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Ključne besede: univerzitetni študij, študentska problematika, humanistični moment, kritična obravnava
Objavljeno v DiRROS: 29.09.2021; Ogledov: 849; Prenosov: 177
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Povzetek: Hymenoptera venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we provide an overview of the current knowledge and recent findings in understanding induced immune mechanisms during different phases of venom immunotherapy. We focus on protection mechanisms that occur early, during the build-up phase, and on the immune tolerance, which occurs later, during and after Hymenoptera venom immunotherapy. The short-term protection seems to be established by the early desensitization of mast cells and basophils, which plays a crucial role in preventing anaphylaxis during the build-up phase of treatment. The early generation of blocking IgG antibodies seems to be one of the main reasons for the lower activation of effector cells. Long-term tolerance is reached after at least three years of venom immunotherapy. A decrease in basophil responsiveness correlates with tolerated sting challenge. Furthermore, the persistent decline in IgE levels and, by monitoring the cytokine profiles, a shift from a Th2 to Th1 immune response, can be observed. In addition, the generation of regulatory T and B cells has proven to be essential for inducing allergen tolerance. Most studies on the mechanisms and effectiveness data have been obtained during venom immunotherapy (VIT). Despite the high success rate of VIT, allergen tolerance may not persist for a prolonged time. There is not much known about immune mechanisms that assure longterm tolerance post-therapy.
Ključne besede: allergy and immunology, hypersensitivity, immunotherapy, immune tolerance, venoms, Hymenoptera, Hymenoptera venom, short-term protection, long-term tolerance
Objavljeno v DiRROS: 16.08.2021; Ogledov: 900; Prenosov: 284
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Povzetek: Background: Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate PHD1, PHD2 and PHD3 mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS). Methods: Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. PHD1, PHD2 and PHD3 mRNA expressions were measured using RT-qPCR. Results: The PHD1 and PHD2 mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both p < 0.0001). PHD1 and PHD2 expression in tumours was positively correlated (rs = 0.82; p < 0.0001) and correlated well with HIF pathway downstream genes HIF1A, PKM2 and PDK1. Decreased PHD1 and PHD2 were associated with larger tumour size, higher tumour stage (PHD1 only) and squamous cell carcinoma. Patients with low PHD1 and patients with low PHD2 expression had shorter OS than patients with high PHD1 (p = 0.02) and PHD2 expression (p = 0.01). PHD1 showed borderline independent prognostic values in multivariate analysis (p = 0.06). In contrast, we found no associations between PHD3 expression and any of the observed parameters. Conclusions: Our results show that reduced expression of PHD1 and PHD2 is associated with the development and progression of NSCLC. PHD1 could be further assessed as a prognostic marker in NSCLC.
Ključne besede: non-small-cell lung carcinoma, prognosis, non-small cell lung cancer, mRNA expression, prolyl hydroxylase domain proteins
Objavljeno v DiRROS: 21.05.2021; Ogledov: 1241; Prenosov: 882
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Povzetek: Modeli razvoja gozdov napovedujejo razvoj dreves in gozdnih sestojev glede na drevesne, sestojne, rastiščne in gozdnogospodarske dejavnike. Zaradi kompleksne narave gozdnih ekosistemov in dolgih proizvodnih ciklov je modeliranje razvoja gozdov pomemben sestavni del upravljanja gozdov. Sestojni modeli so bili prepoznani kot primerni za podporo odločanju pri upravljanju z gozdovi. Primer takega modela je švicarski model SiWaWa, ki smo ga preizkusili v pričujoči raziskavi. Na štirih vzorcih po 50 stalnih vzorčnih ploskev v negospodarjenih in gospodarjenih čistih bukovih in čistih smrekovih enomernih sestojih smo izvedli simulacije razvoja gozdov za obdobje 10 let, nato pa smo primerjali dejanske vrednosti in modelske napovedi za sestojno temeljnico G, število dreves N in srednje temeljnični premer Dg. Napovedovanje razvoja čistih bukovih gozdov je bilo zadovoljivo točno; v negospodarjenih sestojih je celotna napaka RMSE za sestojno temeljnico znašala 2,35 m2 /ha, v gospodarjenih sestojih pa 3,42 m2/ha ob upoštevanju le posekanih dreves in 4,35 m2/ha ob upoštevanju celotne mortalitete. Enako ne moremo trditi za napovedovanje razvoja čistih smrekovih sestojev. Pri slednjih so bile mere točnosti znatno slabše, saj so RMSE za napovedano sestojno temeljnico znašali 8,94 m2/ha za negospodarjene in 6,13 m2/ha ter 6,11 m2/ha za gospodarjene sestoje ob upoštevanju poseka oziroma celotne mortalitete. Model SiWaWa, ki je parametriziran za švicarske gozdove, se zdi uporaben za simuliranje razvoja čistih bukovih gozdov brez simuliranega ukrepanja (poseka) ali z njim. Zanesljive simulacije razvoja čistih smrekovih sestojev pa model zaenkrat še ne omogoča.
Ključne besede: model razvoja gozdov, gozdni sestoj, gozdna inventura, simulacije razvoja gozdov, sestojna temeljnica, število dreves, srednje temeljnični premer
Objavljeno v DiRROS: 08.03.2021; Ogledov: 1602; Prenosov: 492
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Povzetek: Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown. Methods: In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data. Results: HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival. Conclusions: Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
Ključne besede: biomarkers, heat-shock proteins, chronic obstructive pulmonary disease, urine, heat shock protein 27
Objavljeno v DiRROS: 25.01.2021; Ogledov: 1465; Prenosov: 1010
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