Development of an electrical impedance tomography set-up for the quantification of mineralization in biopolymer scaffolds

Objective. 3D cell cultures are becoming a fundamental resource for in-vitro studies, as they mimic more closely in-vivo behavior. The analysis of these constructs, however, generally rely on destructive techniques, that prevent the monitoring over time of the same construct, thus increasing the results variability and the resources needed for each experiment. Approach. In this work, we focus on mineralization, a crucial process during maturation of artificial bone models, and propose electrical impedance tomography (EIT) as an alternative non-destructive approach. In particular, we discuss the development of an integrated hardware/software system capable of acquiring experimental data from 3D scaffolds and reconstructing the corresponding conductivity maps. We also show how the same software can test how the measurement is affected by biological features such as scaffold shrinking during the culture. Main results. An initial validation, comprising the acquisition of both a non-conductive phantom and alginate/gelatin scaffolds with known calcium content will be presented, together with the in-silico study of a cell-induced mineralization process. This analysis will allow for an initial verification of the systems functionality while limiting the effects of biological variability due to cell number and activity. Significance. Our results show the potential of EIT for the non-destructive quantification of matrix mineralization in 3D scaffolds, and open to the possible long term monitoring of this fundamental hallmark of osteogenic differentiation in hybrid tissue engineered constructs

Microstructured soft devices for the growth and analysis of populations of homogenous multicellular tumor spheroids

: Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating a large number of uniformly sized spheroids, but commercially available systems often do not enable researchers to perform complete culturing and analysis pipelines and the mechanical properties of their culture environment are not commonly matching those of the target tissue. We herein report a simple method to obtain custom-designed self-built microwell arrays made of polydimethylsiloxane or agarose for uniform 3D cell structure generation. Such materials can provide an environment of tunable mechanical flexibility. We developed protocols to culture a variety of cancer and non-cancer cell lines in such devices and to perform molecular and imaging characterizations of the spheroid growth, viability, and response to pharmacological treatments. Hundreds of tumor spheroids grow (in scaffolded or scaffold-free conditions) at homogeneous rates and can be harvested at will. Microscopy imaging can be performed in situ during or at the end of the culture. Fluorescence (confocal) microscopy can be performed after in situ staining while retaining the geographic arrangement of spheroids in the plate wells. This platform can enable statistically robust investigations on cancer biology and screening of drug treatments

Energy autonomous systems : future trends in devices, technology, and systems

The rapid evolution of electronic devices since the beginning of the nanoelectronics era has brought about exceptional computational power in an ever shrinking system footprint. This has enabled among others the wealth of nomadic battery powered wireless systems (smart phones, mp3 players, GPS, …) that society currently enjoys. Emerging integration technologies enabling even smaller volumes and the associated increased functional density may bring about a new revolution in systems targeting wearable healthcare, wellness, lifestyle and industrial monitoring applications

5.26 Left Ventricular Hypertrophy Prevalence by Different Left Ventricular Mass Indexes

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Diet, dietary supplements and age-related macular degeneration (AMD)

Age-related macular degeneration (AMD) is a progressive disorder primarily affecting the macula, the central region of the retina involved with central vision. It is the leading cause of blindness in developed countries, accounting for 50% of blindness. Some risk factors are not reversible (genetics, age, darker iris pigmentation, previous cataract surgery, and hyperopic refraction), while others are considered reversible (smoking habit, obesity, incorrect diet). Among macronutrients, alcohol intake and food\u2019s glycaemic index appear to be the strongest AMD risk factors. However, the most investigated protective factors for AMD are micronutrients, and in particular antioxidants (especially carotenoids), minerals (especially zinc), polyunsaturated fatty acids and vitamin D. The Age-Related Eye Disease Study (AREDS) was the first large-scale randomised controlled clinical trial to demonstrate the benefit of vitamin and mineral supplementations in preventing the progression to advanced AMD. The AREDS formulation included antioxidants such as vitamin C 500 mg, vitamin E 400 IU and \u3b2-carotene 15 mg, associated to zinc (zinc oxide 80 mg and cupric oxide 2 mg). This level of antioxidants and zinc was considerably higher than the amount in any daily multivitamin supplement and it is difficult to achieve from diet alone. In conclusion, modifying environmental factors is currently the only approach to reduce the genetic risk of AMD. Clinicians should provide dietary advice and, in particular, prescribe evidence-based dietary supplements to susceptible individuals to postpone or prevent the vision-disabling consequences of AMD

Antidiabetic properties of berberine: from cellular pharmacology to clinical effects.

Berberine is an alkaloid highly concentrated in the roots, rhizomes and stem bark of various plants. It affects glucose metabolism increasing insulin secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting mitochondrial function, activating the adenosine monophosphate-activated protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine also increases glucose transporter-4 (GLUT-4) and glucagon like peptide-1 (GLP-1) levels. Upon GLP-1 receptors activation, adenylyl cyclase is activated and cyclic adenosine monophosphate (cAMP) generated, leading to activation of second messenger pathways and closure of adenosine triphosphate-dependent potassium channels. Increased intracellular potassium causes depolarisation, and calcium influx through the voltage dependent calcium channels occurs. This intracellular calcium increase stimulates the migration and exocytosis of the insulin granules. In glucose consuming tissues, such as adipose, liver or muscle cells, berberine affects both GLUT-4 and retinol binding protein-4 (RBP-4) in favour of glucose uptake into cells, stimulates glycolysis by AMPK activation and has effects on the peroxisome proliferator-activated receptor \uf067 (PPAR\uf067) molecular targets and on the phosphorylation of insulin receptor substrate 1 (IRS-1), finally resulting in decreased insulin resistance. Moreover, recent studies suggest that berberine could have a direct action on carbohydrate metabolism in the intestine. The antidiabetic and insulin-sensitizing effect of berberine has also been confirmed in a few relatively small short-term clinical trials. The tolerability is high for low dosages, with some gastrointestinal complaints appearing with the use of high dosages

Validazione di Pulse Wave Velocity e Augmentation Index come metodiche per la valutazione non invasiva della rigidit\ue0 arteriosa

La rigidit\ue0 delle arterie \ue8 alla base di numerose complicanze ed eventi cardiovascolari, nonch\ue9 il principale responsabile della malattia aterosclerotica e dei piccoli vasi. Scopo del nostro studio \ue8 stato quello di validare la misurazione di Pulse Wave Velocity (PWV) e Augmentation Index (AI) come procedura applicabile nella pratica clinica quotidiana per la valutazione della rigidit\ue0 arteriosa. Il nostro lavoro ha coinvolto 45 soggetti sani volontari (23 giovani, et\ue0 media 24\ub13 anni, e 22 adulti, et\ue0 media 55\ub13 anni) e 10 pazienti (64\ub112 anni) con fibrillazione atriale sottoposti a cardioversione elettrica esterna. Le derivazioni periferiche dell\u2019elettrocardiogramma e i flussi arteriosi carotideo e femorale sono stati registrati mediante strumentazione commerciale standard; il polso di pressione radiale \ue8 stato prelevato mediante un tonometro (Millar). Tutta la strumentazione \ue8 stata interfacciata con un computer per consentire la visualizzazione, la memorizzazione e la successiva elaborazione dei segnali. PWV \ue8 stato calcolato come rapporto tra la distanza tra la fossetta giugulare e la congiungente le due spine iliache antero-superiori ed il ritardo della propagazione del flusso tra i siti considerati. L\u2019AI aortico \ue8 stato derivato dalla tonometria radiale e dalla pressione sanguigna periferica brachiale utilizzando una funzione matematica di trasferimento gi\ue0 validata e pubblicata[1]. I valori ottenuti di PWV ed AI sono stati correlati ad et\ue0, sesso e pressione arteriosa. I soggetti patologici sono stati sottoposti a queste indagini prima e dopo la cardioversione per valutare eventuali modifiche indotte dalla terapia. AI aumenta significativamente con l\u2019et\ue0 (p=0,03) mentre \ue8 indipendente dal sesso. PWV \ue8 maggiore nei maschi ed aumenta con l\u2019et\ue0 (p=0,08). I pazienti con FA presentano valori di AI pi\uf9 alti rispetto agli adulti sani (p<0,001), mentre non abbiamo evidenziato differenze significative sia per AI sia per PWV tra i valori ottenuti prima e dopo la cardioversione. Ci\uf2 pu\uf2 essere dovuto alla persistenza dell\u2019adattamento instauratosi nel sistema cardiocircolatorio a causa della patologia. In conclusione, la valutazione di PWV ed AI potrebbe essere uno strumento utile per ottenere un quadro pi\uf9 completo del sistema cardiovascolare di un soggetto anche se sono necessari ulteriori studi a supporto di ci\uf2 La semplicit\ue0, velocit\ue0 di esecuzione e la non-invasivit\ue0 delle metodiche renderebbero le stesse fruibili nella pratica clinica quotidiana e ben accette ai pazienti. 1. Karamanoglu M, O\u2019Rourke MF et al.: An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. Eur Heart J 1993; 14: 160-167

Metformin and its clinical use: new insights for an old drug in clinical practice

Metformin is generally recommended as first-line treatment in type 2 diabetes, especially in overweight patients, but in recent years new indications for its use have emerged. Metformin has been found to be safe and efficacious both as monotherapy and in combination with all oral antidiabetic agents and insulins. If metformin use during pregnancy and the lactation period is supported by few data, it could be indicated for women with polycystic ovary syndrome, since it could diminish circulating androgens and insulin resistance, thus ameliorating the ovulation rate. Metformin seems to reduce cancer risk, which appears to be increased in diabetics, and is a promising agent for oncoprevention and chemotherapy combinations. Moreover, metformin could find a place in the treatment of non-alcoholic fatty liver disease. Lactic acidosis could be decreased by avoiding metformin use in patients with hypovolemia, sepsis, renal impairment, hypoxic respiratory diseases and heart failure, in the preoperative period and before intravenous injection of contrast media