Milić, Nataša

BACKGROUND: Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. METHODS: We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. RESULTS: Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho ( P =0.018); increased leptin ( P =0.016) and leptin/adiponectin ratio ( P =0.027), and increased extracellular vesicles positive for tissue factor ( P =0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment ( P =0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women ( P =0.003). CONCLUSIONS: Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia.

Background and Objectives: Total knee arthroplasty (TKA) has become the treatment of choice for advanced osteoarthritis. The aim of this paper was to show the possibilities of optimizing the Perth CT protocol, which is highly effective for preoperative planning and postoperative assessment of alignment. Materials and Methods: The cross-sectional study comprised 16 patients for preoperative planning or postoperative evaluation of TKA. All patients were examined with the standard and optimized Perth CT protocol using advance techniques, including automatic exposure control (AEC), iterative image reconstruction (IR), as well as a single-energy projection-based metal artifact reduction algorithm for eliminating prosthesis artifacts. The effective radiation dose (E) was determined based on the dose report. Imaging quality is determined according to subjective and objective (values of signal to noise ratio (SdNR) and figure of merit (FOM)) criteria. Results: The effective radiation dose with the optimized protocol was significantly lower compared to the standard protocol (p < 0.001), while in patients with the knee prosthesis, E increased significantly less with the optimized protocol compared to the standard protocol. No significant difference was observed in the subjective evaluation of image quality between protocols (p > 0.05). Analyzing the objective criteria for image quality optimized protocols resulted in lower SdNR values and higher FOM values. No significant difference of image quality was determined using the SdNR and FOM as per the specified protocols and parts of extremities, and for the presence of prothesis. Conclusions: Retrospecting the ALARA (‘As Low As Reasonably Achievable’) principles, it is possible to optimize the Perth CT protocol by reducing the kV and mAs values and by changing the collimation and increasing the pitch factor. Advanced IR techniques were used in both protocols, and AEC was used in the optimized protocol. The effective dose of radiation can be reduced five times, and the image quality will be satisfactory.

Tryptophan (TRP) catabolites exert neuroactive effects, with the plethora of evidence suggesting that kynurenic acid (KYNA), a catabolite of the kynurenine pathway (KP), acts as the regulator of glutamate and acetylcholine in the brain, contributing to the schizophrenia pathophysiology. Newer evidence regarding measures of KP metabolites in the blood of schizophrenia patients and from the central nervous system suggest that blood levels of these metabolites by no means could reflect pathological changes of TRP degradation in the brain. The aim of this study was to investigate plasma concentrations of TRP, kynurenine (KYN) and KYNA at the acute phase and remission of schizophrenia in a prospective, case-control study of highly selected and matched schizophrenia patients and healthy individuals. Our study revealed significantly decreased KYN and KYNA in schizophrenia patients (p < 0.001), irrespective of illness state, type of antipsychotic treatment, number of episodes or illness duration and no differences in the KYN/TRP ratio between schizophrenia patients and healthy individuals. These findings could be interpreted as indices that kynurenine pathway might not be dysregulated in the periphery and that other factors contribute to observed disturbances in concentrations, but as our study had certain limitations, we cannot draw definite conclusions. Further studies, especially those exploring other body compartments that participate in kynurenine pathway, are needed.

Background and Objectives: The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods: PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results: A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions: This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes.

Introduction: Risk stratification in patients with COVID-19 is a challenging task. Early warning scores (EWSs) are commonly used tools in the initial assessment of critical patients. However, their utility in patients with COVID-19 is still undetermined. Aim: This study aimed to discover the most valuable predictive model among existing EWSs for ICU admissions and mortality in COVID-19 patients. Materials and methods: This was a single-center cohort study that included 3608 COVID-19 patients admitted to the University Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia, between 23 June 2020, and 14 April 2021. Various demographic, laboratory, and clinical data were collected to calculate several EWSs and determine their efficacy. For all 3608 patients, five EWSs were calculated (MEWS, NEWS, NEWS2, REMS, and qSOFA). Model discrimination performance was tested using sensitivity, specificity, and positive and negative predictive values. C statistic, representing the area under the receiver operating characteristic (ROC) curve, was used for the overall assessment of the predictive model. Results: Among the evaluated prediction scores for 3068 patients with COVID-19, REMS demonstrated the highest diagnostic performance with the sensitivity, PPV, specificity, and NPV of 72.1%, 20.6%, 74.9%, and 96.8%, respectively. In the multivariate logistic regression analysis, aside from REMS, age (p < 0.001), higher CT score (p < 0.001), higher values of urea (p < 0.001), and the presence of bacterial superinfection (p < 0.001) were significant predictors of mortality. Conclusions: Among all evaluated EWSs to predict mortality and ICU admission in COVID-19 patients, the REMS score demonstrated the highest efficacy.

Participating in research plays an essential role in improving the practice of healthcare. This cross-sectional study enrolled 100PhD students who attended the course “Informatics for researchers” at Medical Faculty University of Belgrade. The total ATR scale demonstrated excellent reliability (α=0.899) with 0.881 for Positive attitudes to 0.695 for Relevance to life. PhD students in Serbia showed high degree of positive attitudes toward research. Faculty could administer ATR scale to determine students’ standpoints towards research, to maximize the impact of the research course and enhance participation in research.

In this cross-sectional survey the Attitude Towards Plagiarism (ATP) questionnaire was administered to 100 PhD students to measure their attitudes towards plagiarism. The results showed that the students had low scores for positive attitudes and subjective norms, but moderate scores for negative attitudes towards plagiarism. Additional courses on plagiarism should be introduced in PhD studies to promote responsible research practices in Serbia.

AbstractBackgroundPreeclampsia (PE), a pregnancy specific hypertensive disorder, has been associated with elevated risk for strokes, cognitive decline, and smaller brain volumes later in life. As severe PE has been associated with the highest risks for cerebrovascular disease, we hypothesized that circulating extracellular vesicles (EVs) of neurovascular origin will be detectable in women years after severe PE as a marker of persistent neurovascular damage and amyloid‐β.MethodA cohort of 40 women with histories of normotensive pregnancies (control group) and age‐ and parity‐matched to 40 women with history of mild (n = 33) and severe (n = 7) PE were identified using the Rochester Epidemiology Project. Diagnosis of severe PE was ascertained based on clinical criteria (Table). While none of the women had any major cardiovascular events, our previous study of this cohort has demonstrated that total gray matter volumes were smaller in women with a history of preeclampsia and late‐life hypertension compared with the other groups. Blood‐borne EVs derived from neurovascular cellular activation were determined by standardized digital flow cytometry. Plasma concentration of amyloid‐β was measured by ELISA. Differences among the groups were tested by ANOVA, with the least difference test for pos hoc analysis. The association between EVs and MRI brain imaging was assessed by Pearson correlation coefficient.ResultWomen with history of severe PE had a significantly higher concentration of amyloid‐β carrying EVs compared to controls (p = 0.003). EVs positive for the markers of blood‐brain barrier‐ endothelial damage (LDL‐R) and inflammatory coagulation pathway activator (tissue factor), were significantly higher in women with history of severe PE compared to controls (p = 0.008 and p = 0.002, respectively), as well as to the women with history of mild PE. Plasma concentration of total amyloid‐β was also significantly greater in women with history of severe vs. mild PE (p = 0.037) (Table). The number of tissue factor positive EVs was negatively correlated with total gray matter volume (cm3) (p<0.05).ConclusionWomen with a history of severe PE demonstrate elevated levels of markers of neuroinflammation and neurovascular damage, as well as greater amyloid‐β secretion. Excessive inflammation may contribute to previously described brain atrophy in these women.