A 3D mathematical model of coupled stem cell-nutrient dynamics in myocardial regeneration therapy.

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.

Photo thermal effect graphene detector featuring 105 Gbit s-1 NRZ and 120 Gbit s-1 PAM4 direct detection.

One of the main challenges of next generation optical communication is to increase the available bandwidth while reducing the size, cost and power consumption of photonic integrated circuits. Graphene has been recently proposed to be integrated with silicon photonics to meet these goals because of its high mobility, fast carrier dynamics and ultra-broadband optical properties. We focus on graphene photodetectors for high speed datacom and telecom applications based on the photo-thermo-electric effect, allowing for direct optical power to voltage conversion, zero dark current, and ultra-fast operation. We report on a chemical vapour deposition graphene photodetector based on the photo-thermoelectric effect, integrated on a silicon waveguide, providing frequency response >65 GHz and optimized to be interfaced to a 50 Ω voltage amplifier for direct voltage amplification. We demonstrate a system test leading to direct detection of 105 Gbit s-1 non-return to zero and 120 Gbit s-1 4-level pulse amplitude modulation optical signals.

Toward the improvement of 3D-printed vessels' anatomical models for robotic surgery training.

Multi-Detector Computed Tomography is nowadays the gold standard for the pre-operative imaging for several surgical interventions, thanks to its excellent morphological definition. As for vascular structures, only the blood flowing inside vessels can be highlighted, while vessels' wall remains mostly invisible. Image segmentation and three-dimensional-printing technology can be used to create physical replica of patient-specific anatomy, to be used for the training of novice surgeons in robotic surgery. To this aim, it is fundamental that the model correctly resembles the morphological properties of the structure of interest, especially concerning vessels on which crucial operations are performed during the intervention. To reach the goal, vessels' actual size must be restored, including information on their wall. Starting from the correlation between vessels' lumen diameter and their wall thickness, we developed a semi-automatic approach to compute the local vessels' wall, bringing the vascular structures as close as possible to their actual size. The optimized virtual models are suitable for manufacturing by means of three-dimensional-printing technology to build patient-specific phantoms for the surgical simulation of robotic abdominal interventions. The proposed approach can effectively lead to the generation of vascular models of optimized thickness wall. The feasibility of the approach is also tested on a selection of clinical cases in abdominal surgery, on which the robotic surgery is performed on the three-dimensional-printed replica before the actual intervention.

New frontiers and emerging applications of 3D printing in ENT surgery: a systematic review of the literature.

3D printing systems have revolutionised prototyping in the industrial field by lowering production time from days to hours and costs from thousands to just a few dollars. Today, 3D printers are no more confined to prototyping, but are increasingly employed in medical disciplines with fascinating results, even in many aspects of otorhinolaryngology. All publications on ENT surgery, sourced through updated electronic databases (PubMed, MEDLINE, EMBASE) and published up to March 2017, were examined according to PRISMA guidelines. Overall, 121 studies fulfilled specific inclusion criteria and were included in our systematic review. Studies were classified according to the specific field of application (otologic, rhinologic, head and neck) and area of interest (surgical and preclinical education, customised surgical planning, tissue engineering and implantable prosthesis). Technological aspects, clinical implications and limits of 3D printing processes are discussed focusing on current benefits and future perspectives.

From CT scanning to 3D printing technology: a new method for the preoperative planning of a transcutaneous bone-conduction hearing device.

SUMMARY: The aim of the present study was to assess the feasibility and utility of 3D printing technology in surgical planning of a transcutaneous bone-conduction hearing device (Bonebridge®) (BB), focusing on the identification of the proper location and placement of the transducer. 3D printed (3DP) models of three human cadaveric temporal bones, previously submitted to CT scan, were created with the representation of a topographic bone thickness map and the sinus pathway on the outer surface. The 3DP model was used to detect the most suitable location for the BB. A 3DP transparent mask that faithfully reproduced the surface of both the temporal bone and the 3DP model was also developed to correctly transfer the designated BB area. The accuracy of the procedure was verified by CT scan: a radiological marker was used to evaluate the degree of correspondence of the transducer site between the 3DP model and the human temporal bone. The BB positioning was successfully performed on all human temporal bones, with no difficulties in finding the proper location of the transducer. A mean error of 0.13 mm was found when the transducer site of the 3DP model was compared to that of the human temporal bone. The employment of 3D printing technology in surgical planning of BB positioning showed feasible results. Further studies will be required to evaluate its clinical applicability.

An innovative strategy for the identification and 3D reconstruction of pancreatic cancer from CT images.

We propose an innovative tool for Pancreatic Ductal AdenoCarcinoma 3D reconstruction from Multi-Detector-Computed Tomography. The tumor mass is discriminated from health tissue, and the resulting segmentation labels are rendered preserving information on different hypodensity levels. The final 3D virtual model includes also pancreas and main peri-pancreatic vessels, and it is suitable for 3D printing. We performed a preliminary evaluation of the tool effectiveness presenting ten cases of Pancreatic Ductal AdenoCarcinoma processed with the tool to an expert radiologist who can correct the result of the discrimination. In seven of ten cases, the 3D reconstruction is accepted without any modification, while in three cases, only 1.88, 5.13, and 5.70 %, respectively, of the segmentation labels are modified, preliminary proving the high effectiveness of the tool.

A lower bound on the number of mechanisms for discriminating fourth and higher order spatial correlations.

Research on single striate cortical neurons has often concentrated on their responses to stimuli defined by two-point correlations. Texture discrimination studies using a relatively small palette of isotrigon textures have indicated that we are sensitive to third and higher-order spatial correlations. To further evaluate the underlying mechanisms of texture discrimination subjects discriminated random binary noise patterns from ten new isotrigon texture types. Factor analysis revealed that as few as three mechanisms may govern the detection of fourth and higher order image structure. This supports the findings of previous studies using different isotrigon textures. The computation of higher-order correlations by the brain is neurophysiologically plausible. The mechanisms identified in this study may represent some short range nonlinear combination of recursive and/or rectifying processes.

Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson's disease.

OBJECTIVES: The monoamine oxidase B inhibitors selegiline and rasagiline have not been compared in head-to-head clinical trials in patients with early Parkinson's disease.  The aim of this review was to compare the efficacy of these two agents in this setting. MATERIALS AND METHODS: Randomized, placebo-controlled trials with an endpoint of the mean change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) total score were included. Analysis included calculation of the standardized mean differences (SMDs) with 95% confidence intervals (CIs) and Forest Plot analyses for comparisons of pooled results. RESULTS: Five studies with selegiline (n = 1029) and four with rasagiline (n = 820) were included. Treatment duration was 2.5-9 months. Both selegiline and rasagiline showed significant SMDs versus placebo (-0.690, 95% CI -0.811, -0.569 and -1.025, 95% CI -1.230, -0.820; respectively), indicating a significant effect of both drugs on UPDRS. The SMD between selegiline and rasagiline was not significantly different (SMD 0.079; 95% CI -0.010, +0.167). CONCLUSIONS: It appears that selegiline and rasagiline have comparable efficacy in improving Parkinsonian symptoms in patients with early stage disease.

Locally countable properties and the perceptual salience of textures.

The human ability to discriminate structured from uniformly random binary textures has been shown to exploit third- and higher-order pixel correlations. We examine this ability in an experiment using a large number of texture families that can only be distinguished on the basis of these higher-order correlations. This study investigates statistical models based on possible explanatory variables involving spatial interactions of up to four pixels. Some of these explanatory variables have been recently associated with natural images, and others are somewhat less intuitive and are used here for the first time, to our knowledge. Our models are constructed using intraclass and cross-class feature selection by means of lasso/elastic net optimization and extensive cross-validation. We focus on a special set of locally countable image measures that seem to parsimoniously capture the observed discrimination performance. Among the measures underpinning the best models, we highlight a concept that can only exist in nine-pixel or larger image patches, but nonetheless is calculable based on the multiplicity of specific four-pixel patches in a texture. We show that this single geometric concept provides significant clues to explain texture discrimination.

Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model.

Therapeutic strategies for the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are actually minimally effective on patients' survival and quality of life. Although stem cell therapy has raised great expectations, information on the involved molecular mechanisms is still limited. Here we assessed the efficacy of the systemic administration of adipose-derived mesenchymal stem cells (ASC), a previously untested stem cell population, in superoxide-dismutase 1 (SOD1)-mutant transgenic mice, the animal model of familial ALS. The administration of ASC to SOD1-mutant mice at the clinical onset significantly delayed motor deterioration for 4-6 weeks, as shown by clinical and neurophysiological tests. Neuropathological examination of ASC-treated SOD1-mutant mice at day 100 (i.e. the time of their best motor performance) revealed a higher number of lumbar motorneurons than in phosphate-buffered saline-treated SOD1-mutant mice and a restricted number of undifferentiated green fluorescent protein-labeled ASC in the spinal cord. By examining the spinal cord tissue factors that may prolong neuronal survival, we found a significant up-regulation in levels of glial-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) after ASC treatment. Considering that ASC produce bFGF but not GDNF, these findings indicate that ASC may promote neuroprotection either directly and/or by modulating the secretome of local glial cells toward a neuroprotective phenotype. Such neuroprotection resulted in a strong and long-lasting effect on motor performance and encourages the use of ASC in human pathologies, in which current therapies are not able to maintain a satisfying neurological functional status.

Patient-specific aortic endografting simulation: from diagnosis to prediction.

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.

[Trend of the asbestos related diseases mortality in workers of a company in the province Cremona which manufactured asbestos products]. / Andamento delle patologie e della mortalità asbesto correlate in lavoratori di un'azienda della provincia di Cremona che produceva manufatti in amianto.

The study analyzes the trend of asbestos-related diseases and mortality in workers of a company in the province of Cremona which manufactured asbestos products. It is confirmed that the exposure to a high concentration of asbestos fibers (estimated to more than 20 fibers/cc) strictly correlates with the onset of pathologies from asbestos. In the studied population were found 19 cases of neoplastic diseases (12 mesotheliomas and 7 bronchopulmonary carcinomas). This figure, compared to the company working population, which over the years has been an average of 80 units, while not enabling to calculate an incidence rate due to the lack of reliable data on population, is indicative of a very significant cause-effect relationship since these are neoplastic diseases that can still arise. So it is necessary to continue the health monitoring of formerly exposed workers and appropriate to try to extend it to all workers of the asbestos compartment.

Combined brain voxel-based morphometry and diffusion tensor imaging study in idiopathic restless legs syndrome patients.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the presence of abnormalities in the brain of patients with restless legs syndrome (RLS) using voxel-based morphometry and diffusion tensor imaging (DTI). METHODS: Twenty patients and twenty controls were studied. Voxel-based morphometry analysis was performed using statistical parametric mapping (SPM8) and FSL-VBM software tools. For voxel-wise analysis of DTI, tract-based spatial statistics (TBSS) and SPM8 were used. RESULTS: Applying an appropriate threshold of probability, no significant results were found either in comparison or in correlation analyses. CONCLUSIONS: Our data argue against clear structural or microstructural abnormalities in the brain of patients with idiopathic RLS, suggesting a prevalent role of functional or metabolic impairment.

Epidemiologic features of patients affected by herpes zoster: database analysis of the Ferrara University Dermatology Unit, Italy.

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.

Mutagenicity evaluation with Ames test of hydro-alcoholic solution of terpenes.

Mutagenic properties of terpenes (both synthesis and plant derived) have been tested, up to now, as a single molecule. A terpenes containing hydro-alcoholic solution deriving from frankincense and myrrh resins and hyssop essential oil was assayed for mutagenicity by means of ames test. Extraction technique conducted with electromagnetic fields at room temperature enabled to obtain a solution of free active molecules that did not undergo thermal degradation and characterized by biocidal activity. In order to verify lack of mutagenic hazard in coming into contact with human, the solution was appropriately diluted and tested with Salmonella typhimurium TA98, TA1535 and YG1024 strains, both in absence and in presence of metabolic system S9. For none of the tested conditions a 2-fold increase of induced revertants, as regards to spontaneous, was registered. The ratio between induced and spontaneous His+ revertants (Mutagenic Index) was around 1.00 in all the determinations and no statistically significant differences have been identified comparing the sample and the negative control. A similar result has been obtained for the dose-response curve. In conclusion, we verified that tested terpenes solution lacks of mutagenicity on Salmonella typhimurium with and without metabolic activator so this plant extract can be safely used as biocide.

Graph rigidity, cyclic belief propagation, and point pattern matching.

A recent paper [1] proposed a provably optimal polynomial time method for performing near-isometric point pattern matching by means of exact probabilistic inference in a chordal graphical model. Its fundamental result is that the chordal graph in question is shown to be globally rigid, implying that exact inference provides the same matching solution as exact inference in a complete graphical model. This implies that the algorithm is optimal when there is no noise in the point patterns. In this paper, we present a new graph that is also globally rigid but has an advantage over the graph proposed in [1]: Its maximal clique size is smaller, rendering inference significantly more efficient. However, this graph is not chordal, and thus, standard Junction Tree algorithms cannot be directly applied. Nevertheless, we show that loopy belief propagation in such a graph converges to the optimal solution. This allows us to retain the optimality guarantee in the noiseless case, while substantially reducing both memory requirements and processing time. Our experimental results show that the accuracy of the proposed solution is indistinguishable from that in [1] when there is noise in the point patterns.

Degree of antioxidant protection: a parameter to trace the origin and quality of goat's milk and cheese.

Traceability is an essential tool in reassuring consumers and traders that food is as safe, authentic, and of good quality as expected. Today, food traceability procedures often consist of attached documents and declarations, but scientific parameters that could objectively identify a product would be preferable. Scientific efforts in this area are mostly focused on selection and validation of experimental indicators that would be useful for tracing a food product in any step of its commercial life, describing its raw materials, processing procedures, and storage conditions. In this research, milk and cheese samples from zero grazing and grazing goats were studied to identify a tracing parameter correlated to the feeding system. In particular, alpha-tocopherol and cholesterol were analyzed by HPLC on a normal phase column and were combined to calculate the degree of antioxidant protection (DAP). This parameter, expressed as the molar ratio between antioxidant compounds and an oxidation target, is useful for tracing and distinguishing products from grazing and zero-grazing animals. Degree of antioxidant protection values greater than 7.0 x 10(-3) were found in samples from grazing goats and values lower than 7.0 x 10(-3) were found in samples from zero-grazing goats, for both milk and cheese, meaning that cholesterol was highly protected against oxidative reactions when herbage was the only feed or was dominant in the goat diet. The reliability of DAP to measure the antioxidant protection of cholesterol appeared more effective when the feeding system was based on grazing than when cut herbage was utilized indoors by animals. The DAP index was able to distinguish dairy products when the grazed herbage in the goats' diet exceeded 15%.

PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas.

We have used a novel variant of the human oestrogen receptor (ER)-positive MCF-7 cell line, TMX2-28, as a model to study breast cancer. TMX2-28 cells show no detectable levels of mRNA or protein expression for the ER and express basal cytokeratins (CKs) 5, 14, and 17. cDNA microarray comparison between TMX2-28 and its parent cell line, MCF-7, identified 1402 differentially expressed transcripts, one of which was, phospholipase D1 (PLD1). Using real-time RT-PCR, we confirmed that PLD1 mRNA levels are 10-fold higher in TMX2-28 cells than in MCF-7 cells. We next examined PLD1 expression in human breast carcinomas. Phospholipase D1 mRNA levels were higher in breast tumours that expressed high-mRNA levels of basal CKs 5 and/or 17, but PLD1 mRNA levels were not significantly higher in ER-negative tumours. Phospholipase D1 protein was overexpressed in 10 of 42 (24%) breast tumours examined by IHC. Phospholipase D1 was overexpressed in 6 of 31 ER-positive tumours and 4 of 11 ER-negative tumours. Phospholipase D1 was overexpressed in three of the four tumours that showed high CK5/17 expression. Five PLD1-positive tumours were negative for phospho-Akt expression, but positive for phospho-mammalian target of rapamycin (mTOR) expression. The other five PLD1-positive breast tumours showed positive expression for phospho-Akt; however, only two of these cases were positive for phospho-mTOR. In this study, we report that PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas.

Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn's disease of mild-to-moderate activity or in remission: Retrospective study.

Although conventional glucocorticosteroids are the main treatments for active Crohn's disease, several problems are associated with steroid dependence and steroid-related adverse events. To assess the efficacy and safety of oral beclomethasone dipropionate (BDP) coated tablets in adults with mild-to-moderate Crohn's disease. Thirty-four patients (age 18-70years) with a diagnosis of Crohn's disease confirmed by conventional criteria (barium enema, clinical criteria, colonoscopy, histology) were retrospectively evaluated in the study. All subjects received a treatment schedule with BDP 5-10mg/day for 24weeks. BDP significantly (p=0.005) reduced mean Crohn's Disease Activity Index (CDAI) score from 169.6 at baseline to 123.2 after 24weeks. Clinical success was evident at 24weeks in 66.7% of patients with initial active disease, and remission was maintained at week 24 in 93.8% of patients with remission at baseline. Overall, female non-smokers had the best response to treatment. BDP was well tolerated and the only adverse events observed were nausea (n=1), facial erythema (n=1) and one patient with raised fasting blood glucose level. These results clearly suggest that oral BDP coated tablets are effective and safe for treatment of mild-to-moderate Crohn's disease of ileal or ileal-right colonic localisation.