Aurea diagnosis of pneumomediastinum. A case report

Pericarditis and spontaneous pneumomediastinum are among the pathologies that are in differential diagnoses when a patient describes dorsal irradiated chest pain: if the patient is young, male, and long-limbed, it is necessary to exclude an acute aortic syndrome firstly. We present the case of a young man who arrived at the Emergency Department for chest pain: an echocardiogram performed an immediate diagnosis of pericarditis. However, if the patient had performed a chest X-ray, this would have enabled the observation of pneumomediastinum, allowing a correct diagnosis of pneumomediastinum and treatment. The purpose of this report is to highlight the importance of the diagnostic process

Free and poly-methyl-methacrylate-bounded BODIPYs: photodynamic and antimigratory effects in 2D and 3D cancer models

Several limitations, including dark toxicity, reduced tumor tissue selectivity, low photostability and poor biocompatibility hamper the clinical use of Photodynamic therapy (PDT) in cancer treatment. To overcome these limitations, new PSs have been synthetized, and often combined with drug delivery systems, to improve selectivity and reduce toxicity. In this context, BODIPYs (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) have recently emerged as promising and easy-to-handle scaffolds for the preparation of effective PDT antitumor agents. In this study, the anticancer photodynamic effect of newly prepared negatively charged polymethyl methacrylate (nPMMA)-bounded BODIPYs (3@nPMMA and 6@nPMMA) was evaluated on a panel of 2D- and 3D-cultured cancer cell lines and compared with free BODIPYs. In particular, the effect on cell viability was evaluated, along with their ability to accumulate into the cells, induce apoptotic and/or necrotic cell death, and inhibit cellular migration. Our results indicated that 3@nPMMA and 6@nPMMA reduce cancer cell viability in 3D models of HC116 and MCF7 cells more effectively than the corresponding free compounds. Importantly, we demonstrated that MDA-MB231 and SKOV3 cell migration ability was significantly impaired by the PDT treatment mediated by 3@nPMMA and 6@nPMMA nanoparticles, likely indicating the capability of this approach to reduce metastatic tumor potential

Rapidly fatal West Nile virus meningoencephalitis in an immunocompetent patient: a case report

Abstract Background West Nile virus (WNV) is a Flaviviridae most often transmitted by mosquitos. Clinical manifestations vary from no symptoms to neuroinvasive disease. Mortality is rare, but patients with neuroinvasive disease have a fatality rate of 4-14%. Diagnosis is made on epidemiological, clinical and serological criteria. Treatment is based on symptomatic and support therapy. WNV neuroinvasive disease seems associated to advancing age and diabetes, but poor prognosis risk factors are still not clearly recognized. During 2017-2018 10 patients affected by WNV infection were admitted to our Hospital (Policlinico of Modena): 3 patients had a rapid fatal outcome and 3 needed intensive care transfer. We report the most representative case. Case Report A 81-yr-old man from Emilia-Romagna was admitted to our unit with a 6 days history of fever (>38℃), fatigue, nausea, vomiting, hiccough and mild cognitive impairment treated with amoxicillin. Past medical history: type 2 diabetes mellitus, arterial hypertension, permanent pacemaker for type 3 atrioventricular block. Referred exposure to farm animals. No recent travels abroad. Chest x-ray showed a retrocardiac opacity, so empiric levofloxacin was started for suspected community acquired pneumonia. After two days the patient began lethargic with a Glasgow Come Score < 8. Neuroinvasive WNV disease was confirmed by electroencephalogram and rachicentesis. Before serologic results acyclovir and dexamethasone were initiated without benefit and patient diedon the fifth day after admission. Conclusions Risk factors for poor prognosis related to WNV Infection are still not clearly identified. Our patient underwent unexpected rapid clinical deterioration before invasive treatment could positively affect prognosis. This underlines the importance of clinical alert to WNV infections during transmission season in endemic areas and the necessity of more data on fatal WNV cases to define criteria to promptly recognize high-risk patients. Keywords encephalitis; meningoencephalitis; neuroinvasive disease; West Nile virus; fatal meningoencephalitis

Renal infarction as an uncommon cause of abdominal pain. A case report

Renal infarction is a rare cause of abdominal pain whose diagnosis is often misunderstood or severely delayed. The difficulty in identifying this time-dependent condition greatly limits the possibilities of therapeutic intervention and determines the loss of renal parenchyma that could have been saved with prompt diagnosis. It is, therefore, essential to include renal infarction in the differential diagnosis in case of abdominal pain and to identify this pathology beforehand. We present a case of a 65-yearold male with atrial fibrillation in therapy with Edoxaban who was admitted to the hospital for acute onset of widespread abdominal pain with nausea, vomit, and a worsening of renal function according to the laboratory tests. An abdominal computed tomography with contrast confirmed the presence of a bilateral renal infarction. The patient developed chronic kidney disease and was discharged on anticoagulant therapy. The aim of this paper is, therefore, to increase physician awareness towards this condition, the best opportunity to diagnose early renal infarction and to establish acute and long-term therapy

Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component of the green alga Caulerpa cylindracea that has invaded the entire Mediterranean basin—is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays. On the basis of these results, we candidate CAU as a causal factor of the metabolic and behavioural disorders observed in Diplodus sargus, a native edible fish of high ecological and commercial relevance, feeding on C. cylindracea. Moreover, given the considerable interest in PPAR activators for the treatment of relevant human diseases, our findings are also discussed in terms of a possible nutraceutical/pharmacological valorisation of the invasive algal biomasses, supporting an innovative strategy for conserving biodiversity as an alternative to unrealistic campaigns for the eradication of invasive pest

Mesenchymal stromal cell: new applications for regenerative medicine

In the last decades mesenchymal stromal cells (MSC), intriguing for their multilineage plasticity and their proliferation activity in vitro, have been intensively studied for innovative therapeutic applications. In the first project, a new method to expand in vitro adipose derived-MSC (ASC) while maintaining their progenitor properties have been investigated. ASC are cultured in the same flask for 28 days in order to allow cell-extracellular matrix and cell-cell interactions and to mimic in vivo niche. ASC cultured with this method (Unpass cells) were compared with ASC cultured under classic condition (Pass cells). Unpass and Pass cells were characterized in terms of clonogenicity, proliferation, stemness gene expression, differentiation in vitro and in vivo and results obtained showed that Unpass cells preserve their stemness and phenotypic properties suggesting a fundamental role of the niche in the maintenance of ASC progenitor features. Our data suggests alternative culture conditions for the expansion of ASC ex vivo which could increase the performance of ASC in regenerative applications. In vivo MSC tracking is essential in order to assess their homing and migration. Super-paramagnetic iron oxide nanoparticles (SPION) have been used to track MSC in vivo due to their biocompatibility and traceability by MRI. In the second project a new generation of magnetic nanoparticles (MNP) used to label MSC were tested. These MNP have been functionalized with hyperbranched poly(epsilon-lysine)dendrons (G3CB) in order to interact with membrane glycocalix of the cells avoiding their internalization and preventing any cytotoxic effects. In literature it is reported that labeling of MSC with SPION takes long time of incubation. In our experiments after 15min of incubation with G3CB-MNP more then 80% of MSC were labeled. The data obtained from cytotoxic, proliferation and differentiation assay showed that labeling does not affect MSC properties suggesting a potential application of G3CB nano-particles in regenerative medicine

In vitro quantitative analysis of mesenchymal stromal cells migration towards tumours

Analysis of in vitro migration of cell populations plays a key role in studying a wide range of dynamic cell behaviours. Cell migration is dependent on a multitude of signals ranging from growth factors to chemokines secreted by injured cells and/or respondent immune cells. In the last decade, several studies were addressed to investigate tropism of Mesenchymal Stromal Cells (MSC) for some types of cancers. Understanding the factors involved in regulating MSC migration towards tumours is essential to ultimately develop novel clinical strategies aiming at using MSC as vehicles to deliver antitumor drugs. However, the mechanism behind MSC migration is still in its infancy, and the main cause is the lack of quantitative methods to analyse the MSC motion. The analysis of objects motion relies on image-based tracking techniques and several methods have been recently proposed to track cells in vitro. However the vast majority of them are limited to fluorescently labelled cells. Very few tracking tools can analyze images taken using label-free microscopy techniques (e.g. phase contrast), that do not compromise the biological status of the cell and are the most common ways to observe living cells. However, to accurately track irregular-shaped, flat, and poor contrasted cells, such as MSC observed in phase-contrast, is really challenging. Furthermore, the majority of the tracking tools require relevant image processing skills, which strongly limits their practical usefulness within the biologist community. User-friendly and versatile open source software with track editing possibilities would boost live cell analysis research. In this work we introduced CellTracker, a user-friendly open-source software tool for tracking cells, including MSC. CellTracker is freely available at: http://celltracker.website/ and it works with Windows, Macintosh, and UNIX-based systems. By using CellTracker and \u3bc-Slide Chemotaxis2D (IBIDI, Madison, Wisconsin, USA) we performed experiments to analyse the motility of MSC when seeded near to cancer cells, simply seeding MSC in a chamber communicating to another one containing conditioned medium from MG-63 osteosarcoma cells. As negative and chemotaxis controls, we used respectively fresh culture medium and culture medium supplemented with serum. From the CellTracker analysis we could not detect any significant change in MSC motility towards the culture medium with or without serum, whereas a different behaviour was observed by using culture conditioned medium taken from flasks previously containing MG-63 cells. We can therefore argue that MSC migration towards tumour cells is mediated by the presence of specific proteins (e.g. chemokines) secreted by cancer cells in the culture medium. These preliminary results pave the way for future applications such as the possibility to develop hybrid disposable diagnostic devices where biological fluids (e.g. blood) sampled from the area of interest are analysed by using the MSC motility as a cancer sensor

Rapid and efficient magnetization of mesenchymal stem cells by dendrimer-functionalized magnetic nanoparticles

Rapid and efficient magnetization of human bone marrow stromal cells (BMSC) through functionalized magnetic nanoparticles (MNP).; MNP were functionalized with poly(epsilon-lysine) dendrons exposing carboxybetaine residue (CB-MNP) to enhance binding to the cellular glycocalix. BMSC were incubated with CB-MNP or non-functionalized PAA-MNP for 5-30 min in suspension.; CB-MNP functionalization increased the magnetization efficiency by threefold. Remarkably, 66% of cells were magnetized after only 5 min and the maximum efficiency of >80% was reached by 15 min. BMSC viability, proliferation and differentiation were not impaired: actually, adipogenic and osteogenic differentiation were even improved.; Carboxybetaine-dendron functionalization ensured rapid and efficient BMSC magnetization and allowed innovative suspension labeling, with a potential for bypassing adhesion culture of progenitors for regenerative medicine

Co-Density Distribution Maps for Advanced Molecule Colocalization and Co-Distribution Analysis

Cellular and subcellular spatial colocalization of structures and molecules in biological specimens is an important indicator of their co-compartmentalization and interaction. Presently, colocalization in biomedical images is addressed with visual inspection and quantified by co-occurrence and correlation coefficients. However, such measures alone cannot capture the complexity of the interactions, which does not limit itself to signal intensity. On top of the previously developed density distribution maps (DDMs), here, we present a method for advancing current colocalization analysis by introducing co-density distribution maps (cDDMs), which, uniquely, provide information about molecules absolute and relative position and local abundance. We exemplify the benefits of our method by developing cDDMs-integrated pipelines for the analysis of molecules pairs co-distribution in three different real-case image datasets. First, cDDMs are shown to be indicators of colocalization and degree, able to increase the reliability of correlation coefficients currently used to detect the presence of colocalization. In addition, they provide a simultaneously visual and quantitative support, which opens for new investigation paths and biomedical considerations. Finally, thanks to the coDDMaker software we developed, cDDMs become an enabling tool for the quasi real time monitoring of experiments and a potential improvement for a large number of biomedical studies