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Subterranean habitats around the world can shelter diversified and threatened faunal communities. However, issues related to alterations in the landscape and structure of subterranean habitats still need to be better understood. Therefore, we used a multi-spatial scale analysis of land cover, land use, and cave habitats to predict the diversity of communities of subterranean invertebrates. We hypothesized that changes in land cover promote alterations in both faunal richness and composition and microhabitat diversity and that microhabitat features determined subterranean biodiversity. Sixteen limestone caves were sampled in Brazil at micro, meso, and macro scales using quadrats (1m²), transects (100 meters) as sample units inside caves and buffers with the radius of 100 and 250 meters in the surroundings of the cave entrances. Models performed showed that land cover and land use influenced cave environments, regarding both microhabitats traits and terrestrial invertebrate richness and composition. We also observed a relationship between microhabitat structure and terrestrial invertebrate richness and composition. Our results showed that deforested areas had negative effects on species richness and changed their composition, while natural areas had positive effects on microhabitat diversity. The same effects were observed for both 100 and 250 meters buffers. Invertebrate richness was negatively predicted by deforested areas while positively predicted by natural areas. Richness was also positively predicted by the combination of all microhabitat traits, and dissimilarity of fauna was influenced by microhabitat diversity in mesoscale and microscale by all microhabitat elements. The results highlight the importance of the landscape surrounding the caves to conserve the subterranean habitats and their fauna. Due to the spatial and temporal changes in the global environmental scenario, we argue the urgency of further detailed studies in fragmented landscapes to define minimum areas of protection for cave environments.

Stem cell therapy is a promising treatment for the regeneration of myocardial tissue injured by an ischemic event. Mathematical modeling of myocardial regeneration via stem cell therapy is a challenging task, since the mechanisms underlying the processes involved in the treatment are not yet fully understood. Many aspects must be accounted for, such as the spread of stem cells and nutrients, chemoattraction, cell proliferation, stages of cell maturation, differentiation, angiogenesis, stochastic effects, just to name a few. In this paper we propose a 3D mathematical model with a free boundary that aims to provide a qualitative description of some main aspects of the stem cell regenerative therapy in a simplified scenario. The paper mainly focuses on the description of the shrinking of the necrotic core during treatment. The stem cell and nutrients dynamics are described through coupled reaction-diffusion problems. Proliferation, chemoattraction, tissue regeneration and nutrient consumption are included in the model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We sought to evaluate the additional value of left atrial appendage (LAA) 3D printing derived from computed tomography (CCT) in determining the size for LAA occlusion (LAAO) devices as compared to standard measurement by using occurrence of LAA leak as endpoint., Methods: We evaluated 6 patients with LAA leak (cases) and 14 matched patients without LAA leak (controls) after LAAO. For each group, a patient-specific 3D printed model of LAA was manufactured using CT pre-operative images. The size recommended by the 3D printed model was compared with the size of the implanted device., Results: Compared to the 3D printed model, 55% of the devices were underestimated, the two sizing approaches agreed in 35% of the patients, while the 3D printed model overestimated the size in 10% of patients. The prevalence of LAA leak was significantly higher in the subset of patients with underestimation of prosthesis implanted with the standard approach as compared to the other patients (p = 0.019)., Conclusion: 3D printing of the LAA may provide additional value to standard practice for LAAO device prosthesis sizing with the potential impact to reduce LAA leak., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this study was the characterization of the in vitro cytotoxic properties of a recently isolated diterpene compound, 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone (compound 1), extracted from Salvia corrugata, versus human cell lines., Main Methods: We used as model study immortalized breast epithelial cells MCF10A and two ERBB2 + breast cancer (BCa) cell lines, SKBR-3 and BT474. Compound 1 was isolated by methanolic extraction from regenerated shoots of Salvia corrugata Vahl, and purified by high pressure liquid chromatography (HPLC). Flow cytometry (FCM) was employed for cell cycle, apoptosis and reactive oxygen species (ROS) analysis. Cell morphology was assessed by immunofluorescence and transmission electron microscopy (TEM)., Key Findings: Compound 1 inhibited cell survival of all breast cell lines. In particular, compound 1 promoted cell cycle arrest in the G0/G1 phase and apoptosis along with impairment of the mitochondrial function, which was reflected in a gross alteration of the mitochondrial network structure. Furthermore, we also detected a potent activation of the ERK1/2 kinase, which suggested the induction of reactive oxygen species (ROS). Partial rescue of survival obtained with n-acetylcysteine (NAC) when coadminstered with compound 1 further supported a contribution of ROS mediated mechanisms to the growth-arrest and proapoptotic activity of compound 1 in both BCa cell lines. ROS production was indeed confirmed in SKBR-3., Significance: Our findings show that compound 1 has a cytotoxic activity against both human normal and cancer cell lines derived from breast epithelia, which is mediated by ROS generation and mitochondrial damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Thoracic endovascular repair (TEVAR) is currently considered the therapy of choice for complicated type B acute aortic dissection (TBAAD). Although several papers have reported good outcomes at short- and medium-term follow-up, some questions still remain regarding the long-term durability and re-intervention rate during follow-up., Methods: We describe a case of a patient originally treated with TEVAR for TBAAD complicated by impending aortic rupture., Results: Endovascular repair successfully excluded the flow through the primary entry tear but during the 12-year follow-up period the patient experienced several complications and re-interventions. Various full-size three-dimensional (3D) models of the patient-specific vasculature were printed to better explain the different interventional interventions over the 12 years of follow-up and as a hands-on tool for medical education., Conclusions: The present case report, involving long-term follow-up, provides an example of the effectiveness and the safety of TEVAR for the treatment of complicated TBAAD shown at short and medium-term follow-up. However, the long-term complications that were observed in this patient during follow-up support the importance of lifelong CTA surveillance. Furthermore, this study confirms the capability of 3D printing technology as a powerful tool to support communication with patients and residents' education through the physical analysis of the real cases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Aims: Perception of quality of care is important in the management of patients with chronic diseases, particularly inflammatory bowel disease., Aims and Methods: This longitudinal study aimed to investigate variations of the Quality of Care through the Patients' Eyes (QUOTE-IBD) questionnaire scores one year after the basal evaluation in the Studio Osservazionale quaLità cUre malatTIe crOniche intestiNali (SOLUTION-1) study., Results: Of the cohort of 992 patients, 936 were evaluable. The QUOTE-IBD score overcame satisfactory levels of more than the 80%, overall and in all subdomains except for the "Continuity of Care" sub-dimension (mean, 8.3; standard deviation, 1.49), scored satisfactory only by 34% of the patients. No significant changes in satisfaction were recorded overall, or considering patients subgroups. Significant differences were found at the end of the follow-up between physicians' and patients' perceptions of quality of care, with the former over-rating their performance in "Continuity of Cares" and under-rating "Costs", "Competence", and "Accessibility" sub-domains of the score (p<0.05 for all)., Conclusion: Perceived quality of care in a large cohort of Italian patients with inflammatory bowel disease remains unchanged after one-year follow-up and was not significantly affected by disease activity or therapeutic interventions. Differences between physicians' and patients' perceptions of quality of care should be taken into account., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In order to assess if an extra virgin olive oil (EVOO) can be acknowledged with the health claim related to olive oil polyphenols (Reg. EU n.432/2012), a new method to quantify these species in EVOO, by means of liquid-liquid extraction followed by HPLC-DAD/MS/MS of the hydroalcoholic extract, has been developed and validated. Different extraction procedures, different types of reverse-phase analytical columns (Synergi Polar, Spherisorb ODS2 and Kinetex) and eluents have been tested. The chromatographic column Synergi Polar (250×4.6mm, 4μm), never used before in this kind of application, provided the best results, with water and methanol/isopropanol (9/1) as eluents. The method allows the quantification of the phenolic alcohols tyrosol and hydroxytyrosol, the phenolic acids vanillic, p-coumaric and ferulic acids, secoiridoids derivatives, the lignans, pinoresinol and acetoxypinoresinol and the flavonoids luteolin and apigenin. The new method has been applied to 20 commercial EVOOs belonging to two different price range categories (3.78-5.80 euros/L and 9.5-25.80 euros/L) and 5 olive oils. The obtained results highlight that acetoxypinoresinol, ferulic acid, vanillic acid and the total non secoiridoid phenolic substances resulted to be significantly higher in HEVOOs than in LEVOOs (P=0.0026, 0.0217, 0.0092, 0.0003 respectively). For most of the samples analysed there is excellent agreement between the results obtained by applying the HPLC method adopted by the International Olive Council and the results obtained by applying the presented HPLC method. Results obtained by HPLC methods have been also compared with the ones obtained by the colorimetric Folin-Ciocalteu method., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We assessed whether polymers of N-acetylglucosamine (GlcNAc) have any pathogenetic role in Alzheimer's disease (AD). First, by using specific dyes, we found deposits of polymers of GlcNAc in sporadic but not in familial AD. We found that neurons and microglia exposed to GlcNAc and uridine diphosphate (UDP)-GlcNAc are able to form GlcNAc polymers, which display a significant neurotoxicity in vitro. Moreover, the exposure of organotypic hippocampal cultures to the same compounds led to synaptic impairment with decreased levels of syntaxin and synaptophysin. In addition, acute hippocampal slices treated with GlcNAc/UDP-GlcNAc showed a clear reduction of long-term potentiation of excitatory synapses. Finally, we demonstrated that microglial cells are able to phagocytose chitin particles and, when exposed to GlcNAc/UDP-GlcNAc, show cellular activation and intracellular deposition of GlcNAc polymers that are eventually released in the extracellular space. Taken together, our results indicate that both microglia and neurons produce GlcNAc polymers, which trigger neurotoxicity both directly and through microglia activation. GlcNAc polymer-driven neurotoxicity offers novel pathogenic insights in sporadic AD and new therapeutic options., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background Aims: Adipose-derived mesenchymal stromal cells (ASC) are known to promote neuroprotection and neuroregeneration in vitro and in vivo. These biological effects are probably mediated by paracrine mechanisms. In recent years, nanovesicles (NV) and microvesicles (MV) have been shown to play a major role in cell-to-cell communication. We tested the efficacy of NV and MV obtained from ASC in mediating neuroprotection and neuroregeneration in vitro., Methods: We exposed neuronal cells (both cell line and primary cultures) to oxidative stress in the presence or not of NV or MV., Results: In this experimental setting, we found that low doses of NV or MV protected neurons from apoptotic cell death. We then assessed the neuroregenerative effect of NV/MV in cerebellar slice cultures demyelinated with lysophosphatidylcholine. We observed that low but not higher doses of NV and MV increased the process of remyelination and activated nestin-positive oligodendroglial precursors., Conclusions: Taken together, our data in vitro support the relevance of ASC vesicles as a source of protecting and regenerating factors that might modulate the microenvironment in neuro-inflammatory as well as in neurodegenerative disorders. The present findings may suggest that stromal cell-derived vesicles might represent a potential therapeutic tool, enabling the safe administration of stromal cell effector factors, avoiding the cellular counterpart., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Traditional surgical repair of ascending aortic pseudoaneurysm is complex, technically challenging, and associated with significant mortality. Although new minimally invasive procedures are rapidly arising thanks to the innovations in catheter-based technologies, the endovascular repair of the ascending aorta is still limited because of the related anatomical challenges. In this context, the integration of the clinical considerations with dedicated bioengineering analysis, combining the vascular features and the prosthesis design, might be helpful to plan the procedure and predict its outcome. Moving from such considerations, in the present study we describe the use of a custom-made stent-graft to perform a fully endovascular repair of an asymptomatic ascending aortic pseudoaneurysm in a patient, who was a poor candidate for open surgery. We also discuss the possible contribution of a dedicated medical images analysis and patient-specific simulation as support to procedure planning. In particular, we have compared the simulation prediction based on pre-operative images with post-operative outcomes. The agreement between the computer-based analysis and reality encourages the use of the proposed approach for a careful planning of the treatment strategy and for an appropriate patient selection, aimed at achieving successful outcomes for endovascular treatment of ascending aortic pseudoaneurysms as well as other aortic diseases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report a female patient with ichthyosis, epilepsy, mental retardation, hypergonadotrophic hypogonadism, polyneuropathy, and cranial dysmorphisms. This clinical picture may satisfy the main diagnostic criteria that characterize Rud syndrome (RS), a rare neurocutaneous disease. The patient underwent extensive clinical evaluation, neurophysiological studies (wakefulness and sleep EEG, EMG), dermatological and endocrinological evaluation and neuroimaging study (3 Tesla brain MRI). Interestingly, brain MRI unveiled a malformation of cortical development, never reported previously in RS. Although seizure semiology and EEG features could not provide clear cut information suggesting a focal onset, the role of this MRI finding in the genesis of the epileptic seizures cannot be ruled out. The finding of a focal cortical dysplasia in RS might be related to genetic abnormalities affecting the development of both epidermis and neural structures with the same embryological origin., (Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Steroids, the mainstay of Crohn's disease treatment, have been associated with systemic side effects., Aim: To evaluate the efficacy and tolerability of beclomethasone dipropionate for maintaining remission induced by a short course of systemic steroids in patients with Crohn's ileitis with or without right colonic involvement., Methods: Patients (n=84) with active Crohn's disease who achieved remission during a 2-week prednisone run-in period were randomised to receive beclomethasone dipropionate for 24 weeks or continue prednisone for a further 2 weeks followed by placebo for 22 weeks. The primary outcome was relapse rate (Crohn's Disease Activity Index score>150 and an increase of ≥60 points from baseline) or withdrawal due to disease deterioration., Results: The relapse rate was 23.3% and 53.8% in beclomethasone dipropionate and placebo groups, respectively (p=0.027). According to Kaplan-Meier analysis, the cumulative relapse rate was 38.0% in the beclomethasone dipropionate group and 56.0% in the placebo group (p=0.025). Six percent and 1.7% of all adverse events in the beclomethasone dipropionate and placebo groups, respectively, were endocrine-related., Conclusion: These results demonstrate that beclomethasone dipropionate significantly reduces the relapse rate in post-active Crohn's ileitis patients compared with placebo after induction of remission with a short course of systemic steroids, and is well tolerated., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Botulinum neurotoxins (BoNTs) are among the most toxic substances known. Surveillance and diagnostics require methods for rapid detection of BoNTs in complex media such as foodstuffs and human serum. We have developed in vitro assays to specifically detect the protease activity of botulinum neurotoxin B (BoNT/B) on a time scale of minutes. Cleavage of the BoNT/B substrate VAMP2, a membrane SNARE protein associated with synaptic vesicles, was monitored using real-time surface plasmon resonance to measure vesicle capture by specific antibodies coupled to microchips. The assay is functional in low-ionic-strength buffers and stable over a wide range of pH values (5.5-9.0). Endoproteolytic cleavage of VAMP2 was detected in 10 min with 2 pM native BoNT/B holotoxin. Contamination of liquid food products such as carrot juice, apple juice, and milk with low picomolar amounts of BoNT/B was revealed within 3h. BoNT/B activity was detected in sera from patients with type B botulism but not in healthy controls or patients with other neurological diseases. This robust, sensitive, and rapid protein chip assay is appropriate for monitoring BoNT/B in food products and diagnostic tests for type B botulism and could replace the current in vivo mouse bioassay., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: The recent authorization and commercialization in the USA of a "Zoster vaccine" with high antigenic titer opens interesting perspectives of prevention against herpes zoster (HZ). This disease is characterized by a vesicular rash with dermatomeric extension and by moderate to severe pain. Many patients present with post-herpetic neuralgia. In Italy, complete and recent epidemiological data are not available., Patients and Methods: We evaluated the epidemiological features of patients presenting with HZ observed at the Ferrara University Dermatology unit from 2000 to 2008. The following data were collected: gender, age, residence, date and place of consultation, localization, and therapy., Results: The place of consultation was often (43%) not specified; in the remaining 57% of cases, patients were sent from general and ophthalmology emergency rooms. The most frequent localizations were: 32% ophthalmic; 16.5% thoracic; 16% facial. Most patients were treated with oral antiviral drugs for seven days. According to localization and severity, topical or oral antibiotics, analgesics, neurotrophic drugs were prescribed., Conclusions: This data, although not representative of all cases in the province of Ferrara, confirmed the epidemiological impact of Zoster, which brings a number of patients to use the hospital and specialized structures for diagnosis and cure., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)