outcomes in patients with CRSwNP as a comorbidity. Methods: This is a post-hoc analysis from the Italian multi-center observational retrospective ANANKE study. Patients were divided into two groups based on self-reported CRSwNP. Baseline clinical and laboratory features in the 12 months prior to benralizumab prescription were collected. Data of change over time of blood eosinophils, annualized exacerbations rates (AER), asthma control, lung function, oral corticosteroids (OCS) use, and benralizumab discontinuation were collected during the observation period. Results: At baseline, the 110 patients with CRSwNP were less frequently female (50.9% vs 74.2%) and obese (9.1% vs. 22.6%) with higher eosinophils (605 vs. 500 cells/mm3) and OCS use when compared to patients without CRSwNP. Similar reductions of AER were seen (-95.8% vs. -91.5% for any exacerbation and -99.1% vs. -92.2% for severe exacerbations in patients with and without CRSwNP, respectively). During benralizumab treatment, comorbid SEA+CRSwNP was associated with a lower risk of any exacerbation (p = 0.0017) and severe exacerbations (p = 0.025). After a mean ± SD exposure of 10.3 ± 5.0 months, half of the SEA+CRSwNP patients eliminated OCS use. No discontinuation for safety reasons was recorded. Conclusions: This study helped to confirm the baseline clinical features that distinguish patients with and without CRSwNP being prescribed benralizumab. Numerically enhanced OCS reduction and lower exacerbation risk were observed in patients with SEA and comorbid CRSwNP treated with benralizumab