Search

Nucleotide excision repair (NER) is crucial for repairing bulky lesions and crosslinks in DNA caused by exogenous and endogenous genotoxins. The number of studies that have considered DNA repair as a biomarker is limited, and therefore one of the primary objectives of the European COST Action hCOMET (CA15132) was to assemble and analyze a pooled database of studies with data on NER activity. The database comprised 738 individuals, gathered from 5 laboratories that ran population studies using the comet-based in vitro DNA repair assay. NER activity data in peripheral blood mononuclear cells (PBMCs) were normalized and correlated with various host-related factors, including sex, age, body mass index (BMI), and smoking habits. This multifaceted analysis uncovered significantly higher NER activity in female participants compared to males (1.08 ± 0.74 vs. 0.92 ± 0.71; P = 0.002). Higher NER activity was seen in older subjects (> 30 years), and the effect of age was most pronounced in the oldest females, particularly those over 70 years (P = 0.001). Females with a normal BMI (< 25 kg/m2) exhibited the highest levels of NER, whereas the lowest NER was observed in overweight males (BMI ≥ 25 kg/m2). No independent effect of smoking was found. After stratification by sex and BMI, higher NER was observed in smoking males (P = 0.017). The biological implication of higher or lower repair capacity remains unclear; the inclusion of DNA repair as a biomarker in molecular epidemiological trials should elucidate the link between health and disease status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

Populations affected by war may experience food insecurity, which could predispose them to eating disorders. A cross-sectional study was conducted among health sciences students in Northern Kosovo from November 2018 to March 2019. Data were collected using the sociodemographic Night Eating Questionnaire (NEQ), the Beck Depression Inventory (BDI), and the Beck Anxiety Inventory (BAI). The study sample comprised 534 students. The prevalence of students who had at least mild depression (BDI ≥ 10) was 20.6%. More frequent night eating was consistently associated with a higher EDI score in the total sample as well as in the subgroup of students whose EDI score was ≥ 10. In addition, having poorer sleep quality and having more anxiety symptoms were associated with having stronger depressive symptoms. In a population of health sciences students who live in a post-conflict region, night eating is associated with having stronger depressive symptoms.

Background: Doppler ultrasound examination of blood vessels has a significant role in planning and identifying parameters that affect the functioning and maturation of arteriovenous fistula (AVF). Our goal was to determine the predictive parameters of Doppler ultrasound, measured at different time distances, which affect the maturation of AVF for hemodialysis., Materials and Methods: The research was a retrospective cohort study. The criteria for selecting patients in our study was the existence of information on ultrasound examinations of the lumen of blood vessels before the creation of AVF, as well as lumens of fistula conduits and blood flow measurements, at time intervals of 6-8 weeks and 2-4 months, after the creation of AVF, which we recorded in 105 patients. The respondents were divided into two groups: a group of patients with immature, and mature fistulas. Basic demographic data, clinical characteristics of the responders and laboratory parameters were analyzed., Results: By comparing clinical and laboratory parameters between the group of subjects with and without AVF maturation, a statistically significant difference was determined between the lumen of the proximal radial vein (p = 0.008) and the lumen of the distal radial vein (p = 0.001). The diameter of the fistulous veins (p = 0.037), and the blood flow through the AVF 6-8 weeks (p = 0.001) and 2-4 months (p = 0.001) after its creation were statistically significantly higher in subjects with mature fistulas. By univariate regression analysis, brachial vein (p = 0.04), proximal (p = 0.011) and distal radial artery (p = 0.001), fistula vein, after 6-8 weeks (p = 0.002), blood flow through AVF 6-8 weeks (p = 0.001) and 2-4 months (p = 0.001) after AVF creation, are statistically significant parameters. Predictive parameters of AVF maturation are AVF blood flow after 6-8 weeks (p = 0.010) and AVF blood flow after 2-4 months (p = 0.001)., Conclusion: Our research confirmed that greater the blood flow through AVF, at time intervals of 6-8 weeks and 2-4 months after creation, the better the maturation., Competing Interests: There are no conflicts of interest., (© 2024 Indian Journal of Nephrology | Published by Scientific Scholar.)

Background/Objectives: Endovascular embolization is an effective treatment option for cerebral arteriovenous malformation (AVM) and dural arteriovenous fistulas (DAVFs). The objective of this study was to assess the safety and efficacy of Menox TM in patients with cranial dural arteriovenous fistulas. Methods : From January 2021 to January 2023, 19 patients with intracranial DAVFs underwent embolization procedures. All patients were treated by embolization with Menox TM or/and in combination with other embolization products such as Onyx (Covidien, Irvine, California), PHIL (MicroVention, Tustin, California), and Squid (Balt Extrusion, Montmorency, France). Treatment approaches were selected depending on the anatomical location of the fistula. Patients were monitored and followed-up for 12 months. Results : The patients' mean age was 56.26 ± 16.49 years. Of these 19 patients, 58% ( n = 11) were treated with the Menox TM liquid embolizing agent (LEA) alone or in combination with different LEAs, while n = 7 were treated with other LEAs and 1 patient was treated solely with coils. Complete occlusion of DAVFs with Menox TM and other agents was evident in 68.4% ( n = 13/19) of patients. Complete occlusion (100%) was observed in the sinus rectus, transverse sinus, and diploic veins of the orbital roof, while complete occlusion was observed in 50% of falcotentorial patients and 60% of superior sagittal sinus patients. The lowest rate of complete fistula obliteration was observed in the dural carotid cavernous fistula (CCF) group (25%). An intra-procedural adverse event occurred in one patient. No other post-procedural adverse events were noted. Furthermore, in patients treated with Menox TM , total occlusion was achieved in 72.7% ( n = 8) of patients, whereas the non-Menox TM group had 62.5% ( n = 5) of patients with 100% occlusion and 37.5% ( n = 3) of patients with subtotal occlusion. Conclusions : Outcomes using Menox TM alone and in combination with other agents were effective, and it is safe for the treatment of dural arteriovenous fistulas., Competing Interests: The authors declare no conflicts of interest.

Late-Onset Alzheimer's Disease (LOAD) is a heterogeneous neurodegenerative disorder with complex etiology and high heritability. Its multifactorial risk profile and large portions of unexplained heritability suggest the involvement of yet unidentified genetic risk factors. Here we describe the "whole person" genetic risk landscape of polygenic risk scores for 2218 traits in 2044 elderly individuals and test if novel eigen-PRSs derived from clustered subnetworks of single-trait PRSs can improve the prediction of LOAD diagnosis, rates of cognitive decline, and canonical LOAD neuropathology. Network analyses revealed distinct clusters of PRSs with clinical and biological interpretability. Novel eigen-PRSs (ePRS) from these clusters significantly improved LOAD-related phenotypes prediction over current state-of-the-art LOAD PRS models. Notably, an ePRS representing clusters of traits related to cholesterol levels was able to improve variance explained in a model of the brain-wide beta-amyloid burden by 1.7% (likelihood ratio test P = 9.02 × 10-7). All associations of ePRS with LOAD phenotypes were eliminated by the removal of APOE-proximal loci. However, our association analysis identified modules characterized by PRSs of high cholesterol and LOAD. We believe this is due to the influence of the APOE region from both PRSs. We found significantly higher mean SNP effects for LOAD in the intersecting APOE region SNPs. Combining genetic risk factors for vascular traits and dementia could improve current single-trait PRS models of LOAD, enhancing the use of PRS in risk stratification. Our results are catalogued for the scientific community, to aid in generating new hypotheses based on our maps of clustered PRSs and associations with LOAD-related phenotypes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy., Methods and Results: Forty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal., Conclusions: OSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea., Trial Registration: NCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125 ., (© 2024. The Author(s).)

Introduction: Cancer is a leading cause of morbidity and mortality worldwide, and coordinated research efforts are vital to improve global outcomes. Clinical or translational research is usually planned, coordinated and executed by clinical researchers. With this survey we aimed to identify the main hurdles in front of young clinical investigators in oncology., Methods and Materials: An anonymized survey was distributed using social media between April and November 2022. Target population were health-care professionals in the field of oncology - physicians, nurses and researchers. We divided participants according to working experience (<40 vs. >40 years of age) and country of practice (Europeans vs. non-Europeans)., Results: We received 121 responses from participants practicing in 36 countries. Eighty-seven (72%) of the participants were under 40 years. Eighty-nine (74%) were from European countries and thirty-two (26%) were from non-European. Experienced and European professionals were more likely to be involved in all different aspects of clinical trials. The main source of funding - independently of geographic location - were industry grants. Investigators out of Europe have less participation in international grants. Over 50% of participants dedicate time for clinical research from their personal time and are not paid for it. Almost 50% of investigators don't have access to an experienced mentor in their institution., Conclusion: The majority of respondents to our survey are active clinical researchers. Our data indicate that access to education and training as well as possibilities for appropriate networking, and specifically lack of mentorship, are key limiting factors in developing clinical research by healthcare professionals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

In April 2020, the Aboriginal and Torres Strait Islander COVID-19 Point-of-Care (POC) Testing Program was initiated to improve access to rapid molecular-based SARS-CoV-2 detection in First Nations communities. At capacity, the program reached 105 health services across Australia. An external review estimated the program contributed to averting between 23,000 and 122,000 COVID-19 infections within 40 days of the first infection in a remote community, equating to cost savings of between AU$337 million and AU$1.8 billion. Essential to the quality management of this program, a customised External Quality Assessment (EQA) program was developed with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP). From July 2020 to May 2022, SARS-CoV-2 EQA participation ranged from 93 to 100%. Overall concordance of valid EQA results was high (98%), with improved performance following the first survey. These results are consistent with those reported by 12 Australian and 4 New Zealand laboratories for three SARS-CoV-2 RNA EQA surveys in March 2020, demonstrating that SARS-CoV-2 RNA POC testing in primary care settings can be performed to an equivalent laboratory analytical standard. More broadly, this study highlights the value of quality management practices in real-world testing environments and the benefits of ongoing EQA program participation.

Previous research focused on the conventional approaches to test psychometric characteristics of the Night Eating Questionnaire (NEQ). The purpose of this research was to examine the psychometric properties of the Night Eating Questionnaire using the Rasch model in a sample of university students. The study was carried out from November 2018 to March 2019 on 300 students in health sciences at the University of Pristina temporarily seated in Kosovska Mitrovica, who completed the NEQ. A confirmatory factor analysis (CFA) suggested that the Serbian version mirrored the original NEQ structure: Goodness of fit index = 0.978, Comparative fit index = 0.996, Tucker-Lewis index = 0.995, Root Mean Square Error of Approximation = 0.011 and Standardized Root Mean Square Residual = 0.057. The Cronbach's alpha coefficient for the total scale was 0.627. The Rasch analysis showed that the item separation index classified the items into six groups based on their level of difficulty. The person reliability index separated well night eaters from day eaters. Few items did not fit the adequate range for the infit/outfit statistics. Overall, there were several groups of NEQ items that have a distinctive difficulty level, but the difference was not a remarkable one. This means that most students did not have night eating syndrome (NES), despite various levels of item difficulty. The NEQ performs well in the efforts to distinguish people who eat and do not eat at night. Most students reported conventional eating patterns and only a few had NES. The properties of the NEQ warrant its use in further night eating research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Stents have become very important devices in the treatment of intracranial aneurysms. Flow diverters as high metal coverage stents are developed for hemodynamic treatment of challenging intracranial aneurysms. High level of metal coverage can also be achieved by implementing regular stents telescopically one in another. We present the case of a patient successfully treated for giant aneurysm of basilar artery bifurcation by a "Stent-within-a-Stent" technique. After stent implantation, coil embolization was performed using multiple-sized platinum helical coils. Control angiography performed at the end of the procedure revealed aneurysm occlusion. After 3 years, the patient is fully neurologically recovered, without pyramidal deficit, independently active and able to work., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Severe acute respiratory infections (SARI) are estimated to be the cause of death in about 19% of all children younger than 5 years globally. The outbreak of coronaviral disease (COVID-19) caused by SARS-CoV-2, increased considerably the burden of SARI worldwide. We used data from a vaccine effectiveness study to identify the factors associated with SARS CoV-2 infection among hospitalized SARI patients. We recruited SARI patients at 3 hospitals in Serbia from 7 April 2022-1 May 2023. We collected demographic and clinical data from patients using a structured questionnaire, and all SARI patients were tested for SARS-CoV-2 by RT-PCR. We conducted an unmatched test negative case-control study. SARS-CoV-2 infected SARI patients were considered cases, while SARS CoV-2 negative SARI patients were controls. We conducted bivariate and multivariable logistic regression analysis in order to identify variables associated with SARS-CoV-2 infection. We included 110 SARI patients: 74 were cases and 36 controls. We identified 5 factors associated with SARS-CoV-2 positivity, age (OR  =  1.04; 95% CI  =  1.01-1.07), having received primary COVID-19 vaccine series (OR  =  0.28; 95% CI  =  0.09-0.88), current smoking (OR  =  8.64; 95% CI  =  2.43-30.72), previous SARS CoV-2 infection (OR  =  3.48; 95% CI  =  1.50-8.11) and number of days before seeking medical help (OR  =  0.81; 95% CI  =  0.64-1.02). In Serbia during a period of Omicron circulation, we found that older age, unvaccinated, hospitalized SARI patients, previously infected with SARS CoV-2 virus and those who smoked, were more likely to be SARS-CoV-2-positive; these patient populations should be prioritized for COVID vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Stosic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Global rise in antibiotic utilization has been strongly associated with the resistance of bacteria to antibiotics. The COVID-19 saw an increase in the use of antibiotics in some countries. The aim of this study was to evaluate antibiotic utilization from 2006 to 2021 in the Republic of Serbia., Methods: Data on antibiotic use were retrieved from the national annual reports on the official website of the Medicines and Medical Devices Agency of Serbia during the period 2006 to 2021. To evaluate trends in the use of antibiotics in Serbia, linear, and joint regression analyses were performed., Results: The analysis of the antibiotics use over a sixteen-year period included a total of 50 antibiotics. A significant increase during the COVID-19 pandemic was observed for glycylcyclines that is, new-generation tetracyclines (tigecycline), third-generation cephalosporins (ceftazidime, ceftriaxone, and cefixime), respiratory fluoroquinolones (levofloxacin and moxifloxacin), carbapenems (ertapenem), and oxazolidinones (linezolid) utilization. Moreover, an almost negligible use of new β-lactam/β-lactamase inhibitors during the prepandemic period increased significantly during the COVID-19 pandemic period., Conclusions: A significant increasing trend in the use of specific antibiotics classified as the "Watch" and "Reserve" antibiotics during the pandemic period was observed., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology in Alzheimer's Disease (AD). Protective and cognitive-enhancing roles for the nicotinic α5 subunit have been identified, but this gene has not been closely examined in the context of human aging and dementia. Therefore, we investigate the nicotinic α5 gene CHRNA5 and the impact of relevant single nucleotide polymorphisms (SNPs) in prefrontal cortex from 922 individuals with matched genotypic and post-mortem RNA sequencing in the Religious Orders Study and Memory and Aging Project (ROS/MAP). We find that a genotype robustly linked to increased expression of CHRNA5 (rs1979905A2) predicts significantly reduced cortical β-amyloid load. Intriguingly, co-expression analysis suggests CHRNA5 has a distinct cellular expression profile compared to other nicotinic receptor genes. Consistent with this prediction, single nucleus RNA sequencing from 22 individuals reveals CHRNA5 expression is disproportionately elevated in chandelier neurons, a distinct subtype of inhibitory neuron known for its role in excitatory/inhibitory (E/I) balance. We show that chandelier neurons are enriched in amyloid-binding proteins compared to basket cells, the other major subtype of PVALB-positive interneurons. Consistent with the hypothesis that nicotinic receptors in chandelier cells normally protect against β-amyloid, cell-type proportion analysis from 549 individuals reveals these neurons show amyloid-associated vulnerability only in individuals with impaired function/trafficking of nicotinic α5-containing receptors due to homozygosity of the missense CHRNA5 SNP (rs16969968A2). Taken together, these findings suggest that CHRNA5 and its nicotinic α5 subunit exert a neuroprotective role in aging and Alzheimer's disease centered on chandelier interneurons., (© 2024. The Author(s).)

Few countries provided multiple COVID-19 vaccines for their citizens right from the start of mass immunization. In Serbia, four vaccines were available. Circumstances in which people had several options to choose from are unique. The purpose of this study was to identify motivators behind COVID-19 vaccination and the choice of COVID-19 vaccine among people who were immunized against COVID-19. Qualitative interviews with 35 vaccinated people aged > 18 years were conducted in May 2021 at the Institute of Public Health of Serbia, a reference institution for vaccination. Interviews were audio-recorded, transcribed and data were analyzed using qualitative content analysis. Four topics emerged: 1) Decision to receive COVID-19 vaccine; 2) Sources of information about the vaccine; 3) Choice of the COVID-19 vaccine and 4) Anti-vaccination sentiment around the vaccinated people. Participants were classified in two groups: those who were determined to receive the vaccine and those who were hesitant. People who were hesitant decided to receive the vaccine after reviewing the information collected from various sources, especially physicians. Although some participants accepted any vaccine regardless of their characteristics, there were others who had explicit preferences. These preferences stemmed mainly from their beliefs about particular vaccine's efficacy and safety, COVID-19 status (previous infection), living or lifestyle circumstances (residence or travel abroad), doctor's recommendation (underlying health status) or trust in expertise of that particular manufacturer's country of origin. Opting for appropriate vaccine was motivated by reasons specific to various individuals, which enabled them to make choices in line with their preferences and values.

Sleep and depression have a complex, bidirectional relationship, with sleep-associated alterations in brain dynamics and structure impacting a range of symptoms and cognitive abilities. Previous work describing these relationships has provided an incomplete picture by investigating only one or two types of sleep measures, depression, or neuroimaging modalities in parallel. We analyze the correlations between brainwide neural signatures of sleep, cognition, and depression in task and resting-state data from over 30,000 individuals from the UK Biobank and Human Connectome Project. Neural signatures of insomnia and depression are negatively correlated with those of sleep duration measured by accelerometer in the task condition but positively correlated in the resting-state condition. Our results show that resting-state neural signatures of insomnia and depression resemble that of rested wakefulness. This is further supported by our finding of hypoconnectivity in task but hyperconnectivity in resting-state data in association with insomnia and depression. These observations dispute conventional assumptions about the neurofunctional manifestations of hyper- and hypo-somnia, and may explain inconsistent findings in the literature., (© 2023. The Author(s).)

Background: HIV testing in the Northern Kosovo province is challenging, because the infrastructure is being rebuilt after the ethnic conflict. The purpose of this research was to examine self-perceived risk for acquiring HIV infection and factors associated with risk assessment among university students., Methods: Students completed a questionnaire on socio-demographic data, knowledge about HIV prevention and transmission, attitudes toward people living with (PLHIV) and self-perceived risk for HIV infection. The self-perceived risk was categorized as low, unknown and high., Results: The majority of students (72.5%) assessed their risk as low, 8.5% assessed their risk as high and 19.1% did not know their risk. Compared to low self-perceived risk, high self-perceived HIV risk was associated with being male, having lower knowledge about HIV prevention, less strong Segregation and protection attitude toward PLHIV, stronger Ignorance and indifference attitude toward PLHIV and positive opinion about gays/lesbians. Students who perceived own risk for acquiring HIV as high had lower knowledge about HIV transmission and prevention. However, those who were previously tested for HIV, despite their poorer knowledge about HIV prevention, assess their HIV-related risk as low., Conclusions: Students assessed their risk of HIV infection mostly as low. Still, lower knowledge of HIV prevention has been consistently associated with a high and unknown risk of HIV. Moreover, being ignorant and indifferent about PLHIV was associated with increased self-perceived HIV risk. These findings highlight the need for continuous specialized HIV-related education to reduce fear and stigma of PLHIV and HIV testing as well as risky behaviors., (© 2023. The Author(s).)

Background and Objectives : Elderly people may have difficulties understanding the quality and quantity of information about the COVID-19 epidemic, which can put an additional mental strain on their health and well-being. The purpose of this study was to explore the processing of COVID-19 information among older people. Materials and Methods : A qualitative study was carried out in summer 2021. The sampling was based on the snowball method. This approach allowed us to communicate with the next potential participants relatively freely and without reservations. Two female researchers (both MD, PhD) conducted the interviews. All interviews were held in Serbian. The data were analyzed using qualitative content analysis. Results : The interviews were conducted with 13 participants (average age 71 years). The analysis of qualitative content suggested that four topics could be identified: (1) sources of information, (2) information interest and need, (3) reporting of information and (4) suggestions for better reporting. The participants were troubled by the excess of information, repetitive information about death tolls, unqualified people in media discussing the pandemic and inconsistent reporting. These features caused the participants to feel the psychological burden in processing all the pieces of information. Conclusions : The elderly people in Serbia followed mainstream media to get information about COVID-19; however, they perceived a variety of problems with reporting, which made the understanding of the information difficult and psychologically burdensome. These findings should be taken into consideration when delivering health-related information to elderly people.

Background: KRAS activating mutations are considered the most frequent oncogenic drivers and are correlated with radio-resistance in multiple cancers including non-small cell lung cancer (NSCLC) and colorectal cancer. Although KRAS was considered undruggable until recently, several KRAS inhibitors have recently reached clinical development. Among them, MRTX849 (Mirati Therapeutics) showed encouraging clinical outcomes for the treatment of selected patients with KRAS G12C mutated NSCLC and colorectal cancers. In this work, we explore the ability of MRTX1257, a KRAS G12C inhibitor analogous to MRTX849, to radio-sensitize KRAS G12C+/+ mutated cell lines and tumors., Methods: Both in vitro and in vivo models of radiotherapy (RT) in association with MRTX1257 were used, with different RAS mutational profiles. We assessed in vitro the radio-sensitizing effect of MRTX1257 in CT26 KRAS G12C+/+ , CT26 WT, LL2 WT and LL2 NRAS KO (LL2 NRAS -/- ) cell lines. In vivo, we used syngeneic models of subcutaneous CT26 KRAS G12C+/+ tumors in BALB/c mice and T cell deficient athymic nu/nu mice to assess both the radio-sensitizing effect of MRTX1257 and its immunological features., Results: MRTX1257 was able to radio-sensitize CT26 KRAS G12C+/+ cells in vitro in a time and dose dependent manner. Moreover, RT in association with MRTX1257 in BALB/c mice bearing CT26 KRAS G12C+/+ subcutaneous tumors resulted in an observable cure rate of 20%. However, no durable response was observed with similar treatment in athymic nude mice. The analysis of the immune microenvironment of CT26 KRAS G12C+/+ tumors following RT and MRTX1257 showed an increase in the proportion of various cell subtypes including conventional CD4 + T cells, dendritic cells type 2 (cDC2) and inflammatory monocytes. Furthermore, the expression of PD-L1 was dramatically down-regulated within both tumor and myeloid cells, thus illustrating the polarization of the tumor microenvironment towards a pro-inflammatory and anti-tumor phenotype following the combined treatment., Conclusion: This work is the first to demonstrate in vitro as in vivo the radio-sensitizing effect of MRTX1257, a potent KRAS G12C inhibitor compatible with oral administration, in CT26 KRAS G12C mutated cell lines and tumors. This is a first step towards the use of new combinatorial strategies using KRAS inhibitors and RT in KRAS G12C mutated tumors, which are the most represented in NSCLC with 14% of patients harboring this mutational profile., (© 2023. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that presents and progresses in various ways, making prognostication difficult. Several paradigms exist for providers to elucidate prognosis in a way that addresses not only the amount of time a patient has to live, but also a patient's quality of their life moving forward. Prognostication, with regard to both survivability and quality of life, is impacted by several features that include, but are not limited to, patient demographics, clinical features on presentation, and over time, access to therapy, and access to multidisciplinary clinics. An understanding of the impact that these features have on the life of a patient with ALS can help providers to develop a better and more personalized approach for patients related to their clinical prognosis after a diagnosis is made. The ultimate goal of prognostication is to empower patients with ALS to take control and make decisions with their care teams to ensure that their goals are addressed and met., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Methotrexate (MTX) reduces rheumatoid arthritis activity and ameliorates the long-term functional status in these patients. To achieve this aim, patients need to take their medication regularly. Nevertheless, non-adherence to MTX still remains a considerable issue in the management of rheumatoid arthritis. Objective: This study aimed to estimate the adherence to methotrexate in patients with rheumatoid arthritis and to identify specific non-adherence risk factors. Methods : A cross-sectional study included 111 patients (mean age 56.2 ± 10.6 years, 78.4% female, and mean disease duration 6 years (3-13)). Three adherence self-assessment questionnaires were used: the Compliance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale, HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% of patients (MARS-5), and 82.9% of patients (VAS questionnaire). All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r = 0.364, r = 0.329, respectively, p < 0.001 for both) and between the VAS and MARS-5 scores (r = 0.496, p < 0.001). A significant positive prediction was shown for urban residence (0.347 (0.134-0.901), p = 0.030) using the MARS-5, female sex (0.264 (0.095-0.730), p = 0.010) according to the CQR19, and for a dose of methotrexate (0.881 (0.783-0.992), p = 0.036) using the VAS, while negative predictions were shown for comorbidity number (3.062 (1.057-8.874), p = 0.039) and depression (1.142 (1.010-1.293), p = 0.035) using the MARS-5 and for older age (1.041 (1.003-1.081), p = 0.034) according to the CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for methotrexate adherence in the multivariate logistic regression. Conclusions: We showed non-adherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.

The aim of our study was to examine the position of vaccinated people regarding the proposal for mandatory and seasonal vaccination against COVID-19 in Serbia. A cross-sectional study was conducted in a sample of people who came to receive a third dose of COVID-19 at the Institute of Public Health of Serbia in September and October 2021. Data were collected by means of a sociodemographic questionnaire. The study sample comprised 366 vaccinated adults. Factors associated with the belief that vaccination against COVID-19 should become mandatory were being married, being informed about COVID-19 from TV programmes and medical journals, trust in health professionals, and having friends affected by COVID-19. In addition to these predictors, factors associated with the belief that COVID-19 vaccination should become seasonal were being older, consistently wearing facemasks, and not being employed. The results of this study highlight that trust in information delivery, evidence-based data, and healthcare providers may be a major driver of mandatory and seasonal vaccine uptake. A careful assessment of the epidemiological situation, the capacity of the health system, and the risk-benefit ratio is needed in order to introduce seasonal and/or mandatory vaccination against COVID-19.

The intake of food later in the evening can have harmful health consequences. Some researchers suggest that having certain personality characteristics may be associated with the onset of eating disorders. There is a lack of studies on personality traits and night eating in a complex socio-political setting. The purpose of this study was to examine the association between personality traits and more intense night eating among students in northern Kosovo. A cross-section study was conducted in a population of health science students at the University in Kosovska Mitrovica. Students completed a socio-demographic questionnaire, Night Eating Questionnaire (NEQ), HEXACO-60 personality inventory, Beck's Depression Inventory (BDI) and Beck's Anxiety Inventory (BAI). The independent variables (exposures) were the six domains of the HEXACO-60 (Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness and Openness to Experience). The study outcome was the NEQ score. The study sample consisted of 534 students. The prevalence of night eating syndrome was 3.0%. The multivariate linear regression model suggested that stronger Extraversion and Openness to Experience were associated with more frequent night eating. Additionally, later bedtime, poorer sleep quality and higher scores on BDI and BAI were associated with more frequent night eating across all six models of models of personality traits. In a population of health science students who live in a complex socio-political environment, extraversion and openness to experience traits were associated with more frequent night eating. These findings could help researchers and clinicians tailor specific behavioral therapies to match the personality traits of people with night eating issues.

Tularemia was diagnosed for a 33-year-old pregnant woman in Serbia after a swollen neck lymph node was detected at gestation week 18. Gentamicin was administered parenterally (120 mg/d for 7 d); the pregnancy continued with no complications and a healthy newborn was delivered. Treatment of tularemia optimizes maternal and infant outcomes.

Neuroinflammation and the activation of microglial cells are among the earliest events in Alzheimer's disease (AD). However, direct observation of microglia in living people is not currently possible. Here, we indexed the heritable propensity for neuroinflammation with polygenic risk scores (PRS), using results from a recent genome-wide analysis of a validated post-mortem measure of morphological microglial activation. We sought to determine whether a PRS for microglial activation (PRS mic ) could augment the predictive performance of existing AD PRSs for late-life cognitive impairment. First, PRS mic were calculated and optimized in a calibration cohort (Alzheimer's Disease Neuroimaging Initiative (ADNI), n=450), with resampling. Second, predictive performance of optimal PRS mic was assessed in two independent, population-based cohorts (total n=212,237). Our PRS mic showed no significant improvement in predictive power for either AD diagnosis or cognitive performance. Finally, we explored associations of PRS mic with a comprehensive set of imaging and fluid AD biomarkers in ADNI. This revealed some nominal associations, but with inconsistent effect directions. While genetic scores capable of indexing risk for neuroinflammatory processes in aging are highly desirable, more well-powered genome-wide studies of microglial activation are required. Further, biobank-scale studies would benefit from phenotyping of proximal neuroinflammatory processes to improve the PRS development phase.

Our aim was to investigate gut colonization with carbapenem-resistant Enterobacterales (CRE) in the population of preterm neonates at discharge from a tertiary care center in Serbia. The study included 350 randomly selected neonates/infants discharged in the period April 2018-May 2019. CRE colonization was present in 88/350 (25.1%) of patients. Klebsiella pneumoniae producing KPC and OXA-48 carbapenemase were detected in 45 and 42 subjects, respectively, while NDM producing Escherichia coli was identified in one patient only. All OXA-48 strains harbored bla CTX-M-15 , while both bla TEM and bla SHV were present in all but one KPC-producing strain. CRE isolates exhibited a multidrug resistance pattern with uniform fluoroquinolone resistance, universal susceptibility to colistin, and variable susceptibility to aminoglycosides. Administration of carbapenems was common (~50%) and it was strongly associated with colonization, as well as the combinational therapeutic regimens that included meropenem, contrary to ampicillin-sulbactam/colistin therapy and prolonged course of the initial therapy (ampicillin/amikacin ≥ 7 days). Other risk factors for CRE carriage were level of immaturity, admission to neonatal intensive care unit, prolonged hospitalization and invasive procedures. Although the rate of clinically and/or laboratory proven systemic infections was significantly higher among colonized patients, CRE infection was confirmed in one patient only (1.1%) that was colonized with NDM E. coli . Clonal relatedness of CRE isolates was high, with seven and eight clusters detected among KPC (N = 30) and OXA-48 (N = 37) producing strains, respectively. The follow up of the 31 KPC-colonized patients after discharge from hospital revealed common decolonization within one month (~68%). In conclusion, our results demonstrated a high rate of CRE colonization that is most likely related to carbapenem consumption and lack of screening as important infection prevention practice.

Background: The bidirectional relationship between sleep disturbances and depression is well documented, yet the biology of sleep is not fully understood. Mitochondria have become of interest not only because of the connection between sleep and metabolism but also because of mitochondria's involvement in the production of reactive oxygen species, which are largely scavenged during sleep., Methods: Genome-wide association studies (GWAS) of eight accelerometry-derived sleep measures were performed across both the autosomal and mitochondrial DNA (mtDNA) among two severity levels of depression in UK Biobank participants. We calculated SNP heritability for each of the sleep measures. Linear regression was performed to test associations and mitochondrial haplogroups., Results: Variants included in the GWAS accounted for moderate heritability of bedtime (19.6%, p = 4.75 × 10 -7 ), sleep duration (16.6%, p = 8.58 × 10 -6 ) and duration of longest sleep bout (22.6%, p = 4.64 × 10 -4 ). No variants passed genome-wide significance in the autosomal genome. The top hit in the severe depression sample was rs145019802, near GOLGA8B, for sleep efficiency (p = 1.17 × 10 -7 ), and the top hit in the broad depression sample was rs7100859, an intergenic SNP, and nap duration (p = 1.25 × 10 -7 ). Top mtDNA loci were m.12633C > A of MT-ND5 with bedtime (p = 0.002) in the severe sample and m.16186C > T of the control region with nap duration (p = 0.002) in the broad sample., Conclusion: SNP heritability estimates support the involvement of common SNPs in specific sleep measures among depressed individuals. This is the first study to analyze mtDNA variance in sleep measures in depressed individuals. Our mtDNA findings, although nominally significant, provide preliminary suggestion that mitochondria are involved in sleep., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The Kosovo province is being considered as a high-risk region for the spread of HIV., Objective: To estimate the prevalence and factors associated with HIV testing in a sample of university students from the Serbian northern Kosovo province., Material and Methods: A questionnaire examining socio-demographic characteristics, HIV-related knowledge, attitudes towards people living with HIV (PLHIV) and HIV testing was used in data collection. A total of 1,017 students from the University of Priština temporarily seated in Kosovska Mitrovica completed the questionnaire., Results: Only 5.4% of students have previously been tested for HIV, even though the majority (70.9%) had a positive approach to HIV testing. Factors associated with having been tested for HIV were being male and younger, having interest in HIV testing and having previous contact with PLHIV. Being more knowledgeable about HIV and having stronger positive attitude towards PLHIV, being older, receiving information about HIV through friends and special educational programs, using condom at last sexual intercourse, having positive opinion on gays/lesbians and previous contact with PLHIV were associated with positive approach to HIV testing., Conclusion: Having a positive approach to HIV testing does not suggest that students would take the HIV test. However, students who have low HIV-related knowledge, negative approach or lack of interest in HIV testing (believing that there is no need to take it) would likely never take the HIV test. Increasing HIV-related knowledge, acceptance of PLHIV and access to testing facilities should be public health priorities to raise HIV testing rates., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 Milic M et al.)

Background/Aim: The occurrence of germ cell tumour (GCT) in the elderly is rare, with scarce data available. The aim of this study was to understand the clinical outcomes of patients with GCT in patients aged > 45 years. Materials and Methods: A retrospective study was conducted in a large tertiary cancer centre in north-west London. Between 1 January 2003 and 31 March 2022, 108 cases of GCT in men aged > 45 years were identified and treated at the Mount Vernon Cancer Centre. The median age at diagnosis was 54 years (range = 45−70 years). Results: The 5-year survival rate of all patients was 96%, and the toxicity profile was similar to the younger age group. Conclusion: Older patients with GCT are able to tolerate chemotherapy; however, care must be taken to prevent life-threatening complications using appropriate dose modification.

Rationale and Aim: At the beginning of the COVID-19 pandemic in March 2020, the Serbian government instituted a 24-h curfew for people aged ≥65 years for 2 months. The aim of this study was to examine the experiences and perceptions of curfew for older people in Serbia 15 months after the curfew had ended., Methods: In-depth interviews were carried out with 23 older adults from urban areas in Serbia. We identified the first three participants, while others were selected using the snowballing method. The interviews were audio-recorded, transcribed and data were analyzed according to guidelines for qualitative studies., Results: Six topics emerged: (1) perception of the curfew announcement; (2) attitude toward the curfew; (3) organization of daily living; (4) mood; (5) frustrations/limitations and 6) making sense of the curfew 15 months after. Older people in this study overall remember not feeling disturbed by the curfew because they perceived it as prevention, especially because this population group is considered to have the highest rate of mortality from COVID-19. Some people remember being extremely frustrated because of the restrictions and considered them unnecessary. Most people remembered that the lack of social interactions and lack of physical activity were the most difficult to cope with., Conclusions: Although challenging and bothersome, the majority of older people in this study accepted the curfew as an appropriate measure to avoid catching the virus and combat the COVID-19 pandemic., (© 2021 John Wiley & Sons Ltd.)

The purpose of this study was to compare climacteric symptoms associated with health-related quality of life (HRQOL) among women from Madrid (Spain) and Belgrade (Serbia). A cross-sectional study included 461 women from Madrid and 513 women from Belgrade aged 40-65 years. Climacteric symptoms and HRQOL were examined using the Menopause Rating Scale (MRS). There were no differences in MRS total score ( p  = 0.873), somato-vegetative and urogenital domain scores regarding country groups. However, women from Belgrade had poorer psychological domain score than women from Madrid ( p  = 0.027). Madrilenian women were more likely to have worse MRS score if they were coupled, had gynaecological complaints and longer duration of amenorrhoea. In Belgradian women, having higher level of education and using hormone-replacement therapy was associated with worse MRS score. Midlife women from Madrid and Belgrade had similar perception of intensity of urogenital and somato-vegetative climacteric symptoms. Belgradian women, however, perceived psychological symptoms as more severe.IMPACT STATEMENT What is already known on this subject? Social and cultural meanings of menopause vary across countries. It is quite delicate to strike a balance between two or more populations of women that can be compared, but also have specific features that are unique to their area. Similarities such as position of women in the society, access to education, contraception and safe induced abortion can facilitate this comparison. What do the results of this study add? Spanish and Serbian women rated similarly somato-vegetative and urogenital complaints, but Serbian women had worse psychological symptoms compared to Spanish women. Spanish women were more likely to endure climacteric symptoms until they withdraw spontaneously. Serbian women of higher education were more likely to use hormone-replacement therapy to manage climacteric complaints. What are the implications of these findings for clinical practice and/or further research? This study is the first to compare climacteric symptoms between women in Spain and Serbia. Despite the universality of menopause, culture seems to play a major role in differences in the perception of specific climacteric symptoms. Examination of quality of life in menopausal transition is an important measure of health status and should become a part of the routine health care in midlife.

The extent of shared and distinct neural mechanisms underlying major depressive disorder (MDD), anxiety, and stress-related disorders is still unclear. We compared the neural signatures of these disorders in 5,405 UK Biobank patients and 21,727 healthy controls. We found the greatest case–control differences in resting-state functional connectivity and cortical thickness in MDD, followed by anxiety and stress-related disorders. Neural signatures for MDD and anxiety disorders were highly concordant, whereas stress-related disorders showed a distinct pattern. Controlling for cross-disorder genetic risk somewhat decreased the similarity between functional neural signatures of stress-related disorders and both MDD and anxiety disorders. Among cases and healthy controls, reduced within-network and increased between-network frontoparietal and default mode connectivity were associated with poorer cognitive performance (processing speed, attention, associative learning, and fluid intelligence). These results provide evidence for distinct neural circuit function impairments in MDD and anxiety disorders compared to stress disorders, yet cognitive impairment appears unrelated to diagnosis and varies with circuit function.

Oxidative stress that leads to oxidatively damaged DNA, plays a crucial role in chronic obstructive pulmonary disease (COPD) as well as in the onset of neurodegenerative diseases. The consequent genomic instability is the first neuropathological event found in the preclinical phase of cognitive impairment (CI), and the level of DNA damage is closely related to the degree of dementia. Since CI has been associated with COPD, we investigated the extent of DNA damage in isolated lymphocytes with the Comet assay, in a group of severe COPD patients with cognitive function measured by the Mini-Mental State Examination (MMSE). An increase in DNA damage was observed in COPD patients with dementia (MMSE≤24), although the difference was only borderline (22.4 ± 6.9 vs. 18.5 ± 7.1; p = 0.055). Meta-analysis, including the results of the current study, confirmed that patients with MMSE≤ 24 showed higher level of DNA damage than patients with MMSE> 24. We observed a significant reduction (p < 0.001) in the MMSE score in patients with cognitive decline in areas I (Orientation), III (Attention and Calculus) and V (Language). Only the temporal orientation category in area I was also associated with the level of oxidative damage, with higher levels of MDA (p < 0.01) and DNA damage (p < 0.03). Patients with the lowest temporal orientation score had a 12% higher mean DNA damage (Odds Ratio=1.12; 95% confidence interval (95%CI) 1.01-1.25; p < 0.036). Temporal orientation is a component of most screening tests for the diagnosis of cognitive impairment, on the bases that disorientation is a common factor in dementia. Present results show that each component of cognitive decline can have a different etiopathogenesis and clinical relevance. A more thorough assessment of the cognitive functions of patients starting COPD rehabilitation, together with the assessment of DNA and the level of oxidative stress, can provide essential information to adapt and customize the rehabilitation project., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Republic of Serbia applied the booster dose of the following COVID-19 vaccines: BNT162b2 mRNA (Pfizer-BioNTech), Sinopharm BBIBP-CorV (Vero Cell®), Gam-COVID-Vac (Sputnik V) and ChAdOk1 nCoV-19 (AstraZeneca). We aimed to examine the immunogenicity and reactogenicity of the booster dose and identify factors related to immune response and adverse events. Panel study, conducted during August and September 2021, included 300 persons receiving the booster dose at the Institute of Public Health of Serbia. Blood samples were taken on the day of receiving the booster dose, and after 7 and 28 days. When applying homologous regimen, the average increase in anti-spike immunoglobulin G was 8782.2 (after 7 days), 1213.9 after 28 days, while 9179.5 (after 7 days) and 16,728.1 after 28 days of heterologous regimen. Sinopharm BBIBP-CorV (p < 0.001) and Sputnik V (p < 0.001), age 65 and over (p = 0.001) and currently smoking (p < 0.001) were independently associated with lower levels of anti-spike immunoglobulin G. Female sex (OR = 1.77; 95%CI = 1.01−3.12), previous COVID-19 infection (OR = 3.62; 95%CI = 1.13−11.63) and adverse events after the second dose (OR = 2.66; 95%CI = 1.33−5.32) were independently associated with intense systemic adverse events 7 days after. Booster dose significantly increased antibodies titers, especially 28 days after heterologous regimen, without a significant increase in reactogenicity.

Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual's ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOMET (EU-COST CA15132). A group of approximately 1911 individuals, was gathered from 8 laboratories which run population studies with the comet-based in vitro DNA repair assay. BER incision activity data were normalized and subsequently correlated with various host factors. BER was found to be significantly higher in women. Although it is generally accepted that age is inversely related to DNA repair, no overall effect of age was found, but sex differences were most pronounced in the oldest quartile (>61 years). No effect of smoking or occupational exposures was found. A body mass index (BMI) above 25 kg/m 2 was related to higher levels of BER. However, when BMI exceeded 35 kg/m 2 , repair incision activity was significantly lower. Finally, higher BER incision activity was related to lower levels of DNA damage detected by the comet assay in combination with formamidopyrimidine DNA glycosylase (Fpg), which is in line with the fact that oxidatively damaged DNA is repaired by BER. These data indicate that BER plays a role in modulating the steady-state level of DNA damage that is detected in molecular epidemiological studies and should therefore be considered as a parallel endpoint in future studies., (Copyright © 2022. Published by Elsevier B.V.)

Despite major research and clinical efforts, lung cancer remains the leading cause of cancer-related death. While the delivery of conformal radiotherapy and image guidance of stereotactic body radiotherapy (SBRT) have revolutionized the treatment of early-stage non-small-cell lung cancer (NSCLC), additional research is needed to elucidate underlying mechanisms of resistance and identify novel therapeutic combinations. Clinical progress relies on the successful translation of pre-clinical work, which so far has not always yielded expected results. Improved clinical modelling involves characterizing the preclinical models and selecting appropriate experimental designs that faithfully mimic precise clinical scenarios. Here, we review the current role of SBRT and the scope of pre-clinical armamentarium at our disposal to improve successful clinical translation of pre-clinical research in the radiation oncology of NSCLC.

A man in his early 20s, originally from north-central Africa, presented with a high incidental serum creatinine level. A non-contrast CT scan was taken which was suggestive of urinary schistosomiasis. The diagnosis was confirmed on obtaining biopsies from the bladder. Due to bilateral hydronephrosis, an attempt at bilateral renal decompression was made. This failed to improve renal function. He eventually underwent a right nephrectomy. He is in end-stage renal failure, undergoing long-term dialysis, and has been placed on the waiting list for renal transplant., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Radiotherapy and cisplatin-based combination chemotherapy are accepted standard-of-care treatments for metastatic seminoma with excellent survival outcomes but with established short- and long-term morbidity. Carboplatin monotherapy may be a less toxic alternative; however early historic studies at AUC7 showed inferior outcomes., Objectives: To evaluate multi-institutional data on and toxicity and longer-term survival for metastatic seminoma patients treated with the single-agent carboplatin AUC10., Methods: We undertook a multi-institutional analysis incorporating all men with the International Germ Cell Cancer Collaborative Group good-prognosis metastatic seminoma treated until 2018. Carboplatin AUC10 was given every 21 days. Toxicity, progression-free survival (PFS), disease-specific survival (DSS) and overall survival were noted. Variables predictive of progression were identified., Results and Limitations: 216 patients were treated. The three-year PFS rate was 96.5%, and five-year DSS was 98.3%. There were seven relapses, of which 5 were successfully salvaged with further chemotherapy ± surgery, and three non-seminoma-related deaths. There were no treatment-related deaths. Of 148/216 evaluable patients for toxicity, 37% and 27% suffered >/ = grade III neutropenia and thrombocytopenia, respectively. Twelve percent of patients needed a platelet or blood transfusion (or both). The incidence of febrile neutropenia was 5%., Conclusion: For metastatic seminoma, carboplatin AUC10 harbours a similar oncological efficacy to established therapies, with a low failure risk. The major acute toxicity was myelosuppression. Our study establishes carboplatin AUC10 as another standard-of-care treatment option for good-prognosis metastatic seminoma, with a potentially lower toxicity profile than other therapies., Competing Interests: Conflict of interest statement All authors declare no conflict of interest in respect of this manuscript., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of this prospective cohort study was to determine the prevalence of gut colonization with multidrug-resistant (MDR) bacteria, risk factors for colonization, infection risk, and outcomes among preterm neonates hospitalized at a tertiary-care center in Serbia. During the period from December 2017 to April 2018, 103 neonates were screened for rectal carriage at admission and on the seventh day of life. Characterization of MDR strains was done by conventional microbiology and molecular methods. Out of 61 (59.2%) colonized neonates, 12 (11.6%) were found colonized at admission, while 49 (47.6%) became colonized at the study site. Among a total of 72 MDR isolates, extended-spectrum beta-lactamase (ESBL)-producing enterobacteria prevailed (56/72, 77%), followed by Acinetobacter baumannii (14/72, 19%). The majority of ESBL-producing strains carried multiple genes ( bla TEM/ bla CTX-M-15 or bla TEM/ bla SHV). Longer previous hospitalization and delivery by cesarean section were associated with MDR colonization, while mechanical ventilation was a risk factor for colonization at the study site. Infections due to MDR bacteria were more frequent among colonized than non-colonized neonates, but not significantly, and mortality was low (1%) in the studied neonates. These results indicate that hospitalized preterm neonates in Serbia are rapidly colonized with a diversity of MDR species and resistance phenotypes/genotypes.

Purpose: The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss., Methods: Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy., Results: No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD., Conclusions: We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to examine the association between exposure to indoor SHS and self-reported HRQoL among healthy non-smoking students at the University of Belgrade, Serbia and Kosovska Mitrovica located in the post-conflict Kosovo province. Students who presented at Student Public Health Center in Belgrade in 2009 and Kosovska Mitrovica in 2015 for mandatory health checks were invited to participate. Data were collected using socio-demographic and behavioral questionnaire, health-related quality of life questionnaire Short Form-36 (SF-36) and Beck Depression Inventory (BDI). A total of 82.3% students in Belgrade sample and 76.0% in Kosovska Mitrovica sample reported daily exposure to indoor SHS. After adjustment for socio-demographic characteristics and behavior, daily exposure to indoor SHS for more than 6 hours was associated with poorer Vitality (β = -5.55, 95% confidence interval [CI] -9.49, -1.61) and Mental Health (β = 5.00, 95% CI-8.94, -1.07) only among students at the University of Belgrade. This study showed that the association between longer daily indoor SHS exposure and poor mental health HRQoL was not consistent in non-conflict and post-conflict setting. This association was not found in a post-conflict setting. Strict no smoking policies are needed in student housing, university campuses and all public spaces.

This study aimed to generate a linguistic equivalent of the COVID Stress Scales (CSS) in the Serbian language and examine its psychometric characteristics. Data were collected from September to December 2020 among the general population of three cities in Republic of Serbia and Republic of Srpska, countries where the Serbian language is spoken. Participants completed a socio-demographic questionnaire, followed by the CSS and Perceived Stress Scale (PSS). The CSS was validated using the standard methodology (i.e., forward and backward translations, pilot testing). The reliability of the Serbian CSS was assessed using Cronbach's alpha and McDonald's omega coefficients and convergent validity was evaluated by correlating the CSS with PSS. Confirmatory factor analysis was performed to examine the construct validity of the Serbian CSS. This study included 961 persons (52.8% males and 47.2% females). The Cronbach's alpha coefficient of the Serbian CSS was 0.964 and McDonald's omega was 0.964. The Serbian CSS with 36 items and a six-factorial structure showed a measurement model with a satisfactory fit for our population (CMIN/DF = 4.391; GFI = 0.991; RMSEA = 0.025). The CSS total and all domain scores significantly positively correlated with PSS total score. The Serbian version of the CSS is a valid and reliable questionnaire that can be used in assessing COVID-19-related distress experienced by Serbian speaking people during the COVID-19 pandemic as well as future epidemics and pandemics., Competing Interests: The authors have declared that no competing interests exist.

Objective: Intestinal hypomotility delays achievement of full enteral feeds and normalization of stooling patterns in preemies. We hypothesized that introduction of prokinetic drug in addition to enemas would improve intestinal motility., Primary Outcome: time needed to achieve full enteral feeds and normal stooling pattern. Secondary outcome: day when start of minimal enteral feeding was feasible, necrotizing enterocolitis incidence, length of hospitalization and whether daily meconium evacuation is more effective than evacuation in presence of clinical symptoms only., Study Design: A randomized controlled trial was conducted from December 1st, 2015. until December 1st, 2016. in level III neonatal unit on 67 preterm infants ≤ 32 gestational weeks and intestinal hypomotility. Infants were allocated to: Group 1 - treated with saline enemas twice daily until normal stooling pattern was achieved; and Group 2 - treated with erythromycin and enemas. Infants with intestinal hypomotility, hospitalized from December 1st, 2014. to December 1st, 2015. were assigned to group 3, and were treated with enemas only when symptoms of abdominal distension or absence of stool for 48 hours were observed., Results: Total of 127 neonates was included in this study; 33 were assigned to Group 1, 34 to Group 2, and 60 to Group 3. There was no significant difference in number of days needed to reach full enteral feeds: 25 vs. 26 days and normal stooling pattern: 18 vs. 15 between groups 1 and 2. Time needed to achieve full enteral feeds and normal stooling pattern in groups 1 and 2 were significantly shorter when compared to group 3. No difference in length of hospitalization between the groups was observed., Conclusions: Erythromycin did not improve the patient outcome, although therapy protocol in group 1 and group 2 were more effective than therapy used in patients in group 3.

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

HIV-related stigma could delay the identification and treatment of persons living with HIV (PLHIV), particularly in regions affected by ethnic conflicts. The aims of this study were to assess attitudes towards PLHIV and examine factors associated with stronger positive attitudes towards PLHIV among university students in the Serbian province of Kosovo. A cross-sectional study was conducted at the University of Pristina temporarily settled in Kosovska Mitrovica during the academic year 2013-2014. A total of 1,017 first- and fourth-year students completed an anonymous questionnaire about socio-demographic characteristics, PLHIV, high-risk groups for acquiring HIV and health behaviour. The main outcome measure was the Attitude Score (ATS), calculated as a sum of points awarded for all attitude-related items. The majority of students (84%) expressed positive attitudes towards PLHIV, while others were indecisive. Most students held negative opinions about persons who use drugs (64%), homosexual persons of both genders (50%) and sex workers (42%). Being female (odds ratio [OR] = 1.49, 95% confidence interval [CI] 1.05-2.09) and older (OR = 1.13, 95% CI 1.03-1.24), not doing paid work while studying (OR = 3.35, 95% CI = 1.63-6.84), studying health-related disciplines (β = -0.113, 95% CI = -0.085 to -2.747), having stronger positive attitudes towards homosexual persons of both genders (OR = 0.77, 95% CI = 0.64-0.94) and not using illicit drugs (β = 2.08, 95% CI = 1.03-4.20) were associated with stronger positive attitudes towards PLHIV. Social inclusion of PLHIV and individuals at high risk for acquiring HIV could help reduce the HIV-related stigma., (© 2020 John Wiley & Sons Ltd.)

Aim: To describe an Acinetobacter baumannii outbreak among preterm neonates in a neonatal intensive care unit (NICU) in Serbia., Methods: A case-control study was conducted in the NICU at the Institute of Neonatology, Belgrade, Serbia. The case definition of A. baumannii bloodstream infection (BSI) was blood culture confirmation of systemic infection. Isolation, identification and susceptibility testing were performed using conventional methods. Molecular characterization of isolates included resistance gene detection, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. Outcomes and clinical and demographic data were obtained from patients' medical records. An infection prevention team was formed and infection control interventions were implemented., Findings: During the outbreak period (May-July 2018), there were 13 cases of A. baumannii BSI among 82 hospitalized neonates. All A. baumannii strains were carbapenem resistant and susceptible to colistin. Molecular characterization of the isolates revealed that they harboured bla OXA66 and bla OXA72 beta-lactamases and belonged to sequence type 636, while the PFGE pattern indicated clonal spread. Lower gestational age, lower Apgar score, vaginal delivery and mechanical ventilation were risk factors for A. baumannii infection. Four patients died, eight patients were treated successfully with colistin, and one patient with sepsis and meningitis on dual ampicillin-sulbactam and colistin therapy recovered with sequelae. The outbreak was eventually controlled by reinforcement of the infection control measures based on a multi-tiered interventional approach., Conclusion: This is the first description of an outbreak of BSI among preterm neonates caused by A. baumannii bla OXA66 /bla OXA72 /ST636 in Serbia., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The hydrogen-bond-accepting abilities for more than 100 organic molecules are quantified using 19 F and 31 P NMR spectroscopy with pentafluorobenzoic acid (PFBA) and phenylphosphinic acid (PPA) as commercially available, inexpensive probes. Analysis of pyridines and anilines with a variety of electronic modifications demonstrates that changes in NMR shifts can predict the secondary effects that contribute to H-bond-accepting ability, establishing the ability of PFBA and PPA binding to predict electronic trends. The H-bond-accepting abilities of various metal-chelating ligands and organocatalysts are also quantified. The measured Δδ( 31 P) and Δδ p ( 19 F) values correlate strongly with Hammett parameters, p K a of the protonated HBA, and proton-transfer basicity (p K BH+ ).

Background: Evidence suggests that people who live in regions affected by the armed conflict are more likely to smoke., Objective: The purpose of this study was to assess factors associated with smoking status in a sample of students in the northern Kosovo province., Materials and Methods: A total of 514 students enrolled in University in Kosovska Mitrovica, Kosovo, were recruited between April to June 2015 at Student Public Health Center during mandatory health checks. Participants filled in socio-demographic and behavioral questionnaire and Beck Depression Inventory (BDI). Based on responses about smoking, students were categorized in non-smokers, former smokers, light smokers (1-13 cigarettes/day) and heavy smokers (> 13 cigarettes/day)., Results: Of 514 students, 116 (22.6%) classified themselves as smokers. Higher education level of fathers (Odds ratio [OR]=2.89, 95% confidence interval [CI] 1.30-6.44, p=0.009), not living with smokers (OR=0.42, 95%CI 0.15-0.97, p=0.017) and longer exposure to second hand smoke (OR=1.07, 95%CI 1.01-1.13, p=0.036) was associated with former smoking. Studying medical and natural sciences (OR=2.07, 95%CI 1.05-4.18, p=0.040), consuming alcohol (OR=2.98, 95%CI 1.19-10.03, p=0.020), living with smokers (OR=2.88, 95%CI 1.49-5.56, p=0.002), longer exposure to second hand smoke (OR=1.06, 95%CI 1.01-1.11, p=0.019) and having a more intense depressive symptoms (OR=1.08, 95%CI 1.03-1.13, p=0.002) was associated with light smoking. Being male (OR=0.22, 95%CI 0.07-0.41, p=0.001), older (OR=1.47, 95%CI 1.21-1.78, p=0.001), living with smokers (OR=3.78, 95%CI 1.69-8.07, p=0.001), longer daily exposure to second-hand smoke (OR=1.10, 95%CI 1.04-1.16, p=0.001), and having more severe depressive symptoms (OR=1.12, 95%CI 1.07-1.18, p=0.001) were associated with heavy smoking., Conclusion: Smoking prevention and cessation programs should include the entire community, because exposure to environmental second hand smoke may facilitate initiation and more intense smoking. Screening of student smokers for depression should be prioritized in the process of rebuilding the framework for primary and secondary prevention in the post-conflict period., (© 2021 Gazibara T et al.)

Although studies on HIV knowledge have previously been conducted in central Serbia and southern Kosovo, none has included the Serbian population residing in the northern part of the Kosovo province. The aim of this study was to assess HIV-related knowledge and to estimate factors contributing to a higher HIV-related knowledge level among Serbian university students in the Kosovo province. A cross-sectional study including 1017 first- and fourth-year students enrolled at the University of Pristina temporarily seated in Kosovska Mitrovica was carried out during the academic year 2013-2014. The students completed a 31-item questionnaire comprising demographic data, HIV transmission knowledge and attitude towards HIV testing. Data were statistically analysed. Students demonstrated good knowledge of HIV (average 32.8 ± 3.3 out of a maximum 42). Only 5% of the students reported having been tested for HIV. Factors associated with being more knowledgeable about HIV were studying health-related disciplines (β = -0.09; 95% confidence interval [CI] -0.13, 0.00), using the internet as a source of information about HIV (β = -1.09; 95% CI -1.65, -0.52), having a positive attitude towards HIV testing (β = -0.43; 95% CI -0.59, -0.26), having a low self-perceived risk for HIV infection (β = 0.41; 95% CI 0.23, 0.56) and the position that one would keep the same level of contact with an HIV-positive person after learning their HIV status (β = 0.38; 95% CI 0.21, 0.55). Setting up specialized classes on this topic at high schools and universities could help to increase the awareness of HIV infection and promote HIV testing and a positive attitude towards HIV-positive persons.

Financial reimbursements after receiving the coronavirus disease 2019 (COVID-19) vaccine have been criticized in the literature. This strategy has been described as payment to receive the vaccines, undue inducement, and unethical. We are aware that healthcare workers who work in primary healthcare, prevention, and public health may encounter similar reasons from people who refuse vaccination against COVID-19. For this reason, we are compelled to clarify these claims and provide arguments for all healthcare workers who might be challenged by such reasoning. In this critical review, we discuss why the claims against financial incentives that have been presented in the literature are erroneous.