Quality of life of adult patient with hemophilia and treatment adherence

Uvod: Hemofilija je redka dedna bolezen, ki prizadene predvsem moške in je vezana na kromosom X. Posledica je pomanjkanje koagulacijskega faktorja VIII ali IX in nagnjenost h krvavitvam. Delimo jo na hemofilijo A in B, glede na resnost bolezni pa na blago, zmerno in hudo obliko hemofilije. Spremljajo jo spontane krvavitve v sklepe in mišice. Bolezen zdravimo profilaktično ali po potrebi z dodajanjem manjkajočega koagulacijskega faktorja. Najpogostejša posledica je hemofilna artropija, ki je posledica krvavitev v sklepe. Namen: Želeli smo ugotoviti adherenco na zdravljenje odraslih bolnikov s hemofilijo v Sloveniji in njihovo kvaliteto življenja. Poleg tega smo ugotavljali še značilnosti bolezni bolnikov s hemofilijo v Sloveniji in njihov življenjski slog. Metode dela: Teoretična izhodišča za diplomsko delo smo poiskali v literaturi iz zbirk Medline, Cinahl, UpToDate, Pub Med in z brskalnikom Google učenjak. Vključili smo 36 odraslih bolnikov z zmerno in hudo obliko hemofilije v Sloveniji, starih med 22 in 73 let. Pri raziskovalnem delu smo uporabili dva preverjena anketna vprašalnika, VERITAS-PRO in SF-36. Z VERITAS-PRO smo merili adherenco na zdravljenje v šestih dimenzijah in z SF-36 kvaliteto življenja s 36 trditvami. Pridobljene podatke smo prikazali z deskriptivno statistiko. Rezultati: Adherenca na zdravljenje bolnikov s hemofilijo je na vseh šestih dimenzijah dobra. Najboljša adherentnost se je izkazala pri odmerjanju in najslabša, vendar kljub temu še zmeraj dobra, pri komunikaciji. Le eden izmed anketiranih bolnikov je bil neadherenten, saj je imel število točk nad mejno vrednostjo (57). Bolniki ocenjujejo svojo kvaliteto življenja kot slabo. Mentalno zdravje v povprečju ocenjujejo bolje, kot pa fizično zdravje. Razprava in zaključek: Odrasli bolniki s hemofilijo imajo dobro adherenco na zdravljenje, kljub temu pa kvaliteto življenje v smislu zdravja ocenjujejo kot slabo. Rezultati odstopajo od rezultatov nekaterih drugih študij, kjer so ocene za kvaliteto življenja višje ali nižje. Vsem pa je skupno, da bolniki svojo kvaliteto življenja bolje ocenjujejo v smislu mentalnega zdravja v primerjavi z fizičnim zdravjem. Razlog za slabšo kvaliteto življenja v povezavi z zdravjem bi lahko bil, da v otroštvu niso prejemali ustreznega zdravljenja, saj ga takrat ni bilo.Introduction: Hemophilia is a rare hereditary disease that mainly affects men and is linked to the X chromosome. The result is a lack of coagulation factor VIII or IX and a tendency to bleed. It is divided into hemophilia A and B, and according to the severity of the disease, into mild, moderate and severe forms of hemophilia. It is accompanied by spontaneous bleeding into the joints and muscles. The disease is treated prophylactically or, if necessary, by adding the missing coagulation factor. The most common consequence is hemophilic arthrosis, which is the result of bleeding into the joints. Purpose: We wanted to determine the adherence to treatment of adult patients with hemophilia in Slovenia and their quality of life. In addition, we determined the disease characteristics of hemophilia patients in Slovenia and their lifestyle. Purpose: We wanted to determine the adherence to treatment of adult patients with hemophilia in Slovenia and their quality of life. In addition, we determined the disease characteristics of hemophilia patients in Slovenia and their lifestyle. Methods: The theoretical starting points for the diploma work were searched in the literature from the Medline, Cinahl, UpToDate, Pub Med collections and with the Google Scholar browser. We included 36 adult patients with moderate and severe hemophilia in Slovenia, aged between 22 and 73 years. In the research work, we used two verified questionnaires, VERITAS-PRO and SF-36. With VERITAS-PRO we measured adherence to treatment in six dimensions and with SF-36 quality of life with 36 statements. We presented the obtained data with descriptive statistics. Results: Adherence to the treatment of patients with hemophilia is good on all six dimensions. The best adherence was found in dosing and the worst, but still good, in communication. Only one of the surveyed patients was non-adherent, as he had a score above the threshold value (57). Patients rate their quality of life as poor. On average, mental health is rated better than physical health. Discussion and conclusion: Adult patients with hemophilia have good adherence to treatment, but despite this, they rate the quality of life in terms of health as poor. The results deviate from the results of some other studies, where the scores for the quality of life are higher or lower. What they all have in common is that patients rate their quality of life better in terms of mental health compared to physical health. The reason for the worse quality of life in relation to health could be that they did not receive adequate treatment in childhood, as it did not exist then

Fast profiling of protease specificity reveals similar substrate specificities for cathepsins K, L and S

Proteases are important effectors of numerous physiological and pathological processes. Reliable determination of a protease's specificity is crucial to understand protease function and to develop activity-based probes and inhibitors. During the last decade, various proteomic approaches for profiling protease substrate specificities were reported. Although most of these approaches can identify up to thousands of substrate cleavage events in a single experiment, they are often time consuming and methodologically challenging as some of these approaches require rather complex sample preparation procedures. For such reasons their application is often limited to those labs that initially introduced them. Here, we report on a fast and simple approach for proteomic profiling of protease specificities (fast profiling of protease specificity (FPPS)), which can be applied to complex protein mixtures. FPPS is based on trideutero-acetylation of novel N-termini generated by the action of proteases and subsequent peptide fractionation on Stage Tips containing ion-exchange and reverse phase chromatographic resins. FPPS can be performed in 2 days and does not require extensive fractionation steps. Using this approach, we have determined the specificity profiles of the cysteine cathepsins K, L and S. We further validated our method by comparing the results with the specificity profiles obtained by the N-terminal combined fractional diagonal chromatography method. This comparison pointed to almost identical substrate specificities for all three cathepsins and confirmed the reliability of the FPPS approach. All MS data have been deposited in the ProteomeXchange with identifiers PXD001536 and PXD001553 (; )

Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells

Extracellular cysteine cathepsins are known to drive cancer progression, but besides degradation of extracellular matrix proteins little is known about their physiological substrates and thus the molecular mechanisms they deploy. One of the major mechanisms used by other extracellular proteases to facilitate cancer progression is proteolytic release of the extracellular domains of transmembrane proteins or ectodomain shedding. Here we show using a mass spectrometry-based approach that cathepsins L and S act as sheddases and cleave extracellular domains of CAM adhesion proteins and transmembrane receptors from the surface of cancer cells. In cathepsin S-deficient mouse pancreatic cancers, processing of these cathepsin substrates is highly reduced, pointing to an essential role of cathepsins in extracellular shedding. In addition to influencing cell migration and invasion, shedding of surface proteins by extracellular cathepsins impacts intracellular signaling as demonstrated for regulation of Ras GTPase activity, thereby providing a putative mechanistic link between extracellular cathepsin activity and cancer progression. The MS data is available via ProteomeXchange with identifier PXD002192