Novel surface-tethered estrogen polymeric platforms in cardiovascular regenerative medicine

L���estradiol (E2) est une hormone femelle qui joue un r��le essentiel, �� la fois dans la r��gulation et dans la d��termination de certaines conditions physiologiques in vivo, telle que la diff��renciation et la prolif��ration cellulaire. Lorsque l���E2 est donn�� en suppl��ment, par exemple dans le cas de th��rapie hormonale, deux effets sont observ��s, un effet g��nomique et un effet non-g��nomique, de par son interaction avec les r��cepteurs �� ��strog��ne du noyau ou de la membrane cellulaire, respectivement. L���effet non-g��nomique est plus difficile �� ��tudier biologiquement parce que l���effet se produit sur une ��chelle de temps extr��mement courte et �� cause de la nature hydrophobe de l���E2 qui r��duit sa biodisponibilit�� et donc son accessibilit�� aux cellules cibles. C���est pourquoi il est n��cessaire de d��velopper des syst��mes d���administration de l���E2 qui permettent de n�����tudier que l���effet non-g��nomique de l�����strog��ne. Une des strat��gies employ��e consiste �� greffer l���E2 �� des macromol��cules hydrophiles, comme de l���albumine de s��rum bovin (BSA) ou des dendrim��res de type poly(amido)amine, permettant de maintenir l���interaction de l���E2 avec les r��cepteurs d�����strog��ne de la membrane cellulaire et d�����viter la p��n��tration de l���E2 dans le noyau des cellules. Toutefois, ces syst��mes macromol��cules-E2 sont critiquables car ils sont peu stables et l���E2 peut se retrouver sous forme libre, ce qui affecte sa localisation cellulaire. L���objectif de cette th��se est donc de d��velopper de nouvelles plateformes fonctionnalis��es avec de l���E2 en utilisant les approches de synth��ses ascendantes et descendantes. Le but de ces plateformes est de permettre d�����tudier le m��canisme de l���effet non-g��nomique de l���E2, ainsi que d���explorer des applications potentielles dans le domaine biom��dical. L���approche ascendante est bas��e sur un ligand d���E2 activ��, l���acide 17,��-��thinylestradiol-benzo��que, attach�� de fa��on covalente �� un polym��re de chitosan avec des substitutions de phosphorylcholine (CH-PC-E2). L���estradiol est sous forme de pro-drogue attach��e au polym��re qui s���auto-assembler pour former un film. L���effet biologique de la composition chimique du film de chitosan-phosphorylcholine a ��t�� ��tudi�� sur des cellules endoth��liales. Les films de compositions chimiques diff��rentes ont pr��alablement ��t�� caract��ris��s de fa��on physicochimique. La topographie de la surface, la charge de surface, ainsi que la rh��ologie des diff��rents films contenant 15, 25, ou 40% molaires de phosphorylcholine, ont ��t�� ��tudi��s par microscopie �� force atomique (AFM), potentiel z��ta, r��sonance plasmonique de surface et par microbalance �� cristal de quartz avec dissipation (QCM-D). Les r��sultats de QCM-D ont montr�� que plus la part molaire en phosphorylcholine est grande moins il y a de fibrinog��ne qui s���adsorbe sur le film de CH-PC. Des cellules humaines de veine ombilicale (HUVECs) cultiv��es sur des films de CH-PC25 et de CH-PC40 forment des amas cellulaire appel��s sph��ro��des au bout de 4 jours, alors que ce n���est pas le cas lorsque ces cellules sont cultiv��es sur des films de CH-PC15. L���attachement de l���estradiol au polym��re a ��t�� caract��ris�� par plusieurs techniques, telles que la r��sonance magn��tique nucl��aire de proton (1H NMR), la spectroscopie infrarouge avec transform��e de Fourier �� r��fraction totale att��nu��e (FTIR-ATR) et la spectroscopie UV-visible. La nature hydrogel des films (sa capacit�� �� retenir l���eau) ainsi que l���interaction des films avec des r��cepteurs �� E2, ont ��t�� ��tudi��s par la QCM-D. Des ��tudes d���imagerie cellulaires utilisant du diac��tate de diaminofluoresceine-FM ont r��v��l�� que les films hydrogels de CH-PC-E2 stimulent la production d���oxyde nitrique par les cellules endoth��liales, qui joue un r��le protecteur pour le syst��me cardiovasculaire. L���ensemble de ces ��tudes met en valeur les r��les diff��rents et les applications potentielles qu���ont les films de type CH-PC-E2 et CH-PC dans le cadre de la m��decine cardiovasculaire r��g��n��rative. L���approche descendante est bas��e sur l���attachement de fa��on covalente d���E2 sur des ilots d���or de 2 ��m dispos��s en rang��es et espac��s par 12 ��m sur un substrat en verre. Les ilots ont ��t�� pr��par��s par photolithographie. La surface du verre a quant �� elle ��t�� modifi��e �� l���aide d���un tripeptide cyclique, le cRGD, favorisant l���adh��sion cellulaire. L���attachement d���E2 sur les surfaces d���or a ��t�� suivi et confirm�� par les techniques de SPR et de QCM-D. Des ��tudes d���ELISA ont montr�� une augmentation significative du niveau de phosphorylation de la kinase ERK (marqueur important de l���effet non-g��nomique) apr��s 1 heure d���exposition des cellules endoth��liales aux motifs alternant l���E2 et le cRGD. Par contre lorsque des cellules canc��reuses sont d��pos��es sur les surfaces pr��sentant des motifs d���E2, ces cellules ne croissent pas, ce qui sugg��re que l���E2 n���exerce pas d���effet g��nomique. Les r��sultats de l���approche descendante montrent le potentiel des surfaces pr��sentant des motifs d���E2 pour l�����tude des effets non-g��nomiques de l���E2 dans un mod��le in vitro.

Bespoke Radiology e-Learning

Introduction: Foundation doctors are expected to assess and interpret plain x-ray studies of the chest/abdomen before a definitive report is issued by senior staff. The Royal College of Radiologists have published guidelines (RCR curriculum) on the scope of plain film findings medical students should be familiar with.1 Studies have shown that the x-ray interpretation without feedback does not significantly improve diagnostic ability. 2 Queen���s University, Belfast Trust Radiology and Experior Medical developed an online system to assess individual student ability to interpret X-ray findings. Over a series of assessments each student���s profile is built up, identifying strengths and weakness. The system can then create bespoke individual assessments re-evaluating previously identified weak areas and quantifying interpretative skill improvement. Aim: To determine how readily an online system is adopted by senior medical students, investigating if increasing exposure to x-ray interpretation combined with cyclical formative feedback enhances performance. Methods: The system was offered to all 270 final year medical students as an online resource. The system comprised a series of 20 weekly 30 minute assessments, containing normal and abnormal x-rays within the RCR curriculum. After each assessment students were given formative feedback, including their own result, annotated answers, peer group comparison and a breakdown of areas of strength and weakness. Focus groups of 4-5 students addressed student perspectives of the system, including ease of use, image resolution, system performance across different operating platforms, perceived value of formative feedback loops, breakdown of performance and the value of bespoke personalised assessments. Research Ethics Approval was granted for the study. Data analysis was via two-sided one-sample t-test; initial minimal recruitment was estimated as 60 students, to detect a mean 10% change in performance, with a standard deviation of 20%. Results and Discussion: Over 80% (n = XXX/270) of the student cohort engaged with the study. Student baseline average was 39%, increasing to 62% by the exit test. The steadily sustained improvement (57% relative performance in interpretative diagnostic accuracy) was despite increasing test difficulty. Student feedback via focus groups was universally positive throughout the examined domains. Conclusion: The online resource proved to be valuable, with high levels of student engagement, improving performance despite increasingly difficulty testing and positive learner experience with the system. References: 1. Undergraduate Radiology Curriculum, The Royal College of Ra, April 2012. Ref No. BFCR(12)4 The Royal College of Radiologists, April 2012 2. I Satia, S Bashagha, A Bibi, R Ahmed, S Mellor, F Zaman. Assessing the accuracy and certainty in interpretating chest x-rays in the medical division. Clin Med August 2013 Vol.13 no. 4 349-352<br/>

Organizational responses to technological discontinuities: the case of the American College of Radiology (ACR)

A long history of organizational research has shown that organizations are affected significantly by changes in technology. Scholars have given particular attention to the effects of so-called disruptive or discontinuous technological changes. Studies have repeatedly shown that established, incumbent organizations tend to suffer deep performance declines (and even complete demise) in the face of such changes, and researchers have devoted much attention to identifying the organizational conditions and processes that are responsible for this persistent and widespread pattern of adaptation failure. This dissertation, which examines the response of the American College of Radiology (ACR) to the emergence of nuclear magnetic resonance imaging technology (NMR), aims to contribute to this well-established research tradition in three distinct and important ways. First, it focuses on a fundamentally different type of organization, a professional association, rather than the technology producers examined in most prior research. Although technologies are well known to be embedded in ���communities��� that include technology producers, suppliers, customers, governmental entities, professional societies, and other entities, most prior research has focused on the responses and ultimate fate of producers alone. Little if any research has explored the responses of professional organizations in particular. Second, the study employs a sophisticated process methodology that identifies the individual events that make up the organization���s response to technological change, as well as the overall sequence through which these events unfold. This process approach contrasts sharply with the variance models used in most previous studies and offers the promise of developing knowledge about how adaptation ultimately unfolds (or fails to). Finally, the project also contributes significantly through its exploration of an apparently successful case of adaptation to technological change. Though nuclear magnetic resonance imaging posed a serious threat to the ACR and its members, this threat appears to have been successfully managed and overcome. Although the unique nature of the organization and the technology under study place some important limits on the generalizablity of this research, its findings nonetheless provide some important basic insights about the process through which social organizations can successfully adapt to discontinuous technological changes. These insights, which may also be of substantial relevance to technology producer organizations, will also be elaborated.

N��veis de refer��ncia de diagn��stico em procedimentos pedi��tricos de medicina nuclear

Introdu����o: A Medicina Nuclear (MN) �� uma modalidade imagiol��gica em grande expans��o na atualidade, tornando-se especialmente importante em pediatria. Considerando a elevada radiosensibilidade das crian��as, torna-se crucial otimizar os v��rios procedimentos dentro desta modalidade. Objetivo: Determinar N��veis de Refer��ncia de Diagn��stico (NRD���s) para procedimentos de MN Pedi��trica num dos centros de excel��ncia nacional e comparar os valores obtidos com a literatura internacional. Material e M��todos: Foi realizada uma an��lise retrospetiva dos cabe��alhos Digital Imaging and Communications in Medicine (DICOM) de Tomografia por Emiss��o de Posit��es (PET-CT) dispon��veis no Picture Archiving and Communication System (PACS), de modo a recolher os valores de CT Dose Index (CTDIvol-mGy), Dose Length Product (DLP-mGy.cm), atividade administrada, o g��nero, peso, altura e idade foram recolhidos; De modo a obter os valores de dose relativos a outros procedimentos de MN foram analisados documentos em formato papel. Considerando a idade dos doentes foi estabelecida a categoriza����o et��ria de forma a determinar os NRD���s locais com base no percentil 75 dos valores de dose. Resultados: Os NRD���s para a atividade administrada em rec��m-nascidos (0 anos) para a Cintigrafia Renal e Cistografia Direta foi de 26MBq (0,70 e 0,69mCi, respetivamente). Na Renocintigrafia, o valor obtido foi 30MBq (0,80mCi). Para o exame de PET-CT corpo inteiro, os NRD���s para a atividade administrada, CTDIvol e DLP, para os 15 anos foi de 296MBq, 3,23mGy e de 396,79mGy.cm, respectivamente. Para a Cintigrafia do esqueleto o valor obtido para os 15 anos foi de 684MBq (17,5mCi). Conclus��es: Ap��s a compara����o com os resultados publicados em outros estudos verificaram-se algumas diferen��as, sendo os valores de NRD locais obtidos acima dos n��veis apresentados.

Role of nuclear redox control, intra-population heterogeneity and oxygen tension in human amniotic fluid stem cells aging

Amniotic fluid stem cells (hAFSC) are emerging as a potential therapeutic approach for various disorders. The low number of available hAFSC requires their ex vivo expansion prior to clinical use, however, during their in vitro culture, hAFSC quickly reach replicative senescence. The principal aim of this study was to investigate the aging process occurring during in vitro expansion of hAFSC, focusing on the redox control that has been reported to be affected in premature and physiological aging. My results show that a strong heterogeneity is present among samples that reflects their different behaviour in culture. I identified three proteins, namely Nox4, prelamin A and PML, which expression increases during hAFSC aging process and could be used as new biomarkers to screen the samples. Furthermore, I found that Nox4 degradation is regulated by sumoylation via proteasome and involves interactions with PML bodies and prelamin A. Since various studies revealed that donor-dependent differences could be explained by cell-to-cell variation within each patient, I studied in deep this phenomenon. I showed that the heterogeneity among samples is also accompanied by a strong intra-population heterogeneity. Separation of hAFSC subpopulations from the same donor, using Celector�� technology, showed that an enrichment in the last eluted fraction could improve hAFSC application in regenerative medicine. One of the other problems is that nowadays hAFSC are expanded under atmospheric O2 concentration, which is higher than the O2 tension in their natural niches. This higher O2 concentration might cause environmental stress to the in vitro cultured hAFSCs and accelerate their aging process. Here, I showed that prolonged low oxygen tension exposure preserves different hAFSC stemness properties. In conclusion, my study pointed different approaches to improve in vitro hAFSC expansion and manipulation with the purpose to land at stem cell therapy.

Assessment Of The Fixation Of Mandibular Symphysis Fractures Using Conical Cannulated Screws: Mechanical And Photoelastic Tests.

The aim of this study was to use mechanical and photoelastic tests to compare the performance of cannulated screws with other fixation methods in mandibular symphysis fractures. Ten polyurethane mandibles were allocated to each group and fixed as follows: group PRP, 2 perpendicular miniplates; group PLL, 1 miniplate and 1 plate, parallel; and group CS, 2 cannulated screws. Vertical linear loading tests were performed. The differences between mean values were analyzed with the Tukey test. The photoelastic test was carried out using a polariscope. The results revealed differences between the CS and PRP groups at 1, 3, 5, and 10 millimeters of displacement. The photoelastic test confirmed higher stress concentration in all groups close to the mandibular base, whereas the CS group showed it throughout the region assessed. Conical cannulated screws performed well in mechanical and photoelastic tests.

Evaluation Of Different Treatment Methods Against Denture Stomatitis: A Randomized Clinical Study.

The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.

High Diagnostic Accuracy And Reproducibility Of Fine-needle Aspiration Cytology For Diagnosing Salivary Gland Tumors: Cytohistologic Correlation In 182 Cases.

The purpose of this study was to assess the efficacy and reproducibility of the cytologic diagnosis of salivary gland tumors (SGTs) using fine-needle aspiration cytology (FNAC). The study aimed to determine diagnostic accuracy, sensitivity, and specificity and to evaluate the extent of interobserver agreement. We retrospectively evaluated SGTs from the files of the Division of Pathology at the Clinics Hospital of S��o Paulo and Piracicaba Dental School between 2000 and 2006. We performed cytohistologic correlation in 182 SGTs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 94%, 100%, 100%, 100%, and 99%, respectively. The interobserver cytologic reproducibility showed significant statistical concordance (P��<��.0001). FNAC is an effective tool for performing a reliable preoperative diagnosis in SGTs and shows high diagnostic accuracy and consistent interobserver reproducibility. Further FNAC studies analyzing large samples of malignant SGTs��and reactive salivary lesions are needed to confirm their accuracy.

Emergent Antiferromagnetism Out Of The Hidden-order" State In Uru2si2: High Magnetic Field Nuclear Magnetic Resonance To 40 T."

Very high field (29)Si-NMR measurements using a fully (29)Si-enriched URu(2)Si(2) single crystal were carried out in order to microscopically investigate the hidden order (HO) state and adjacent magnetic phases in the high field limit. At the lowest measured temperature of 0.4 K, a clear anomaly reflecting a Fermi surface instability near 22 T inside the HO state is detected by the (29)Si shift, (29)K(c). Moreover, a strong enhancement of (29)K(c) develops near a critical field H(c) ��� 35.6 T, and the ^{29}Si-NMR signal disappears suddenly at H(c), indicating the total suppression of the HO state. Nevertheless, a weak and shifted (29)Si-NMR signal reappears for fields higher than H(c) at 4.2 K, providing evidence for a magnetic structure within the magnetic phase caused by the Ising-type anisotropy of the uranium ordered moments.

Fine Needle Aspiration Cytology In The Diagnosis Of Perioral Adverse Reactions To Cosmetic Dermal Fillers.

Facial cosmetic procedures are increasingly requested, and dermal filler materials have been widely used as a nonsurgical option since the 1980s. However, injectable fillers have been implicated in local adverse reactions. Therefore, the aim of this article was to describe the use of fine needle aspiration cytology (FNAC) in the diagnosis of foreign-body reactions to the perioral injection of dermal fillers. A 69-year-old woman presented with a painful nodule on her right nasolabial fold. Intraoral FNAC was performed, and cytologic smears were examined under optical and polarized light microscopy, showing birefringent microspheres, confirming the diagnosis of an adverse reaction caused by polymethyl methacrylate filler. FNAC is a less invasive method to confirm the diagnosis of adverse reactions caused by perioral cosmetic dermal fillers.

Five Years Of Implementation Of Guidelines In Hematology And Transfusion Medicine In Brazil.

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Stromal Myofibroblasts In Squamous Cell Carcinoma Of The Tongue In Young Patients - A Multicenter Collaborative Study.

The purpose of this study was to evaluate the presence of myofibroblasts, frequently associated with a more aggressive neoplastic behavior, in oral tongue squamous cell carcinoma (TSCC) of young patients and to compare with the distribution observed in older patients. Tumor samples from 29 patients younger than 40 years old affected by TSCC were retrieved and investigated for the presence of stromal myofibroblasts by immunohistochemical reactions against �� smooth muscle actin, and the results obtained were compared to TSCC cases affecting older patients. No positive reaction could be found in the stromal areas devoid of neoplastic tissue, whereas myofibroblasts were present in 58.6% of the lesions in young patients and in 75.9% of the older ones. No significant difference was found when comparing the invasive front and the overall stroma of both groups, and no correlation could be obtained with stromal �� smooth muscle actin expression, higher tumor grades or clinical stage (P > .05). There was no significant difference between the presence of stromal myofibroblasts of TSCC affecting young and old individuals.

Observation Of D0 Meson Nuclear Modifications In Au+au Collisions At Sqrt[s(nn)] = 200 Gev.

We report the first measurement of charmed-hadron (D(0)) production via the hadronic decay channel (D(0) ��� K(-) + ��(+)) in Au+Au collisions at sqrt[s(NN)] = 200 GeV with the STAR experiment. The charm production cross section per nucleon-nucleon collision at midrapidity scales with the number of binary collisions, N(bin), from p+p to central Au+Au collisions. The D(0) meson yields in central Au + Au collisions are strongly suppressed compared to those in p+p scaled by N(bin), for transverse momenta p(T) > 3 GeV/c, demonstrating significant energy loss of charm quarks in the hot and dense medium. An enhancement at intermediate p(T) is also observed. Model calculations including strong charm-medium interactions and coalescence hadronization describe our measurements.