Mechanism of Antiradical Activity of Coumarin-Trihydroxybenzohydrazide Derivatives: A Comprehensive Kinetic DFT Study.

As part of this study, the mechanisms of the antioxidant activity of previously synthesized coumarin-trihydrobenzohydrazine derivatives were investigated: (E)-2,4-dioxo-3-(1-(2-(2″,3″,4″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate (1) and (E)-2,4-dioxo-3-(1-(2-(3″,4″,5″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate (2). The capacity of the compounds to neutralize HO• was assessed by EPR spectroscopy. The standard mechanisms of antioxidant action, Hydrogen Atom Transfer (HAT), Sequential Proton Loss followed by Electron Transfer (SPLET), Single-Electron Transfer followed by Proton Transfer (SET-PT), and Radical Adduct/Coupling Formation (RAF/RCF) were examined using the QM-ORSA methodology. It was estimated that the newly synthesized compounds, under physiological conditions, exhibited antiradical activity via SPLET and RCF mechanisms. Based on the estimated overall rate constants (koverall), it can be concluded that 2 exhibited a greater antiradical capacity. The obtained values indicated a good correlation with the EPR spectroscopy results. Both compounds exhibit approximately 1.5 times more activity in comparison to the precursor compound used in the synthesis (gallic acid).

Evaluation of Risk Factors for the Occurrence of Limb Fractures in Children Due to Unintentional Injury in Podgorica, Montenegro, Mediterranean.

Background and Objectives: Limb injuries in childhood are very common, with most of them being unintentional and often accompanied by soft tissue injuries. The aim of our study was to determine the risk factors that contribute to the occurrence of limb fractures as the most common type of accidental injury to children in our conditions. Materials and Methods: This study was designed as a prospective clinical analysis of predictive factors with a "nested" case-control study. It included all patients under the age of 18 who were diagnosed with unintentional limb injury and limb fracture due to accidental injury, at the Clinical Center of Montenegro, Podgorica, in the period of 7 January 2020-30 June 2021. Results: The gender of the child and the occurrence of the fracture are not related, and a statistically significant relationship was found between the occurrence of the fracture and the place of residence, the child's age, body mass index (BMI), the affected limb, the method of injury, and the mental state of the parents of the injured child, as well as their economic status. It was proved that the older the child was, the lower the chance of injury, while multivariate analysis proved that BMI could be a predictor of accidental fracture. The most common method of accidental limb fractures in children was a fall from a height. Conclusions: The analysis of factors that influence the occurrence of children's injuries is of great importance for public health. Such and similar research can enable a better understanding of the factors that influence accidental injuries, and therefore influence the prevention of these injuries by organizing various educational materials at the primary healthcare level or at the school level, for both children and parents.

An Effective, Green Synthesis Procedure for Obtaining Coumarin-Hydroxybenzohydrazide Derivatives and Assessment of Their Antioxidant Activity and Redox Status.

In this study, green synthesis of two derivatives of coumarin-hydroxybenzohydrazide, (E)-2,4-dioxo-3-(1-(2-(2,3,4-trihydroxybenzoyl)hydrazyl)ethylidene)-chroman-7-yl acetate (C-HB1), and (E)-2,4-dioxo-3-(1-(2-(3,4,5-trihydroxybenzoyl)hydrazyl)ethylidene)chroman-7-yl acetate (C-HB2) is reported. Using vinegar and ethanol as a catalyst and solvent, the reactions were carried out between 3-acetyl-4-hydroxy-coumarin acetate and corresponding trihydroxybenzoyl hydrazide. The antioxidant potential of these compounds was investigated using the DPPH and ABTS assays, as well as the FRAP test. The obtained results reveal that even at very low concentrations, these compounds show excellent radical scavenging potential. The IC50 values for C-HB1 and C-HB2 in relation to the DPPH radical are 6.4 and 2.5 µM, respectively, while they are 4.5 and 2.0 µM in relation to the ABTS radical. These compounds have antioxidant activity that is comparable to well-known antioxidants such as gallic acid, NDGA, and trolox. These results are in good correlation with theoretical parameters describing these reactions. Moreover, it was found that inhibition of DPPH● follows HAT, while inactivation of ABTS+● follows SET-PT and HAT mechanisms. Additionally, coumarin-hydroxybenzohydrazide derivatives induced moderate cytotoxic activity and show significant potential to modulate redox status in HCT-116 colorectal cancer cells. The cytotoxicity was achieved via their prooxidative activity and ability to induce oxidative stress in cancer cells by increasing O2˙- concentrations, indicated by increased MDA and GSH levels. Thus, ROS manipulation can be a potential target for cancer therapies by coumarins, as cancer cells possess an altered redox balance in comparison to normal cells. According to the ADMET analysis, the compounds investigated show good pharmacokinetic and toxicological profiles similar to vitamin C and gallic acid, which makes them good candidates for application in various fields of industry and medicine.

Five-year disease-free survival in FIGO IA stage endometrial cancer patients: Tertiary institution experience in a developing country.

Purpose: Endometrial cancer is characterized as histopathological, molecular, genetic, biological, and very diverse group of malignancies. Due to the need to precisely define the indications for adjuvant treatment in recent years, there has been a division made according to risk groups based on prognostic factors, which identify patients at risk for disease relapse, who may benefit from adjuvant therapy. The aim of this research was to examine the clinical and morphological factors that influence disease-free survival (DFS) and overall survival (OS) in patients with FIGO IA stage endometrial cancer. Material and methods: A retrospective clinical study was conducted, primarily based on the identification of factors that influence five-year DFS and OS. The study integrated data of FIGO IA stage endometrial cancer patients, who presented to gynecological oncology board for the first time after operative treatment, from January 1, 2016 to January 1, 2022. Adjuvant radiotherapy was applied to patients with an initially higher risk of disease progression. Length of survival was analyzed using Kaplan-Meier method, while log-rank test was used to assess differences between groups. Results: The results show that 5-year OS for 93 patients was 89.2% and DFS was 88.2%. Application of adjuvant brachytherapy, number of deliveries, MRI staging, type of institution where the surgery was performed influenced DFS. Pathohistological characteristics of tumor indicated a statistically significant impact on DFS. Conclusions: Application of adjuvant brachytherapy in high-intermediate and high-risk patients contributes to DFS increase. Moreover, the existence of a pre-operative MRI assessment of the stage of disease as well as the type of healthcare provided by an institution where the surgery was performed, significantly affect DFS.

Quantitative and Qualitative Characteristics of Atherosclerotic Plaques on Carotid Arteries in Patients with Antiphospholipid Syndrome: The Role of MDCT Angiography.

INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterious and venous thrombosis, miscarriage, and the presence of antiphospholipid antibodies (aPL) in the blood. As we know, APS is also characterised by accelerated atherosclerotic degeneration with an increased risk of thrombosis in all blood vessels, including the carotid arteries. Carotid artery stenosis can manifest in many different ways. The aim of this study is to present the results of our multidetector computerised tomography angiography (MDCTA) analysis of the carotid arteries in patients with primary and secondary APS compared with a control group. MATERIALS AND METHODS: This study examined 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with secondary antiphospholipid syndrome (SAPS). The results were compared with a control group also comprising 50 patients. The groups were analysed with respect to age, sex and the presence of well-established risk factors for vascular disease. The study was conducted using MDCTA, where we analysed the quantitative and qualitative (morphologic) characteristics of carotid artery lesions. RESULTS: Patients from the control group had significantly elevated levels of cholesterol and triglycerides in comparison with patients with PAPS and SAPS (p < 0.001 and p < 0.05). The results show that carotid artery lesions were significantly more common in patients with APS (PAPS, n = 40, CI95: 0.50-0.75, p = 0.0322 and SAFS, n = 54, CI95: 0.59-0.80, p = 0.0004) than within the control group (n = 23). There was a statistically significant difference between patients with APS and the control group with respect to lesions in the distal segments (n = 27, CI95: 0.67-0.95, p = 0.0001), bulbi and proximal segments (n = 21, CI95: 0.84-1.00, p = 0.000005). The number of patients with one lesion (L) (n = 27) was significantly greater than the number of those with three (n = 10, CI95: 0.56-0.86, p = 0.0051) or four (n = 3, CI95: 0.73-0.98, p = 0.00001) lesions. There were also more patients with two lesions (n = 24) than those with four (n = 3) (CI95: 0.71-0.97, p = 0.00005). Carotid artery stenosis was shown as a percentage of the carotid artery lumen diameter (%DS). Stenosis of up to 30%, was more common in patients in the PAPS group (n = 12) than in the control group (n = 3) (CI95: 0.52-0.96, p = 0.0201), while the SAPS group (n = 17) had an even larger disparity (CI95: 0.62-0.97, p = 0.0017). We observed a highly significant difference in the frequency of stenoses between 30% and 50% DS between the PAPS group (n = 24) and the control group (n = 7) (CI95: 0.59-0.90, p = 0.0023), as well as the SAPS group (n = 30) (CI95: 0.65-0.92, p = 0.0002). A qualitative analysis of plaque morphology revealed that patients with PAPS had significantly more soft tissue lesions (n = 23) compared with calcified lesions (n = 2) (CI95: 0.74-0.99, p = 0.00003), as well as more mixed plaques (n = 9) and calcified plaques (n = 2) (CI95: 0.48-0.98, p = 0.0348). Patients within the SAPS group had significantly more soft tissue (n = 35) than calcified lesions (n = 3) (CI95: 0.79-0.98, p = 0.00000021), as well as more mixed lesions (n = 21) compared with calcified (n = 3) (CI95: 0.68-0.97, p = 0.0002). CONCLUSIONS: Our study shows that subclinical manifestations of carotid artery lesions were more common in patients with APS. We came to the conclusion that MDCTA is an accurate diagnostic method because it is a safe method that provides us with a great quantity of accurate information about the characteristics of atheromatous plaques, which aids us in the further planning of treatment for patients with APS.

Brixia Chest X-ray Score, Laboratory Parameters and Vaccination Status for Prediction of Mortality in COVID-19 Hospitalized Patients.

Chest X-ray has verified its role as a crucial tool in COVID-19 assessment due to its practicability, especially in emergency units, and Brixia score has proven as a useful tool for COVID-19 pneumonia grading. The aim of our study was to investigate correlations between main laboratory parameters, vaccination status, and Brixia score, as well as to confirm if Brixia score is a significant independent predictor of unfavorable outcome (death) in COVID-19 patients. The study was designed as a cross-sectional multicentric study. It included patients with a diagnosed COVID-19 infection who were hospitalized. This study included a total of 279 patients with a median age of 62 years. The only significant predictor of unfavorable outcome (death) was Brixia score (adjusted odds ratio 1.148, p = 0.022). In addition, the results of the multiple linear regression analysis (R2 = 0.334, F = 19.424, p < 0.001) have shown that male gender (B = 0.903, p = 0.046), severe COVID-19 (B = 1.970, p < 0.001), and lactate dehydrogenase (B = 0.002, p < 0.001) were significant positive predictors, while albumin level (B = -0.211, p < 0.001) was a significant negative predictor of Brixia score. Our results provide important information about factors influencing Brixia score and its usefulness in predicting the unfavorable outcome (death) of COVID-19 patients. These findings have clinical relevance, especially in epidemic circumstances.

Oral Health and Oral Health-Related Quality of Life in Patients with Primary Sjögren's Syndrome.

Background and Objectives: Oral disorders, frequently observed in patients with primary Sjögren's syndrome, can profoundly affect patients' daily lives and well-being, as oral health represents a fundamental part of general health. Saliva plays an essential part in maintaining and protecting oral health, so the decrease in its quantity and quality leads to chronic oral discomfort alongside a broad spectrum of problems. The objective of the present study was to evaluate the oral health of patients with primary Sjögren's syndrome and establish its effect on the different domains of their oral health-related quality of life (OHRQoL). Materials and Methods: The research was designed as an observational case-control study with prospective data collection. Eighty patients, divided into two groups based on their oral status, participated in the study. All subjects underwent a complete oral examination. The OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14). Results: The most prevalent oral manifestation was exfoliative cheilitis, while 30% of subjects complained of chewing and swallowing difficulties. The OHIP-14 summary score was significantly higher in the patients with oral lesions (26.0 (5.0) vs. 17.0 (4.0), respectively; p < 0.001). Oral manifestations, systemic involvement, medication, and periodontal indexes were significantly associated with OHIP-14 scores. Conclusions: Patients with oral alterations had a substantially decreased OHRQoL. These findings emphasize the importance of oral diseases for patients' well-being. Therefore, it is essential for dentists to be included in the multidisciplinary teams managing primary Sjögren's syndrome, as improving patients' oral status would lead to better oral health and enhanced OHRQoL.

Analysis and Forecast of Indicators Related to Medical Workers and Medical Technology in Selected Countries of Eastern Europe and Balkan.

Health indicators measure certain health characteristics in a specific population or country and can help navigate the health systems. As the global population is rising, the demand for an increase in the number of health workers is simultaneously rising. The aim of this study was to compare and predict the indicators related to the number of medical workers and medical technologies in selected countries in Eastern Europe and Balkan in the studied period. The article analyzed the reported data of selected health indicators extracted from the European Health for All database. The indicators of interest were the number of physicians, pharmacists, general practitioners and dentists per 100,000 people. To observe the changes in these indicators through the available years, we used linear trends, regression analysis and forecasting to the year 2025. The regression analysis shows that the majority of the observed countries will experience an increase in the number of general practitioners, pharmacists, health workers/professionals and dentists, as well as in the number of computerized tomography scanners and the number of magnetic resonance units, predicted to occur by 2025. Following trends of medical indicators can help the government and health sector to focus and navigate the best investments for each country according to the level of their development.

Investigational new drugs for the treatment of Dravet syndrome: an update.

INTRODUCTION: While there are already approved anticonvulsants for treatment of children with Dravet syndrome, disease modifying therapy is at its beginning. AREAS COVERED: This narrative review is updating the latest information about efficacy and safety of both anticonvulsant and disease modifying investigational drugs for Dravet syndrome. Relevant publications were searched for in MEDLINE, GOOGLE SCHOLAR, SCINDEKS, and CLINICALTRIALS.GOV databases, from the dates of their foundation till January 2023. EXPERT OPINION: The main advancements were made in the treatment of Dravet syndrome with confirmed haploinsufficiency of SCN1A gene. The application of antisense oligonucleotides has so far proven to be the most successful within disease-modifying therapy, but it also requires further refinement of the methodology of application and delivery to target cells, as well as additional testing of the effectiveness of antisense oligonucleotides outside of TANGO technology. Also, the full potential of gene therapy has yet to be explored, given that high capacity adenoviral vectors that can incorporate the SCN1A gene have recently been prepared.

Does the Expression of Vascular Endothelial Growth Factor (VEGF) and Bcl-2 Have a Prognostic Significance in Advanced Non-Small Cell Lung Cancer?

Lung cancer is the most common cause of mortality from malignant tumors worldwide. The five-year survival rate for people with advanced stages varies considerably, from 35.4% to 6.9%. The angiogenic potential of bcl2 is not well known, nor is the way in which tumor cells with excessive bcl2 expression affect VEGF production. Hypothetically, given that tumor growth, progression and metastasis are dependent on angiogenesis, the antiapoptotic effect is expected to form a link between these two molecules. The aim of this study was to evaluate the relationship between bcl-2 and VEGF expression, clinicopathological features and survival in 216 patients with advanced NSCLC. Archival tumor tissues were examined by immunohistochemistry for the expression of bcl-2 and VEGF. Immunoreactivity for bcl-2 was observed in 41.4% of NSCLCs, 51% of squamous and 34.8% of adenocarcinomas-expressed Bcl-2. There was an inverse correlation of mononuclear stromal reaction and bcl-2 expression in adenocarcinoma (p < 0.0005). A total of 71.8% NSCLCs were VEGF positive, 56% of squamous and 82.2% of adenocarcinomas. High level of VEGF expression was significantly associated with histology type (p = 0.043), low histology grade (p = 0.014), clinical stage IV (p = 0.018), smoking history (p = 0.008) and EGFR mutations (p = 0.026). There was an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC patients (p = 0.039, r = -0.163). Two-year survival of patients with unresectable NSCLC was 39.3%, and 50% of patients were alive at 17 months. Our results demonstrated no difference in survival for patients in advanced NSCLC grouped by bcl-2 and VEGF status. Additionally, we observed an inverse correlation in the expression of Bcl-2 and VEGF in NSCLC and mononuclear reaction and bcl-2 expression in adenocarcinomas.

Degradation Mechanisms of 4,7-Dihydroxycoumarin Derivatives in Advanced Oxidation Processes: Experimental and Kinetic DFT Study.

Coumarins represent a broad class of compounds with pronounced pharmacological properties and therapeutic potential. The pursuit of the commercialization of these compounds requires the establishment of controlled and highly efficient degradation processes, such as advanced oxidation processes (AOPs). Application of this methodology necessitates a comprehensive understanding of the degradation mechanisms of these compounds. For this reason, possible reaction routes between HO• and recently synthesized aminophenol 4,7-dihydroxycoumarin derivatives, as model systems, were examined using electron paramagnetic resonance (EPR) spectroscopy and a quantum mechanical approach (a QM-ORSA methodology) based on density functional theory (DFT). The EPR results indicated that all compounds had significantly reduced amounts of HO• radicals present in the reaction system under physiological conditions. The kinetic DFT study showed that all investigated compounds reacted with HO• via HAT/PCET and SPLET mechanisms. The estimated overall rate constants (koverall) correlated with the EPR results satisfactorily. Unlike HO• radicals, the newly formed radicals did not show (or showed negligible) activity towards biomolecule models representing biological targets. Inactivation of the formed radical species through the synergistic action of O2/NOx or the subsequent reaction with HO• was thermodynamically favored. The ecotoxicity assessment of the starting compounds and oxidation products, formed in multistage reactions with O2/NOx and HO•, indicated that the formed products showed lower acute and chronic toxicity effects on aquatic organisms than the starting compounds, which is a prerequisite for the application of AOPs procedures in the degradation of compounds.

Can MDCT Enhancement Patterns Be Helpful in Differentiating Secretory from Non-Functional Adrenal Adenoma?

Background and Objectives: Primary adrenal tumors (AT) are a heterogeneous group of neoplasms due to their functional heterogeneity, which results in the diverse clinical presentation of these tumors. The purpose of this study was to examine cross-sectional imaging characteristics using multi-detector computed tomography (MDCT) to provide insight into the lesion characterization and functional status of these tumors. The radionuclide imaging using Technetium-99m radiolabeled hydrazinonicotinylacid-d-phenylalanyl1-tyrosine3-octreotide (99mTc-HYNIC-TOC), was also used in the diagnostic evaluation of these tumors. Materials and Methods: This cross-sectional study included 50 patients with confirmed diagnoses of AT (21 hormone-secreting and 29 non-functional) at the University Clinical Center, Kragujevac, Serbia, during the 2019-2022 year period. The morphological and dynamic characteristics using MDCT were performed, using qualitative, semi-quantitative, and quantitative analysis. Absolute washout (APW) and relative washout (RPW) values were also calculated. A semi-quantitative analysis of all visual findings with 99mTc-HYNIC-TOC was performed to compare the tumor to non-tumor tracer uptake. Results: A statistically significant difference was found in the MDCT values in the native phase (p < 0.05), the venous phase (p < 0.05), and the delayed phase (p < 0.001) to detect the existence of adrenal tumors. Most of these functional adrenocortical lesions (n = 44) can be differentiated using the delayed phase (p < 0.05), absolute percentage washout (APW) (p < 0.05), and relative percentage washout (RPW) (p < 0.001). Furthermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumor existence (p < 0.001). There is a positive correlation between radionuclide imaging scan and APW to detect all AT (p < 0.01) and adrenocortical adenomas as well (p < 0.01). Conclusions: The results can be very helpful in a diagnostic algorithm to quickly and precisely diagnose the expansive processes of the adrenal glands, as well as to learn about the advantages and limitations of the mentioned imaging modalities.

In silico study of inhibitory capacity of sacubitril/valsartan toward neprilysin and angiotensin receptor.

Heart failure (HF) is a life-threatening condition that occurs when the heart cannot pump enough blood and oxygen to meet the body's needs. It affects mostly the elderly, commonly from the male population, especially those with obesity, diabetes, or some other chronic condition. It can be treated with different medications, and promising results were shown by a relatively new medicament called Entresto. Results obtained from molecular docking and molecular dynamics simulations to examine the inhibitory capacity of Entresto are presented in this study. Parameters obtained by the molecular docking simulations show that both parts of Entresto (sacubitril (SAC) and valsartan (VAL)) interact with targeted proteins, and inhibit their physiological function. Simulations of molecular dynamics revealed some interesting inhibitory patterns. SAC was discovered to produce structural alterations in neprilysin by binding to it, reducing neprilysin's physiological activity. In addition to blocking the active site, SAC binding causes the enzyme's structure to become less compact over time, causing changes in its biochemical characteristics and preventing the enzyme from performing its biological function. Similar to SAC, VAL also causes deviations in the structure of angiotensin receptors. The angiotensin receptor GPCR (G-protein-coupled receptors) is immersed in the lipid bilayer, and changes in the tertiary structure are only visible through RMSD and RMSF, not by examining R g. In this regard, MD simulations validated the results of molecular docking simulations, demonstrating that both SAC and VAL had inhibitory potential towards the neprilysin and angiotensin receptors, respectively.

Ascites as First Atypical and Only Clinical Manifestation of De Novo Follicular Lymphoma.

Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma and is usually initially detected in lymph nodes. Primary extranodal NHL is most commonly primarily localized in the gastrointestinal tract. We present one unusual case of ileum FL with ascites as the first clinical sign. The 73-year-old female patient was presented to the emergency department for evaluation of mild abdominal pain and abdominal swelling that had been going on for three days followed by bloating and occasional pain in the spine. The abdominal contrast-enhanced CT revealed the contrast stagnation in the distal part of the ileum. The ileum wall about 11 cm in length was thickened up to 2.9 cm and the tumor mass infiltrated all layers of ileum mesenteric lymphadenopathy up to 2 cm in diameter and significant ascites. On the upper ileum wall, the vegetative mass was described 3 cm in diameter. The patient had an emergent laparotomy with the ileocolic resection and latero-lateral ileocolic anastomosis. The microscopy finding of terminal ileum and the regional lymph nodes showed domination of cleaved cells with irregular nuclei which correspond to centrocytes. There were 0-15 large non-cleaved cells corresponding to centroblast in the microscopy high-power field. The final diagnosis was follicular lymphoma, the clinical stage 2E and histological grade by Berard and Mann criteria 1-2.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2-. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

Synthesis and Cytotoxicity Evaluation of Novel Coumarin-Palladium(II) Complexes against Human Cancer Cell Lines.

Two newly synthesized coumarin-palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and 1H-13C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds.

The Shape of Nasopalatine Canal as a Determining Factor in Therapeutic Approach for Orthodontic Teeth Movement-A CBCT Study.

The aim of this study was to evaluate the impact of the nasopalatine canal (NPC) shape and its morphometric characteristics on expected teeth movement by assessing the distance to maxillary central incisors (MCIs) according to NPC type. The retrospective study was performed on 133 CBCT images. The following parameters were obtained: the antero-posterior diameter (A-P) of the nasal foramen (NF), canal length, A-P and mediolateral diameter (M-L) of the incisive foramen (IF), and the distance between NPC and MCIs. With the exception of being hourglass-shaped, each NPC shape showed specific impacts of NPC shape on the relationship between NPC diameters at different sections and distances to MCIs. In banana-shaped NPC, a significant correlation was observed for A-P NF diameter, while in cylindrical-shaped NPC, a significant correlation was observed for NPC length. The increase in M-L IF, A-P IF, A-P NF, and NPC length in funnel-shaped NPC may be a risk factor for interventions that could result in teeth movement. According to the results, it seems that the proposed methodological approach for analysis of CBCT slices in the anterior maxilla may offer detailed information that could be an additional tool in planning the procedures that result in expected teeth movement.

Morphological and Morphometric Characteristics of Anterior Maxilla Accessory Canals and Relationship with Nasopalatine Canal Type-A CBCT Study.

This study aimed to evaluate principal morphological and morphometric characteristics of accessory canals (ACs) of the anterior maxilla, as well as to analyze the relationship with nasopalatine canal (NPC) type. The results of our study showed that ACs were observed in almost 50% of participants. They were mostly presented bilaterally and in a curved shape, with a palatal foramen position. The morphometric characteristics of ACs were significantly influenced by NPC type. NPC type had the strongest impact on the distance between the NPC and AC, as well as on the distance between the AC and the facial aspect of buccal bone wall, in inferior parts of the alveolar ridge. On the other hand, the distance between the AC and central incisors was not significantly influenced by NPC shape in the lower region of the anterior maxilla. However, the participants with the banana-type of the NPC expressed the reduction in distance from the AC to the central incisor at the upper part in comparison with the subjects with the cylindrical-type of the NPC. On the basis of the results of this study, the simultaneous estimation of ACs and the NPC seems reasonable, as this approach may be useful in the prevention of complications which could occur during implant surgery interventions.

Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage is a type of spontaneous hemorrhagic stroke, which is caused by a ruptured cerebral aneurysm. Cerebral vasospasm (CVS) is the most grievous complication of subarachnoid hemorrhage (SAH). The aim of this study was to examine the risk factors that influence the onset of CVS that develops after endovascular coil embolization of a ruptured aneurysm. MATERIALS AND METHODS: The study was designed as a cross-sectional study. The patients included in the study were 18 or more years of age, admitted within a period of 24 h of symptom onset, diagnosed and treated at a university medical center in Serbia during a 5-year period. RESULTS: Our study showed that the maximum recorded international normalized ratio (INR) values in patients who were not receiving anticoagulant therapy and the maximum recorded white blood cells (WBCs) were strongly associated with cerebrovascular spasm, increasing its chances 4.4 and 8.4 times with an increase of each integer of the INR value and 1,000 WBCs, respectively. CONCLUSIONS: SAH after the rupture of cerebral aneurysms creates an endocranial inflammatory state whose intensity is probably directly related to the occurrence of vasospasm and its adverse consequences.

Measurement of Bone Mineral Density in Children with Cerebral Palsy from an Ethical Issue to a Diagnostic Necessity.

INTRODUCTION: Due to concerns about cumulative radiation exposure in the pediatric population, it is not standard practice to perform dual-energy X-ray absorptiometry (DXA) analysis in the diagnostic process of musculoskeletal disorders, such as cerebral palsy (CP). This study aimed to evaluate the bone mineral density (BMD) in children with CP and the ethical justification of applying DXA analysis in these children. Material and Methods. In this monocentric retrospective analysis, data were collected from children and adolescents with CP who were treated for a primary illness for three years. A clinical examination, which included a DXA analysis, recommended by the multidisciplinary team, was performed. After applying inclusion and exclusion criteria, 60 scans remained for statistical analysis. BMD and Z-scores for the lumbar spine (LS), and hip right and left femoral neck (RFN and LFN, respectively), and total hip (TH) were recorded. RESULTS: The average age of children with CP when DXA analysis was first performed was about 7 years. The BMD (mean ± SD) at LS (LS-BMD) of all patients was 0.612 ± 0.12, at RFN 0.555 ± 0.11, at LFN 0.572 ± 0.1, and at TH (TH-BMD) 0.581 ± 0.13. The values of the Z-score (mean ± SD) at LS of all patients were -2.5 ± 0.22, at RFN -2.2 ± 0.21, at LFN -2.25 (SD = 0.2), and at TH -2.3 (SD = 0.23). There was no statistical significance between age and gender; however, BMI, walking ability, fracture history, and pattern of CP had a significant impact on BMD and Z-score values of these children. CONCLUSION: The results of our study clearly indicate that children with CP have a higher risk of low BMD, osteoporosis, and bone fractures, which makes it ethically justifiable to perform the DXA analysis in these children.