Major depressive disorder (MDD) is a severe illness imposing an increasing social and economic burden worldwide. Numerous rodent models have been developed to investigate the pathophysiology of MDD. One of the best characterized and most widely used models is the chronic mild stress (CMS) model which was developed more than 30 years ago by Paul Willner. More than 2000 published studies used this model, mainly to assess novel compounds with potential antidepressant efficacy. Most of these studies examined the behavioral consequences of stress and concomitant drug intervention. Much fewer studies focused on the CMS-induced neurobiological changes. However, the stress-induced cellular and molecular changes are important as they may serve as potential translational biomarkers and increase our understanding of the pathophysiology of MDD. Here, we summarize current knowledge on the structural and molecular alterations in the brain that have been described using the CMS model. We discuss the latest neuroimaging and postmortem histopathological data as well as molecular changes including recent findings on microRNA levels. Different chronic stress paradigms occasionally deliver dissimilar findings, but the available experimental data provide convincing evidence that the CMS model has a high translational value. Future studies examining the neurobiological changes in the CMS model in combination with clinically effective antidepressant drug intervention will likely deliver further valuable information on the pathophysiology of MDD.

Background: Effective testing is an essential tool for controlling COVID-19. We aimed to analyse the data from first-wave PCR test results in Hungary's Southern Transdanubian region to improve testing strategies.Methods: We performed a retrospective analysis of all suspected COVID-19 cases between 17 March and 8 May 2020, collecting epidemiological, demographic, clinical and outcome data (ICU admission and mortality) with RT-qPCR test results. Descriptive and comparative statistical analyses were conducted.Results: Eighty-six infections were confirmed among 3,657 tested patients. There was no difference between the positive and negative cases in age and sex distribution; however, ICU admission (8.1 vs. 3.1%, p = 0.006) and in-hospital mortality (4.7 vs. 1.6%, p = 0.062) were more frequent among positive cases. Importantly, none of the initially asymptomatic patients (n = 20) required ICU admission, and all survived. In almost all cases, if the first test was negative, second and third tests were performed with a 48-h delay for careful monitoring of disease development. However, the positive hit rate decreased dramatically with the second and third tests compared to the first (0.3 vs. 2.1%, OR = 0.155 [0.053–0.350]). Higher E-gene copy numbers were associated with a longer period of PCR positivity.Conclusion: In our immunologically naïve suspected COVID-19 population, coronavirus infection increased the need for intensive care and mortality by 3–4 times. In the event of the exponential phase of the pandemic involving a bottleneck in testing capacity, a second or third test should be reconsidered to diagnose more coronavirus infections.

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments.

Western honey bees (Apis mellifera) are important pollinators in the ecosystem and also play a crucial economic role in the honey industry. During the last decades, a continuous decay was registered in honey bee populations worldwide, including Hungary. In our study, we used metagenomic approaches and conventional PCR screening on healthy and winter mortality affected colonies from multiple sites in Hungary. The major goal was to discover presumed bee pathogens with viral metagenomic experiments and gain prevalence and distribution data by targeted PCR screening. We examined 664 honey bee samples that had been collected during winter mortality from three seemingly healthy colonies and from one colony infested heavily by the parasitic mite Varroa destructor in 2016 and 2017. The subsequent PCR screening of honey bee samples revealed the abundant presence of Apis mellifera filamentous virus (AmFV) for the first time in Central Europe. Based on phylogeny reconstruction, the newly-detected virus was found to be most closely related to a Chinese AmFV strain. More sequence data from multiple countries would be needed for studying the detailed phylogeographical patterns and worldwide spreading process of AmFV. Here we report the prevalent presence of this virus in Hungarian honey bee colonies.

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of 18 World Health Organization, considering its potential to create a public health emergency and more 19 importantly, the absence of efficacious drugs and/or vaccines regarding treatment. The highly lethal 20 nature characteristic to CCHFV restricts research to BSL-4 laboratories, which complicates effective 21 research and developmental strategies. In consideration of antiviral therapies, RNA interference can 22 be used to suppress viral replication by targeting viral genes. RNA interference uses small 23 interfering RNAs (siRNAs) to silence genes. The aim of our study was to design siRNAs that inhibit 24 CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected 25 with CCHFV after transfection with the siRNAs. Following 72 hours, nucleic acid from the 26 supernatant was extracted for Droplet Digital PCR analysis. Among the investigated siRNAs we 27 identified four effective candidates against all three segments of CCHF genome: one for the S and 28 M segments, whilst two for the L segment. Consequently, blocking any segment of CCHFV leads to 29 changes in the virus copy number that indicates an antiviral effect of the siRNAs in vitro. The most 30 active siRNAs were demonstrated a specific inhibitory effect against CCHFV in a dose-dependent 31 manner. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication 32 in vitro. This promising result can be used in future anti-CCHFV therapy developments.33