Nutritional Status and Quality of Life in Patients with Oral Squamous Cell Carcinoma Before and After Surgical Oncological Treatment: A Single-Center Retrospective Study.

BACKGROUND Oral squamous cell carcinoma (OSCC) is the most common of head and neck malignancies in well-developed countries. In most cases, patients with OSCC experience a degree of nutritional status disturbances and decreased quality of life (QoL). This study aimed to compare nutritional status and QoL in 51 patients before and after surgery for OSCC. MATERIAL AND METHODS Fifty-one eligible patients with OSCC were followed during a 3-year period (2019-2022). For all patients, we determined body mass index (BMI), serum albumin (ALB), prognostic nutritional index, and nutritional risk index before and after treatment. Also, all patients completed a standardized QoL questionnaire before and after treatment. The obtained data were compared between the groups by using the t test and multivariate Cox regression. RESULTS The values of BMI and NRI were statistically significantly different between the preoperative and postoperative measurements (24.1 kg/m² vs 21.1 kg/m², and 103 vs 100.1, respectively, P=0.001), while values of ALB and prognostic nutritional index did not differ significantly (41.35 g/L vs 39.1 g/L, and 48.5 vs 46.2, respectively). Dysphagia (P=0.03) and chewing problems (P=0.04) were found to be the 2 most important factors decreasing the QoL of patients. CONCLUSIONS Based on our results, BMI and NRI were the most sensitive parameters of nutritional status. Dysphagia and chewing problems were the 2 most important factors affecting the QoL in patients with OSCC.

Novel N-pyrocatechoyl and N-pyrogalloyl hydrazone antioxidants endowed with cytotoxic and antibacterial activity.

Over the years, pharmacological agents bearing antioxidant merits arose as beneficial in the prophylaxis and treatment of various health conditions. Hazardous effects of radical species hyperproduction disrupt normal cell functioning, thus increasing the possibility for the development of various oxidative stress-associated disorders, such as cancer. Contributing to the efforts for efficient antioxidant drug discovery, a thorough in vitro and in silico assessment of antioxidant properties of 14 newly synthesized N-pyrocatechoyl and N-pyrogalloyl hydrazones (N-PYRs) was accomplished. All compounds exhibited excellent antioxidant potency against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The extensive in silico analysis revealed multiple favorable features of N-PYRs to inactivate harmful radical species, which supported the obtained in vitro results. Also, in silico experiments provided insights into the preferable antioxidant pathways. Prompted by these findings, the cytotoxicity effects and the influence on the redox status of cancer HCT-116 cells and healthy fibroblasts MRC-5 were evaluated. These investigations exposed four analogs exhibiting both cytotoxicity and selectivity toward cancer cells. Furthermore, the frequently uncovered antimicrobial potency of hydrazone-type hybrids encouraged investigations on G+ and G- bacterial strains, which revealed the antibacterial potency of several N-PYRs. These findings highlighted the N-PYRs as excellent antioxidant agents endowed with cytotoxic and antibacterial features.

Oregano (Origanum vulgare) Essential Oil and Its Constituents Prevent Rat Kidney Tissue Injury and Inflammation Induced by a High Dose of L-Arginine.

This study aimed to evaluate the protective action of oregano (Origanum vulgare) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.

Seroprevalence Study of Anti-HBs Antibodies in the General Population of Vojvodina, Serbia.

Background and Objectives: Hepatitis B (HB) is a major global health problem and a potentially life-threatening disease caused by the hepatitis B virus (HBV). Also, it is an important cause of morbidity and mortality worldwide. Thanks to serological surveys, testing hepatitis B surface antibodies (anti-HBs) allows for serological assessments of their prevalence. The presence of anti-HBs, which protects against HBV infection, can be attributed to HB vaccination or natural HBV infection. The aim of our study was to evaluate the prevalence of HB surface antibodies (anti-HBs) as an indicator of collective immunity against HBV in the general population of the Autonomous Province of Vojvodina, Serbia. In addition, to distinguish whether anti-HBs were induced by the vaccine or by infection, the presence of antibodies against the hepatitis B core antigen (anti-HBc) was tested among those who were anti-HBs-positive. Materials and Methods: A total of 3467 residual sera samples, collected according to the specifications of the European Sero-Epidemiology Network 2 (ESEN2) study, from April 2015 to March 2016, were screened for the presence of anti-HBs using a chemiluminescence immunoassay. The difference between categorical variables was tested using the chi-square test. Results: Overall, 1870 (53.9%, 95% CI: 52.3-55.6) participants tested positive for anti-HBs. The median age of the study participants was 17 years (IQR 9-35). The anti-HB seroprevalence decreased with age, ranging from 80.7% (95% CI: 78.9-82.4) in the 1-19-year-old group to 16.4% (95% CI: 12.0-20.9) in the ≥60 years' age group. A total of 71 (3.8%, 95% CI: 2.9-4.7) serum samples were also anti-HBc-positive. Higher prevalence, but not statistically significant, was noticed in women (4.1%, 95% CI: 2.8-5.4) compared with men (3.5, 95% CI: 2.4-4.8) (p = 0.542). Also, there was a significant difference across the age groups, where those ≥60 years old had a prevalence of 65.9% (95% CI: 51.9-79.9) and the age category of 1-19-year-olds had just 0.2% (95% CI: 0.0-0.4) (p < 0.001). Conclusions: This study provides a comprehensive assessment of the anti-HBs seroprevalence of the general population in Vojvodina and provides an opportunity to better shape the national preventive strategy related to HBV.

Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014-2023) in Vojvodina, Serbia.

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

Distributions of Platelet-Derived Growth Factor Receptor-α Positive Cells and Interstitial Cells of Cajal in the Colon of Rats with Diabetes Mellitus Type 2.

Background and Objectives: Diabetic gastroenteropathy (DG) is a common complication of diabetes mellitus type 2. Interstitial cells are non-neural cells of mesenchymal origin inserted between nerve elements and smooth muscle cells, necessary for normal function and peristaltic contractions in the gastrointestinal (GI) tract. There are at least two types of interstitial cells within the GI muscle layer-interstitial cells of Cajal (ICC) and interstitial platelet-derived growth factor receptor α-positive cells (IPC). The mechanism of diabetic gastroenteropathy is unclear, and interstitial cells disorders caused by metabolic changes in diabetes mellitus (DM) could explain the symptoms of DG (slow intestinal transit, constipation, fecal incontinence). The aim of this study was to identify PDGFRα and c-kit immunoreactive cells in the colon of rats with streptozotocin-nicotinamide-induced diabetes mellitus type 2, as well as to determine their distribution in relation to smooth muscle cells and enteric nerve structures. Materials and Methods: Male Wistar rats were used, and diabetes type 2 was induced by an intraperitoneal injection of streptozotocin, immediately after intraperitoneal application of nicotinamide. The colon specimens were exposed to PDGFRα and anti-c-kit antibodies to investigate interstitial cells; enteric neurons and smooth muscle cells were immunohistochemically labeled with NF-M and desmin antibodies. Results: Significant loss of the intramuscular ICC, myenteric ICC, and loss of their connection in intramuscular linear arrays and around the ganglion of the myenteric plexus were observed with no changes in nerve fiber distribution in the colon of rats with diabetes mellitus type 2. IPC were rarely present within the colon muscle layer with densely distributed PDGFRα+ cells in the colon mucosa and submucosa of both experimental groups. In summary, a decrease in intramuscular ICC, discontinuities and breakdown of contacts between myenteric ICC without changes in IPC and nerve fibers distribution were observed in the colon of streptozotocin/nicotinamide-induced diabetes type 2 rats.

Antioxidant and cytotoxic activities of selected salicylidene imines: experimental and computational study.

Selected salicylidene imines were evaluated for their antioxidant and cytotoxic potentials. Several of them exerted potent scavenging capacity towards ABTS radical and hydrogen peroxide. The insight into the preferable antioxidative mechanism was reached employing density functional theory. In the absence of free radicals, the SPLET mechanism is dominant in polar surroundings, while HAT is prevailing in a non-polar environment. The results obtained for the reactions of the most active compounds with some medically relevant radicals pointed out competition between HAT and SPLET mechanisms. The assessment of their cytotoxic properties revealed inhibition of ER-a human breast adenocarcinoma cells or estrogen-independent prostate cancer cells. Molecular docking study with the cyclooxygenase (COX) 2 enzyme was performed to examine the most probable bioactive conformations and possible interactions between the tested derivatives and COX-2 binding pocket.

Contactless Real-Time Heartbeat Detection via 24 GHz Continuous-Wave Doppler Radar Using Artificial Neural Networks.

The measurement of human vital signs is a highly important task in a variety of environments and applications. Most notably, the electrocardiogram (ECG) is a versatile signal that could indicate various physical and psychological conditions, from signs of life to complex mental states. The measurement of the ECG relies on electrodes attached to the skin to acquire the electrical activity of the heart, which imposes certain limitations. Recently, due to the advancement of wireless technology, it has become possible to pick up heart activity in a contactless manner. Among the possible ways to wirelessly obtain information related to heart activity, methods based on mm-wave radars proved to be the most accurate in detecting the small mechanical oscillations of the human chest resulting from heartbeats. In this paper, we presented a method based on a continuous-wave Doppler radar coupled with an artificial neural network (ANN) to detect heartbeats as individual events. To keep the method computationally simple, the ANN took the raw radar signal as input, while the output was minimally processed, ensuring low latency operation (<1 s). The performance of the proposed method was evaluated with respect to an ECG reference ("ground truth") in an experiment involving 21 healthy volunteers, who were sitting on a cushioned seat and were refrained from making excessive body movements. The results indicated that the presented approach is viable for the fast detection of individual heartbeats without heavy signal preprocessing.

Prevalence of oncogenic Human papillomavirus and genetic diversity in the L1 gene of HPV16 HPV 18 HPV31 and HPV33 found in women from Vojvodina Province Serbia.

The main purpose of this paper is to estimate the pre-vaccination prevalence of 12 hrHPV types among 564 women from Vojvodina province (Serbia). The corrected contingency coefficient (Ccorr) was used to estimate the importance of association of examined HPV types and cytological diagnosis. The highest association with the abnormal cytology was observed for HPV 16 (Ccorr = 0.493) in all age groups of participants. The effect of HPV 16 was especially clear within the group of women older than 35 years (Ccorr = 0.691), compared with women younger than 35 (Ccorr = 0.333). The molecular characterization at the level of L1 gene of HPV 16, 18, 31 and 33 variants was for the first time assessed in our region. Nearly all HPV 16 isolates cluster with variant lineage A (96.4%) the remaining isolates clustering with variant lineage D. All of HPV 18 and HPV 33 isolates are clustering within the lineage A while isolates of HPV 31 group with lineages A and C. This contributes to understanding of intrinsic geographical and biological differences of examined HPV types and could be useful for development of cervical cancer screening strategies in Vojvodina (Serbia) and diagnosis of HPV related cervical cancer in general.

Distribution of Collagen I, III, and IV and Laminin in the Human Liver during Prenatal Development.

In the absence of systematized data on the extracellular matrix components during prenatal liver development, the present study aimed to investigate the time of appearance and distribution of collagen types I, III, and IV and laminin. The study material included embryonic and fetal livers, aged 7-37 weeks, categorized into 3 trimesters. The material was stained using hematoxylin-eosin and immunohistochemistry methods for the identification of collagen I, III, and IV and laminin. Collagen I was detected near the end of the first trimester in the capsules and walls of interlobular veins. As the liver matures, collagen I is increasingly abundant in the capsules, portal area connective tissues, arterial walls, interlobular veins, sinusoids, and central veins. Collagen III and collagen IV appear in the middle of the first trimester in the capsules, portal areas, and walls of central veins, as well as the sinusoids particularly. In trimesters 2 and 3, these collagens are increasingly present in all the structures, but collagen IV is also present in nerve fibers. Laminin is sporadically present adjacent to the sinusoids in trimester 1, while in trimesters 2 and 3 this protein commonly appears in the walls of arteries and interlobular veins, in the basal membrane of bile ducts, and in nerve fibers. The contents of collagen I, III, and IV increase during prenatal development in the liver capsule, arterial and vein walls, sinusoids, and portal area. Laminin expression is consistent with that of the collagens with the exception that, within lobules, laminin disappears with liver maturation.

Immunohistochemical Heterogeneity of the Endothelium of Blood and Lymphatic Vessels in the Developing Human Liver and in Adulthood.

The endothelium of liver sinusoids in relation to the endothelium of other blood vessels has specific antigen expression similar to the endothelium of lymphatic vessels. Bearing in mind that there is no consensus as to the period or intensity of the expression of certain antigens in the endothelium of blood and lymphatic vessels in the liver, the aim of our study was to immunohistochemically investigate the dynamic patterns of the expression of CD31, CD34, D2-40, and LYVE-1 antigens during liver development and in adulthood on paraffin tissue sections of human livers of 4 embryos, 38 fetuses, 6 neonates, and 6 adults. The results show that, in a histologically immature liver at the end of the embryonic period, CD34 molecules are expressed only on vein endothelium localized in developing portal areas, whereby the difference between portal venous branches and CD34-negative central veins belongs to the collecting venous system. In the fetal period, with aging, expression of CD34 and CD31 molecules on the endothelium of central veins and blood vessels of the portal areas increases. Sinusoidal endothelium shows light and sporadic CD34 immunoreactivity in the late embryonic and fetal periods, and is lost in the neonatal and adult periods, unlike CD31 immunoreactivity, which is poorly expressed in the fetal and neonatal periods but is present in adults. The endothelium of sinusoids and lymphatic vessels express LYVE-1, and the endothelium of lymphatic vessels express LYVE-1 and D2-40 but not CD34. Similarity between the sinusoidal and lymphatic endothelium includes the fact that both types are LYVE-1 positive and CD34 negative.

Testing for viral material in water of public bathing areas of the Danube during summer, Vojvodina, Serbia, 2014.

From August to September 2014 a water quality study was conducted on five popular public Danube beaches in Vojvodina, Serbia. To assess the safety of Danube water for bathing, physical, chemical, bacteriological tests were performed. While many parameters for monitoring the quality of water are regulated by law, there are neither national nor international legislations addressing the presence of viruses in recreational waters. In this study, we performed analyses that surpassed national requirements, and investigated if adenovirus, enterovirus or rotavirus genetic material was present in samples of recreational water collected for quality monitoring. Of 90 water samples obtained during the study, enterovirus material was not found in any sample, but adenovirus and rotavirus genetic materials were respectively detected in 60 and 31 samples. Statistical analyses showed a significant correlation between adenovirus DNA and total coliforms in the water. Even when water samples were adequate for recreational use, adenoviruses were detected in 75% (57/76) of such samples. Our results indicate that implementation of viral indicators in recreational water might be helpful to better assess public health safety. This might be particularly relevant in areas where urban wastewater treatment is insufficient and surface waters affected by wastewater are used for recreation.

A preliminary trial of the sedation induced by intranasal administration of midazolam alone or in combination with dexmedetomidine and reversal by atipamezole for a short-term immobilization in pigeons.

OBJECTIVE: To assess the sedative and immobilization effect of intranasal administration (INS) of midazolam (MID) without or with INS dexmedetomidine (DXM), and some physiological changes induced by the drugs. The ability of INS atipamezole to reverse the DXM component was also assessed. STUDY DESIGN: Prospective 'blinded' experimental study. ANIMALS: In total, 15 pigeons. METHODS: Pigeons were sedated by INS MID alone at a dose of 5 mg kg(-1) (group MID, n = 6) or in combination with INS DXM at a dose 80 µg kg(-1) (group MID-DXM, n = 6). Measurements were made of heart rate (HR), respiratory rate (fR ) and cloacal temperature (CT). The degree of sedation was assessed at 15 minutes prior to, immediately after, and at intervals until 100 minutes after drug administrations. Following MID-DXM, INS atipamezole (250 µg kg(-1) ) was administered and the same indices measured 5 and 10 minutes later. RESULTS: MID had no effect on HR and fR , and although CT decreased, it remained within physiological range. MID-DXM caused significant falls in HR, fR and CT that persisted until the end of sedation. Atipamezole antagonized sedation and cardiorespiratory side effects of MID-DXM within 10 minutes of application. In addition, for MID compared to MID-DXM, the lowest sedation scores [10 (7-14) and 10.5 (5-14) versus 2 (1-4) and 2 (1-5)] were achieved in the 10th and 20th minute versus the 20th and 30th minute of the sedation, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: MID alone, given INS had minimal side effects on vital functions but caused inadequate immobilization of pigeons for restraint in dorsal recumbency. MID-DXM caused an effective degree of immobilization from 20 to 30 minutes after administration, at which time birds tolerated postural changes without resistance. Atipamezole antagonized both side effects and sedation, but complete recovery had not occurred within 10 minutes after its application.

Seroepidemiology of Human Parvovirus B19 Infection among the Population of Vojvodina, Serbia, over a 16-Year Period (2008-2023).

This study aimed to estimate the serological status and dynamic changes in the prevalence of Parvovirus B19 (PVB19) antibodies within the general population residing in the northern part of the Republic of Serbia (Province of Vojvodina) during a 16-year period. Serum samples were analyzed for Human PVB19-specific IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Throughout the study period, the overall seroprevalence was 49.51%. Approximately 10% of patients exhibited a serologic profile positive for PVB19 IgM antibodies. Notably, seroprevalence varied significantly, ranging from 9.12% in the pediatric cohort (ages 1-4 years) to 65.50% in the adult demographic (40-59 years old). Seroprevalence was higher (51.88%) among women compared to men (42.50%). Immunologically naive pregnant women in the age groups 26-36 and 36-45 years had 45% (OR = 0.55, 95% CI: 0.31-1.00) and 52% (OR = 0.48; 95% CI: 0.24-0.94) lower odds of having negative IgM and IgG compared to those in age group 16-25 years old. Improved knowledge of the epidemiology of PVB19 may assist clinicians in the differential diagnosis of PVB19 clinical manifestations. The PVB19 detection is particularly important for monitoring individuals in risk groups such as women of reproductive age, medical staff, patients with hematological disorders, and those with immunodeficiency.

Pertussis Epidemiology in the Autonomous Province of Vojvodina, Serbia, 1948-2023.

Pertussis continues to be a significant public health concern. We aimed to examine the epidemiological characteristics of pertussis in Vojvodina, which accounts for almost a third of Serbia's population. Our aim was to determine the overall and age-specific incidence and mortality rates of pertussis in Vojvodina from 1948 to 2023, as well as the coverage of immunization against pertussis from 1960 to 2023. In the period 1948-2023, 42,259 cases of pertussis were reported. Following the introduction of the DTwP vaccine (1960) in Serbia, the reported incidence of pertussis began to decline. In 2001, for the first time since introduction of pertussis surveillance in Vojvodina, no pertussis cases were reported. Since 2012, the reported incidence of pertussis has once again increased, and peaked (41.1/100,000) in 2023, approaching the incidence rates recorded shortly after the introduction of DTwP vaccine. A shift in the age profile of pertussis from children aged 0-6 years to school-aged children (7-14 years) occurred between 2012 and 2023, when 48.3% of pertussis cases occurred in this age group. Although the incidence rates of pertussis among individuals aged 20 years and older were significantly lower than among younger age groups, there is evidence of an increasing trend in pertussis cases, particularly among those aged 40-49 years, since 2012. Based on the findings of this study, it is imperative to introduce additional booster doses of the aP vaccine for individuals aged 14 years, along with implementing maternal immunization strategies targeting women of childbearing age.

αB-crystallin promotes oncogenic transformation and inhibits caspase activation in cells primed for apoptosis by Rb inactivation.

The retinoblastoma (Rb) tumor suppressor gene is frequently inactivated in cancer, resulting in deregulated activation of E2F transcription factors, which promote S-phase entry, p53-dependent and p53-independent apoptosis. Transformed cells evade p53-dependent apoptosis initiated by Rb inactivation by TP53 mutation. However, the mechanisms by which cancer cells circumvent p53-independent apoptosis in this context are poorly understood. Because Rb inactivation primes cells for apoptosis by p53-independent induction of procaspases, we postulated that αB-crystallin, an inhibitor of procaspase-3 activation, would suppress caspase activation in cells with combined Rb and p53 inactivation. Notably, αB-crystallin is commonly expressed in ER/PR/HER2 "triple-negative" breast carcinomas characterized by frequent Rb loss and TP53 mutation. We report that αB-crystallin (-/-) knock out (KO) MEFs immortalized by dominant negative (DN) p53 are resistant to transformation by the adenovirus E1A oncoprotein, which inactivates Rb, while wild-type (WT) MEFs are readily transformed by DN p53 and E1A. αB-crystallin (-/-) KO MEFs stably expressing DN p53 and E1A were more sensitive to chemotherapy-induced caspase-3 activation and apoptosis than the corresponding WT MEFs, despite comparable induction of procaspases by E1A. Similarly, silencing Rb in WT and αB-crystallin (-/-) KO MEFs immortalized by DN p53 increased procaspase levels and sensitized αB-crystallin (-/-) KO MEFs to chemotherapy. Furthermore, silencing αB-crystallin in triple-negative breast cancer cells, which lack Rb and express mutant p53, enhanced chemotherapy sensitivity compared to non-silencing controls. Our results indicate that αB-crystallin inhibits caspase activation in cells primed for apoptosis by Rb inactivation and plays a novel oncogenic role in the context of combined Rb and p53 inactivation.

Enhancement of strong-field multiple ionization in the vicinity of the conical intersection in 1,3-cyclohexadiene ring opening.

Nonradiative energy dissipation in electronically excited polyatomic molecules proceeds through conical intersections, loci of degeneracy between electronic states. We observe a marked enhancement of laser-induced double ionization in the vicinity of a conical intersection during a non-radiative transition. We measured double ionization by detecting the kinetic energy of ions released by laser-induced strong-field fragmentation during the ring-opening transition between 1,3-cyclohexadiene and 1,3,5-hexatriene. The enhancement of the double ionization correlates with the conical intersection between the HOMO and LUMO orbitals.

Pyrazolone-type compounds (part II): in vitro and in silico evaluation of antioxidant potential; structure-activity relationship.

The pyrazolone class comprises a variety of hybrid compounds displaying diverse biological actions. Although studied for decades, these compounds are still of interest due to their facile chemical transformations. In our previous work, we presented the synthetic route of functionalised pyrazolone derivatives. The presence of pyrazolone structural motif in many drugs, such as edaravone, prompted us to investigate the antioxidant features of the selected compounds. In this paper, we provide an extensive in vitro and in silico description of the antioxidant properties of selected pyrazolone analogues. The obtained in vitro results revealed their great antiradical potency against the DPPH radical (IC50 values in the 2.6-7.8 µM range), where the best results were obtained for analogues bearing a catechol moiety. Density functional theory (DFT) was used to assess their antioxidant capacity from the thermodynamic aspect. Here, good agreement with in vitro results was achieved. DFT was employed for the prediction of the most preferable radical scavenging pathway, also. In polar solvents, the SPLET mechanism is a favourable scavenging route, whereas in nonpolar solvents the HAT is slightly predominant. Furthermore, antioxidant mechanisms were studied in the presence of relevant reactive oxygen species. The obtained values of the reaction enthalpies with the selected radicals revealed that HAT is slightly prevailing in polar solvents, while the SPLET mechanism is dominant in nonpolar solvents. Regarding the well-known antioxidant features of the drug edaravone, these findings represent valuable data for this pyrazolone class and could be used as the basis for further investigations.

Epidemiological Transition and Strategies for the Control of Hepatitis A in Serbia.

BACKGROUND: Improvements in socioeconomic and hygienic conditions during the past decades led to declining hepatitis A (HA) seroprevalence in many countries. Aiming at informing HA vaccination policy, we assessed current epidemiological trends in Serbia by analyzing surveillance data for 2002-2021. METHODS: Data on cases and outbreaks were obtained from the Serbian national surveillance database and descriptively analyzed. HA incidence was calculated in relation to time, patients' residence, and demographics. RESULTS: Overall, 13,679 HA cases and 419 outbreaks were recorded with the highest incidence in the southeast. Downward HA trends were observed, while infant mortality was halved, and gross domestic product based on purchasing power parity (GDP PP) per capita, tripled. The average incidence dropped from 14.8 (95% CI 14.4-15.2)/100,000) in 2002-2006 to 1 (95% CI 0.9-1.1)/100,000)/100,000 in 2017-2021, while the number of outbreaks decreased (from 174 to 14). Sporadic cases and family clusters living in poor sanitary conditions occurred in recent years. The contact route of transmission was dominant (410/419, 97.9%). The highest average age-specific HA incidence shifted from 5-9 years in 2002-2006 to 10-19 years in 2017-2021.Serbia is transitioning towards very low HA endemicity. Enhanced surveillance and vaccination of high-risk groups are recommended as future public health priorities.