ESPERIENZE DI PARTOANALGESIA NELL'OSPEDALE DELLA VALLE DEL SERCHIO

Lo scopo della tesi è quello di valutare l'andamento e l'uso della peridurale nonchè il gradimento da parte delle partorienti in un reparto di ostetricia di un piccolo ospedale di periferia.I dati confermano la validità della tecnica peridurale e confermano anche gli eccellenti risultati raggiunti dove il 69% delle partorienti ne hanno beneficiato, un ulteriore conferma è dato dal livello di soddisfazione che è risultato elevato nella stragrande maggioranza delle partorienti ed il 97% ripeterebbe tale esperienza in caso di nuova gravidenza

Secretome of bovine amniotic and endometrial cells: application for in vitro embryo production.

Some maternal miRNAs are involved in early stage embryos [Abd El Naby, 2011]. Microvesicles (MVs)have been suggested as carrier of miRNAs for maternal-to-embryonic communication during the firstdays of early development [Mondou, 2012]. MVs, together with soluble factors, are components ofconditioned media (CM) produced by cells during their culture. Aim of this study was to understand therole of CM, MVs and supernatant (SN, obtained from CM deprived of MVs) secreted by bovineendometrial and amnion cells on embryo development.In vitro produced embryos were cultured in SOFaa alone (CTR) or supplemented on day 5 postfertilizationwith 10% of endometrial or amniotic CM or SN or 100x106 MVs/ml.The blastocyst rate obtained culturing embryos with amniotic CM and MVs was not significantlydifferent from the CTR (34.17±3.29%, 32.82±3.26% and 35.45±2.53% respectively). The rate obtained byamniotic SN was 25.80±2.83% and statistically lower (P<0.05) than the other groups. The rate obtainedby endometrial products were lower than CTR and the other conditions. The ICM of embryos culturedin medium supplemented with amniotic components had a higher number of cells than the CTR group:30.4±1.83 and 29.42±1.27 for CM and MVs respectively compared to 27.6±1.44 for CTR (P<0.05).Our data showed that exposing the embryos to the amniotic secretome does not improve theblastocyst rate, but increases their quality. The hypothesis is that miRNAs contained into MVs maycontribute to the production of better quality embryos and that amniotic secretome supplies a morephysiological environment for the embryo development

Intraocular Metastases Secondary to Breast Carcinoma Correlates With Upregulation of Estrogen and Progesterone Receptor Expression in the Primary Tumor

To compare estrogen (ER), progesterone (PR), and human epidermal growth factor-2 (HER2) receptor expression in the primary tumor of patients affected by choroidal metastases from breast carcinoma (BC) versus those with extraocular metastases

Cherry picking or depth-oriented strategic investing? Evidence from SRI activity

Today, socially responsible investing (SRI) represents the youngest financial-services industry that investors can exploit to implement their investment strategies. Although literature in this field is growing, additional research is needed to disentangle the factors affecting the performance of SRI funds. This paper focuses on the analysis of the influence that the depth of investment strategy by SRI funds may have on the investment performance, whereas larger SRI funds have a stronger capacity to address their investment choices. We used a sample of 149 USA SRI funds referring to the Social Investment Forum (SIF) Foundation in the period 2005-2010. We found that depth of investment strategy decreases the capacity of large SRI funds to reach positive financial returns if a broad sustainability investment strategy is pursued. On the other hand, SRI funds able to focus the attention on specific environmental, social, governance, or product criteria do increase their capacity to reach positive financial performance. This paper contributes to the existing literature by examining the depth of the sustainability investment strategy by SRI funds and investigating the moderating effect that peculiar investment strategies have on the well-known relation between size and performance of SRI funds. major-bidi;mso-bidi-theme-font:major-bidi;mso-ansi-language:EN-GB;mso-fareast-language: ZH-CN;mso-bidi-language:AR-SA'>This paper analyzes the wealth distribution taking into account the reaction of the market to the alliance as an indicator of a successful strategy. It explores the case of the automobile industry, which is characterised by a high use of inter-firm cooperation, such as strategic alliances and mergers & acquisitions, to effectively compete in the global market and face the global crisis

Angioleiomyoma of the knee: An uncommon cause of leg pain. A systematic review of the literature

Abstract Objective Angioleiomyoma is a rare benign painful soft tissue tumor, whose knee location is rare. Due its rarity, and not characteristic aspect on MRI the preoperative diagnosis is difficult. Methods We performed a systematic review of the literature, including a case of venous type angioleiomyoma that we have recently managed. Results A total of 24 published papers with 30 cases (including our illustrative case) were identified and included in our review. The mean patient age was 42.3 years (range18-63). The average size of the lesion was 17.8 mm. The presenting symptom was leg pain in 90% of cases. On magnetic resonance imaging (MRI), the lesion appeared isointense in T1 in 80% of cases and hyperintense on T2 in 90% of cases. Avid homogeneous enhancement after gadolinium administration was detected in 94% of cases. All patients underwent surgery and total resection was achieved in 100% of cases. No recurrence was observed after a mean follow-up of 19.5 months. Conclusion Angioleiomyoma occurs rarely in the knee and generally is associated with localized or radiating pain. The preoperative diagnosis is difficult also after completion of MRI study and requires high index of suspicion. Angioleiomyoma widens the spectrum of soft tissue lesions of the extremities and should be included in the differential diagnosis of lesions in this area

Second surgery for recurrent glioblastoma: A concise overview of the current literature

Optimal treatment for recurrent glioblastoma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients, as several studies provide evidence for a longer overall survival in selected patients with recurrent glioblastoma who underwent second surgery and other studies report a limited impact of second surgery in the clinical course. In this paper, a review of the current literature was performed to analyze the role of reoperation in patients with recurrent glioblastoma and to report the overall survival from diagnosis, progression-free survival and quality of life. Using PubMed and Ovid Medline databases, we performed a review of the literature of the last seven years, finding a total of 28 studies and 2279 patients who underwent second surgery, that were included in the final analysis. The median overall survival from diagnosis and the median survival from second surgery were 18.5 months and 9.7 months, respectively. Extent of resection at reoperation improves overall survival, even in patients with subtotal resection at initial operation. Preoperative performance status and age are important predictors of a longer survival, reason why younger patients with a good preoperative performance status could benefit from reoperation

Bladder tissue passive response to monotonic and cyclic loading

The fundamental passive mechanical properties of the bladder need to be known in order to design the most appropriate long-term surgical repair procedures and develop materials for bladder reconstruction. This study has focused on the bladder tissue viscoelastic behavior, providing a comprehensive analysis of the effects of fibers orientation, strain rate and loading history. Whole bladders harvested from one year old fat pigs (160 kg approximate weight) were dissected along the apex-to-base direction and samples were isolated from the lateral region of the wall, as well as along apex-to-base and transverse directions. Uniaxial monotonic (stress relaxation) and cyclic tests at different frequencies have been performed with the Bose Electroforce® 3200. Normalized stress relaxation functions have been interpolated using a second-order exponential series and loading and unloading stress-strain curves have been interpolated with a non-linear elastic model. The passive mechanical behavior of bladder tissue was shown to be heavily influenced by frequency and loading history, both in monotonic and cyclic tests. The anisotropy of the tissue was evident in monotonic and in cyclic tests as well, especially in tests performed on an exercised tissue and at high frequencies. In contrast, transverse and apex-to-base samples demonstrated an analogous relaxation behavior

EQUINE AND BOVINE MICROVESICLES DERIVED FROM AMNIOTIC PROGENITOR CELLS IN REGENERATIVE AND REPRODUCTIVE TOPICS

Durante questo progetto di dottorato sono stati condotti studi per comprendere la capacit\ue0 delle cellule mesenchimali amniotiche (AMCs) di agire attraverso meccanismi paracrini. La prima fase del disegno sperimentale ha valutato l\u2019efficacia delle AMCs sulla proliferazione delle cellule endometriali (EDCs) in assenza di un contatto cellula-cellula. Le EDCs sono state co-coltivate in un sistema trans-well con le AMCs o sono state coltivate in presenza del loro medium condizionato (CM). In entrambe le condizioni sperimentali \ue8 stato osservato un aumento del tasso di proliferazione delle EDCs definendo, cos\uec, il ruolo cruciale dei fattori secreti dalle AMCs come mediatori dell'azione delle cellule staminali. Il CM \ue8 composto da fattori solubili e non-solubili rappresentati da microvescicole (MVs). Per capire il ruolo delle MVs e del loro contenuto nell\u2019azione paracrina, la seconda fase del disegno sperimentale \ue8 stata incentrata sull\u2019individuazione del tipo di MVs secrete dalle AMCs e sulla loro efficacia in processi infiammatori in vitro su due importanti modelli sperimentali nella specie equina quali l\u2019endometrio ed il tendine. La produzione di MVs \ue8 stata ottimizzata attraverso un\u2019ultracentrifugazione del CM a 100.000 g per 1 ora. Attraverso lo strumento Nanosight \ue8 stato calcolato che la produzione di MVs da AMCs equine \ue8 di circa 2550\ub171 particelle/cellula, con una dimensione media di 258\ub155 nm. La microscopia elettronica a trasmissione ha confermato la presenza di vescicole cellulari che per dimensioni e modalit\ue0 di secrezione sono state classificate come shedding vesicles. Per capire se le cellule endometriali (EDCs) e tendinee (TNCs) fossero target delle MVs secrete dalle AMCs, \ue8 stata studiata l\u2019incorporazione delle medesime dopo marcatura con un fluorocromo lipofilico quale il PKH-26. Dopo uno studio di una curva dose-risposta \ue8 stato osservato che la dose ottimale per l'incorporazione di MVs in EDCs \ue8 stata di 40x106 MVs/ml a 72 h e per le TNCs di 40x106 MVs/ml a 24-48h. Per esaminare l'abilit\ue0 delle MVs nel contrastare un processo infiammatorio, entrambe le linee cellulari sono state stressate in vitro con LPS e trattate con MVs. La vitalit\ue0 cellulare, l'espressione di alcuni geni pro-infiammatori ed il rilascio delle rispettive citochine sono stati i parametri impiegati per valutare l\u2019efficacia delle MVs. Per entrambe le linee cellulari, il tasso di apoptosi \ue8 drammaticamente salito nelle cellule trattate con LPS, rispetto al controllo (CTR). LPS ha indotto un aumento significativo dell'espressione di TNF-\u3b1, IL-6 e IL-1\u3b2 in EDCs e di MMP-1, MMP-9, MMP-13 e TNF-\u3b1 in TNCs. Le MVs sono state in grado di contrastare l'effetto di LPS, diminuendo il tasso di apoptosi in entrambe le linee cellulari e riducendo il livello di espressione dei geni pro-infiammatori. Una conferma di questi dati \ue8 stata ottenuta attraverso l'analisi delle citochine pro-infiammatorie (TNF-\u3b2 and IL-6) ed anti-infiammatorie (TGF-\u3b1) rilasciate dalle EDCs nel terreno di coltura, confermando l'abilit\ue0 delle MVs di trasportare molecole capaci di contrastare la risposta infiammatoria in cellule stressate con LPS. Data l'importanza del contenuto in miRNA delle MVs, sia nelle AMCs sia nelle loro MVs \ue8 stata studiata la presenza di tre miRNA (miR-335, miR-146a, and miR-26a-2) coinvolti nella regolazione dei processi infiammatori. Questi tre miRNA sono stati identificati sia nelle AMCs sia nelle MVs, di conseguenza, \ue8 possibile ipotizzare che l'espressione genica dopo infiammazione con LPS e trattamento con MVs possa essere stato modulato dal trasferimento di miRNAs dalle MVs alle cellule target. Successivamente a questi studi, si \ue8 tentato di capire quanto in un processo rigenerativo possa essere imputato alle MVs e quanto ai fattori solubili presenti nel CM e, a questo proposito, \ue8 stata valutata l\u2019abilit\ue0 delle MVs di inibire la proliferazione delle cellule periferiche mononucleate del sangue (PBMC). La loro azione \ue8 stata comparata a quello del CM e del sovranatante (SN) ottenuto dal CM dopo scorporazione delle MVs. Il CM ed il SN hanno manifestato capacit\ue0 immunosoppressiva ma, anche dopo un trattamento di sonicazione al fine del rilascio del loro contenuto, le MVs non hanno dimostrato quest\u2019abilit\ue0. Questi risultati portano a dedurre che le MVs sono in grado di trasportare informazioni alle cellule target attraverso molecole capaci di contrastare l'effetto infiammatorio dovuto all'uso di LPS ma, tenendo in considerazione la mancanza di effetto immunomodulatorio, probabilmente in vivo la loro azione \ue8 integrata anche dalla presenza dei fattori solubili presenti nel CM. I meccanismi paracrini materno-fetali sono di vitale importanza ai fini dell\u2019instaurarsi di una gravidanza, per cui si \ue8 ritenuto interessante studiare questi meccanismi durante la produzione in vitro di embrioni bovini. Le differenti componenti del secretoma (CM, SN e MVs) ottenute da AMCs ed EDCs bovine sono state aggiunte al terreno di coltura embrionale a differenti giorni di coltura. I risultati hanno dimostrato che il giorno 5 \ue8 il migliore momento per la supplementazione e che le MVs di AMCs portano a migliori risultati qualitativi. Questi dati sono stati confermati dalla valutazione di alcuni geni coinvolti nell'apoptosi e nella protezione contro specie reattive dell'ossigeno. I motivi per i quali le MVs di AMCs si siano dimostrate migliori di quelle secrete dalle EDCs non sono ancora conosciuti ma \ue8 probabile che le EDCs coltivate in monostrato in vitro vadano incontro a de-differenziamento che altera la qualit\ue0 del loro secreto. In conclusione, \ue8 possibile affermare che le AMCs sono una linea cellulare affascinante in quanto derivano da materiale di scarto biologico, e quindi a basso costo, e possono essere impiegate in medicina rigenerativa per la loro capacit\ue0 di trasportare informazioni alle cellule target. Le MVs possono offrire un nuovo strumento terapeutico privo di cellule nell\u2019ambito della nanomedicina.During this PhD project, studies were carried out to understand the ability of amniotic mesenchymal cells (AMCs) to act by paracrine mechanism. At first, AMCs and their conditioned medium (CM) were investigated in an in vitro model using equine endometrial cells (EDCs) as target. Proliferation of EDCs was studied co-culturing them with AMCs in a trans-well system or in presence of AMC-CM. In both conditions, there was a significant increase in EDC proliferation rate, defining the crucial role of factors secreted by AMCs in stem cells action. CM is composed of soluble factors and no-soluble factors as microvesicles (MVs). In this context, in the second step of this project, the presence and the type of AMC-MVs were identified to understand their role in regenerative medicine. The production of MVs was optimized through a CM ultracentrifugation at 100.000 g for 1 hour. Microvesicle production from equine AMCs was 2550\ub171 particles/cell, with a mean dimension of 258\ub155 nm. The transmission electron microscopy confirmed the presence of extra-cellular vesicles that were classified as shedding vesicles for their size and modality of secretion. In order to understand if endometrial cells (EDCs) tendon cells (TNCs) were target of these MVs, an incorporation study was performed labelling MVs with a lipophilic fluorochrome such as PKH-26. By a dose-response curve, the optimal conditions of incorporation were at 72 h at a concentration of 40x106 MVs/ml for EDCs, and at 24-72 h at a concentration of 40x106 MVs/ml for TNCs. In order to study MVs ability to counteract an in vitro inflammation, EDCs and TNCs challenged with LPS and treated with MVs were evaluated by viability cell tests, by expression of some pro-inflammatory genes, and by release of respective cytokines. For both cell types, the apoptosis rate increased dramatically in cells treated with LPS if compared to the control (CTR). LPS significantly upregulated the expression of TNF-\u3b1, IL-6 and IL-1\u3b2 in EDCs and of MMP-1, MMP-9, MMP-13 and TNF-\u3b1 in TNCs. MVs were able to counteract the action of LPS, decreasing the apoptosis rate and reducing in the expression levels of the pro-inflammatory genes in both cell lines. Coherent results were obtained through the analysis of pro-inflammatory (TNF-\u3b2 and IL-6) and anti-inflammatory (TGF-\u3b1) cytokines released by EDCs in the culture medium, confirming the ability of MVs to transport molecules able to counteract the stress induced by LPS. Since MVs contain various active molecules, the presence of three miRNAs (miR-335, miR-146a, and miR-26a-2) was investigated, as they are involved in the regulation of inflammation. The selected miRNAs have been found in both AMCs and their MVs, so the previously observed downregulation of gene expression could be correlated to miRNA transfer from MVs to target cells. Moreover, the ability of MVs to inhibit peripheral blood mononuclear cell (PBMC) was evaluated, but MVs, also after lysis by sonication to release their content, were not able to inhibit PBMC proliferation despite to CM and SN. These results led to hypothesize that MVs brought to the target cells some molecules able to counteract the inflammatory situation due to the LPS but, taking into account the lack of their immunomodulatory action, probably, for an in vivo healing, soluble factor of CM are necessary too. Paracrine mechanism are essential also in maternal-fetal communication. In this context, we studied these mechanisms during bovine in vitro embryo production. Different components of secretome (CM, SN and MVs) from bovine AMCs and EDCs were supplemented to the embryo culture media at different days of culture. The results demonstrated that the day 5 of culture is the best time point for the supplementation of these components and that AMCs-MVs provided the best environment for the embryo concerning the blastocyst quality. These data were confirmed by the evaluation of genes involved in apoptosis and reactive oxygen species protection. The reasons for which the MVs of AMCs have proved better than those secreted by EDCs are not yet known but it is likely that in vitro culture of EDCs in monolayer may induce a de-differentiation that alters the quality of their secretion. As conclusion of this project, it is possible to speculate that AMCs are fascinating in view of producing off-the-shelf products, at low cost, and their use in regenerative medicine for their capacity to carry information to the target cells. The MVs may offer a new therapeutic cell-free tool in nanomedicine

Cross-Talk between PPARγ and Insulin Signaling and Modulation of Insulin Sensitivity

PPARγ activation in type 2 diabetic patients results in a marked improvement in insulin and glucose parameters, resulting from an improvement of whole-body insulin sensitivity. Adipose tissue is the major mediator of PPARγ action on insulin sensitivity. PPARγ activation in mature adipocytes induces the expression of a number of genes involved in the insulin signaling cascade, thereby improving insulin sensitivity. PPARγ is the master regulator of adipogenesis, thereby stimulating the production of small insulin-sensitive adipocytes. In addition to its importance in adipogenesis, PPARγ plays an important role in regulating lipid, metabolism in mature adipocytes by increasing fatty acid trapping. Finally, adipose tissue produces several cytokines that regulate energy homeostasis, lipid and glucose metabolism. Disturbances in the production of these factors may contribute to metabolic abnormalities, and PPARγ activation is also associated with beneficial effects on expression and secretion of a whole range of cytokines