Bioethical Aspects Across Medicine: The Care of Cardiovascular Diseases in Brazil

Bioethics applied to medicine extrapolates the traditional medical concepts of non-maleficence (primum non nocere) and beneficence (bonum facere) and regards to justice, autonomy, equity, protection, compassion and humanization, not considering people just like patients, but understanding the complex existence of each single person. Worldwide, the morbidity and mortality indices regarding to diseases of heart and blood vessels became progressively grater. For countries in development, like Brazil, these numbers are even more expressive and this increase trend seems to be caused by wider exposition of population to some risk factors. This article broaches an intersection between bioethics and medicine, focusing the reality of cardiovascular diseases in Brazil and the necessity of doctors to base their behavior in bioethical paradigms.

Cost-Effectiveness Analysis for Surgical, Angioplasty, or Medical Therapeutics for Coronary Artery Disease 5-Year Follow-Up of Medicine, Angioplasty, or Surgery Study (MASS) II Trial

Background-The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n = 203), percutaneous coronary intervention (PCI, n = 205), or medical treatment alone (MT, n = 203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies. Methods and Results-We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19 967.00 for PCI; and $18 263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI (P<0.01). The event-free plus angina-free costs were $16 553.00, $25 831.00, and $24 614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI (P>0.05). Conclusions-In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI.

Narrowing the gap of personalized medicine in emerging countries: the case of multiple endocrine neoplasias in Brazil

The finished version of the human genome sequence was completed in 2003, and this event initiated a revolution in medical practice, which is usually referred to as the age of genomic or personalized medicine. Genomic medicine aims to be predictive, personalized, preventive, and also participative (4Ps). It offers a new approach to several pathological conditions, although its impact so far has been more evident in mendelian diseases. This article briefly reviews the potential advantages of this approach, and also some issues that may arise in the attempt to apply the accumulated knowledge from genomic medicine to clinical practice in emerging countries. The advantages of applying genomic medicine into clinical practice are obvious, enabling prediction, prevention, and early diagnosis and treatment of several genetic disorders. However, there are also some issues, such as those related to: (a) the need for approval of a law equivalent to the Genetic Information Nondiscrimination Act, which was approved in 2008 in the USA; (b) the need for private and public funding for genetics and genomics; (c) the need for development of innovative healthcare systems that may substantially cut costs (e.g. costs of periodic medical followup); (d) the need for new graduate and postgraduate curricula in which genomic medicine is emphasized; and (e) the need to adequately inform the population and possible consumers of genetic testing, with reference to the basic aspects of genomic medicine.

The use of remote sensing imagery for monitoring recovery in the aftermath of a natural disaster: the Hurricane Katrina Case

Although Recovery is often defined as the less studied and documented phase of the Emergency Management Cycle, a wide literature is available for describing characteristics and sub-phases of this process. Previous works do not allow to gain an overall perspective because of a lack of systematic consistent monitoring of recovery utilizing advanced technologies such as remote sensing and GIS technologies. Taking into consideration the key role of Remote Sensing in Response and Damage Assessment, this thesis is aimed to verify the appropriateness of such advanced monitoring techniques to detect recovery advancements over time, with close attention to the main characteristics of the study event: Hurricane Katrina storm surge. Based on multi-source, multi-sensor and multi-temporal data, the post-Katrina recovery was analysed using both a qualitative and a quantitative approach. The first phase was dedicated to the investigation of the relation between urban types, damage and recovery state, referring to geographical and technological parameters. Damage and recovery scales were proposed to review critical observations on remarkable surge- induced effects on various typologies of structures, analyzed at a per-building level. This wide-ranging investigation allowed a new understanding of the distinctive features of the recovery process. A quantitative analysis was employed to develop methodological procedures suited to recognize and monitor distribution, timing and characteristics of recovery activities in the study area. Promising results, gained by applying supervised classification algorithms to detect localization and distribution of blue tarp, have proved that this methodology may help the analyst in the detection and monitoring of recovery activities in areas that have been affected by medium damage. The study found that Mahalanobis Distance was the classifier which provided the most accurate results, in localising blue roofs with 93.7% of blue roof classified correctly and a producer accuracy of 70%. It was seen to be the classifier least sensitive to spectral signature alteration. The application of the dissimilarity textural classification to satellite imagery has demonstrated the suitability of this technique for the detection of debris distribution and for the monitoring of demolition and reconstruction activities in the study area. Linking these geographically extensive techniques with expert per-building interpretation of advanced-technology ground surveys provides a multi-faceted view of the physical recovery process. Remote sensing and GIS technologies combined to advanced ground survey approach provides extremely valuable capability in Recovery activities monitoring and may constitute a technical basis to lead aid organization and local government in the Recovery management.

Genetic characterization, population history and evolutionary medicine perspective in two native south american populations: Yanesha and Wichi

Two Amerindian populations from the Peruvian Amazon (Yanesha) and from rural lowlands of the Argentinean Gran Chaco (Wichi) were analyzed. They represent two case study of the South American genetic variability. The Yanesha represent a model of population isolated for long-time in the Amazon rainforest, characterized by environmental and altitudinal stratifications. The Wichi represent a model of population living in an area recently colonized by European populations (the Criollos are the population of the admixed descendents), whose aim is to depict the native ancestral gene pool and the degree of admixture, in relation to the very high prevalence of Chagas disease. The methods used for the genotyping are common, concerning the Y chromosome markers (male lineage) and the mitochondrial markers (maternal lineage). The determination of the phylogeographic diagnostic polymorphisms was carried out by the classical techniques of PCR, restriction enzymes, sequencing and specific mini-sequencing. New method for the detection of the protozoa Trypanosoma cruzi was developed by means of the nested PCR. The main results show patterns of genetic stratification in Yanesha forest communities, referable to different migrations at different times, estimated by Bayesian analyses. In particular Yanesha were considered as a population of transition between the Amazon basin and the Andean Cordillera, evaluating the potential migration routes and the separation of clusters of community in relation to different genetic bio-ancestry. As the Wichi, the gene pool analyzed appears clearly differentiated by the admixed sympatric Criollos, due to strict social practices (deeply analyzed with the support of cultural anthropological tools) that have preserved the native identity at a diachronic level. A pattern of distribution of the seropositivity in relation to the different phylogenetic lineages (the adaptation in evolutionary terms) does not appear, neither Amerindian nor European, but in relation to environmental and living conditions of the two distinct subpopulations.

Lifelines in case of Natural Disaster Emergencies

In order to handle Natural disasters, emergency areas are often individuated over the territory, close to populated centres. In these areas, rescue services are located which respond with resources and materials for population relief. A method of automatic positioning of these centres in case of a flood or an earthquake is presented. The positioning procedure consists of two distinct parts developed by the research group of Prof Michael G. H. Bell of Imperial College, London, refined and applied to real cases at the University of Bologna under the coordination of Prof Ezio Todini. There are certain requirements that need to be observed such as the maximum number of rescue points as well as the number of people involved. Initially, the candidate points are decided according to the ones proposed by the local civil protection services. We then calculate all possible routes from each candidate rescue point to all other points, generally using the concept of the "hyperpath", namely a set of paths each one of which may be optimal. The attributes of the road network are of fundamental importance, both for the calculation of the ideal distance and eventual delays due to the event measured in travel time units. In a second phase, the distances are used to decide the optimum rescue point positions using heuristics. This second part functions by "elimination". In the beginning, all points are considered rescue centres. During every interaction we wish to delete one point and calculate the impact it creates. In each case, we delete the point that creates less impact until we reach the number of rescue centres we wish to keep.

From Folke Medicine to Medicine Chemistry: Study, Using in Vitro and Cellular Assays, of Receptors Mechanism Involved in the Activities of Natural Compounds

My Doctorate Research has been focused on the evaluation of the pharmacological activity of a natural extract of chestnut wood (ENC) towards the cardiovascular and gastrointestinal system and on the identification of the active compounds. The ENC has been shown to contain more than 10% (w/w) of phenolic compounds, of which tannins as Vescalgin and Castalgin are the more representative. ENC cardiovascular effects have been investigated in guinea pig cardiac preparations; furthermore its activity has been evalueted in guinea pig aorta strips. ENC induced transient negative chronotropic effect in isolated spontaneously beating right atria and simultaneously positive inotropic effect in left atria driven at 1 Hz. Cardiac cholinergic receptors are not involved in the negative chronotropic effect and positive inotropic effects are not related to adrenergic receptors. In vascular smooth muscle, natural extract of chestnut did not significantly change the contraction induced by potassium (80 mM) or that induced by noradrenaline (1μM). In guinea pig ileum, ENC reduced the maximum response to carbachol in a concentrationdependent manner and behaved as a reversible non competitive antagonist. In guinea pig ileum, the antispasmodic activity of ENC showed a significant antispasmodic activity against a variety of different spasmogenic agents including histamine, KCl, BaCl2. In guinea pig proximal colon, stomach and jejunum, ENC reduced the maximum response to carbachol in a concentrationdependent manner and behaved as a reversible non competitive antagonist. ENC contracted gallbladder guinea pig in a reversible and concentration-dependent manner. This effect does not involve cholinergic and cholecystokinin receptors and it is reduced by nifedipine. ENC relaxed Oddi sphincter smooth muscle. The cholecystokinetic and Oddi sphincter relaxing activities occurred also in guinea pigs fed a lithogenic diet. The cholecystokinetic occurred also in human gallbladder. The Fractionation of the extract led to the identification of the active fraction.

Progettazione e implementazione di una rete di sensori mobili Arduino per scenari di Disaster Recovery

Sommario Il progetto descritto in questo documento consiste nella realizzazione di una prima applicazione pratica di uno specifico studio di ricerca rivolto al ripristino di reti wireless in scenari post-calamità naturali. In principio è stata descritta un’ampia analisi delle problematiche di rete che si vengono a creare in seguito ad eventi catastrofici. Successivamente, analizzando le varie tecniche e tecnologie oggetto di studio di diversi gruppi di ricerca, si è scelto di collaborare con il progetto STEM-Mesh, essendo ancora in fase sperimentale, il quale affronta il problema di ristabilire la connettività di rete in questi particolari scenari, attraverso l’utilizzo di tecnologie Cognitive Radio (CR), mobilità controllata e principi di reti auto-organizzanti. Di questo primo approccio pratico sono state poi descritte le fasi di progettazione, implementazione e testing. Nella fase di progettazione sono state studiate le componenti hardware e software che rispettassero il più possibile i requisiti e le caratteristiche dei dispositivi “staminali” STEM-Node cuore del progetto STEM-Mesh, ovvero dei dispositivi wireless altamente auto-riconfiguranti ed auto-organizzanti che possono diventare dispositivi sostituivi ai nodi compromessi in una rete, riconfigurandosi appunto in base alle funzionalità interrotte. Nella fase di implementazione si è passati alla stesura del codice, in Python e Wiring, abilitante il dispositivo STEM-Node. Infine nella fase di testing si è verificato che i risultati fossero quelli desiderati e che il sistema realizzato funzionasse come previsto.

3D nanostructured microcarriers for cell therapy in regenerative medicine

Supercritical Emulsion Extraction technology (SEE-C) was proposed for the production of poly-lactic-co-glycolic acid microcarriers. SEE-C operating parameters as pressure, temperature and flow rate ratios were analyzed and the process performance was optimized in terms of size distribution and encapsulation efficiency. Microdevices loaded with bovine serum insulin were produced with different sizes (2 and 3 µm) or insulin charges (3 and 6 mg/g) and with an encapsulation efficiency of 60%. The microcarriers were characterized in terms of insulin release profile in two different media (PBS and DMEM) and the diffusion and degradation constants were also estimated by using a mathematical model. PLGA microdevices were also used in a cultivation of embryonic ventricular myoblasts (cell line H9c2 obtained from rat) in a FBS serum free medium to monitor cell viability and growth in dependence of insulin released. Good cell viability and growth were observed on 3 µm microdevices loaded with 3 mg/g of insulin. PLGA microspheres loaded with growth factors (GFs) were charged into alginate scaffold with human Mesenchimal Steam Cells (hMSC) for bone tissue engineering with the aim of monitoring the effect of the local release of these signals on cells differentiation. These “living” 3D scaffolds were incubated in a direct perfusion tubular bioreactor to enhance nutrient transport and exposing the cells to a given shear stress. Different GFs such as, h-VEGF, h-BMP2 and a mix of two (ratio 1:1) were loaded and alginate beads were recovered from dynamic (tubular perfusion system bioreactor) and static culture at different time points (1st, 7th, 21st days) for the analytical assays such as, live/dead; alkaline phosphatase; osteocalcin; osteopontin and Van Kossa Immunoassay. The immunoassay confirmed always a better cells differentiation in the bioreactor with respect to the static culture and revealed a great influence of the BMP-2 released in the scaffold on cell differentiation.

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.

Identity formation at the beginning of the twenty-first century: Intersubjectivity, art, and medicine in Siri Hustvedt’s works

„Ich bin, weil du bist“ – so lautet eines der Schlüsselzitate in What I Loved, dem 2003 erschienenen dritten Roman der zeitgenössischen amerikanischen Autorin Siri Hustvedt. Die Bedeutung von Beziehung und Interaktion für die Identitätsbildung spielt eine zentrale Rolle nicht nur in diesem Roman, sondern auch in ihrem Gesamtwerk, das vier Romane, ein memoir, drei Essay-Sammlungen und einen Lyrikband umfasst. Hustvedt erforscht die Identität als ein vielschichtiges Produkt bewusster und unbewusster Verknüpfungen innerhalb der sozialen und biologischen Umwelt. Das Bewusstsein wird als eine dialogisch geprägte Entität gezeigt, dessen Identität erst durch die Beziehung auf ein Anderes geformt werden kann. Um dem Mysterium der menschlichen Identitätsfindung nachzuspüren, bedient sich Hustvedt sowohl philosophischer, psychoanalytischer, biologischer als auch kunsttheoretischer Diskurse. In ihren Romanen stellt sich die Frage nach der Erklärung von Identität als komplexe Problematik dar: Ist die Beziehung zu anderen Menschen vor allem durch unsere Entwicklung als Kind und die Nähe zu Bezugspersonen geprägt? In welchem Ausmaß ist das Empfinden von Subjektivität beeinflusst von körperlichen und unbewussten Mechanismen? Inwiefern ist die Wahrnehmung visueller Kunst eine Kooperation zwischen Betrachter und Künstler? rnDiesen und anderen Fragen geht diese Dissertation nach, indem sie Hustvedts Werk als Anlass für eine Analyse intersubjektiver Strukturen der Identität nimmt. Die Intersubjektivitätsphiloso¬phien von Hegel, Buber, Bakhtin, Husserl, und Merleau-Ponty dienen hierbei als Ausgangspunkt für die Interpretation von relationaler Identität in Hustvedts Werken. Die Dissertation konzentriert sich auf Hustvedts Darstellung der Beziehung zwischen Selbst und Anderem in der Photographie und in der Malerei, der Überschreitung von Körpergrenzen in Hysterie und Anorexie sowie der Auswirkung des Verlustes von Bezugspersonen auf die persönliche Identität. Entscheidend für den Hustvedtschen Kunstbegriff ist das Zusammenspiel von Kunstobjekt, Künstler und Betrachter. Die Grenzen zwischen Innerem und Äußeren werden aufgelöst: mal wird der Rezipient Teil des Kunstwerks, mal verschmilzt der Künstler förmlich mit seinem Objekt. Auch hier wird wiederum deutlich, dass Identität nur in Wechselbeziehung und als zwischenmenschliche Kooperation entsteht. Hustvedt betritt durch ihre einzigartige Auseinandersetzung mit den Wechselbeziehungen und fragilen Grenzen zwischen Ich und Umwelt Neuland auf dem Gebiet der literarischen Identitätsforschung, da sie ihr Prinzip des „mixing,“ des unausweichlichen Eindringens fremder Substanz in die eigene Identität, aus dem Blickwinkel dieser verschiedenen Erklärungsansätze beleuchtet. rn

Fractal sets and their applications in medicine

La geometria euclidea risulta spesso inadeguata a descrivere le forme della natura. I Frattali, oggetti interrotti e irregolari, come indica il nome stesso, sono più adatti a rappresentare la forma frastagliata delle linee costiere o altri elementi naturali. Lo strumento necessario per studiare rigorosamente i frattali sono i teoremi riguardanti la misura di Hausdorff, con i quali possono definirsi gli s-sets, dove s è la dimensione di Hausdorff. Se s non è intero, l'insieme in gioco può riconoscersi come frattale e non presenta tangenti e densità in quasi nessun punto. I frattali più classici, come gli insiemi di Cantor, Koch e Sierpinski, presentano anche la proprietà di auto-similarità e la dimensione di similitudine viene a coincidere con quella di Hausdorff. Una tecnica basata sulla dimensione frattale, detta box-counting, interviene in applicazioni bio-mediche e risulta utile per studiare le placche senili di varie specie di mammiferi tra cui l'uomo o anche per distinguere un melanoma maligno da una diversa lesione della cute.

Studio, Realizzazione e Simulazione di SaveMe, un'applicazione Android per il Disaster Recovery

Quando avvengono disastri naturali, spesso la copertura dati viene a mancare e le infrastutture o sono danneggiate o sono sovraccariche; in questo modo è difficile comunicare sia da parte delle persone che hanno bisogno di aiuto, sia da parte dei soccorritori che cercano di organizzare i soccorsi. Con questa tesi si è voluto realizzare un'applicazione Android che permetta agli utenti di segnalare il proprio bisogno di aiuto, anche se il device non ha una connessione internet attiva. L'applicazione, sfruttando il Wi-Fi e il Wi-Fi Direct, cercherà di formare una rete di dispositivi, attraverso la quale i messaggi di aiuto degli utenti verranno scambiati tra i device. Questa rete, man mano, si allargherà fino ad arrivare ad includere device che avranno una connessione dati attiva. Questi comunicheranno con il mio server, al quale manderanno tutti i messaggi che gli sono arrivati. I dati del server, ossia i messaggi che sono stati mandati dagli utenti, verranno mostrati sul sito ltw1528.web.cs.unibo.it. Attraverso questo sito, i soccorritori potranno vedere la posizione degli utenti in stato di bisogno, cosicché potranno mandarli un messaggio di soccorso, che si propagherà nella rete formatasi in precedenza, ed organizzare i soccorsi in maniera ottimale. Si è anche voluto fare uno studio simulativo per testare la scalabilità dell'applicazione e per raccogliere dati statistici, quali il delay medio tra l'arrivo del messaggio al device con connessione dati e il tempo in cui è stato creato, l'influenza sulla batteria del numero dei messaggi scambiati e il numero degli host, il delay tra il tempo di invio e il tempo di arrivo nello scambio di messaggi al variare del numero degli host.