The interaction between XBP1 and eNOS contributes to endothelial cell migration

Trabalho final de mestrado integrado em Medicina área científica de Urologia, apresentado á Faculdade de Medicina da Universidade de CoimbraINTRODUÇÃO: Nas últimas décadas a nefrectomia parcial tem assumido um papel de destaque no tratamento do carcinoma de células renais. Esta técnica, também denominada cirurgia poupadora de nefrónios, permite remover o tumor na totalidade, preservando o parênquima renal adjacente. As suas indicações tornaram-se mais abrangentes à medida que os resultados se mostraram cada vez mais promissores. Assim, actualmente a nefrectomia parcial é o tratamento padrão do carcinoma de células renais, em detrimento da tradicional nefrectomia radical. Discute-se agora qual das duas, nefrectomia parcial aberta ou laparoscópica, é a melhor opção. OBJECTIVOS: Rever as evidências científicas relativas ao tratamento do carcinoma de células renais pela nefrectomia parcial, aberta e laparoscópica, definindo o papel actual de cada uma delas nesta área. MÉTODOS: Pesquisa na PubMed e Medline de artigos relativos a nefrectomia radical e nefrectomia parcial aberta e laparoscópica, publicados entre 1997 e 2009. Consulta das “Guidelines” da Associação Europeia de Urologia. DESENVOLVIMENTO: A nefrectomia parcial mostra resultados oncológicos semelhantes aos da nefrectomia radical, permitindo uma menor morbilidade renal a longo prazo. A nefrectomia parcial aberta é agora o tratamento recomendado pelas “Guidelines” da Associação Europeia de Urologia para o tratamento de tumores com diâmetro inferior a 4 cm, limitados ao rim, mesmo quando o rim contralateral é normal. As indicações poderão ainda ser alargadas para tumores até 7 cm de diâmetro, dependendo das características do tumor. A nefrectomia parcial laparoscópica, embora tecnicamente mais exigente, é uma boa opção de tratamento em centros com experiência na realização da técnica, revelando bons resultados a curto prazo. CONCLUSÕES: A nefrectomia parcial aberta é actualmente o tratamento padrão do carcinoma de células renais. A nefrectomia parcial laparoscópica revela resultados a curto prazo semelhantes aos da nefrectomia parcial aberta, contudo são necessários estudos confirmando esses resultados a longo prazoINTRODUCTION: In the last decades partial nephrectomy have had an important role in the treatment of renal cell carcinoma. This surgery, also known as nephron-sparing surgery, allows to remove the tumor and to preserve the surrounding healthy renal parenchyma. Moreover, with the evolution of the technique its indications got more comprehensive. So, nowadays, partial nephrectomy is the standard treatment for renal cell carcinoma, instead of the traditional radical nephrectomy. There is now a discussion between which of the two, open or laparoscopic partial nephrectomy, is the best option. OBJECTIVES: Review the scientific evidences related to the treatment of renal cell carcinoma through open and laparoscopic partial nephrectomy, defining the actual role of both in this area. METHODS: Research articles related to radical nephrectomy, open and laparoscopic partial nephrectomies at PubMed and Medline publications between 1997 and 2009. Consult of the Guidelines of European Urology Association. DEVELOPMENT: Partial nephrectomy shows oncological outcomes similar to those of radical nephrectomy with less renal morbidity at long-term follow-up. Open partial nephrectomy is now the recommended treatment by the Guidelines of European Urology Association for the treatment of tumors less than 4 cm, limited to the kidney, even when the other kidney is normal. Indications can also include tumors less than 7 cm, depending on the characteristics of the tumor. Laparoscopic partial nephrectomy, although technically more demanding, is a good option in specialized centers and reveals similar results in a short-term. CONCLUSIONS: Nowadays open partial nephrectomy is the standard treatment of renal cell carcinoma. Laparoscopic partial shows similar results as open surgery in a short-term, however, more studies are needed to confirm this results at long-term. Key-words: Open partial nephrectomy, laparoscopic partial nephrectomy, renal cell carcinoma, indications, results

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Lettres de cinéma

Considérée comme un problème de mise en scène, la lettre au cinéma est un motif propice à stimuler l’imagination des cinéastes. Qu’elle soit le motif privilégié d’un cinéaste comme Max Ophuls ou d’un genre comme le mélodrame hollywoodien, l’objet de documentaires à la gloire du General Post Office britannique ou l’occasion de poèmes chez Tony Harrison, envoyée de façon anonyme dans la Treizième lettre, perdue dans Retour à Cold Mountain ou déchirée dans Sueurs froides, la lettre se révèle un agent dramatique à part entière. Jouant des écarts spatiotemporels permettant toutes sortes de circulations spatiales ou signifiantes, elle instaure un mode de communication spécifique au sein du film mais aussi avec le spectateur. Si l’adaptation de récits épistolaires à l’écran reste une gageure, certains cinéastes n’hésitent pas à concevoir leur film comme une lettre adressée à l’absent, que ce soit le père défunt chez Nathaniel Kahn, Dieu chez Neil Jordan ou le futur spectateur chez Jonas Mekas. L’écriture épistolaire rejoint ici celle du journal intime, toutes deux centrées sur l’écriture de soi dans le moment présent. De la missive insérée dans le film au film conçu comme lettre, les articles de ce recueil proposent donc une exploration de l’écriture épistolaire à l’écran dans le domaine du cinéma anglophone, jusqu’à la signature et autres inscriptions du nom propre, clôture de l’identité et du courrier

The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling

The epidermal growth factor (EGF) receptor has an important role in cellular proliferation, and the enzymatic activity of phospholipase C (PLC)-gamma1 is regarded to be critical for EGF-induced mitogenesis. In this study, we report for the first time a phospholipase complex composed of PLC-gamma1 and phospholipase D2 (PLD2). PLC-gamma1 is co-immunoprecipitated with PLD2 in COS-7 cells. The results of in vitro binding analysis and co-immunoprecipitation analysis in COS-7 cells show that the Src homology (SH) 3 domain of PLC-gamma1 binds to the proline-rich motif within the Phox homology (PX) domain of PLD2. The interaction between PLC-gamma1 and PLD2 is EGF stimulation-dependent and potentiates EGF-induced inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ increase. Mutating Pro-145 and Pro-148 within the PX domain of PLD2 to leucines disrupts the interaction between PLC-gamma1 and PLD2 and fails to potentiate EGF-induced IP3 formation and Ca2+ increase. However, neither PLD2 wild type nor PLD2 mutant affects the EGF-induced tyrosine phosphorylation of PLC-gamma1. These findings suggest that, upon EGF stimulation, PLC-gamma1 directly interacts with PLD2 and this interaction is important for PLC-gamma1 activityclose333

The ILD detector at the ILC

The International Large Detector, ILD, is a detector concept which has been developed for the electron-positron collider ILC. The detector has been optimized for precision physics in a range of energies between 90 GeV and 1 TeV. ILD features a high precision, large volume combined silicon and gaseous tracking system, together with a high granularity calorimeter, all inside a 3.5 T solenoidal magnetic field. The paradigm of particle flow has been the guiding principle of the design of ILD. In this document the required performance of the detector, the proposed implementation and the readiness of the different technologies needed for the implementation are discussed. This is done in the framework of the ILC collider proposal, now under consideration in Japan, and includes site specific aspects needed to build and operate the detector at the proposed ILC site in Japan

International Large Detector: Interim Design Report

The ILD detector is proposed for an electron-positron collider with collision centre-of-mass energies from 90~\GeV~to about 1~\TeV. It has been developed over the last 10 years by an international team of scientists with the goal to design and eventually propose a fully integrated detector, primarily for the International Linear Collider, ILC. In this report the fundamental ideas and concepts behind the ILD detector are discussed and the technologies needed for the realisation of the detector are reviewed. The document starts with a short review of the science goals of the ILC, and how the goals can be achieved today with the detector technologies at hand. After a discussion of the ILC and the environment in which the experiment will take place, the detector is described in more detail, including the status of the development of the technologies foreseen for each subdetector. The integration of the different sub-systems into an integrated detector is discussed, as is the interface between the detector and the collider. This is followed by a concise summary of the benchmarking which has been performed in order to find an optimal balance between performance and cost. To the end the costing methodology used by ILD is presented, and an updated cost estimate for the detector is presented. The report closes with a summary of the current status and of planned future actions