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In December 2019 a newly described single-stranded coronavirus, later named SARS-CoV-2, started its expansion around the world and subsequently caused a global pandemic, affecting the lives of millions of people worldwide. SARS-CoV-2 can bind multiple receptors on different cells and thus invade many target organs, including the respiratory and gastrointestinal mucous membranes, lungs, central nervous system, heart, etc. This virus can affect the kidney tissue both directly and as a consequence of other organ involvement or of the treatment administered, causing acute kidney injury and leaving long term squeals that worsen the prognosis. We describe three patients with acute kidney injury and subsequent acute renal failure at the background of coronaviral infection.

Background: The diagnosis of chronic kidney disease (CKD) is usually delayed, when significant functional renal impairment has already occurred. The diagnosis is complex and clinical and laboratory investigations play a crucial role. There are well-established markers of CKD – serum creatinine and cystatin C. However, the search for new reliable biomarkers that aid in the assessment of kidney function and predict the evolution of the disease is still in progress.

We provide the first known comparative assessment of metazoan parasite communities in two taxonomically and ecologically related sparids, Boops boops and Spicara maena, that are common in the coastal infralittoral habitats in the Mediterranean. Using abundant data for infracommunities in three localities off the Algerian coasts of the Mediterranean, we tested the general prediction that the phylogenetic proximity of the two hosts, their overlapping geographical distribution and habitat occupation, as well as the similar feeding habits and diet would contribute to a homogenization of their parasite community composition and structure. The regional fauna of parasites of B. boops and S. maena along the Algerian coasts of the western Mediterranean was species-rich (36 species) and dominated by heteroxenous species (27 spp; of these 20 digenean spp.). The phylogenetic relatedness between the two hosts resulted in a large number of shared parasites (56 %, 20 spp.). However, the significant overlap in the parasite faunas of the two sparid hosts and their similar feeding habits and diet did not translate into homogeneous parasite community pattern; a significant differentiation in terms of both, composition and structure, was observed.

Copper (Cu) and zinc (Zn) are essential for life. Body Cu and Zn content depends on variety of factors - age, gender, and diet, type of drinking water, geographical location and genetic predisposition. Copper status becomes even more relevant not only in rare genetic disorders such as Wilson disease but in diseases such as cardiovascular ones, impaired glucose tolerance and neuro-degenerative and tumor diseases. The study aimed to examine the distribution of serum Cu and Zn in a representative group of the Bulgarian population and to describe factors which influence metal content. It also aimed to describe the link between serum Cu levels and the frequency of Alzheimer’s disease (AD) in Bulgarians. Cu and Zn in serum were measured in 379 individuals (172 males and 207 females) from 5 different regions in Bulgaria by flame atomic absorption using AAnalyst 400, Perkin Elmer. Statistical analyses were performed by SPSS, 19. Median and inert-quartile range (IQR) for blood Cu were 15.89 (13.87-7.89) μmol/L and for Zn - 13.00 (11.7-14.68) μmol/L in the examined group. Higher Cu levels in females than in males were found (p < 0.001). Decrease of Zn with aging was established (p > 0.05). Significant difference (p < 0.05) was found in serum Cu between young people (< 30 year old) and adults over 61 year old. Statistically significant difference in Cu and Zn was observed (p < 0.05) in respect of residences. Difference without significance was measured between serum lipids and serum Cu (p = 0.541) and Zn (p = 0.741).

Pre-analytical factors of variation need to be carefully considered and investigated in efforts to harmonize all aspects of the total testing process. This study aimed to evaluate contamination and stability in copper (Cu) analysis of serum and urine by flame atomic absorption spectroscopy (FAAS) and to compare the stability of urine Cu in controls and in D-penicillamine (D-PA) administration. Cu was measured by AAnalyst 400, Perkin Elmer, USA. Blood was collected in BD Vacutainer®SSTTM II Advance tubes and BD Vacutainer® Trace Element tubes. Sterile polyethylene and polypropylene vessels for collection, transportation, storage and preliminary preparation of samples were used in urinalysis. Stability in serum and 24 h urine was evaluated in two temperature regimens: 15-25°C and 2-8°C, for particular time of storage. No significant differences (p = 0.20) in Cu concentration was found between the two types of tested tubes with patient`s sera. The stability of the samples (serum and urine) was better at refrigeration temperature. In urine the stability was better in D-PA administration.Standardization of Cu analysis could be achieved by assessing the aspects of pre-analytical factors of variations.

Wilson’s disease is an inherited autosomal recessive disorder of copper balance leading to accumulation of copper mainly in liver and brain result from absent or reduced function of copper-transporting P-type ATPase. Copper is an essential trace element but in Wilson’s disease it accumulate to the point of toxicity. D-penicillamine is a classic drug for treatment of Wilson’s disease. Its major effect is to promote the urinary copper excretion. The use of D-penicillamine in the therapy of Wilson’s disease is known to be complicated by the development of various glomerular diseases. In this report we describe the development of nephrotic syndrome after 2 years treatment with D-penicillamine in a 31-year-old male undergoing treatment for Wilson’s disease, with a prompt regression at the discontinuation of the drug. We present this case to draw attention to the rare complication as nephrotic syndrome in patients with Wilson’s disease under D-penicillamine treatment and possible underlying causes. It is strongly necessary the therapy and clinical condition of patients with Wilson’s disease to be monitoring regularly - we recommended monthly.

Industrial vibrations are the cause of hand-arm vibration syndrome, characterized by a polymorphic clinical picture. The aim of the study is to improve the diagnostics, treatment and prevention of hand-arm vibration syndrome in workers. Material and methods: The object of the study are 65 cases of hand-arm vibration syndrome in workers of enterprises in Northern Bulgaria. The persons were hospitalized in the Department of Occupational Diseases, University Hospital - Pleven in the period 2019 - 2023. The group was related with a length of service of more than 5 years. Clinical, laboratory, functional, imaging and statistical methods were applied. Results and discussion: The impairments of the examined persons are expressed in four clinical syndromes: neurological, vascular, bone-joint-muscular and auditory-vestibular. Socially significant diseases were found in 91% of the examined persons. Conclusions: Hand-arm vibration syndrome is a current health problem for workers in various branches of production in Bulgaria. Damage to persons exposed to long-term (more than 5 years) vibration exposure is manifested by a variety of clinical symptoms, summarized in four main syndromes - neurological, vascular, bone-joint-muscular and auditory-vestibular. Individuals in the first to second and second stages of vibration disease predominate among the studied contingent of workers. Prolonged vibration exposure predisposes to socially significant diseases such as diabetes mellitus, coronary heart disease, arterial hypertension, etc.

The species diversity of the genera Mononchus Bastian, 1865 and Coomansus Jairajpuri & Khan, 1977 was assessed in a study of the mononchid nematodes from a wide range of riparian habitats in Bulgaria. Four species were identified based on morphological and morphometric data: Coomansus parvus (de Man, 1880), Mononchus truncatus Bastian, 1865, Mononchus pseudoaquaticus sp. nov., and Mononchus sp. The first three species were characterised both morphologically and molecularly (18S and 28S rRNA gene sequences) and the integration of these data and phylogenetic analyses provided support for their distinct species status. This paper provides detailed descriptions, morphometric data for multiple species populations, drawings and photomicrographs, and the first taxonomically verified sequences for C. parvus (n = 6), M. truncatus (sensu stricto) (n = 4) and M. pseudoaquaticus sp. nov. (n = 3). Comparative sequence and phylogenetic analyses suggested that the utility of the 18S rRNA gene for species delimitation is rather limited at least for some species complexes within the genus Mononchus. At the generic and suprageneric level, the 18S and 28S rDNA phylogenies both recovered the three genera represented by two or more species (Mononchus, Mylonchulus, and Parkellus) as monophyletic with strong support, the Mononchidae as paraphyletic, the Anatonchidae as monophyletic, and there was no support for a sister-group relationship between Mylonchulus and Mononchus. A key to the species of Mononchus is provided to facilitate the identification of the currently recognised 31 species.

AbstractCytomegalovirus (CMV) infection is widespread and usually asymptomatic in immunocompetent individuals. However, during immune suppression, especially after hematopoietic stem cell transplantation (HSCT), viral reactivation may result in symptomatic infection and end-organ disease. Because there is high incidence of CMV seropositivity in Bulgaria, CMV infection/reactivation is an expected common complication in HSCT recipients which requires frequent monitoring. CMV reactivation monitoring via qRT PCR has a significant role in terms of the moment of initiating pre-emptive therapy in these high-risk patients in order to avoid the development of CMV disease and better clinical management. The aim of this study was to determine and analyze the incidence of CMV reactivation in HSCT recipients in a new transplant center in Bulgaria. The incidence of early CMV reactivation after HSCT in our center is very high (76.7%) most likely related to the high-risk donor/recipient (D/R) profile of our recipients. The mean period from HSCT to the first positive PCR result was quite short, 21.5 days on average. The highest-risk group donor-/recipient+ (D-/R+) experienced the longest and the highest levels of viremia, as well as the highest number of reactivations. The nature of the D/R status most significantly affected the degree of viral load. Our data demonstrate the essential role of monitoring of CMV with reliable and sensitive laboratory methods, such as qRT-PCR to avoid development of CMV disease in high-risk patients.

Abstract. Bulgarian animal husbandry has undergone several transformations since the country's accession to the EU. The declining levels of institutional support in recent years have necessitated the optimization of activities and the rational use of available resources. This requires the introduction of modern digital management methods for livestock farms. The aim of the present study is to assess the digitalization in supply planning for optimization of stocks in animal husbandry. To achieve this goal it is necessary to solve the following tasks: to analyze the problems in the cyclical supply of feed stocks; to study the models for optimization of stocks in animal husbandry; to assess the possibilities for digitalization of the processes of supply and management of feed stocks. The expectations from the research are that digitalization of the processes will optimize the supplies and stocks in animal husbandry, which is a prerequisite for efficiency and continuity of the production process. The results of the study show that consistently optimizing the existing, warranty, and preparatory stock is crucial for enhancing efficiency on any animal husbandry farm. Integrating digital technologies to monitor, analyze, optimize, and schedule these stocks can enhance farm efficiency, mitigate risks, and safeguard the environment.

Garment workers are exposed to various factors in the work environment, classified as physical and ergonomic. Occupational injuries of the spine develop as a result of the action of harmful production factors, the most important of which are overstrain, vibrations and an unfavorable production microclimate. The aim of the study is to improve the health and prevention of spine injuries among garment workers. The subject of the study is 75 cases of spine injuries in garment workers. The persons were hospitalized in University Hospital - Pleven during the period 2019-2023. Clinical, laboratory, functional, imaging and statistical research methods were used. Treatment with medication and physical factors was carried out. In 93% of the patients, an improvement in clinical syndromes and the performance of activities of daily living was found. 7% of the examined persons required surgical treatment. Conclusions: Spinal injuries are a current health problem among garment workers. Combined medication and physical therapy is an effective and practically applicable therapeutic approach for the investigated disabilities.

Chickenpox is often described as a benign disease. However, patients with varicella and coinfection with COVID-19 may develop severe respiratory infection. The interest in the presented case arose from the unusual fast progress of the chickenpox which led to a lethal outcome in a patient with unsuspected COVID-19, proven by PCR after his death. The underlying disease – cancer of the tongue was in remission and wasn’t a cause for immunosuppression which could be a reason for the clinical course of the disease. Aim: To present an interesting case of a 44-year-old man with a previous diagnosis of oral cancer who died after he was diagnosed with varicella and tested positive postmortem for COVID-19. Patient and method: A 44-year-old patient was admitted to the hospital urgently and stayed for 3 and a half hours in the clinic of infectious diseases of UMHAT "St. George", Plovdiv, with a diagnosis of varicella. The patient has accompanying diseases like oral cancer (root of the tongue) and hypertension. Epidemiological data are for contact and fresh infection with varicella, progressing rapidly and beginning of symptoms of respiratory insufficiency and lethal outcome. Due to the fulminant course and the short period of time, the positive PCR result for COVID-19 was proved after the patient died. Conclusions: Unsuspected comorbidity of COVID-19 and varicella without any other reason for immunosuppression could induce unusual severe course of the chickenpox.

Preeclampsia is described as a systemic illness associated with pregnancy. It is characterized by symptoms such as edema, proteinuria (the presence of excess proteins in the urine), hypertension (high blood pressure), and dysfunction. Recent research has extensively investigated the role of oxidative stress in the pathophysiology of preeclampsia. Oxidative stress refers to an imbalance between the production of reactive oxygen species and the body's ability to detoxify them or repair the resulting damage. Despite the research focus on oxidative stress, there is currently no consensus among researchers regarding the mechanisms that lead to the occurrence of preeclampsia in expectant mothers. The present review aims to advance the understanding of the underlying causes of preeclampsia by addressing the main biomarkers of oxidative stress. In summary, preeclampsia is a complex condition associated with pregnancy, and its pathophysiology has been the subject of extensive research, particularly in connection to oxidative stress. However, the lack of agreement among researchers indicates that the exact mechanisms leading to preeclampsia in expectant mothers are still not fully understood and may vary across different studies or perspectives.

Many pathogenic microorganisms can induce a complex series of immunologic, endothelial-cell and cascades activation and dysfunctions. These events induce the development of hypersensitivity vasculitis. Case report: We report the case of 13 years-old girl with hypersensitivity vasculitis, which developed during the course of a mixed infection with beta-hemolytic streptococcus and EBV infection. A month before hospitalization the girl had two episodes of purulent tonsillitis for which she received antibiotic treatment. After a week period without complains she is presented again with high temperature, chills, photophobia, insomnia, muscle pains, maculopapular rash that involves the body and suppurative tonsillitis. In the next days haemorrhagic macules, papules and patches appeared on the face, neck, legs, billateral conjunctival ecchymosis, epistaxis and tonsillar hemorrhage. The medical condition manifests with deteriorated condition of the child, septic fever, generalized lymphadenopathy and hepatosplenomegaly. The clinical presentation is enriched with symptoms of acute nephritic syndrome. There is a history of several tick bites and contact with dogs, without clinical evidence for Erythema migrans. Conclusions: This case is a demonstration of a severe clinical course of Hypersensitivity vasculitis with acute nephritic syndrome as a result of the identified co-infection beta-hemolytic streptococcus and EBV infection. The clinical course is due to the development of complicated pathogenic and immunologic mechanisms. The positive serology for B. Burgdorferi without the presentation of the specific symptoms of Lyme disease is due to cross reaction. Longterm clinical and laboratory follow-up showed complete recovery.

Phospholipases find versatile applications across industries, including detergent production, food modification, pharmaceuticals (especially in drug delivery systems), and cell signaling research. In this study, we present a strain of Bacillus paranthracis for the first time, demonstrating significant potential in the production of phosphatidylcholine-specific phospholipase C (PC-PLC). The investigation thoroughly examines the B. paranthracis PUMB_17 strain, focusing on the activity of PC-PLC and its purification process. Notably, the PUMB_17 strain displays extracellular PC-PLC production with high specific activity during the late exponential growth phase. To unravel the genetic makeup of PUMB_17, we employed nanopore-based whole-genome sequencing and subsequently conducted a detailed genome annotation. The genome comprises a solitary circular chromosome spanning 5,250,970 bp, featuring a guanine–cytosine ratio of 35.49. Additionally, two plasmids of sizes 64,250 bp and 5845 bp were identified. The annotation analysis reveals the presence of 5328 genes, encompassing 5186 protein-coding sequences, and 142 RNA genes, including 39 rRNAs, 103 tRNAs, and 5 ncRNAs. The aim of this study was to make a comprehensive genomic exploration that promises to enhance our understanding of the previously understudied and recently documented capabilities of Bacillus paranthracis and to shed light on a potential use of the strain in the industrial production of PC-PLC.

Objectives and Study: Chronic kidney diseases in childhood are with variable etiology and clinical presentation. The purpose of this study is to investigate the influence of the chronic kidney diseases over the psychical status of these children and their close relatives and to make assessment how the disease intergrades with their neuro-psychological development and quality of life. Methods: 36 children aged from 7-18 with different chronic kidney diseases and a group of 36 adults (their close relatives) are included in the study (gr.A). The control group consists of 36 children with acute kidney diseases and their parents (gr.B). The parents were interviewed after a preliminary conversation and the Zung depression scale was assessed. In children, the EPQ Ayzenk test was performed after a preliminary talk and interview. Psychological tests of the children and adults were performed when the diagnosis was established and in 12-months intervals. Results: In the group of sick children(gr.A) a tendency towards isolation was observed and reduction of contacts. Manifestations of moderate depressive reactions were established in the group of parents when the diagnosis of their child was established.In the course of complex treatment of the chronic kidney disease reduction of parents’ depression was observed. Conclusions: The psychological disturbances are more discreet in children with chronic kidney diseases, while in the group of adults they are more significant to well-expressed. The communication and work of well-trained psychologists with the parents and children would help them to be more adaptive.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered by the lack of human translational models and limitations of analysis techniques for fibrosis. The MASH three-dimensional (3D) InSight™ human liver microtissue (hLiMT) model recapitulates pathophysiological features of the disease. We established an algorithm for automated phenotypic quantification of fibrosis of Sirius Red stained histology sections of MASH hLiMTs model using a digital pathology quantitative single-fiber artificial intelligence (AI) FibroNest™ image analysis platform. The FibroNest™ algorithm for MASH hLiMTs was validated using anti-fibrotic reference compounds with different therapeutic modalities-ALK5i and anti-TGF-β antibody. The phenotypic quantification of fibrosis demonstrated that both reference compounds decreased the deposition of fibrillated collagens in alignment with effects on the secretion of pro-collagen type I/III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-3 and pro-fibrotic gene expression. In contrast, clinical compounds, Firsocostat and Selonsertib, alone and in combination showed strong anti-fibrotic effects on the deposition of collagen fibers, however less pronounced on the secretion of pro-fibrotic biomarkers. In summary, the phenotypic quantification of fibrosis of MASH hLiMTs combined with secretion of pro-fibrotic biomarkers and transcriptomics represents a promising drug discovery tool for assessing anti-fibrotic compounds.

Introduction: Many chronic somatic and psychiatric diseases are associated with oxidative stress and inflammation, both of which have detrimental effects on human health. Aim: To investigate the in vitro antioxidant and in vivo immunomodulatory activities of Satureja montana dry extract. Material and methods: The in vitro antioxidant activity of Satureja montana dry extract was assessed using ORAC, HORAC, and electrochemical methods. Immunomodulatory activity was evaluated in acute and chronic stress models by measuring the serum levels of cytokines TNF-α, IL-6, and IL-1β in a cohort of 112 male 8-week-old Wistar rats. The rats were randomly divided into 7 groups for each of both stress models and then subjected to ELISA analysis (14 groups with 8 rats in each group). The rodents were gavaged with a dry extract of Satureja montana (250 mg/kg and 500 mg/kg), rosmarinic acid (15 mg/kg), and carvacrol (500 mg/kg) for 14 days and 60 days, respectively. Results: We demonstrated that, for all employed in vitro methods, the dried extract of Satureja montana exhibited considerable antioxidant activity. Satureja montana did not significantly lower serum concentrations of TNF-α, IL-6, or IL-1β in either stress model as compared to the positive saline control group. On the other hand, in the acute stress model, a dose of 250 mg/kg of Satureja montana significantly decreased IL-6 in comparison to carvacrol and significantly reduced TNF-α and IL-6 in comparison to rosmarinic acid. Conclusion: Although Satureja montana dry extract has significant antioxidant activity in vitro, its influence on systemic inflammation is still unknown. Future research will look into how it affects serum levels of pro-inflammatory cytokines.

Targeting the inflammation-related molecules with nonsteroidal anti-inflammatory drugs (NSAIDs) represents a promising approach for cancer prevention/therapy. We evaluated the in vitro anticancer effects of meloxicam, lornoxicam, ketoprofen, and dexketoprofen on the proliferation, migration, and apoptosis of human cervical, colorectal, and mammary carcinoma cells. The antiproliferative activity and cytotoxicity of tested NSAIDs on HeLa, HT-29, and MCF-7 cell lines were assessed by the MTT test. The apoptosis-inducing potential was analyzed by fluorescent staining with acridine orange/ethidium bromide and DAPI. Migration activity was assessed by a wound-healing scratch assay. The tested NSAIDs reduced the viability of the used tumor cell lines. The cytomorphological analysis revealed reduced cell density and mitotic activity and the presence of cells with morphological features of early and late apoptosis. Significant inhibition of the migration capacity was established as well. In conclusion, NSAIDs could be candidates for the development of new pharmacological strategies for the treatment and prevention of cancer.

The veterinary medical service in our country has traditions and a history of more than a century. In the twenties of the last century, the geographical position of Bulgaria was assessed, as a potential corridor for the invasion of epizootics and toxic infections from Asia to Europe, from active outbreaks and epizootic diseases (in animals) and zoonoses (in animals and humans) in Asia and the Middle East to Central and Western Europe. This is the reason why the Bulgarian veterinary medical service is expected to organize active anti-epizootic measures, to create a "shield" that would protect both the country and Europe from animal and human infections. The aim of the current paper is to study the possibility of cooperation of privately practicing veterinarians in the country and the benefits of this cooperation in the performance of their functions. The methods that will be used to achieve this goal are analysis and synthesis, induction and deduction, monographic, etc. The expectations of this research are that the cooperation of veterinarians is a prerequisite for better performance of veterinary medical measures to protect the health of animals and people.

Aim: Memory improving and anti-inflammatory properties of cannabidiol (CBD) were investigated in an experimental model of lipopolysaccharide (LPS)-induced inflammation. Materials and methods: Male Wistar rats were randomly divided into 4 groups: control, LPS control, LPS + CBD 5 mg/kg bw, and LPS + CBD 10 mg/kg bw. Animals were treated with CBD 14 days before LPS administration and throughout the experiment. Step-through passive avoidance task, Y-maze, and novel object recognition test (NORT) were used to assess the memory functions. The following parameters were recorded: latency time, spontaneous alternations percentage (SA%) and recognition index (RI). IL-10, IL-6, TNF-α, and IL-1β serum levels were measured to evaluate the immunomodulatory properties of CBD. Results: LPS led to significant decrease of the recorded parameters in all memory tasks. This demonstrated the memory-impairing effect of LPS-induced inflammation. In the Y-maze and NORT tests, both doses of CBD increased SA% and RI, respectively. Significant difference was found in comparison with the LPS controls. Rats from the CBD treated groups showed increased latency in the step-through passive avoidance task. In the short-term memory test, both CBD doses significantly increased this parameter when compared with both control groups (p

Abstract Objectives The study aimed to compare the antibacterial effect of a novel disinfectant, hyper-pure chlorine dioxide (hClO2) to sodium hypochlorite (NaOCl) in various depths of dentin tubules. Materials and methods The distal root of the extracted lower molars was infected artificially with Enterococcus faecalis. The control group was rinsed with saline, and the test groups were irrigated with either 5% NaOCl or 0.12% hClO2. The longitudinally split teeth were stained by viability stain. The coronal third of the root was scanned with a confocal laser scanning microscope. The fluorescent intensities were measured, and the percentage of dead bacteria was calculated at depths up to 950 μm along the dentin tubules. The effect of penetration depth, irrigants, and their interaction on antimicrobial efficacy was determined by the linear mixed model. Results The percentage of dead bacteria was higher both in the NaOCl (45.1 ± 2.3%, p

In the current study, we investigated the effect of creatine monohydrate (CrM) and newly synthesized creatine lysinate (CrLys) in tail suspension (TST) and rotarod tests and their influence on the histology of the skeletal muscles. In the TST, a slight decrease in the immobility time from the 1st to the 3rd week was observed in the group treated with CrM at a dose of 1.5 g/kg/day and CrLys at a dose of 6 g/kg/day. The rotarod test revealed that CrM (1.5 g/kg/day) and CrLys (3 g/kg/day) lead to a significant improvement in motor coordination in the 3rd week. The results from histology showed an increase in the muscle fiber diameter of soleus muscle in animals treated with CrM (3 g/kg/day) and CrLys (6 g/kg/day). The results showed that supplementation with creatine derivatives appears to be a generally effective nutritional ergogenic aid for an improvement of physical performance.

This paper deals with the convergence and dynamics of Chebyshev’s method for simple and multiple zeros of analytic functions. We establish a local convergence theorem that provides error estimates and exact domains of initial approximations to guarantee the Q-cubic convergence of the method right from the first iteration. Applications to some real-world problems as well as theoretical and numerical comparison with the famous Halley’s method are also provided.