Definir les causes del trastorn vocal : un camí complex però imprescindible

La disfonia és una alteració de les qualitats bàsiques de la veu (timbre, alçada, intensitat) que pot afectar la vida social i professional del pacient. La valoració de la disfonia en els protocols mèdics actuals incideix, d'una banda, en els mitjans tecnics que ajuden a definir les característiques d'aquesta disfonia (anàlisi acústica informatitzada) i, de l'altra, en l'exploració de la laringe que permet una classificació de les lesions orgàniques i de la funcionalitat laríngia (laringoestrobosòpia), així com la valoració subjectiva del pacient del seu handicap vocal. Aquest article aborda la multifactorialitat de la disfonia com a símptoma i no com a causa, valorant especialment els aspectes emocionals, i constata la manca de mitjans simples i significatius per a una valoració d'aquests aspectes. D'aquí se'n deriva la necessitat de l'abordatge multidisciplinari, tant en el diagnòstic com en la intervenció en els trastorns de la veu.

The Ret receptor tyrosine kinase pathway functionally interacts with the ERalpha pathway in breast cancer.

A limited number of receptor tyrosine kinases (e.g., ErbB and fibroblast growth factor receptor families) have been genetically linked to breast cancer development. Here, we investigated the contribution of the Ret receptor tyrosine kinase to breast tumor biology. Ret was expressed in primary breast tumors and cell lines. In estrogen receptor (ER)alpha-positive MCF7 and T47D lines, the ligand (glial-derived neurotrophic factor) activated signaling pathways and increased anchorage-independent proliferation in a Ret-dependent manner, showing that Ret signaling is functional in breast tumor cells. Ret expression was induced by estrogens and Ret signaling enhanced estrogen-driven proliferation, highlighting the functional interaction of Ret and ER pathways. Furthermore, Ret was detected in primary cancers, and there were higher Ret levels in ERalpha-positive tumors. In summary, we showed that Ret is a novel proliferative pathway interacting with ER signaling in vitro. Expression of Ret in primary breast tumors suggests that Ret might be a novel therapeutic target in breast cancer.

A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss.

Hearing loss can be caused by a variety of insults, including acoustic trauma and exposure to ototoxins, that principally effect the viability of sensory hair cells via the MAP kinase (MAPK) cell death signaling pathway that incorporates c-Jun N-terminal kinase (JNK). We evaluated the otoprotective efficacy of D-JNKI-1, a cell permeable peptide that blocks the MAPK-JNK signal pathway. The experimental studies included organ cultures of neonatal mouse cochlea exposed to an ototoxic drug and cochleae of adult guinea pigs that were exposed to either an ototoxic drug or acoustic trauma. Results obtained from the organ of Corti explants demonstrated that the MAPK-JNK signal pathway is associated with injury and that blocking of this signal pathway prevented apoptosis in areas of aminoglycoside damage. Treatment of the neomycin-exposed organ of Corti explants with D-JNKI-1 completely prevented hair cell death initiated by this ototoxin. Results from in vivo studies showed that direct application of D-JNKI-1 into the scala tympani of the guinea pig cochlea prevented nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity. Local delivery of D-JNKI-1 also prevented acoustic trauma-induced permanent hearing loss in a dose-dependent manner. These results indicate that the MAPK-JNK signal pathway is involved in both ototoxicity and acoustic trauma-induced hair cell loss and permanent hearing loss. Blocking this signal pathway with D-JNKI-1 is of potential therapeutic value for long-term protection of both the morphological integrity and physiological function of the organ of Corti during times of oxidative stress.

Monitoimipystysorvin NC- ohjelmoinnin kehittäminen CAM käyttöönotolla

Diplomityön tavoitteena oli tehostaa venttiilipesien koneistuksessa käytettävän monitoimipystysorvin NC - ohjelmointia CAM - ohjelman käyttöönotolla. Tutkimus on osa laajempaa kokonaisuutta liittyen koneistusalihankinnan kehittämiseen ja yrityksen kilpailukyvyn ylläpitoon ja parantamiseen liiketoiminta-alueella, jolla on tällä hetkellä hyvät kasvunäkymät. Tavoite rajattiin yritykseen jo aiemmin hankitun WinCAM - ohjelman päivittämiseen ja hyödyntämiseen monitoimipystysorvin NC - ohjelmoinnissa. Tutkimuksen käytännön tavoitteena oli selvittää CAM - ohjelmoinnin käyttömahdollisuudet, sekä luoda CAM - ohjelmistoon pohjautuva, räätälöity NC - ohjelmointikonsepti pilottikohteeseen. Tutkimuksen kokeellisen osuuden muodostivat tällöin nykyisen tuotannon ongelmakohtien löytäminen, koneen ohjelmointitarpeiden kartoitus,sekä menetelmäkehitys. Tutkimuksen päämääränä oli tuotannon tasolla käytettävä järjestelmä, jolla koneen ohjelmointi olisi mahdollista myös vähemmällä konekohtaisella kokemuksella. Nykyisen toimintatavan ongelmina olivat yhtenäisen NC - ohjelmointikäytännön puute, niin valmiiden ohjelmien käytössä kuin uusienkin ohjelmien tekemisessä. Tähän olivat syynä NC - ohjauksen heikko käytettävyys erityisesti sorvauksen osalta. Nämä tekijät yhdistettynä monitoimityöstökoneessa tarvittavaan koordinaatiston hallintaan vaikeuttivat ohjelmointia. Työntekijäkohtaiset erot NC - ohjelmien käytössä, sekä laadultaan vaihtelevat valuaihiot aiheuttivat tuotannon läpäisyaikaan merkittävää vaihtelua. Siten myös koneen kuormituksen säätely oli vaikeaa. Uuden ohjelmointikonseptin toteutuksessa pidettiin etusijalla hyvää käytettävyyttä, sekä uuden menetelmän aukotonta liittymistä olemassa oleviin tuotantojärjestelmiin. Ohjelmointikonseptin toteutuksessa, osaperheestä haettiin selkeästi parametroitaviksi soveltuvat työvaiheet, jotka voitiin hallita yleiskäyttöisillä aliohjelmilla. Tuotteiden muidengeometrioiden hallintaan laadittiin geometriakirjasto, jota voitiin käyttää tavanomaisen graafisen ohjelmoinnin pohjana. Vanhaa toimintatapaa ja diplomityön aikana kehitettyä CAM - ohjelmointijärjestelmää vertailtiin perustuen NC - ohjelmien tehokkuuteen, jota tarkasteltiin saman työvaiheen työstöaikaan perustuen. Tämän lisäksi tärkeän tuloksen muodostavat myös kvalitatiivisetseikat, jotka liittyvät ohjelmointiympäristön käytettävyyteen. CAM - ohjelmoinnin kehittäminen ja käyttöönotto pilottikohteessa sujui pääosin hyvin ja laaditunsuunnitelman mukaisesti. Aiemmin hankalasti ohjelmoitavat työvaiheet, kuten erilaisten laippatasopintojen ja reikäpiirien ohjelmointi muutettiin makrokäyttöön soveltuviksi. Sorvauksessa ongelmia aiheuttaneen tiivistelilan koneistukseen sovellettiin graafista ohjelmointia. Koko tuotannon mittakaavassa NC - ohjelmoinninosuus oli kuitenkin vähäinen, mistä johtuen koneen tuottavuuteen ei tutkimuksenajanjaksolla voitu vaikuttaa. Sen sijaan tuotannon sujuvuuteen oleellisesti vaikuttavaa työtekijöiden 'hiljaisen tiedon' määrää voitiin vähentää vakioimalla ohjelmointia ja siirtämällä tehokkaiksi havaitut menetelmät ohjelmointijärjestelmään.

PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3)

The human PFKFB3 is composed of 19 exons spanning genomic region about 90,6 Kb (GenBank). Alternative splicing variants have been reported. The main variants corresponding to mRNAs of 4453 bp and 4224 bp for the variant 1 u-PFK2 (NM_004566.3) and variant 2 i-PFK2 (NM_001145443.1), respectively...

Phosphorylation of phosphatidylinositol-3-kinase-protein kinase B and extracellular signal-regulated kinases 1/2 mediate reoxygenation-induced cardioprotection during hypoxia.

In vivo exposure to chronic hypoxia (CH) depresses myocardial performance and tolerance to ischemia, but daily reoxyenation during CH (CHR) confers cardioprotection. To elucidate the underlying mechanism, we tested the role of phosphatidylinositol-3-kinase-protein kinase B (Akt) and p42/p44 extracellular signal-regulated kinases (ERK1/2), which are known to be associated with protection against ischemia/reperfusion (I/R). Male Sprague-Dawley rats were maintained for two weeks under CH (10% O(2)) or CHR (as CH but with one-hour daily exposure to room air). Then, hearts were either frozen for biochemical analyses or Langendorff-perfused to determine performance (intraventricular balloon) and tolerance to 30-min global ischemia and 45-min reperfusion, assessed as recovery of performance after I/R and infarct size (tetrazolium staining). Additional hearts were perfused in the presence of 15 micromol/L LY-294002 (inhibitor of Akt), 10 micromol/L UO-126 (inhibitor of ERK1/2) or 10 micromol/L PD-98059 (less-specific inhibitor of ERK1/2) given 15 min before ischemia and throughout the first 20 min of reperfusion. Whereas total Akt and ERK1/2 were unaffected by CH and CHR in vivo, in CHR hearts the phosphorylation of both proteins was higher than in CH hearts. This was accompanied by better performance after I/R (heart rate x developed pressure), lower end-diastolic pressure and reduced infarct size. Whereas the treatment with LY-294002 decreased the phosphorylation of Akt only, the treatment with UO-126 decreased ERK1/2, and that with PD-98059 decreased both Akt and ERK1/2. In all cases, the cardioprotective effect led by CHR was lost. In conclusion, in vivo daily reoxygenation during CH enhances Akt and ERK1/2 signaling. This response was accompanied by a complex phenotype consisting in improved resistance to stress, better myocardial performance and lower infarct size after I/R. Selective inhibition of Akt and ERK1/2 phosphorylation abolishes the beneficial effects of the reoxygenation. Therefore, Akt and ERK1/2 have an important role to mediate cardioprotection by reoxygenation during CH in vivo.

Limited role of the c-Jun N-terminal kinase pathway in a neonatal rat model of cerebral hypoxia-ischemia

D-JNKI1, a cell-permeable peptide inhibitor of the c-Jun N-terminal kinase (JNK) pathway, has been shown to be a powerful neuroprotective agent after focal cerebral ischemia in adult mice and young rats. We have investigated the potential neuroprotective effect of D-JNKI1 and the involvement of the JNK pathway in a neonatal rat model of cerebral hypoxia-ischemia. Seven-day-old rats underwent a permanent ligation of the right common carotid artery followed by 2h of hypoxia (8% oxygen). Treatment with D-JNKI1 (0.3mg/kg intraperitoneally) significantly reduced early calpain activation, late caspase-3 activation and, in the thalamus, autophagosome formation, indicating an involvement of JNK in different types of cell death: necrotic, apoptotic and autophagic. However the size of the lesion was unchanged. Further analysis showed that neonatal hypoxia-ischemia induced an immediate decrease in JNK phosphorylation (reflecting mainly P-JNK1) followed by a slow progressive increase (including P-JNK3 54kDa), whereas c-jun and c-fos expression were both strongly activated immediately after hypoxia-ischemia. In conclusion, unlike in adult ischemic models, JNK is only moderately activated after severe cerebral hypoxia-ischemia in neonatal rats and the observed positive effects of D-JNKI1 are insufficient to give neuroprotection. Thus, for perinatal asphyxia, D-JNKI1 can only be considered in association with other therapies.

Phosphorylation-dependent dimerization and subcellular localization of islet-brain 1/c-Jun N-terminal kinase-interacting protein 1.

Islet-brain 1 [IB1; also termed c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1] is involved in the apoptotic signaling cascade of JNK and functions as a scaffold protein. It organizes several MAP kinases and the microtubule-transport motor protein kinesin and relates to other signal-transducing molecules such as the amyloid precursor protein. Here we have identified IB1/JIP-1 using different antibodies that reacted with either a monomeric or a dimeric form of IB1/JIP-1. By immunoelectron microscopy, differences in the subcellular localization were observed. The monomeric form was found in the cytoplasmic compartment and is associated with the cytoskeleton and with membranes, whereas the dimeric form was found in addition in nuclei. After treatment of mouse brain homogenates with alkaline phosphatase, the dimeric form disappeared and the monomeric form decreased its molecular weight, suggesting that an IB1/JIP-1 dimerization is phosphorylation dependent and that IB1 exists in several phospho- forms. N-methyl-D-aspartate receptor activation induced a dephosphorylation of IB1/JIP-1 in primary cultures of cortical neurons and reduced homodimerization. In conclusion, these data suggest that IB1/JIP-1 monomers and dimers may differ in compartmental localization and thus function as a scaffold protein of the JNK signaling cascade in the cytoplasm or as a transcription factor in nuclei.

El dret a la informació dels pacients: metges i bibliotecaris, un camí per recórrer plegats

Un malalt és, per sobre de tot, un ciutadà amb drets,un dels quals és el de rebre informació adequada sobre la pròpia malaltia. A partir d"experiències dels Estats Units, es mostra que l"exercici d"aquest dret exigeix la participació tant de metges com de bibliotecaris. Finalment, es reivindica el paper del bibliotecari entès com a gestor de la informació medico-sanitària adreçada a metges, pacients i familiars.

Disseny d'una nau bioclimàtica sense ús determinat, ubicat al Polígon Industrial "Camí dels Frares" de Lleida

L'objecte del present projecte tècnic és la descripció de la climatització d'una nau industrial bioclimàtica, fent ús de sistemes passius i si fos necessari, de sistemes actius. El concepte de bioclimàtic procedeix de bios-vida i clima - orientació. El propòsit d'aquest disseny arquitectònic és que des del punt de vista energètic permeti que la nau mantingui un nivell de confort tant en hivern com en estiu, aplicant una sèrie de criteris de disseny a fi d'utilitzar els elements constructius i funcionals propis de l'edifici per tal d'aconseguir un bon control del seu comportament energètic.

Light framing, estructura lleugera; un camí per la estandarització en el procés constructiu. Cas general del sistema light framing i en cas particular del sistema eurodom

Projecte d'una vivenda unifamiliar amb un sistema constructiu mitjançant estructura lleugera on el material principal és la fusta i altres materials sostenibles i mètodes d'execució de prefabricació o in situ.

Projecte de millora del camí de la Tossa – camí de Rosselló, ubicat als TM de Vilanova i Benavent de Segrià, comarca del Segrià

Aquest projecte tracta sobre la millora d’arranjament del camí de la Tossa – camí de Rosselló, ubicat als termes municipals de Vilanova i Benavent de Segrià (Segrià). Els aspectes que s’han volgut millorar són la poca amplada del camí, eliminar i/o modificar revolts perillosos i asfaltar el camí amb un acabat del ferm amb mescla bituminosa. A la Memòria com a punts més rellevants s’hi pot trobar l’objectiu i condicionants del projecte, estudi d’alternatives i enginyeria dels projecte entre d’altres. En aquest últim, s’hi descriuen les opcions adoptades en quant a trànsit, traçat, esplanació, ferm, drenatge i senyalització. Alguns d’aquests punts es troben a més, desglossats detalladament en l’annex a memòria, en aquest annex també hi figuren altres documents rellevants com l’Estudi de Seguretat i Salut i la Justificació de preus.

Projecte d’un camí rural de Bovera a Bellaguarda a la comarca de les Garrigues

El camí projectat es troba situat entre les poblacions de Bovera i Bellaguarda, ambdues es troben situades al sud de la comarca de les Garrigues. Són dos pobles on l’activitat econòmica principal és l’agricultura. És una zona amb un relleu abrupte el qual forma part de la deprecio de l’Ebre, la primera capa del substrat en gran part està formada per terra argilosa, llims i margues, hi ha algun aflorament rocós. La longitud del camí és de 9.664,9 m, un ferm de 5 m d’amplada; al llarg del traçat es supera un desnivell de 341 m.

Projecte de condicionament del camí rural de l’Aiguabarreig al terme municipal de Massalcoreig (Lleida)

El tema d’aquest projecte és el condicionament del camí rural, situat al llarg del riu Cinca, al terme municipal de Massalcoreig (Lleida). Aquest projecte està format per quatre documents, classificats en dos volums. Al primer volum trobem el document número 1, format per la memòria amb els seus annexes on es defineixen les característiques bàsiques a tenir en compte per a realitzar el condicionament del camí, així com el desenvolupament de les activitats. Al segon volum, trobem la resta de documents. En primer lloc, trobem el segon document, els plànols necessaris per a dur a terme l’obra. A continuació, el tercer document és el plec de condicions en el que s’estipulen les normes que s’han de tenir en compte durant l’execució del projecte. Finalment, el quart document, és el pressupost, on hi ha el cost de l’obra.

Condicionament i millora del camí de la carretera de Tarragona a la partida de Grealó de Lleida

Projecte de condicionament i millora d’un camí rural, situat al terme municipal de Lleida. Consisteix bàsicament en la correcció de la traça del camí actual, a fi i efecte, de millorar el seu recorregut tenint en conte les normatives i recomanacions establertes per a camins rurals. Es realitza el càlcul de les petites conques hidrogràfiques i es dissenya un sistema d’evacuacions de les aigües per tal de prolongar la vida útil del camí en qüestió.