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    Effectiveness of Expressive Writing in the Reduction of Psychological Distress During the COVID-19 Pandemic: A Randomized Controlled Trial

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    Objective Due to the wide impact of the COVID-19 pandemic on mental health, the need for scalable interventions that can effectively reduce psychological distress has been recognized. Expressive writing (EW) can be beneficial for different conditions, including depression, suicidal ideation, and coping with trauma. Therefore, we aim to assess the applicability and effectiveness of an online format of EW in the reduction of psychological distress in context of the COVID-19 pandemic. Methods In this parallel-group, randomized controlled trial, participants (n = 120) were randomly allocated to (1) the intervention group-who completed five EW sessions over the 2 week period-or (2) the control group-who received treatment as usual (TAU). Participants were assessed for primary and secondary outcome measures at baseline, post-treatment, and follow-up-1-month after the treatment. The primary outcome was severity of psychological distress assessed at post-treatment, operationalized as Depression Anxiety Stress Scale (DASS) summary score. Secondary outcomes were severity of depression, anxiety, and stress (DASS subscale scores), well-being (WHO-5), subjective perception of quality of life (SQOL), and subjective evaluation of difficulties coping with pandemic, which were also assessed at post-treatment. Per protocol, analysis was conducted with available cases only. Results A less favorable outcome was found in the intervention group on psychological distress, and symptoms of stress, after controlling for baseline scores. Increased stress was recorded in the treatment group, with no effect in the control group. There was no significant difference between the groups on depression, anxiety, well-being, and subjective quality of life. No group effect for any of the outcomes measures was recorded at follow-up. Additional analysis revealed moderation effects of age and gender with older and male participants scoring higher on distress measures. Conclusion Engaging in EW during the pandemic was found to elevate stress; thus, when applied in the context of the COVID-19 pandemic, it may be harmful. Hence, EW or similar self-guided interventions should not be applied without prior evidence on their effects in the context of a pandemic and similar stressful and unpredictable circumstances

    Assessment of the force-velocity relationship during vertical jumps: influence of the starting position, analysis procedures and number of loads

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    This study aimed to compare the reliability and magnitude of the force-velocity (F-V) relationship parameters between the squat jumps performed from the 90 degrees (SJ90) and self-preferred knee angle (SJ(pref)). A secondary aim was to explore the effect of the analysis procedure (force platform [FP] and Samozino's [SAM] method) and the number of loads tested (three- and two-point methods) on the F-V relationships. Twelve men were tested in two sessions during the SJ90 and SJ(pref). Two identical blocks of jumps were performed in each session against three external loads. The F-V relationship parameters (maximum force, maximum velocity, F-V slope and maximum power) were determined at each block through the FP and SAM procedures using the data collected under three (three-point method) or only the two most distant loads (two-point method). The average coefficient of variation (CV) of the four F-V parameters revealed a higher reliability for the SJ90 compared to the SJ(pref) (5.86% vs. 7.55%; CVratio = 1.29) with more pronounced differences using the FP (CVratio = 1.43) than the SAM procedure (CVratio = 1.14), and higher reliability for the SAM compared to the FP (6.14% vs. 7.27%; CVratio = 1.18). The SJ(pref) and SAM procedures provided comparable or higher magnitude of the F-V relationship parameters than the SJ90 and FP, respectively. The three- and two-point methods revealed a comparable reliability and trivial differences in the magnitude of the F-V relationship parameters. The routine testing procedure of the F-V relationship could be simplified using the SJ(pref), the SAM procedure and the two-point method.Peer-reviewed manuscript: [http://rimi.imi.bg.ac.rs/handle/123456789/1128

    Hyperbaric oxygenation protects the kidney against ischemia-reperfusion injury

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    Background: Acute kidney injury (AKI) as a consequence of ischemia is a common clinical event that can lead to unacceptably high morbidity and mortality. Hyperbaric oxygen (HBO2) preconditioning has been shown to prevent ischemia-reperfusion injury (IRI) in different tissues. Objectives: The aim of our study was to compare the effects of HBO2 preconditioning on renal hemodynamics, kidney function and oxidative stress in normotensive and spontaneously hypertensive rats that suffered kidney IRI. Methods: An experiment was performed on Wistar (normotensive) and spontaneously hypertensive rats (SHR). The animals were divided into the following experimental groups: sham-operated rats and rats with or without HBO2 preconditioning 24 hours before post-ischemic AKI induction. Treated rats were placed into experimental HBO2 chambers and exposed to pure oxygen twice a day for two consecutive days (2.026 bar of oxygen) for 60 minutes. AKI was performed the next morning. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 45 minutes. Results: In this study, HBO2 preconditioning significantly improved disturbed renal hemodynamics, major markers of kidney function in plasma (creatinine, urea and phosphate) as well as antioxidant enzymes (superoxide dismutase and catalase) activities in erythrocytes after AKI induction. Also, HBO2 preconditioning decreased lipid peroxidation in plasma after ischemic AKI. Positive effects were observed in both strains of rats. Conclusions: Our results suggest that HBO2 treatment improves renal hemodynamic and kidney function and decreases oxidative stress of Wistar and SHR rats with an AKI episode. Furthermore, it also implies that pre-existing hypertension does not affect the beneficial effects of HBO2 preconditioning

    Paclitaxel inhibits transforming growth factor-beta-increased urokinase-type plasminogen activator expression through p38 MAPK and RAW 264.7 macrophage migration

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    Purpose: Transforming growth factor-beta (TGF-beta) induces alternative macrophage activation that favors tumor progression and immunosuppression. Meanwhile, paclitaxel (PTx) induces macrophage (M phi) polarization towards antitumor phenotype. TGF-beta also increases tumor stroma macrophage recruitment by mechanisms that include cell motility enhancement and extracellular matrix degradation. In this study, we aimed to determine whether PTx regulates macrophage migration and urokinase-type plasminogen activator (uPA) expression induced by TGF-beta. Methods: We used mouse macrophage RAW 264.7 cells treated with PTx and TGF-beta combinations. Proliferation was analyzed by MTT and cell cycle assays. Immunofluorescence was performed to determine tubulin cytoskeleton and Smad3 nuclear localization. Western blot and transcriptional luciferase reporters were used to measure signal transduction activation. Migration was determined by wound healing assay. uPA activity was determined by zymography assay. Results: PTx decreased RAW 264.7 cell proliferation by inducing G2/M cell cycle arrest and profoundly modified the tubulin cytoskeleton. Also, PTx inhibited TGF-beta-induced Smad3 activation. Furthermore, PTx decreased cell migration and uPA expression stimulated by TGF-beta. Remarkably, p38 MAPK mediated PTx inhibition of uPA activity induced by TGF-beta but it was not implicated on cell migration inhibition. Conclusions: PTx inhibits TGF-beta induction of mouse M phi migration and uPA expression, suggesting that PTx, as TGF-beta targeting therapy, may enhance MT anticancer action within tumors

    Potential anti-melanoma activity of Imidazoline I1 receptor agonists

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    Melanoma is the deadliest form of skin cancer. Despite the advancements in targeted BRAF and MEK therapy and immunotherapies, metastatic melanoma patients still have poor prognosis with a median survival of 9 months and a long-term survival rate of 10%. There is an urgent need for novel treatment modalities that target metastatic melanoma. Imidazoline I1 receptor (IR1, IRAS, NISCH) is a scaffolding protein that has been shown to be a tumor suppressor in breast cancer through regulation of cancer cell survival, motility and invasion. IR1 role in metastatic melanoma has not been investigated to date. Of importance, several IR1 agonists are clinically approved for treatment of hypertension. The aim of this study was to examine the IR1 expression in melanoma and the effects of IR1 agonists on melanoma cell viability. To confirm the target expression, we first determined IR1 levels in primary and metastatic melanoma patient samples by qRT-PCR and immunohistochemistry. We found that it is expressed in primary tumors and liver metastases and, to a lesser extent, in metastatic lymph nodes. Next, we examined the activity of IR1 agonists – rilmenidine, clonidine and moxonidine – in a panel of metastatic melanoma cell lines (HTB140, FemX-1, A375 and 518a2) and found that rilmenidine most potently inhibited cell viability. Notably, it was not toxic towards human dermal fibroblasts and keratinocytes. Furthermore, rilmenidine time- and dose- dependently induced cell cycle arrest in G2/M phase and consequent apoptosis. Our results imply that imidazoline I1 receptor is potentially novel anti-melanoma target, and that its already clinically approved agents have promising anti-cancer activity

    Influence of applied CD34+ cell dose on the survival of Hodgkin's lymphoma and multiple myeloma patients following autologous stem cell transplants

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    Background/Aim. Autologous stem cell transplants (ASCTs) improve the rate of overall survival (OS) in patients with hematological malignancies such as multiple myeloma (MM) after induction chemotherapy, aggressive non-Hodgkin's lymphomas (NHL), and relapsed, chemotherapy-sensitive Hodgkin's lymphoma (HL). The study aim was to evaluate influence of applied CD34+ cell quantity on clinical outcome, as well as early post-transplant and overall survival (OS) of HL and MM patients following ASCT. Methods. This study included a total of 210 patients (90 HL/120 MM) who underwent ASCT. Stem cell (SC) mobilization was accomplished by granulocyte-colony stimulating factor (G-CSF) 10–16 μg/kg body mass (bm) following chemotherapy. For proven poor mobilizers, mobilization with G-CSF (16 μg/kgbm) and Plerixafor (24 or 48 mg) was performed. To our best knowledge, it was the first usage of the Plerixafor in our country in the ASCT-setting. Harvesting was initiated merely at "cut-off-value" of CD34+ cells ≥ 20 × 106/L in peripheral blood with "target-dose" of CD34+ cells ≥ 5 × 106/kgbm in harvest. The CD34+ cell count and viability was determined using flow cytometry. Results. The majority of HL patients (76.7%) were infused with > 5.0 × 106/kgbm CD34+ cells, while 68.3% of MM patients were treated by approximately 4.0–5.4 × 106/kgbm CD34+ dose, respectively. Beneficial response (complete/partial remission) was achieved in 83.3% (HL) and 94.2% (MM) patients. Among parameters that influenced survival of HL patients with positive response to the therapy, multivariate analysis (pre-ASCT performance status, CD34+ cell quantity applied, rapid hematopoietic, i.e. lymphocyte and platelet recovery) indicated that higher CD34+ cell dose used, along with pre-ASCT performance status correlated with superior event-free survival (EFS) and OS following ASCT. In MM patients, multivariate analysis (renal impairment, infused CD34+ cell quantity, early platelet recovery) indicated that the number of CD34+ cells infused was the most important parameter that influenced both EFS and OS after ASCT. Conclusion. Data obtained in this study undoubtedly confirmed that CD34+ cell dose applied is an independent factor that may contribute to superior clinical outcome and OS of HL and MM patients following ASCT

    Interlimb Asymmetries and Ipsilateral Associations of Plantar Flexors and Knee Extensors Rate-of-Force Development Scaling Factor

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    Rate of force/torque development scaling factor (RFD-SF/RTD-SF) was recently introduced as a tool to quantify the neuromuscular quickness, and it could have potential for interlimb asymmetry identification. Moreover, positive relationships in RFD-SF ability among different muscle groups were shown, but not in the lower extremity. The first aim of our study was to use RTD-SF for interlimb asymmetry identification. The second aim was to determine associations between plantar flexors (PF) and knee extensors (KE). Forty young healthy athletes (14.8 +/- 1.2 years) performed explosive isometric contractions to a span of torque levels for PF and KE. From rapid isometric contractions, the RTD-SF and linearity (r(2)) of the regression line were calculated. Using RTD-SF we identified 10% (PF) and 15% (KE) of subjects with contralateral asymmetries ( gt 15% criterion). The results revealed significant positive moderate correlation in RTD-SF between PF and KE (r = 0.401, p lt 0.05). We supported that RTD-SF can be a useful tool for interlimb asymmetry identification. Future research about observed asymmetry in rapid submaximal contractions deserves more attention, as most of the functional sport specific activities put high demands on rapid force production. Our study as first confirmed positive associations in RTD-SF ability between muscle groups in lower limbs

    Divlje kanide kao domaćini za vektorima prenosive zoonozne patogene u Srbiji

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    Wild canids are recognized as important reservoir hosts for several vector-borne pathogens and are a good sentinel species for epidemiological surveillance. Identifying the reservoir hosts for particular zoonotic pathogens in a specific area enables the implementation of adequate measures in order to prevent the occurrence of zoonotic diseases in humans and domestic animals. The present review aims to summarize the role of wild canids in the epidemiology of tick-borne zoonoses in Serbia based on previously published papers and to discuss the available data from an epidemiological point of view. The results of previously published studies indicate that wild canids are potential reservoir hosts for several zoonotic tick-borne pathogens in Serbia, and hosts for several tick species which are proven competent vectors. Based on molecular studies conducted so far, the presence of Anaplasma phagocytophilum, was confirmed in jackals while the presence of Candidatus Neoehrlichia micurensis (FU98), Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia lusitaniae was proven by PCR in analyzed red foxes. There is a need for continuous epidemiological monitoring of diseases caused by pathogens previously confirmed in wild canids. Also, further research is needed to reveal the role of other wild and domestic animals in the epidemiology of tick-borne zoonoses in Serbia.Divlje kanide su prepoznate kao važni domaćini rezervoari za nekoliko vektorima prenosivih zoonotskih patogena i predstavljaju dobre sentinel vrste za epidemiološki nadzor. Identifikacija domaćina rezervoara za pojedine zoonotske patogene na određenom području omogućava primenu odgovarajućih mera kako bi se sprečila pojava zoonoza kod ljudi i domaćih životinja. Cilj ove studije bio je da se predstavi uloga divljih kanida u epidemiologiji zoonoza koje se prenose vektorima u Srbiji na temelju prethodno objavljenih radova i da se dostupni podaci prodiskutuju sa epidemiološkog stanovišta. Na osnovu dosadašnjih molekularnih istraživanja u Srbiji, divlje kanide su prepoznate kao potencijalni rezervoari za nekoliko krpeljima prenosivih zoonotskih patogena. Kod šakala je potvrđeno prisustvo Anaplasma phagocytophilum, dok je prisustvo Candidatus Neoehrlichia micurensis (FU98), Borrelia burgdorferi sensu stricto, Borrelia garinii i Borrelia lusitaniae molekularnim metodama potvrđeno kod lisica. Rezultati pokazuju da su divlje kanide potencijalni domaćini rezervoari i izvor zoonotskih patogena u Srbiji i da predstavljaju dobre domaćine za više vrsta krpelja koji su potvrđeni kompetentni vektori pojedinih patogena. Potrebno je kontinuirano epidemiološko praćenje bolesti uzrokovanih patogenima čije je prisustvo prethodno potvrđeno kod divljih kanida. Takođe, potrebna su dodatna istraživanja kako bi se otkrila uloga drugih divljih i domaćih životinja u epidemiologiji zoonoza koje se prenose vektorima u našoj zemlji

    Aronia juice consumption prior to half-marathon race can acutely affect platelet activation in recreational runners

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    Long-distance running, especially in non-professional runners, can increase cardiac arrest risk by enhancing platelet activation and aggregation. Polyphenols can exert cardioprotective effects by positively influencing platelet function. This study aimed to examine the acute effects of polyphenol-rich aronia juice consumption, before simulation of a half-marathon race, on platelet activation and aggregation with leukocytes in recreational runners. In this acute crossover study,10 healthy male runners (age 30.8 +/- 2.3 years) consumed breakfast with 200 mL, of aronia juice or 200 mL of placebo. They warmed-up and ran a simulated half-marathon race (21.1 km). Blood was collected at baseline, and at 15 min, 1 h, and 24 h after the run. All variables were analyzed with 4 (time) x 2 (group)ANOVA with repeated measures on both factors. Results revealed a significant effect of group on platelet activation parameters: P-selectin and CPIIb-IIIa expressions significantly decreased in the aronia group compared with the placebo group (F-[1.(9]) = 10.282, p = 0.011 and F-[1.9] = 7.860, p = 0.021, respectively). The effect of rime was significant on both platelet aggregation markers: platelet-monocyte and platelet-neutrophil aggregates were significantly lower after the race (F-[(3).7] = 4.227, p = 0.014 and F-[3.7] = 70.065, p = 0.000, respectively), with changes more pronounced in the later. All effects remained when platelets were exposed to an agonist. These results suggest that aronia consumption could counteract the half-marathon race-induced changes in platelet function. Novelty Aronia juice consumption significantly decreased the expression of platelet activation markers but did not affect platelet aggregation. The race itself did significantly reduce platelet-neutrophil aggregation. Aronia juice may serve as a supplement beverage for recreational runners to alleviate enhanced platelet reactivity caused by prolonged running.Peer-reviewed manuscript: [http://rimi.imi.bg.ac.rs/handle/123456789/1127

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