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Three Outbreaks of COVID-19 in a Single Nursing Home over Two Years of the SARS-CoV-2 Pandemic
Get PDFOlder people in nursing homes (NH) have been hit particularly hard by the COVID-19 pandemic. We conducted a retrospective study of three outbreaks of COVID-19, occurring during the waves of the initial pre-Alpha, Delta and Omicron SARS-CoV-2 variants, in one NH in suburban Belgrade, Serbia. All staff and 95% residents were vaccinated in February 2021, mostly with BBIBP-CorV, and two thirds were boosted with a third dose in August 2021. COVID-19 was diagnosed by positive PCR and/or antigen test. After the first outbreak, 80 affected individuals were tested for SARS-CoV-2 specific antibodies. The first outbreak involved 64/126 (50.8%) residents and 45/64 (70.3%) staff, the second 22/75 (29.3%) residents and 3/40 (7.5%) staff, and the third involved 36/110 (32.7%) residents and 19/56 (33.9%) staff. Clinical presentation ranged from asymptomatic to severe, with severe cases referred to hospital ICUs. Deaths occurred only in residents, and the case fatality rate was 31.2%, 9.1% and 0%, respectively in outbreaks 1, 2 and 3. Specific IgG antibodies were detected in all 35 residents and 44 of the 45 staff, and higher IgG levels were detected in the residents (417.3±273.5) than in the staff (201.9±192.9, p<0.0001) despite a double difference in age (79.0±7.4 vs. 40.1±11.5 years). Outbreaks 2 and 3 involved four and 23 breakthrough infections, respectively. Older individuals mounted a good immunological response to SARS-CoV-2 infection and vaccination, which prevented significant mortality and severe morbidity in the subsequent outbreaks, despite a significant number of breakthrough infections
Autochthonous infection with Ehrlichia Canis and Hepatozoon Canis in dogs from Serbia
Get PDFAbstract Background The epidemiological status concerning many canine tick-borne diseases (TBDs) in Serbia is still insufficiently known. Objectives Our study aimed to investigate the presence of tick-borne pathogens of the family Anaplasmataceae and Hepatozoon spp., as a cause of illnesses accompanied by clinical signs that can occur in dogs with anaplasmosis, ehrlichiosis and hepatozoonosis. Methods Dogs are included in the study based on the presence of a minimum of three clinical and/or pathological findings that could be associated with anaplasmosis, ehrlichiosis and hepatozoonosis. During the study (April–October 2018), 11 dogs met the conditions to be included in the survey. Identification of the causative agent in the blood of diseased dogs was performed by conventional PCR followed by sequencing. Results The presence of the pathogens was confirmed in three animals (3/11, 27.3%). The presence of Ehrlichia canis was confirmed in 3-month-old female Rottweiler puppy, an 8-year old Miniature Schnauzer female was positive for Hepatozoon canis infection, while 4-year-old mixed breed male dog was co-infected with both mentioned pathogens. These are the first cases of autochthonous infection with E. canis and H. canis in dogs from Serbia confirmed by molecular methods. Conclusions The results of our study indicate the importance of molecular methods to establish a reliable diagnosis of TBDs. Also, the confirmed presence of causative agents of canine monocytic ehrlichiosis and hepatozoonosis in Serbia appeals to veterinary practitioners that it is necessary to exclude the presence of those diseases in suspicious dogs
Prognostic Significance of Systemic Inflammation Markers in Testicular and Penile Cancer: A Narrative Review of Current Literature
Get PDFIn contemporary clinical practice, biomarkers are indispensable in the assessment and management of oncological patients. Although established serum tumor markers (beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP), and lactate dehydrogenase (LDH)) have an indisputably important role in the management of patients with testicular cancer (TC), the application of these tumor markers may be accompanied with certain limitations, implying the need for additional biomarkers. Contrary to TC, there is a lack of established serological biomarkers for penile cancer (PC) and the management of this urological malignancy is based on multiple clinicopathological parameters. Therefore, the identification and rigorous analytical and clinical validation of reliable biomarkers are considered pivotal for improving PC management. Inflammation may be associated with all stages of oncogenesis, from initial neoplastic transformation to angiogenesis, tissue invasion, and metastasis. Accordingly, an array of inflammation-related indices have gained increasing attention as emerging predictors of oncological outcomes. The clinical usefulness of systemic inflammation markers was reported in many urological and non-urological malignancies. The aim of this narrative review is to summarize current scientific data regarding the prognostic and predictive significance of systemic inflammation markers in TC and PC patients
Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis
No full textDexmedetomidine is an adrenergic receptor agonist that has been regarded as neuroprotective in several studies without an objective measure to it. Thus, the aim of this meta-analysis was to analyze and quantify the current evidence for the neuroprotective effects of dexmedetomidine in animals. The search was performed by querying the National Library of Medicine. Studies were included based on their language, significancy of their results, and complete availability of data on animal characteristics and interventions. Risk of bias was assessed using SYRCLE’s risk of bias tool and certainty was assessed using the ARRIVE Guidelines 2.0. Synthesis was performed by calculating pooled standardized mean difference and presented in forest plots and tables. The number of eligible records included per outcome is the following: 22 for IL-1β, 13 for IL-6, 19 for apoptosis, 7 for oxidative stress, 7 for Escape Latency, and 4 for Platform Crossings. At the cellular level, dexmedetomidine was found protective against production of IL-1β (standardized mean difference (SMD) = − 4.3 [− 4.8; − 3.7]) and IL-6 (SMD = − 5.6 [− 6.7; − 4.6]), apoptosis (measured through TUNEL, SMD = − 6.0 [− 6.8; − 4.6]), and oxidative stress (measured as MDA production, SMD = − 2.0 [− 2.4; − 1.4]) exclusively in the central nervous system. At the organism level, dexmedetomidine improved behavioral outcomes measuring escape latency (SMD = − 2.4 [− 3.3; − 1.6]) and number of platform crossings (SMD = 9.1 [− 6.8; − 11.5]). No eligible study had high risk of bias and certainty was satisfactory for reproducibility in all cases. This meta-analysis highlights the complexity of adrenergic stimulation and sheds light into the mechanisms potentiated by dexmedetomidine, which could be exploited for improving current neuroprotective formulations
Human amniotic membrane inhibits migration and invasion of muscle-invasive bladder cancer urothelial cells by downregulating the FAK/PI3K/Akt/mTOR signalling pathway
Get PDFBladder cancer is the 10th most commonly diagnosed cancer with the highest lifetime treatment costs. The human amniotic membrane (hAM) is the innermost foetal membrane that possesses a wide range of biological properties, including anti-inflammatory, antimicrobial and anticancer properties. Despite the growing number of studies, the mechanisms associated with the anticancer effects of human amniotic membrane (hAM) are poorly understood. Here, we reported that hAM preparations (homogenate and extract) inhibited the expression of the epithelial–mesenchymal transition markers N-cadherin and MMP-2 in bladder cancer urothelial cells in a dose-dependent manner, while increasing the secretion of TIMP-2. Moreover, hAM homogenate exerted its antimigratory effect by downregulating the expression of FAK and proteins involved in actin cytoskeleton reorganisation, such as cortactin and small RhoGTPases. In muscle-invasive cancer urothelial cells, hAM homogenate downregulated the PI3K/Akt/mTOR signalling pathway, the key cascade involved in promoting bladder cancer. By using normal, non-invasive papilloma and muscle-invasive cancer urothelial models, new perspectives on the anticancer effects of hAM have emerged. The results identify new sites for therapeutic intervention and are prompt encouragement for ongoing anticancer drug development studies
Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia
Get PDFVariations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients
BMAL1 Regulates Glucokinase Expression Through E-Box Elements In Vitro
No full textThe organization of a circadian system includes an endogenous pacemaker system, input pathways for environmental synchronizing (entraining) stimuli, and output pathways through which the clock regulates physiological and behavioral processes, for example, the glucose-sensing mechanism in the liver. The liver is the central regulator of metabolism and one of our peripherals clocks. In mammals, central to this pacemaker are the transcription factors Circadian Locomotor Output Cycles Kaput (CLOCK) and BMAL1 (Brain and Muscle ARNT-Like 1). BMAL1 dimerizes with CLOCK, and this heterodimer then binds to the E-box promoter elements (CACGTG) present in clock and clock-controlled genes (CCGs). However, we are just beginning to understand how output pathways and regulatory mechanisms of CCGs are involved in rhythmic physiological processes. Glucokinase (GCK) is a fundamental enzyme in glucose homeostasis, catalyzing the high Km phosphorylation of glucose and allowing its storage. Moreover, gck is a dependent circadian gene. This study aims to determine the contribution of clock genes to hepatic gck expression and to define the specific role of E-box sequences on the circadian regulation of hepatic gck. Results showed that gck expression follows a circadian rhythm in rat hepatocytes in vitro. Accordingly, bmal1 expression induces the glucokinase circadian rhythmic expression in hepatocytes and the analysis of human and rat gck promoters, indicating the presence of E-box regions. Moreover, the basal activity of gck promoter was increased by clock/bmal1 co-transfection but inhibited by Period1/Period2 (per1/per2) co-transfection. Thus, the data suggest that the clock proteins tightly regulate the transcriptional activity of the gck promoter
Capacity Development and Harmonization of Food Consumption Data Collection in EFSA EU Menu National Dietary Surveys in Balkan Region-Building: The Evidence Base for Diet Monitoring and Food Systems Transformation
Get PDFHarmonized and standardized collection, processing, and analysis of individual dietary data is essential for nutrition assessment and informed policy decision making. To underpin the harmonization of food consumption data collection methodologies and the development of a common, comprehensive European food consumption database, the European Food Safety Authority (EFSA) supported 36 child and/or adult dietary surveys in 18 EU Member States and four Balkan preaccession countries through the EU Menu Project. Given the lack of relevant and harmonized research and data on food and nutrition in the Balkan region, CENM-IMR and CAPNUTRA scientists focused their activities on capacity building in nutrition research, particularly on the creation of a contemporary, harmonized research infrastructure (RI) that meets European standards. The EFSA EU Menu methodology has been implemented in the Balkans through the adaptation and use of an innovative, comprehensive tool for the standardized collection of food consumption and dietary intake assessment data, the Diet Assess and Plan (DAP). DAP has the essential features of an RI needed to strengthen public health surveillance, monitoring, evaluation, and nutrition research; this is a unique example of a standardized and harmonized tool for assessing dietary intake, i.e., collecting data on food and nutrition in the Balkan region and beyond. It is a concurrent tool for large-scale nutritional epidemiological studies and represents one of the new technologies for dietary intake assessment. National dietary surveys were conducted from 2017 to 2023 among adults aged 10 to 74 years (in Bosnia and Herzegovina, Montenegro, and Serbia) and children aged three months to nine years (in Montenegro, North Macedonia, and Serbia). The collected data on food consumption are internationally comparable with other European countries under the EU Menu Program. The data collected will be used for dietary and exposure risk assessment, establishment of national nutrient reference values, as a basis for the development of food-based dietary guidelines, a tool to provide evidence and infrastructure for public health nutrition policy decisions, and for tailored pathways to transform the food system in the Balkans towards a more nutrition-sensitive and sustainable system
Endemic population dynamics of West Nile virus in mosquitoes from the territory of Serbia
Get PDFPrvi slučajevi infekcije virusom Zapadnog Nila (VZN) u Srbiji zabeleženi su 2012. godine, dok je 2018.,
prema izveštaju Evropskog centra za kontrolu i prevenciju bolesti (ECDC), Srbija prijavila najveći broj
obolelih (385) od svih zemalja jugoistočne Evrope. Cilj ove studije je bio da se genetički okarakterišu
sojevi VZN-a, koji cirkulišu u Srbiji.
U studiji je ispitano 200 pulova komaraca, skupljenih u Beogradu i široj okolini, u okviru redovnog
nadzora koji sprovodi Zavod za biocide i medicinsku ekologiju u Beogradu u periodu od 2018-2020.
Prisustvo VZN-a utvrđeno je reakcijom lančanog umnožavanja (engl. polymerase chain reaction –
PCR), za detekciju NS5 gena, sa primenom Sangerovog DNK sekvenciranja dobijenih PCR produkata
i njihovom preliminarnom identifikacijom primenom BLAST alata u NCBI bazi podataka.
Konstrukcija filogenetskog stabla rađena je primenom metode Bajesove statistike implementirane
u MrBayes softverski paket, uz odgovarajući evolutivni model koji je izabran u jModelTest softveru.
Iz 200 analiziranih pulova komaraca, koji su skupljeni u periodu od 2018-2020, dobili smo 45 sekvenci
NS5 gena VZN-a. Rezultati studije su pokazali da je 22.5% (45/200) pulova komarca bilo pozitivno
na prisustvo VZN-a. Najveći procenat pozitivnih pulova je iz 2018. godine i iznosi 57.8% (26/45),
zatim iz 2019 26.7% (12/45) i iz 2020 15.5% (7/45). Identifikacija dobijenih sekvenci pokazala je da
je u Srbiji trenutno u cirkulaciji samo linija 2 VZN-a. Dalja analiza je potvrdila da su sojevi VZN-a iz
Srbije najsličniji izolatima iz Grčke. Dodatno, u jednom pulu komaraca, uzorkovanom u okolini Šapca
2019. godine, identifikovano je prisustvo Usutu virusa.
Dobijeni rezultati su potvrdili da u Srbiji cirkuliše linija 2 VZN-a kao i da postoji potreba za kontinuiranim
molekularno-bioinformatički nadzorom nad ovim i sličnim zoonotskim virusima.The first cases of West Nile virus (WNV) infection in Serbia recorded in 2012, while in 2018,
according to the report of the European Centre for Disease Control and Prevention (ECDC), Serbia
reported the highest number of cases (385) in the Southeast Europe. The aim of this study was to
genetically characterize strains of WNV circulating in Serbia.
The present study included 200 pools of mosquitoes, collected in Belgrade and the surrounding
area by the Institute for Biocides and Medical Ecology in Belgrade in the period from 2018-2020, as
part of regular surveillance. The presence of WNV was detected by Nested-PCR (Polymerase chain
reaction) method together with specific primers for detection of partial NS5 gene. All obtained specific
PCR products were directly sequenced in both directions. Preliminary sequence identification was
done by BLAST tool (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Bayesian method was employed to
infer the evolutionary relationship of studied sequence dataset, using MrBayes software with the
best-fitting nucleotide substitution model for the final sequence dataset, as selected by jModelTest 2.
In total, 45 partial NS5 gene WNV sequences were obtained from mosquito pools collected in Serbia
between 2018 and 2020. The results obtained in this study showed that 22.5% (45/200) of mosquito
pools were positive for the presence of WNV. The highest percentage of positive pools was detected
in 2018 (57.8% (26/45)), followed by 2019 (26.7% (12/45)) and 2020 (15.5% (7/45)). Phylogenetic
analysis conformed that only linage 2 of WNV is circulating in Serbia. Majority of Serbian isolates
clustered with Greek strains, thus forming the Balkan cluster. Of note, in one mosquito pool sampled
in the Western Serbia in 2019, we detected the presence of Usutu virus.
Results obtained in the present study confirmed the presence of WNV linage 2 in Serbia and the
necessity for continuous molecular-bioinformatic monitoring of zoonotic viruses