Discovery of a new class of potent pyrrolo[3,4-c]quinoline-1,3-diones based inhibitors of human dihydroorotate dehydrogenase: Synthesis, pharmacological and toxicological evaluation.

Twenty N-substituted pyrrolo[3,4-c]quinoline-1,3-diones 3a-t were synthesized by a cyclization reaction of Pfitzinger's quinoline ester precursor with the selected aromatic, heteroaromatic and aliphatic amines. The structures of all derivatives were confirmed by IR, 1H NMR, 13C NMR and HRMS spectra, while their purity was determined using HPLC techniques. Almost all compounds were identified as a new class ofpotent inhibitors against hDHODH among which 3a and 3t were the most active ones with the same IC50 values of 0.11 µM, about seven times better than reference drug leflunomide. These two derivatives also exhibited very low cytotoxic effects toward healthy HaCaT cells and the optimal lipophilic properties with logP value of 1.12 and 2.07 respectively, obtained experimentally at physiological pH. We further evaluated the comparative differences in toxicological impact of the three most active compounds 3a, 3n and 3t and reference drug leflunomide. The rats were divided into five groups and were treated intraperitoneally, control group (group I) with a single dose of leflunomide (20 mg/kg) group II and the other three groups, III, IV and V were treated with 3a, 3n and 3t (20 mg/kg bw) separately. The investigation was performed in liver, kidney and blood by examining serum biochemical parameters and parameters of oxidative stress.

Thymus zygis, Valuable Antimicrobial (In Vitro and In Situ) and Antibiofilm Agent with Potential Antiproliferative Effects.

With the growing issues of food spoilage, microbial resistance, and high mortality caused by cancer, the aim of this study was to evaluate T. zygis essential oil (TZEO) as a potential solution for these challenges. Here, we first performed GC/MS analysis which showed that the tested TZEO belongs to the linalool chemotype since the abundance of linalool was found to be 38.0%. Antioxidant activity assays showed the superiority of TZEO in neutralizing the ABTS radical cation compared to the DPPH radical. The TZEO was able to neutralize 50% of ABTS•+ at the concentration of 53.03 ± 1.34 µg/mL. Antimicrobial assessment performed by employing disc diffusion and minimal inhibitory concentration assays revealed TZEO as a potent antimicrobial agent with the highest inhibition activity towards tested gram-negative strains. The most sensitive on the treatment with TZEO was Enterobacter aerogenes showing an MIC 50 value of 0.147 ± 0.006 mg/mL and a MIC 90 value of 0.158 ± 0.024 mg/mL. Additionally, an in situ analysis showed great effects of TZEO in inhibiting gram-negative E. coli, P. putida, and E. aerogenes growing on bananas and cucumbers. Treatment with the TZEO vapor phase in the concentration of 500 µg/mL was able to reduce the growth of these bacteria on the food models to the extent > 90%, except for E. coli growth on the cucumber, which was reduced to the extent of 83.87 ± 4.76%. Furthermore, a test on the antibiofilm activity of the tested essential oil revealed its biofilm prevention effects against Salmonella enterica which forms biofilms on plastic and stainless-steel surfaces. Performed tests on the TZEO effects towards cell viability showed no effects on the normal MRC-5 cell line. However, the results of MTT assay of TZEO effects on three cancer cell lines (MDA-MB-231, HCT-116, and K562) suggest that TZEO exerted the strongest effects on the inhibition of the viability of MDA-MB-231 cells, especially after long-term treatment in the highest concentration applied with reducing the viability of the cells to 57%. Additionally, results of NBT and Griess assays suggest that TZEO could be a convenient candidate for future testing for developing novel antitumor therapies.

Biological Activity of Cupressus sempervirens Essential Oil.

The aim of this study was to evaluate the antioxidant, antibiofilm, antimicrobial (in situ and in vitro), insecticidal, and antiproliferative activity of Cupressus sempervirens essential oil (CSEO) obtained from the plant leaf. The identification of the constituents contained in CSEO was also intended by using GC and GC/MS analysis. The chemical composition revealed that this sample was dominated by monoterpene hydrocarbons α-pinene, and δ-3-carene. Free radical scavenging ability, performed by using DPPH and ABTS assays, was evaluated as strong. Higher antibacterial efficacy was demonstrated for the agar diffusion method compared to the disk diffusion method. The antifungal activity of CSEO was moderate. When the minimum inhibitory concentrations of filamentous microscopic fungi were determined, we observed the efficacy depending on the concentration used, except for B. cinerea where the efficacy of lower concentration was more pronounced. The vapor phase effect was more pronounced at lower concentrations in most cases. Antibiofilm effect against Salmonella enterica was demonstrated. The relatively strong insecticidal activity was demonstrated with an LC50 value of 21.07% and an LC90 value of 78.21%, making CSEO potentially adequate in the control of agricultural insect pests. Results of cell viability testing showed no effects on the normal MRC-5 cell line, and antiproliferative effects towards MDA-MB-231, HCT-116, JEG-3, and K562 cells, whereas K562 cells were the most sensitive. Based on our results, CSEO could be a suitable alternative against different types of microorganisms as well as suitable for the control of biofilms. Due to its insecticidal properties, it could be used in the control of agricultural insect pests.

Manuka Honey/2-Hydroxyethyl Methacrylate/Gelatin Hybrid Hydrogel Scaffolds for Potential Tissue Regeneration.

Scaffolding biomaterials are gaining great importance due to their beneficial properties for medical purposes. Targeted biomaterial engineering strategies through the synergy of different material types can be applied to design hybrid scaffolding biomaterials with advantageous properties for biomedical applications. In our research, a novel combination of the bioactive agent Manuka honey (MHo) with 2-hydroxyethyl methacrylate/gelatin (HG) hydrogel scaffolds was created as an efficient bioactive platform for biomedical applications. The effects of Manuka honey content on structural characteristics, porosity, swelling performance, in vitro degradation, and in vitro biocompatibility (fibroblast and keratinocyte cell lines) of hybrid hydrogel scaffolds were studied using Fourier transform infrared spectroscopy, the gravimetric method, and in vitro MTT biocompatibility assays. The engineered hybrid hydrogel scaffolds show advantageous properties, including porosity in the range of 71.25% to 90.09%, specific pH- and temperature-dependent swelling performance, and convenient absorption capacity. In vitro degradation studies showed scaffold degradability ranging from 6.27% to 27.18% for four weeks. In vitro biocompatibility assays on healthy human fibroblast (MRC5 cells) and keratinocyte (HaCaT cells) cell lines by MTT tests showed that cell viability depends on the Manuka honey content loaded in the HG hydrogel scaffolds. A sample containing the highest Manuka honey content (30%) exhibited the best biocompatible properties. The obtained results reveal that the synergy of the bioactive agent, Manuka honey, with 2-hydroxyethyl methacrylate/gelatin as hybrid hydrogel scaffolds has potential for biomedical purposes. By tuning the Manuka honey content in HG hydrogel scaffolds advantageous properties of hybrid scaffolds can be achieved for biomedical applications.

Enhancing Electron Correlation at a 3d Ferromagnetic Surface.

Spin-resolved momentum microscopy and theoretical calculations are combined beyond the one-electron approximation to unveil the spin-dependent electronic structure of the interface formed between iron (Fe) and an ordered oxygen (O) atomic layer, and an adsorbate-induced enhancement of electronic correlations is found. It is demonstrated that this enhancement is responsible for a drastic narrowing of the Fe d-bands close to the Fermi energy (EF ) and a reduction of the exchange splitting, which is not accounted for in the Stoner picture of ferromagnetism. In addition, correlation leads to a significant spin-dependent broadening of the electronic bands at higher binding energies and their merging with satellite features, which are manifestations of a pure many-electron behavior. Overall, adatom adsorption can be used to vary the material parameters of transition metal surfaces to access different intermediate electronic correlated regimes, which will otherwise not be accessible. The results show that the concepts developed to understand the physics and chemistry of adsorbate-metal interfaces, relevant for a variety of research areas, from spintronics to catalysis, need to be reconsidered with many-particle effects being of utmost importance. These may affect chemisorption energy, spin transport, magnetic order, and even play a key role in the emergence of ferromagnetism at interfaces between non-magnetic systems.

GC, GC/MS Analysis, and Biological Effects of Essential Oils from Thymus mastchina and Elettaria cardamomum.

Spanish marjoram (Thymus mastichina) and cardamom (Elettaria cardamomum) are traditional aromatic plants with which several pharmacological properties have been associated. In this study, the volatile composition, antioxidative and antimigratory effects on human breast cancer (MDA-MB-468 cell line), antimicrobial activity, and antibiofilm effect were evaluated. Results obtained via treatment of human breast cancer cells generally indicated an inhibitory effect of both essential oils (EOs) on cell viability (after long-term treatment) and antioxidative potential, as well as the reduction of nitric oxide levels. Antimigratory effects were revealed, suggesting that these EOs could possess significant antimetastatic properties and stop tumor progression and growth. The antimicrobial activities of both EOs were determined using the disc diffusion method and minimal inhibition concentration, while antibiofilm activity was evaluated by means of mass spectrometry. The best antimicrobial effects of T. mastichina EO were found against the yeast Candida glabrata and the G+ bacterium Listeria monocytogenes using the disc diffusion and minimal inhibitory concentration methods. E. cardamomum EO was found to be most effective against Pseudomas fluorescens biofilm using both methods. Similarly, better effects of this oil were observed on G- compared to G+ bacterial strains. Our study confirms that T. mastichina and E. cardamomum EOs act to change the protein structure of older P. fluorescens biofilms. The results underline the potential use of these EOs in manufactured products, such as foodstuffs, cosmetics, and pharmaceuticals.

Chemical Composition and Biological Activity of Tanacetum balsamita Essential Oils Obtained from Different Plant Organs.

The aim of this study is to evaluate the chemical composition of Tanacetum balsamita L. essential oils (EOs) obtained from different plant organs, flowers (FEO), leaves (LEO), and stems (SEO), as well as to assess their biological properties. The results obtained by using GC and GC/MS analysis indicate that this plant belongs to the carvone chemotype. Moreover, we examined the oil's antimicrobial and antitumor potential. Antimicrobial effects were determined using minimum inhibitory concentrations assay and the vapor phase method. Obtained results indicate better antimicrobial activity of investigated EO samples compared to the commercially available antibiotics. On the treatment with FEO, Y. enterocolitica and H. influenzae showed high sensitivity, while treatment with LEO and SEO showed the highest effects against S. aureus. The vapor phase method, as an in situ antibacterial analysis, was performed using LEO. Obtained results showed that this EO has significant activity toward S. pneumoniae in the apple and carrot models, L. monocytogenes in the pear model, and Y. enterocolitica in the white radish model. The potential antitumor mechanisms of FEO, LEO, and SEO were determined by the means of cell viability, redox potential, and migratory capacity in the MDA-MB-231 and MDA-MB-468 cell lines. The results show that these EOs exert antiviability potential in a time- and dose-dependent manner. Moreover, treatments with these EOs decreased the levels of superoxide anion radical and increased the levels of nitric oxide in both tested cell lines. The results regarding total and reduced glutathione revealed, overall, an increase in the levels of total glutathione and a decrease in the levels of reduced glutathione, indicating strong antioxidative potential in tested cancer cells in response to the prooxidative effects of the tested EOs. The tested EOs also exerted a drop in migratory capacity, which indicates that they can be potentially used as chemotherapeutic agents.

Mental Health and Quality of Life among Dental Students during COVID-19 Pandemic: A Cross-Sectional Study.

Students are particularly vulnerable from the mental health aspect, which was especially recognized during the COVID-19 pandemic. This study aimed to reveal the impact of COVID-19 on quality of life (QoL) and mental health among dental students. The study was conducted on a sample of 797 students (207 male and 592 female) with an average age of 21.7 ± 2.4, from the School of Dental Medicine, University of Belgrade. The measurements used in the study were the Demographic and Academic Questionnaire, Questionnaire about exposure to COVID-19, COVID-19-Impact on QoL Questionnaire (COV19-QoL), Generalized Anxiety Disorder 7-item (GAD-7) scale, and Patient Health Questionnaire (PHQ-9). The mean total score for COV19-QoL was 2.9 ± 0.9, while the diagnostic criteria of GAD-7 and depression met 19.9% and 31.4% of students, respectively. There was a positive and strong correlation between QoL, anxiety, and depression. During COVID-19, predictors for lower perceptions of QoL were female gender and death of close relatives (p = 0.049, p = 0.005, respectively). At the same time, predictors for GAD were female gender, living in dormitories, and death of close relatives (p = 0.019, p = 0.011, p = 0.028, respectively), while for depression they were year of study, living with parents, and death of close relatives due to COVID-19 (p = 0.012, p = 0.008, p = 0.029, respectively). The study showed that students' QoL and mental health during the pandemic were at high risk.

Homeostatic microbiome disruption as a cause of insulin secretion disorders. Candida albicans, a new factor in pathogenesis of diabetes: A STROBE compliant cross-sectional study.

The study aimed to test the hypothesis that homeostatic microbiome (HM) disorders lead to the increased indirect influence of certain microorganisms (MO) in the gastrointestinal tract, causing a disorder of insulin secretion, insulin resistance, and diabetes. We highlighted Candida and certain types of bacteria since previous in vitro research showed they significantly affect insulin secretion and can cause insulin resistance in obese patients with metabolic syndrome. After determining the type of MO present in the throat swab and the stool, the oral glucose tolerance test (OGTT) test, and analysis of glucose and insulin secretion were performed in patients (n = 38) who were positive for certain types of MO compared to negative patients. Finally, all patients were divided into two groups: overweight patients (body mass index [BMI] < 30) and obese patients (BMI > 30). These two groups were compared for the percentage of certain types of MO to determine which MO can affect an increase in obesity and BMI. The presence of Diphtheroids in the throat (60.5%) reduces insulin secretion in patients compared with the negative group (194.5: 332.4) and the difference was statistically significant (P = .030). The presence of Candida in the throat (10%) increases insulin secretion, but the difference was statistically insignificant. The presence of Candida in the stool (28.9%) also increases insulin secretion and the difference was statistically significant (P = .038). Cumulative results (throat + stool) were similar (180: 332, P = .022). Analysis of BMI showed that the percentage of Diphtheroids in the throat decreases with increased body weight (53.8: 75%) while the percentage of Candida (38.5: 8.3%) and Enterobacter (61.5: 25%) increases, but these differences were statistically insignificant (P > .05). Diphtheroids in the throat can reduce insulin secretion by synthesizing their metabolites. Candida albicans is a conditional pathogen and as a significant indirect factor induces increased insulin secretion and insulin resistance. There are indications that elevated levels of Candida in the intestinal system can cause increased body weight of patients. C albicans should be considered a new factor in the pathogenesis of diabetes.

Chemical Composition, Antitumor Potential, and Impact on Redox Homeostasis of the Essential Oils of Orlaya grandiflora from Two Climate Localities.

It is well known that abiotic components can affect biosynthetic pathways in the production of certain volatile compounds. The aim of this study was to compare the chemical composition of essential oils obtained from Orlaya grandiflora (L.) Hoffm. collected from two localities in Serbia (continental climate, OG1) and Montenegro (Mediterranean climate, OG2) and to assess their antitumor potential on the human colon cancer HCT-116 and breast cancer MDA-MB-231 cell lines. EOs obtained by hydrodistillation were analyzed using GC-MS and GC-FID methods. The results indicate considerable differences in the chemical compositions of the two samples. Although in both samples the main class of volatiles observed was sesquiterpenes (47.5% for OG1 and 70.1% for OG2), the OG1 sample was characterized by a high amount of monoterpene hydrocarbons (29.3%), and sesquiterpene germacrene D (29.5%) as the most abundant compound. On the other hand, the OG2 sample contained a high quantity of oxygenated sesquiterpenes (20.6%), and ß-elemene (22.7%) was the major constituent. The possible antitumor mechanisms of these EOs in the HCT-116 and MDA-MB-231 cell lines were examined by means of cell viability, apoptosis, redox potential, and migratory capacity. The antiviability potential appeared to be dose dependent, since the results showed that both EOs decreased the viability of the tested cells. Stronger antitumor effects were shown in MDA-MB-231 cells after short-term treatment, especially at the highest applied concentration, where the percentage of viability was reduced by over 40%. All tested concentrations of EOs exhibited proapoptotic activity and elevated activity of caspase-3 in a dose- and time-dependent manner. The results also showed decreased concentrations of superoxide anion radical in the treated cells, which indicates their significant antioxidative role. Long-term treatments showed mild recovery effects on cell viability in both cell lines, probably caused by the balancing of redox homeostasis. Elevated levels of nitrites indicate high levels of nitric oxide (NO) production and suggest its higher bioavailability due to the antioxidative environment. The tested EOs also induced a drop in migratory capacity, especially after short-time treatments. Taken together, these results suggest considerable antitumor activity of both EOs, which could have potential therapeutic applications.

Low-Risk Surgical Aortic Valve Replacement in the Era of Transcatheter Aortic Valve Implantation.

Open surgical aortic valve replacement (SAVR) is a viable alternative to transcatheter implantation in low-risk patients. In this light, we evaluated the safety and effectiveness of SAVR performed through conventional and less invasive surgical approaches in a high-volume center. We retrospectively reviewed the records of 395 consecutive patients who underwent open SAVR from January 2019 through December 2019 in our center. We evaluated and compared the operative results and postoperative major adverse outcomes of 3 surgical approaches: full median sternotomy (n=267), upper ministernotomy (ministernotomy) (n=106), and right anterior thoracotomy (minithoracotomy) (n=22). Overall, the 30-day all-cause mortality rate was 0.8% (3 patients). Stroke occurred in 8 patients (2%), disabling stroke in 4 patients (1%), myocardial infarction in 1 (0.2%), and surgical site infection in 13 (3.2%). There was no difference in 30-day mortality rate or incidence of postoperative major adverse events among the 3 surgical groups. Stroke and surgical site infection occurred more frequently, but not significantly so, in the full-sternotomy group. The mean hospital stay was longer after full sternotomy (9.1 ± 5.5 d) than after ministernotomy (7.5 ± 2.9 d) or minithoracotomy (7.4 ± 1.9 d) (P=0.012). Our findings suggest that open SAVR performed in a high-volume center is associated with a low early mortality rate and that less invasive approaches result in faster postoperative recovery and shorter hospital stays.

Antiproliferative, antimigratory, and prooxidative potential of novel platinum(IV) complexes and resveratrol on breast cancer (MDA-MB-231) and choriocarcinoma (JEG-3) cell lines.

Platinum(IV) complexes offer the potential to overcome cisplatin resistance of cancer cells, with possible improved selectivity. Resveratrol, a natural polyphenol with anticancer and antioxidant capacity, could limit the possible side effects of chemotherapeutics on healthy cells. This study investigates the effects of platinum(IV) complexes containing some esters of the ethylenediamine-N,N'-di-S,S-(2,2'-dibenzyl)acetate acid (H2 -S,S-eddba), and resveratrol on proliferation, migration, and redox balance of breast cancer (MDA-MB-231), choriocarcinoma (JEG-3), and human lung fibroblast (MRC-5) cell line. According to IC50 values, all complexes exhibited a significantly stronger antiproliferative effect on tested cell lines compared to cisplatin. Due to reduced adverse effects on MRC-5 cells, the complex containing ethyl-substituent (10 µM) was selected for further examination with resveratrol (25 µM) cotreatment. Resveratrol enhanced the survival of MRC-5 cells while diminished the viability of both used cancer cell lines when applied combined with selected complex. Furthermore, cotreatment of these two compounds decreased the migratory potential of tested cancer cell lines. The examined platinum(IV) complex was able to induce oxidative stress in all tested cell lines. Resveratrol proved to be efficient in protecting MRC-5 cells from complex-induced oxidative damage, while it significantly amplified antiproliferative, antimigratory, and prooxidative effects of platinum(IV) complex on both examined cancer cell lines. These findings may be valuable in elucidating the mechanism of action of platinum(IV) drugs, which should be further investigated.

Neonatal diabetes mellitus due to a new KCNJ11 mutation - 10 years of the patient`s follow-up.

BACKGROUND: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes. CASE: In this report, we describe a 10-year-old girl who is heterozygous for a new missense mutation in the KCNJ11 gene and whose treatment was successfully switched from insulin to sulfonylurea (glibenclamide) therapy when she was one month old. 10-year data on a low-dose of glibenclamide monotherapy showed excellent glycaemic control with no reports of severe hypoglycaemia and microvascular complications. CONCLUSION: An early genetic diagnosis of neonatal diabetes mellitus is highly beneficial because early switch from insulin to sulfonylurea is safe, avoids unnecessary insulin therapy and promotes sustained improvement of glycaemic control on long-term follow-up.

Prediction value of EuroSCORE II in total arterial revascularization and its usage in the evaluation of postoperative complications: Single-center experience.

BACKGROUND: Total arterial revascularization is the most durable and technically the most demanding type of coronary artery bypass grafting procedure. It has proven long-term supremacy in comparison to conventional coronary artery bypass grafting. In our study, we investigated the reliability of EuroSCORE II as a predictor of intrahospital death. We showed its impact on adverse perioperative events. METHODS: In this nonrandomized prospective study, we analyzed 116 consecutive patients who underwent the total arterial revascularization procedure at our Institute from January 2011 until the present. For myocardial revascularization, the most suitable combinations with left internal mammary artery, right internal mammary artery, and radial artery grafts were used. Main fact in this research was intrahospital mortality value in comparison with the value predicted. RESULTS: There were 104 (89.7%) males and 12 (10.3%) females. Mean preoperative EuroSCORE II prediction value was 1.98% and postoperative we obtained 1.72%. Postoperative redo for bleeding was 6%. Positive correlation was proven between the EuoroSCORE II value and intensive care unit stay (0.452; p < 0.001). Among patients who received two internal mammary arteries, the highest EuroSCORE II was among those with presternal wound infection (p = 0.005). Patients with bilateral internal mammary arteries and diabetes showed that they have the highest values of EuroSCORE II and, at the same time, that they are extremely prone to wound problems. CONCLUSIONS: We achieved a lower intrahospital mortality level than it was predicted with preoperative EuroSCORE II value. This tool is a reliable method for preoperative death risk calculation in this group of patients.

Hematoprotective effects and antioxidant properties of ß-glucan and vitamin C against acetaminophen-induced toxicity: an experimental study in rats.

Acetaminophen is widely used as an over-the-counter analgesic and antipyretic drug. The aim of the present study was to investigate the pro-oxidative effects of acetaminophen (300 mg/kg/day i.p.) and antioxidative effects of ß-glucan (4 mg/kg/day i.p.) and/or vitamin C (100 mg/kg/day i.p.) on the blood parameters of treated rats. After 3 days of treatment, hematological and parameters of redox status were measured. Exposure of rats to acetaminophen caused significant changes in some hematological parameters and the glutathione redox cycle, leading to an increased concentration of oxidative stress parameters and the formation of lipid peroxidation, while the activities of antioxidant enzymes were decreased. Administration of ß-glucan and/or vitamin C reduced lipid peroxidation and restored the levels of examined hematological and oxidative stress parameters and improved the activities of antioxidant enzymes. Obtained results demonstrated that acetaminophen has significant pro-oxidative effects and may disrupt redox balance in blood of rats, while the combination of ß-glucan and/or vitamin C amplified the antioxidant defense potential and exhibited a strong hematoprotective activity against acetaminophen-induced toxicity. Therefore, ß-glucan and vitamin C co-treatment may be a promising therapeutic option for the treatment of acute acetaminophen hematotoxicity.

Predictors of in-hospital mortality and complications in acute aortic occlusion: a comparative analysis of patients with embolism and in-situ thrombosis.

BACKGROUND: Acute aortic occlusion (AAO) represents potentially fatal acute vascular emergency that requires prompt diagnosis and intervention. Clinical condition of patients with AAO is frequently severely devastated when surgical intervention is questionable. Our objective was to retrospectively review our institutional experience with AAO and assess predictors of intrahospital mortality and morbidity. METHODS: This is a retrospective single-center cohort study with prospectively collected data between January 1, 2005 and January 1, 2018. The total number of 28 consecutive patients with AAO were included in our analysis. Patients with acute aortic thrombosis manifested by bilateral acute limb ischemia were divided in two groups based on potential caues of AAO (embolism or in-situ thrombosis) differentiated according to condition of aortoilical segment. RESULTS: We identified 28 patients with AAO. All of them underwent either aortobifemoral bypass (N.=20, 71%) or bilateral trans-femoral thrombectomy (N.=8, 29%). The overall in-hospital mortality was 36%. Factors that influenced in-hospital mortality were: paralysis (OR=4.41, 95% CI: 1.88-21.78) and higher lactate values on admission (OR=1.23, 95% CI: 1.09-1.83), postoperative development of severe acute kidney injury (OR=3.08, 95% CI: 1.42-14.66), hemodialysis (OR=10.74, 95% CI: 1.64-109.78) and bowel ischemia (OR=5.19, 95% CI: 1.58-55.63). CONCLUSIONS: Paralysis, higher lactate values, development of acute kidney injury, hemodialysis and bowel ischemia are predictors of worse outcome and may be used for risk stratification of patients with acute aortic occlusion and improve counseling patients and their families about expected postoperative outcomes. Patients with embolism and malignant disease have worse outcome; however, this should be tested in future studies on larger sample.

Evaluation of Toxic Effects of Novel Platinum (IV) Complexes in Female Rat Liver: Potential Protective Role of Resveratrol.

The use of cisplatin in chemotherapy may provoke a deteriorating impact in many vital organs, suggesting the need for more selective derivatives and effective protective cotreatments. This study assesses the effects of three novel Pt(IV) complexes containing ethyl-, propyl- and butyl-esters of the ethylenediamine-N, N'-di-S, S- (2,2'-dibenzyl) acetic acid on liver injury markers, redox parameters, and cell morphology of female rat liver tissue in comparison to cisplatin. In addition, the study evaluates the possible protective effects of resveratrol as well. The rats were divided into ten groups and were administered intraperitoneally with a single dose of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg) and/or resveratrol (25 mg/kg). All treatments caused changes in body weight, food intake, and liver/bw ratio. Acute treatment with novel complexes decreased the levels of TB and TP while elevated the activity of ALT, AST, GGT, ALP which subsequently indicated on the liver damage. All three complexes significantly reduced the levels of LPO, O2.-, NO2- and activity of CAT, while increasing the activity of SOD, GSH-Px, GR, GST, and level of GSH, implying that these compounds could provoke redox balance disruption in liver cells. Moreover, according to the histopathological observations, the novel Pt(IV) complexes exerted stronger hepatotoxicity than cisplatin. Possible protective effects of resveratrol were not detected and even combined with examined compounds it abolished the activity of the antioxidative system of the liver cells causing more intense toxicity. Further investigation is required to elucidate the effects of Pt-based drugs and resveratrol in the estradiol-rich environment of female rats as well their influence on male rats' tissues.

Analysis of Mortality from Carcinomas Primary Localized in Region of Lip, Oral Cavity and Pharynx in Central Serbia, 1999-2015.

BACKGROUND: Lip, oral cavity, and pharyngeal cancers have been globally estimated to account for about 3.8% of all cancer cases and 3.6% of cancer deaths. Mortality of these cancers is generally higher in developing than in developed countries. Overall cancer mortality rate in Serbia is one of the highest in the world. The aim of this study was to determine the mortality rate trends and the most common localization of lip, oral and pharyngeal cancers in Serbia. METHODS: The study was conducted in 2018 as descriptive epidemiological study and included years from 1999 to 2015. The differences in standardized mortality rates and number of deaths were analyzed with regard to age, gender, and tumor localization. Linear trend and regression were used to determine mortality rate trend. RESULTS: There was statistically significant difference in the number of deaths between men and women in the ages of 40 and over (P < 0.01); male/female cancer mortality ratio was 4.56:1. Generally, the most common localization of this carcinoma was hypopharynx. There was no statistically significant increase of mortality rates from these cancers for both genders (males: y = 4.77 + 0.42x, P = 0.069 % change = +20.35; females: y = 1.03 + 0.01x, P = 0.40 % change = +4) during 17-year period. CONCLUSION: Promotion of healthy habits, life-styles and regular inspection of mouth by patients and health professionals should be better prioritized especially in developing countries where implementing and improving national health prevention programs are essential.

Rare-earth (Gd3+,Yb3+/Tm3+, Eu3+) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging.

Taking advantage of the flexibility of the apatite structure, nano- and micro-particles of hydroxyapatite (HAp) were doped with different combinations of rare earth ions (RE3+ = Gd, Eu, Yb, Tm) to achieve a synergy among their magnetic and optical properties and to enable their application in preventive medicine, particularly diagnostics based on multimodal imaging. All powders were synthesized through hydrothermal processing at T ≤ 200 °C. An X-ray powder diffraction analysis showed that all powders crystallized in P63/m space group of the hexagonal crystal structure. The refined unit-cell parameters reflected a decrease in the unit cell volume as a result of the partial substitution of Ca2+ with smaller RE3+ ions at both cation positions. The FTIR analysis additionally suggested that a synergy may exist solely in the triply doped system, where the lattice symmetry and vibration modes become more coherent than in the singly or doubly doped systems. HAp:RE3+ optical characterization revealed a change in the energy band gap and the appearance of a weak blue luminescence (λex = 370 nm) due to an increased concentration of defects. The "up"- and the "down"-conversion spectra of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders showed characteristic transitions of Tm3+ and Eu3+, respectively. Furthermore, in contrast to diamagnetic HAp, all HAp:RE3+ powders exhibited paramagnetic behavior. Cell viability tests of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders in human dental pulp stem cell cultures indicated their good biocompatibility.

Treatment of pediatric vascular injuries: the experience of a single non-pediatric referral center.

BACKGROUND: Pediatric peripheral vascular trauma carries significant risk of complications including limb loss and long-term invalidity. Mechanisms and types of morphological lesions are very diverse. The objectives of this study are to present the experience of a single vascular center in the surgical approach to pediatric vascular injuries, and to analyze the main challenges related to this clinical entity. METHODS: Over a period of 25 years, 17 pediatric peripheral vascular injuries were treated in our institution. Patient's age ranged between one day (newborn) and 15 years (mean: 10.7 years). There were five injuries of upper and 12 injuries of the lower extremity. Preoperative diagnosis was established by clinical examination (N.=4), ultrasonography (N.=1) and angiography (N.=12). Blunt trauma mainly caused arterial thrombosis while penetrating trauma caused arterial laceration or complete transection. Five patients had associated orthopedic injuries (29,4%). There were two posttraumatic pseudoaneurysms and two arterio-venous fistulas. RESULTS: There was no perioperative mortality. Vascular reconstructions included arterial suture (N.=4), thrombectomy + patch angioplasty (N.=1), termino-terminal anastomosis (N.=3), venous anatomic bypass (N.=6), PTFE graft reconstruction (N.=2), and venous extra-anatomic reconstruction (N.=1). Two patients had associated venous injury demanding both arterial and venous reconstruction. In the only case of war trauma treatment ended with limb loss. Other reconstructions presented good early and long-term patency. CONCLUSIONS: Pediatric vascular injuries are extremely challenging issues. Treatment includes broad spectrum of different types of vascular reconstructions. It should be performed by vascular surgeon trained in open vascular treatment or pediatric surgeon with significant experience in vascular surgery.