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Aim To determine the value of IFN (intzerferon)-α in the patients with systemic lupus erythematosus (SLE) and to correlate IFN-α with values of non-specific biochemical parameters of inflammation (C-reactive protein, leukocytes values, erythrocyte sedimentation rate, albumins and globulins). Methods Research included 55 patients with SLE diagnosis and a control group consisted of 25 healthy subjects (during period 2019-2020). IFN (Interferon)-α and non-specific biochemical parameters of inflammation were obtained using standard protocols. Results IFN-α values were independent of gender (p=0.95). The difference in serum IFN-α values in relation with the age in the SLE group was statistically significant (p=0.036). Only serum globulin was significantly higher (p=0.0023) in IFN-α positive compared to IFN-α negative SLE patients. A statistically significant correlation between the values of IFN-α and globulin was proved (r=0.315; p=0.019). No significant correlation was found between other non-specific biochemical parameters and IFN-α values. Conclusion Increased IFN-α values were observed in younger patients, and the correlation between IFN and globulin was proved.

Aim To evaluate the efficacy (rate of recanalization) of therapy with novel oral anticoagulants (NOAC; rivaroxaban, apixaban) compared to conventional treatment (low molecular weight heparin - LMWH and vitamin K antagonist) in the treatment of deep vein thrombosis (DVT) of the proximal segments of lower extremities. Methods The first group consisted of patients diagnosed with DVT and treated with NOAC (n = 100), while the second group consisted of patients diagnosed with DVT, who were treated by conventional treatment (low molecular weight heparin and vitamin K antagonists) (n = 100). In the first group, NOAC was included in the initial treatment. Patients in the second group were treated with LMWH for four days, and on the fifth day vitamin K antagonist was included in therapy, international ratio (INR) was titrated to therapeutic values (2.0-3.0), and then low molecular weight heparin was excluded from the therapy. Results There was a statistically significant difference in the estimated values of free lumen of the blood vessel between the examined groups after 30 days (p=0.0001), after 90 days (p=0.0001) and after 180 days (p=0.0001). After 180 days, the average free lumen values in the NOAC group were 85% (81-89%), which was significantly higher than the free lumen values in the second group, 73% (69-79%). Conclusion The use of NOAC represents more efficient treatment of DVT comparing to vitamin K antagonists.

Z. Gatalica, P. Stafford, S. Vranić

Alpha-methylacyl-CoA racemase (AMACR/P504S) is a mitochondrial and peroxisomal enzyme involved in the branched-chain fatty acid and bile acid metabolism. AMACR is a useful diagnostic biomarker for prostate carcinomas and several other malignancies. Its expression in apocrine breast lesions had been previously reported, but its role in breast cancer progression has not been fully investigated. One hundred fifty breast samples (80 with invasive carcinomas) were studied. The expression of AMACR protein was analyzed using the immunohistochemical method (IHC). Lesions were considered positive if AMACR was detected in ≥10% of the cells at any intensity comprising a histologically defined normal epithelial structure or a pathologic lesion. In addition, AMACR mRNA relative expression was calculated from the whole-transcript RNA-Seq performed on >20,000 diverse tumor samples using a 20,000+ hybrid-capture NGS assay with the transcript capture panel based on the Agilent SureSelect Human All ExonV7. Expression of AMACR protein was restricted to epithelia. It was uncommon in the normal breast (7/81 samples, 9%). Increasing AMACR expression was observed with proliferative epithelial lesions (18% of usual ductal hyperplasias/adenosis, 70% of atypical lesions and 72% of DCIS/LCIS). Invasive ductal carcinomas NST and invasive lobular carcinomas expressed AMACR in 64% and 46%, respectively. The highest AMACR expression was observed in luminal B and HER2-positive breast carcinomas (86-100%). Triple-negative breast carcinomas exhibited AMACR in 50% of the cases. Apocrine lesions showed strong, nearly uniform overexpression of AMACR (100% of metaplasias, hyperplasias and in situ carcinomas and 88% of invasive apocrine carcinomas were positive). RNA-Seq analysis also confirmed AMACR expression in breast carcinomas, although its median value was substantially lower with a lower standard deviation than in prostate carcinomas. Over-expression of AMACR characterizes various proliferative, preinvasive and invasive breast lesions and is not specific to the apocrine morphology. It points to altered lipid metabolism (branched fatty acids) as one of the general characteristics of breast carcinogenesis, like several other malignancies. Its early detection may represent a potential target for cancer progression intervention.

Evangelia Eirini Tsermpini, U. Glamočlija, Fulden Ulucan‐Karnak, Sara Redenšek Trampuž, V. Dolžan

The coronavirus disease (COVID-19) pandemic is a leading global health and economic challenge. What defines the disease’s progression is not entirely understood, but there are strong indications that oxidative stress and the defense against reactive oxygen species are crucial players. A big influx of immune cells to the site of infection is marked by the increase in reactive oxygen and nitrogen species. Our article aims to highlight the critical role of oxidative stress in the emergence and severity of COVID-19 and, more importantly, to shed light on the underlying molecular and genetic mechanisms. We have reviewed the available literature and clinical trials to extract the relevant genetic variants within the oxidative stress pathway associated with COVID-19 and the anti-oxidative therapies currently evaluated in the clinical trials for COVID-19 treatment, in particular clinical trials on glutathione and N-acetylcysteine.

M. M. Horstman-van de Loosdrecht, Tamara Kahmann, F. Ludwig, L. Alic

Nonlinear handheld detection of magnetic nanoparticles is used to assess the lymph node status of cancer patients. Joint sensitivity and resolving power of nonlinear handheld detection can be maximized by optimizing the frequency of the excitation field, which is strongly influenced by Brownian and Néel relaxation. The characteristic frequency of magnetic nanoparticles that defines sensitivity and resolving power is usually assessed by AC susceptometry. In this study, we used SPaQ data to predict handheld detection performance for magnetic nanoparticles with various particle sizes. SPaQ assesses dynamics by measuring the derivative of the magnetization originating from magnetic nanoparticles activated by an alternating excitation field. The ratio between the maximum signal difference and full-width-at-half-maximumis used to estimate the optimal excitation frequency. Thereupon, it was shown that a particle with a combination of Brownian and Néel relaxation is superior in nonlinear handheld detection compared to Brownian or Néel only particles. Moreover, the optimal excitation frequency is generally established at a slightly higher frequency compared to the characteristic frequency assessed by AC susceptometry. Consequently, this insight into the consequences of the dynamic behavior of magnetic nanoparticles under an alternating magnetic field enables the optimization of nonlinear handheld detection for specific clinical applications.

M. Bošković, Stanislav Andreev, D. Schollmeyer, P. Koch

Reaction of diphenylmethanol (4) with n-butyllithium and subsequent treatment with selenium resulted in 12H-dibenzo[d,g][1,2,3]triselenocin-12-ol (5) comprising a novel heterocyclic ring system. The title compound 5 was analyzed by 1H-NMR, 13C-NMR and HPLC. Additionally, the structure of 5 was confirmed by single crystal X-ray diffraction.

Josipa Marin Lovrić, N. Filipović, L. Znaor, Anita Rančić, Joško Petričević, Nenad Kunac, V. Šoljić, M. Saraga-Babic et al.

The expression pattern of the markers p19, Ki-67, MSX1, MSX2, PDL1, pRB, and CYCLINA2 was quantitatively and semiquantitatively analyzed in histologic sections of the developing and postnatal human eye at week 8, in retinoblastoma, and in various uveal melanomas post hoc studies by double immunofluorescence. The p19 immunoreactivity characterized retinal and/or choroidal cells in healthy and tumor tissues: expression was lower in the postnatal retina than in the developing retina and retinoblastoma, whereas it was high in epithelioid melanomas. Ki67 expression was high in the developing eye, retinoblastoma, and choroidal melanomas. MSX1 and MSX2 expression was similar in the developing eye and retinoblastoma, whereas it was absent in the postnatal eye. Their different expression was evident between epithelioid and myxoid melanomas. Similarly, PDL1 was absent in epithelioid melanomas, whereas it was highly expressed in developing and tumor tissues. Expression of pRB and CYCA2 was characteristic of developing and tumorous eye samples but not of the healthy postnatal eye. The observed expression differences of the analyzed markers correlate with the origin and stage of cell differentiation of the tissue samples. The fine balance of expression could play a role in both human eye development and ocular tumorigenesis. Therefore, understanding their relationship and interplay could open new avenues for potential therapeutic interventions and a better understanding of the mechanisms underlying the developmental plasticity of the eye and the development of neoplasms.

A. Maccaro, Davide Piaggio, Marius Vignigbé, Alexander Stingl, L. Pecchia

Summary This project aims to assess and analyse the perception and impact of the COVID-19 pandemic in Benin. The applied research methodology was interdisciplinary and combined field studies that used ethnographic and social research methods with coding and data analysis, leading to theoretical dilemmas, which were analysed from the viewpoint of bioethical reflection. Furthermore, biomedical engineering approaches were used to assess the preparedness to COVID-19. Despite the preparedness to COVID-19 due to the promoted governmental measures, a peculiar management of the pandemic emerged. The latter, although noteworthy, did not overcome the typical challenges of medical locations in low-resource settings. This, together with the controversial spread of information and local beliefs, caused significant economic and social consequences, exceeding the benefits related to the containment of the virus. This research highlights how the emotion of fear, in this specific situation, was herald of dramatic consequences, rather than having a heuristic and empowering effect.

S. Terzić, Emina Vukas-Salihbegović, V. Mišanović, N. Begić

Aim To analyse biochemical markers as possible predictors of death before discharge in cooled newborns following perinatal asphyxia. Methods A total of 91 infants that underwent therapeutic hypothermia after perinatal asphyxia were included. Inclusion criteria for therapeutic hypothermia were Sarnat stage 2 or 3. Data were collected from medical histories regarding gender, gestational age, birth weight, Apgar and Sarnat score; additionally, gas analyses, liver and cardiac enzymes before, and in the first 12 hours after starting therapeutic hypothermia, were evaluated. The patients' characteristics were compared between two groups, survivors and non-survivors. Results Statistical difference was not found between groups regarding gender, gestational age, birth weight, delivery type, 1st and 5th minute Apgar score, seizures, alanine aminotransferase (ALT), creatine kinase (CK), troponin and fibrinogen level. Groups were significantly different regarding acid-base balance (p=0.012), base excess (BE) (p=0.025), lactate (p=0.002), aspartate aminotransferaze (AST), (p=0.011), lactate dehydrogenase (LDH) (p=0.006), activated partial thromboplastin clotting time (aPTT) (p=0.001) and international normalized ratio (INR) (p=0.001). Conclusion Acid-base balance, BE, lactate, AST, LDH, aPTT and INR were significantly higher in the group of cooled newborns after perinatal asphyxia (non-survivors), and can serve as predictors of death before discharge. Combining diagnostic modalities raises a chance for accurate prediction of outcomes of asphyxiated infants.

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