Can a presepsin (SCD14-ST) obtained from tracheal aspirate be a biomarker for early-onset neonatal sepsis

© 2020, University of Kragujevac, Faculty of Science. All rights reserved. In absence of clear clinical signs and clear definition, neonatal sepsis is still one of the major cause of morbidity and mortality. Most researchs in past time was directional on finding new biomarkers with greater sensitivity and specific-ity in detection of neonatal sepsis. The aim of our study was to investigate if presepsin obtained from tracheal asprate in intubated newborns, can be a novel biomarker of systemic bacterial infection. Our ‘’case control’’ study included 60 newborns, 11 with suspected neonatal sepsis. Tracheal aspirate for examination was taken in the usual toilets, in asep-tic conditions, by lavage with 2 ml of 0.9% NaCl in Mucus suction set. In the same day were mesured presepsin (blood), CRP, PCT, leukocytes and neutrophyls, as well as blood cul-ture. Our research showed higher levels for PCT and prese-psin (blood) in septic newborns, as well as in newborns with clinical signs of SIRS. Presepsin obtained from a tracheal aspirate had high score for septic newborns. As the coefficients of simple linear correlation showed, there was quantitative agreement between presepsin (blood) with presepsin (trache-al aspirate)-increase in the value of one leads to an increase in other. In conjunction with an already validated markers of infection, presepsin obtained from tracheal aspirate cam be turned on in diagnostic procedures

Trend of suicide by self-immolation in a 13-year timeline: was the COVID-19 pandemic a potentially important stressor?

IntroductionSelf-immolation is an uncommon way of attempting and committing a suicide, with a fatality rate of 80%. The risk factors in self-immolation victims vary depending on demographic characteristics, socio-economic and cultural factors as well as religious beliefs. Whether the COVID-19 pandemic was a potentially important stressor for self-immolation is still unknown, with insufficient studies examining this issue. Therefore, in this study, we aimed to examine the trend of self-immolation in a 13-year timeline, and the potential association of COVID-19 pandemic with the increase in the incidence and severity of self-immolation injuries in Serbia in 2021.Materials and methodsThe study included hospitalized patients due to intentional burns caused by self-immolation in the period from January 1, 2008 to December 31, 2021. Joinpoint regression analysis was used for the analysis of continuous linear trends of self-immolation cases with change points.ResultsWhile a rising trend was observed in the 2008–2013 time segment, followed by a decline in the upcoming 2013–2016 time segment, a significant increase reached its maximum during COVID-19 pandemic (2021), with annual percent change of 37.1% (p = 0.001). A significant increase in the median number of cases per year was observed during 2021 compared to the previous periods (7.5 vs. 2). Frequency of patients with a psychiatric diagnosis vs. those without a psychiatric diagnosis was significantly higher during than before the COVID-19 period (66.7 vs. 36.1%, p = 0.046).ConclusionIn our study, a significant increase in the frequency of suicide attempts by self-immolation during COVID-19 pandemic was noticed. There was also an increased frequency of pre-existing psychiatric illness among patients during the pandemic period. With limited high-quality data available, the study adds to a rising body of evidence for assessment of outcomes of the pandemic on mental health and recognition of stressors for self-immolation

Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies

We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Frequency of alcohol use among elementary school pupils at Belgrade territory

Introduction Alcoholism is one of the most frequent modern diseases. These kinds of epidemiological studies have not been carried out in this country at a global level. Objective The aim of the study was to establish the spread of alcohol abuse among the young regarding the sex, and find the connection between the alcohol abuse and the consumption of drugs and cigarettes. Methods The study was carried out among the elementary school pupils of the seventh and eighth grade in the area of Belgrade from October 2003 to January 2004. Total of 457 pupils were involved; 229 (50.1%) were boys and 228 (49.9%) girls, aged 12-15 years, the average age being 13.4 years. The method used was the modified questionnaire European School Survey Project on Alcohol and Other Drugs, which the pupils filled in individually, voluntarily and anonymously. χ2-test, Student's t-test, Mann-Whitney Logistic Regression Test were used in statistical processing of the data. Results Almost 70% of the examinees have tried alcohol. Most of the examinees had the first contact with alcohol at the age of 11. Half of our examinees got drunk at least once in their life and about one fifth more than 20 times. The binge form of consumption (five or more drinks in a row) was evident in a quarter of our examinees. Our examinees use alcohol together with other psychoactive substances, mostly marijuana. It was observed that certain types of behavior, such as frequent going out in the evening, were directly related to the abuse of alcohol. Conclusion Two thirds of the examinees have tried alcohol. The first contact with alcohol is shifted to an earlier age (11 years). New trends of alcohol abuse have been noticed, such as binge form of consumption and the connection of use with other psychoactive substances.

Utjecaj autohtonih bakterija mliječne kiseline na proteolizu, mikrostrukturu i senzorska svojstva niskomasnih UF sireva tijekom zrenja

The influence of commercial bacteria Lactococcus lactis ssp. lactis and Lactococcus lactis ssp. cremoris (cheese A) and combinations of autochthonous lactic acid bacteria (LAB) strains Lactobacillus paracasei ssp. paracasei 08, Lactococcus lactis ssp. cremoris 656, Lactococcus lactis ssp. lactis 653 (cheese B and C) on composition, proteolysis, microstructure and sensory properties of low fat cheeses during ripening was investigated. Low fat cast ultra-filtered (UF) cheeses were produced according to the defined production procedure by mixing UF milk protein powder, skim milk and cream. Significant influence of different LAB strains on composition, primary proteolysis and microstructure was not found. Cheeses made with autochthonous LAB showed a higher rate of secondary proteolysis, as well as higher flavour scores, and were more acceptable than control cheese.U radu je utvrđen utjecaj komercijalnih Lactococcus lactis ssp. lactis i Lactococcus lactis ssp. cremoris (sir A) i kombinacija autohtonih bakterija mliječne kiseline (BMK) Lactobacillus paracasei ssp. paracasei 08, Lactococcus lactis ssp. cremoris 656, Lactococcus lactis ssp. lactis 653 i (sir B i C) na sastav, proteolizu, mikrostrukturu i senzorska svojstva niskomasnih sireva tijekom zrenja. Niskomasni sirevi od ultrafiltriranog mlijeka (UF) proizvedeni su prema definiranom tehnološkom postupku proizvodnje miješanjem UF proteina mlijeka u prahu, obranog mlijeka i vrhnja. Nije utvrđen značajan utjecaj različitih BMK na sastav, primarnu proteolizu i mikrostrukturu. Sirevi sa autohtonim BMK odlikovali su se višim stupnjem sekundarne proteolize, kao i boljim senzorskim svojstvima u odnosu na kontrolni sir

The role of glucocorticoid receptor phosphorylation in the model of negative affective states

Objectives. To develop a structural equation model of negative affectivity (NA) that involves interaction of glucocorticoid receptor (GR) signaling, personality dimensions and recent stressful life events. Methods. Seventy participants -35 diagnosed with major depression and 35 healthy controls, were enrolled in the study. Morning plasma cortisol levels were determined by chemiluminescent immunometric assays. Molecular parameters (total nuclear and cytoplasmatic GR, nuclear GR phosphorylated at serine 211 (pGR-211) and at serine 226 (pGR-226) and cytoplasmic FKBP51) were analysed from peripheral blood lymphocytes by Western blot. NA, personality dimensions and stressful life events were assessed by self-report instruments. Results. GR signalling parameters had direct independent effect on measures of NA, with pGR-226 levels showing the strongest correlation, followed by FKBP51 and pGR-211 levels. Neuroticism and extraversion also demonstrated strong independent effect on NA, while recent stressful events did not predict NA directly, but demonstrated a significant effect on personality dimensions. Cortisol, total nuclear GR and total cytoplasmatic GR levels were excluded from the model due to non-significant correlations with NA. Conclusions. Negative affectivity is a transdiagnostic factor in vulnerability to affective disorders and possible therapeutic target. Molecular signature of negative affectivity should incorporate GR phosphorylation with other known biological underpinnings

Phosphorylation of leukocyte glucocorticoid receptor in patients with current episode of major depressive disorder

The impaired glucocorticoid receptor (GR) signaling has long been considered one of the cornerstones in understanding the pathophysiology of depression. Since the phosphorylation of GR is very important for GR function, in this study we investigated whether GR phosphorylation at serine 211 (pGR-S211) and serine 226 (pGR-S226) is altered in patients with current episode of major depressive disorder (MDD). Particularly, in 30 MDD patients and 35 controls we assessed the levels of nuclear total GR (tGR), pGR-S211 and pGR-S226 in peripheral blood mononuclear cells (PBMC) using Western blot technique, along with plasma cortisol concentrations from the same blood samples. Our results demonstrated increased phosphorylation of GR at S226 (p LT 0.001) and, to a less extent, at S211 (p LT 0.05) in MDD patients compared to controls. Consequently, the pGR-S211/pGR-S226 ratio was decreased (p LT 0.05) implying reduced transcriptional activity of GR in MDD patients. MDD subjects had higher cortisol levels than controls and cortisol concentrations were positively correlated with PBMC pGR-S226 levels from the same blood samples. There was no difference in the levels of tGR between MDD and control subjects. The study showed that altered phosphorylation of GR could contribute to impaired GR function related to the pathophysiology of depression. (c) 2012 Elsevier Inc. All rights reserved

Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients

Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-kappa B (NF-kappa B), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-kappa B in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-kappa B. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-kappa B) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients. (C) 2014 S. Karger AG, Base