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Although the chief of the World Health Organization (WHO) has declared the end of the coronavirus disease 2019 (COVID-19) as a global health emergency, the disease is still a global threat. To be able to manage such pandemics in the future, it is necessary to develop proper strategies and opportunities to protect human life. The data on the SARS-CoV-2 virus must be continuously analyzed, and the possibilities of mutation and the emergence of new, more infectious variants must be anticipated, as well as the options of using different preventive and therapeutic techniques. This is because the fast development of severe acute coronavirus 2 syndrome (SARS-CoV-2) variants of concern have posed a significant problem for COVID-19 pandemic control using the presently available vaccinations. This review summarizes data on the SARS-CoV-2 variants that are responsible for severe COVID-19 and the clinical efficacy of the most commonly used vaccines in clinical practice. The consequences after the disease (long COVID or post-COVID conditions) continue to be the subject of studies and research, and affect social and economic life worldwide.

Pooled Immunoglobulin G (IgG), hematin and the membrane-disruptive amphipathic peptide melittin have received attention as powerful biomacromolecules for biomedical and pharmacology applications. Their action on surface properties, oxidation status and epifluorescence properties measured in vitro provide useful information about the functional activity of upper biomacromolecules in erythrocytes in vivo. The hemolysis of erythrocyte membranes, as well as changes in hematocrit and the morphology of erythrocytes, was investigated here via fluorescence microscopy using FITC-concanavalin A binding to cells. The effect of melittin on the membrane capacitance and resistance of model lipid bilayers was probed via electrochemical impedance spectroscopy. Lipid bilayer capacitance was higher in the presence of 0.10 g/L melittin compared to that in the control, which is likely related to bilayer thinning and alterations of the dielectric permittivity of melittin-treated membranes. The biomolecule interactions with red blood cells were probed in physiological media in which the surface of erythrocyte membranes was negatively charged. Surface parameters of erythrocytes are reported upon IgG/hematin and IgG/melittin treatment. Pooled IgG in the presence of melittin, preincubated IgG/hematin preparations promoted a significant decrease in the electrokinetic potential of erythrocytes (Rh-positive). A malondialdehyde (MDA) assay revealed a high rate of lipid peroxidation in erythrocytes treated with IgG/hematin or IgG/melittin preparations. This finding might be a result of pooled IgG interactions with the hematin molecule and the subsequent conformational changes in the protein molecule altering the electrokinetic properties of the erythrocyte membrane related to the Rh group type of erythrocytes. The pooled IgG and hematin are reported to have important consequences for the biophysical understanding of the immunopathological mechanisms of inflammatory, autoimmune and antibody-mediated pathological processes.

Information about the fungal composition of bee bread, and the fermentation processes to which the fungi contribute significantly, is rather scarce or fragmentary. In this study, we performed an NGS-based metagenomics snapshot picture study of the fungal composition of bee bread in four locations in Bulgaria during the most active honeybee foraging period at the end of June 2020. The sampling locations were chosen to differ significantly in climatic conditions, landscape, and anthropogenic pressure, and the Illumina 2 × 250 paired-end reads platform was used for amplicon metagenomics study of the ITS2 region. We found that some of the already reported canonical beneficial core fungal species were present within the studied samples. However, some fungal genera such as Monilinia , Sclerotinia , Golovinomyces , Toxicocladosporium , Pseudopithomyces , Podosphaera and Septoriella were reported for the first time among the dominant genera for a honeybee related product. Anthropogenic pressure negatively influences the fungal composition of the bee bread in two different ways-urban/industrial pressure affects the presence of pathogenic species, while agricultural pressure is reflected in a decrease of the ratio of the beneficial fungi.

Introduction: Vitamin K (VK) is a co-factor in the post-translational gamma glutamic carboxylation of Gla-proteins. VK-dependent coagulation factors are carboxylated in the liver by VK1. Osteocalcin and Matrix-Gla protein (MGP) are carboxylated in extrahepatic tissues by VK2. A model of VK deficiency would be suitable for studying extrahepatic Gla-proteins provided that severe bleeding is prevented., Aim: The aim of this work was to adapt an established protocol of vascular calcification by warfarin-induced inactivation of MGP as a calcification inhibitor, in an attempt to create a broader state of subclinical VK deficiency and to verify its safety., Materials and Methods: Two consecutive experiments, each lasting 4 weeks, were required to modify the dosing schedule of warfa-rin and VK1 and to adapt it to the Wistar rats used. The original high doses of warfarin used initially had to be halved and the protective dose of VK1 to be doubled, in order to avoid treatment-induced hemorrhagic deaths. The second experiment aimed to confirm the efficacy and safety of the modified doses. To verify the VK deficiency, blood vessels were examined histologically for calcium deposits and serum osteocalcin levels were mea-sured., Results: The original dosing schedule induced VK deficiency, manifested by arterial calcifications and dramatic changes in carboxyl-ated and uncarboxylated osteocalcin. The modified dosing regimen caused similar vascular calcification and no bleeding., Conclusion: The modified protocol of carefully balanced warfarin and VK1 doses is an effective and safe way to induce subclinical VK deficiency that can be implemented to investigate VK-dependent proteins like osteocalcin., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hordeum vulgare and Hordeum bulbosum are two closely related barley species, which share a common H genome. H. vulgare has two nucleolar organizer regions (NORs), while the NOR of H. bulbosum is only one. We sequenced the 2.5 kb 25S-18S region in the rDNA of H. bulbosum and compared it to the same region in H. vulgare as well as to the other Triticeae. The region includes an intergenic spacer (IGS) with a number of subrepeats, a promoter, and an external transcribed spacer (5'ETS). The IGS of H. bulbosum downstream of 25S rRNA contains two 143-bp repeats and six 128-bp repeats. In contrast, the IGS in H. vulgare contains an array of seven 79-bp repeats and a varying number of 135-bp repeats. The 135-bp repeats in H. vulgare and the 128-bp repeats in H. bulbosum show similarity. Compared to H. vulgare, the 5'ETS of H. bulbosum is shorter. Additionally, the 5'ETS regions in H. bulbosum and H. vulgare diverged faster than in other Triticeae genera. Alignment of the Triticeae promoter sequences suggests that in Hordeum, as in diploid Triticum, transcription starts with guanine and not with adenine as it is in many other plants.

Intracranial tumors (ICTs) attract numerous scientific teams and tremendous financial resources worldwide. These lesions of the central nervous system (CNS) can be both benign and malignant in biological behavior as well as local or metastatic in origin. We compared data from two studies on primary and metastatic ICTs from Brazil and Bulgaria, based on histopathologically confirmed ICTs from tertiary health centers. Primary ICTs significantly outweigh the frequency of metastatic ICTs. Primary ICTs represent 86.45% in Brazil and 69.17% in Bulgaria, with around 60% of their totals being malignant. There is a statistical dominance of tumors from the neuroepithelial origin, with the most common entry being glioblastoma multiforme. The second-most common primary ICT group comprises tumors of meningeal origin. Metastatic ICTs show great variance; 13.55% in Brazil and 31.38% in Bulgaria of all ICT cases being attributed to them. However, metastatic ICTs are even a more diverse group than neuroepithelial tumors, with the majority of this group comprising metastatic colorectal adenocarcinoma (almost exclusively in males), metastatic breast adenocarcinoma in females, metastatic pulmonary carcinomas (primarily from the non-small cell group with a male predominance), and metastatic melanoma with an even gender ratio., Competing Interests: The authors have declared that no competing interests exist.

Introduction Intracranial tumors (ICTs) are a diverse group of malignancies that pose an immediate threat to patients' lives, no matter their local or metastatic origin, benign or malignant nature. These lesions have severe clinical courses and need to be diagnosed and treated as soon as possible, with pathological verification being the pivotal moment in the process of determining curative modalities. Aim The aim of this study was to compare the incidence of histologically confirmed ICTs in Eastern Bulgaria, based on their type (primary, metastatic, and non-volume occupying lesions (NVOL)), their respective subtypes, and incidence in a descriptive manner. Materials and Methods For a period of five full calendar years (January 1st, 2012 - December 31st, 2016), all histologically confirmed cases of intracranial tumors were prospectively collected from two individual tertiary healthcare institutions. The cases were then statistically analyzed in a descriptive manner, and incidences of primary, metastatic, and NVOL were compared with regards to their specific origins, types, and subtypes. Metastatic tumors were further segregated relative to their intracranial metastatic location. Results The total number of individual ICTs registered in the set timeframe was 822. Primary ICTs represented a total of 66.12% of the histologically confirmed cases, with the most common entries being tumors from a glial and meningeal origin, 30.90% were histologically confirmed as metastatic ICTs, from which the most common entries were of pulmonary origin, and the other 2.94% were NVOL. On behalf of their intracranial metastatic location, metastatic tumors were located predominantly in the supratentorial region, represented as a total of 87.80%, while the other 12.20% were located in the subtentorial region. Based on the descriptive analysis, the annual incidence per 100,000 capita of all ICTs is 9.12, comprised of 6.03 per 100,000 for primary ICTs, 2.82 per 100,000 for metastatic ICTs, and 0.27 per 100,000 for NVOL. The annual incidence of the most commonly diagnosed primary ICTs per 100,000 is 2.36 for meningioma, 2.03 for glioblastoma, and 0.48 for pituitary adenoma. The annual incidence of the most commonly diagnosed metastatic ICTs per 100,000 is 1.32 for lung cancer metastases, 0.28 for gastrointestinal tract (GIT) metastases, 0.22 for melanoma, and 0.17 for breast cancer metastases. Conclusion Based on our results, primary ICTs are operated and biopsied more than two times as much as metastatic ICTs and only a small fraction of neurosurgical interventions are undertaken due to NVOL. Metastatic ICTs are predominantly supratentorial with no evidence of a tumor predominantly metastasizing in the subtentorial region. The demographics reported in the study establish some aspects of age and gender preferences, as well as the annual incidence per 100,000 for the most commonly diagnosed types of ICTs in our population., Competing Interests: The authors have declared that no competing interests exist.

Introduction Head and neck cancer (HNC) comprises a diverse group of oncological entities, originating from various tissue types and organ localizations, situated in the topographical regions of the head and neck (H&N). This single institution retrospective study was aimed at establishing the HNC patient demographics and categorizing the individual incidence of H&N malignancies, regarding their organ of origin and main histopathological type. Materials and methods All histologically verified cases of HNC from a single tertiary referral center were reviewed in a descriptive retrospective manner. Data sampling period was 47 months. Results Male to female ratio of the registered HNC cases was 3.24:1. The mean age of diagnosis was 63.84 ± 12.65 years, median 65 years. The most common HNC locations include the larynx 30.37% (n = 188), lips and oral cavity 29.08% (n = 180), pharynx 20.03% (n = 124) and salivary glands 10.94% (n = 68), with other locations such as the external nose, nasal cavity and sinuses and auricle and external ear canal harboring a minority of the cases. The main histopathological groups include squamous cell carcinoma 76.74% (n = 475) and adenocarcinoma 6.14% (n = 38), with other malignant entries such as other epithelial malignancies, primary tonsillar, mucosa-associated lymphoid tissue or parenchymal lymphomas, connective tissue neoplasias, neuroendocrine and vascular malignancies diagnosed in a minority of cases. Conclusion Considered to be relatively rare, HNC represents a diverse group of oncological entities with individual and specific demographic characteristics. The reported single institution results appear representative of the national incidence and characteristics of HNC., Competing Interests: The authors have declared that no competing interests exist.

Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab-lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count-ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0.05). Statistical analysis of the Ki-67 index divid-ed dichotomously into two groups and patient survival revealed that cases with a high Ki-67 index had no significant difference in survival when compared to those with low expression. Conclusions Based on the reported results, the mean Ki-67 percentage of positive nuclei in GBM tumor sam-ples cannot be used to estimate the survival of patients. However, Ki-67 remains a valuable IHC pathological tool., Competing Interests: The authors have declared that no competing interests exist.

Fragile X syndrome is a neuro-developmental disease caused by transcriptional inactivation of the gene FMR1 (fragile X mental retardation 1) and loss of its protein product FMRP. FMRP has multiple neuronal functions which are implemented together with other proteins. To better understand these functions, the aim of this study was to reveal new protein interactors of dFMRP. In a forward genetic screen, we isolated ethyl-metanesulphonate-induced X-chromosomal modifier mutations of dfmr 1. Four of them were identified and belong to the genes: peb/hindsight , rok , shaggy and ras . They are dominant suppressors of the dfmr 1 overexpression wing phenotype 'notched wings'. These mutations dominantly affected the axonal and synaptic morphology of the lateral ventral neurons (LNv's) in adult Drosophila brains. Heterozygotes for each of them displayed effects in the axonal growth, pathfinding, branching and in the synapse formation of these neurons. Double heterozygotes for both dfmr 1-null mutation and for each of the suppressor mutations showed robust genetic interactions in the fly central nervous system. The mutations displayed severe defects in the axonal growth and synapse formation of the LNv's in adult brains. Our biochemical studies showed that neither of the proteins - Rok, Shaggy, Peb/Hnt or Ras - encoded by the four mutated genes regulates the protein level of dFMRP, but dFMRP negatively regulates the protein expression level of Rok in the brain. Altogether, these data suggest that Rok, Shaggy, Peb/Hnt and Ras are functional partners of dFMRP, which are required for correct wing development and for neuronal connectivity in Drosophila brain.