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The gut microbiota-immune-brain axis is a feedback network which influences diverse physiological processes and plays a pivotal role in overall health and wellbeing. Although research in humans and laboratory mice has shed light into the associations and mechanisms governing this communication network, evidence of such interactions in wild, especially in young animals, is lacking. We therefore investigated these interactions during early development in a population of common buzzards (Buteo buteo) and their effects on individual condition. In a longitudinal study, we used a multi-marker approach to establish potential links between the bacterial and eukaryotic gut microbiota, a panel of immune assays and feather corticosterone measurements as a proxy for long-term stress. Using Bayesian structural equation modeling, we found no support for feedback between gut microbial diversity and immune or stress parameters. However, we did find strong relationships in the feedback network. Immunity was negatively correlated with corticosterone levels, and microbial diversity was positively associated with nestling body condition. Furthermore, corticosterone levels and eukaryotic microbiota diversity decreased with age while immune activity increased. The absence of conclusive support for the microbiota-immune-brain axis in common buzzard nestlings, coupled with the evidence for stress mediated immunosuppression, suggests a dominating role of stress-dominated maturation of the immune system during early development. Confounding factors inherent to wild systems and developing animals might override associations known from adult laboratory model subjects. The positive association between microbial diversity and body condition indicates the potential health benefits of possessing a diverse and stable microbiota.

Abstract Background Exploring the dynamics of gut microbiome colonisation during early-life stages is important for understanding the potential impact of microbes on host development and fitness. Evidence from model organisms suggests a crucial early-life phase when shifts in gut microbiota can lead to immune dysregulation and reduced host condition. However, our understanding of gut microbiota colonisation in long-lived vertebrates, especially during early development, remains limited. We therefore used a wild population of common buzzard nestlings (Buteo buteo) to investigate connections between the early-life gut microbiota colonisation, environmental and host factors. Results We targeted both bacterial and eukaryotic microbiota using the 16S and 28S rRNA genes. We sampled the individuals during early developmental stages in a longitudinal design. Our data revealed that age significantly affected microbial diversity and composition. Nest environment was a notable predictor of microbiota composition, with particularly eukaryotic communities differing between habitats occupied by the hosts. Nestling condition and infection with the blood parasite Leucocytozoon predicted microbial community composition. Conclusion Our findings emphasise the importance of studying microbiome dynamics to capture changes occurring during ontogeny. They highlight the role of microbial communities in reflecting host health and the importance of the nest environment for the developing nestling microbiome. Overall, this study contributes to understanding the complex interplay between microbial communities, host factors, and environmental variables, and sheds light on the ecological processes governing gut microbial colonisation during early-life stages.

Abstract Background A xanthoma is a rare bone condition consisting of a predominant collection of lipid-rich, foamy histiocytes. The central xanthoma of the jaws is a unique benign tumor. Case report A 15-year-old Caucasian male has been presented to our department. He had radiological changes in the area of the left mandibular angle, with an area of diffuse osteolysis of 3.0 cm by 2.0 cm. Computed tomography reveals an area of diffuse osteolysis that starts from the distal root of the lower second molar and reaches the ascending process. A bone biopsy was performed, which revealed a benign proliferative process composed of histiocytic cells involving and infiltrating trabecular bone in a background of loose fibrous connective tissue devoid of any other significant inflammatory infiltrate. The size of the formation was 2.9 cm by 2.0 cm. Immunohistochemical staining for CD68 was strongly positive and negative for S-100 and CD1a. From routine blood tests, cholesterol, triglycerides, and blood sugar are within normal values, which excludes systemic metabolic disease. Subsequent to the surgical intervention, the patient underwent postoperative assessments at intervals of 14, 30, 60 days, and a year later, revealing the absence of any discernible complications during the aforementioned observation periods. Conclusion The diagnosis of primary xanthoma of the mandible is rare and can often be confused with other histiocytic lesions. A differential diagnosis should be made with nonossifying fibroma and Langerhans cell histiocytosis, as in our case. In these cases, immunohistochemistry with CD 68, S-100, and CD1a, as well as blood parameters, are crucial for the diagnosis.

Introduction. Biliary obstruction is a common manifestation of biliopancreatic malignancies, and its relief is an essential part of the treatment algorithm. Currently, there are three techniques to manage malignant biliary obstruction—endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage (PTBD), and endoscopic ultrasound-guided biliary drainage (EUS-BD). ERCP has been adopted as a first-line treatment modality but EUS-BD is gradually emerging as a viable alternative. The aim of the current article is to assess the clinical outcomes of the three nonsurgical biliary drainage procedures. Materials and methods. A total of 102 consecutive patients with unresectable biliopancreatic malignancy inducing biliary obstruction and subjected to palliative treatment by means of ERCP, EUS-BD, or PTBD were retrospectively included in the study. Results. No difference in clinical and technical success of the procedures was found: ERCP—97.2% technical; 88.9% clinical; PTBD—94.4% technical, 72.2% clinical; EUS-BD—90% technical; 83.3% clinical. Adverse events (AEs) and reinterventions were significantly more common in PTBD (38.9% and 52.8%) and ERCP (27.9% and 25%) compared to EUS-BD (10% and 3.3%). Total duration of hospital stay and number of hospitalizations were lower in the EUS-BD compared to PTBD and ERCP groups. Conclusions. In the presence of adequate expertise, EUS-BD may be superior to PTBD and ERCP in achieving and sustaining biliary drainage in the setting of unresectable malignancy.

Introduction: In the period between 1997 and 2010, sibutramine-containing drugs were widely prescribed for obesity and over-weight management. Due to safety concerns, in 2010 all medicines containing sibutramine were urgently withdrawn from the USA and European pharmaceutical market. Although sibutramine is no longer available in pharmaceutical products, there have been numerous reports of mislabeled weight-loss dietary supplements containing sibutramine. Aim: This work aimed to develop and validate an accurate and sensitive high-performance thin-layer chromatographic method for the detection of sibutramine. Materials and methods: The method was developed using a CAMAG HPTLC system. Silica gel 60 F254 aluminum HPTLC plates were used as stationary phase and toluene:ethyl acetate:methanol (7:2:1 v/v/v) as mobile phase. Results: The calibration curve was built in the range of 0.250–1.250 μg/band. The method provided satisfactory linearity, specificity, precision, and accuracy. The LOD and the LOQ were 0.0765 μg/band and 0.2318 μg/band, respectively. Conclusions: The method allows for the simultaneous analysis of multiple samples as well as the rapid and sensitive monitoring of sibutramine levels in dietary supplements.

The Wildlife Malaria Network (WIMANET) is a groundbreaking multinational collaboration focused on studying vector-borne haemosporidian parasites in wildlife. Unlike human malaria, wildlife malaria is found on all continents except Antarctica, with parasites being transmitted by a range of vectors. The complexity and diversity of these parasites makes it necessary to have an interdisciplinary approach to understand and mitigate their impacts. Established in 2023 within the framework of COST-Action (European Cooperation in Science and Technology), WIMANET unites researchers from diverse scientific backgrounds to tackle critical questions about wildlife malaria on a global scale. This meeting report summarises the activities and plans resulting from the 1st meeting of WIMANET's six working groups, spanning the genetic and morphological identification of parasites to understanding the drivers of host-parasite-vector associations from individual to community levels. WIMANET's collaborative efforts aim to fill the knowledge gaps and foster large-scale research initiatives transcending local and regional boundaries.

Blood parasites of the genus Leucocytozoon commonly infect many bird species worldwide and are particularly prevalent in birds of prey. As a vector-borne parasitic disease, the infection occurrence overlaps with that of the dominant vectors: blackflies (Diptera, Simuliidae). These blood-sucking insects are dependent on habitats with flowing freshwaters for the development of their larval stages. We investigated the correlation between the proximity to flowing waters and Leucocytozoon infection probability in common buzzard (Buteo buteo) broods, as well as the occurrence of adult blackflies directly at the nests. In addition, we investigated the survival of captured simuliids in relation to host infection intensity. In total in 2019, we examined 112 different nests, including 297 common buzzard nestlings, with a Leucocytozoon prevalence of 56.6% among the nestlings and of 80.3% at brood level. We found no significant association of Leucocytozoon infection probability with nestling age, the distance to the nearest stream and the sum of the length of streams within a radius of 200 and 1000 m around each nest. The number of blackflies caught around the nest showed a tentative correlation with the probability of Leucocyozoon infection of the nestlings. Among the subsample of 218 blackfly individuals that survived day one after capture, survival averaged 6.2 days. Our results suggest that Leucocytozoon transmission is complex and requires consideration of many factors, related to habitat and vector prevalence, especially given their temporal variation.

This review aims to reveal and summarize the advantages and disadvantages of culture-dependent and culture-independent methods for identifying and characterizing the microbiota of artisanal regional varieties of cheese and the health benefits of these kinds of cheese as a functional food. With the rise of metagenomics studies, the focus is now on using these techniques to explore the genetic diversity in different types of cheese, identifying both known and novel microorganisms. Based on literature data, in addition to the possible roles of microorganisms included in artisanal dairy products on cheese ripening, the health-promoting effects of these bacteria are highlighted as well. The analysis of the literature data available so far showed that metagenomic analysis would allow for obtaining more accurate and rapid results. In addition, cheese microbiota and microbial interactions play an essential role in acidification and flavour development in cheese. The production of microbial bioactive compounds, their role in inhibiting pathogens and spoilage agents, and the probiotic potential are also discussed.

Introduction: Schönlein-Henoch disease is a small vessel vasculitis resulting from IgA-mediated inflammation. It is the most common acute systemic vasculitis in childhood, mainly affecting the skin, gastrointestinal tract, joints, and kidneys. Although the prognosis of Schönlein-Henoch is generally good, gastrointestinal tract involvement is a potential complication, presenting as massive gastrointestinal bleeding, bowel infarction, perforation, as well as intussusception and peritonitis. Aim: In everyday clinical practice, determining markers of gastrointestinal tract involvement is critical when the initial or only available symptoms are related to it. Ultrasound diagnosis is effective as a first-line screening method in children with Schönlein-Henoch purpura and abdominal involvement, in order to objectivize changes in the small intestinal wall, such as thickening, disturbance of its stratification, and intramural bleeding. Materials and methods: Since, until recently, the generally accepted concept that there are neither coagulation disorders nor changes in the small intestinal wall’s ultrasound examination has limited our understanding of the essence of Schönlein-Henoch disease, we looked for more trustworthy indicators. Results: These indicators, such as factor XIII and von Willebrand factor-associated antigen, showed significant deviations from the reference ranges in our study of patients with abdominal pain who had Schönlein-Henoch disease. Conclusions: In conclusion, early assessment of altered coagulation factors f. XIII and vWF:Ag and ultrasound monitoring of changes in the small bowel wall proved to be a valid criterion for therapeutic accuracy as well as avoiding surgical complications.

Two subspecies of Saker Falcon are commonly accepted - Western (Falco cherrug cherrug) and Eastern (Falco cherrug milvipes), which are differentiated by their distribution range and phenotype. In Bulgaria, Western Saker Falcons are breeding ex situ in the Wildlife Rehabilitation and Breeding Centre, part of Green Balkans - Stara Zagora NGO, with the aim of restoring the nesting population of the species in the country and both Western and Eastern - in the Breeding Centre for Birds of Prey in Burgas for the purpose of sale for the needs of falconry in the country and abroad. In 2021, a total of 115 birds from the two breeding centres were sampled. The samples were analysed in Bielefeld University (Germany) at nine microsatellite loci. Structure analyses were performed to establish the optimal explanatory number of groups. We compared the putative genetic groups with the known/expected origin of falcons. A separation in two groups best explained the allelic variation between samples. Out of 68 Saker Falcons with putatively Eastern origin, 66 were ascribed to genetic group 2 and two falcons had unclear, mixed or hybrid genetic fingerprints. Out of 42 Sakers with putatively Western origin, 33 were ascribed to genetic group 1, seven to genetic group 2 and two individuals appeared to have a mixed signature of genetic groups 1 and 2 with dominating alleles of group 2. Five known hybrids were scored as mixed signature with dominating genetic cluster 2. This suggests that the two (Eastern and Western) populations of Saker Falcon origin suggested by the subspecies' definitions are also adequate to be considered in breeding programmes. Genetic cluster 1 might represent the ancestral alleles shared with other falcons, while specific novel alleles allow the discrimination of secured Eastern Sakers (group 2), while these populations may be occasionally invaded by individuals from the west.

Urachal adenocarcinomas, constituting 10 % of bladder adenocarcinomas, pose a significant challenge with limited literature. A 43-year-old male presented with haematuria and abdominal pain, leading to surgical intervention for a 13 cm pelvic tumor. Histopathology identified an intestinal-type primary urachal adenocarcinoma, staged as IIIA, no recurrence on follow-up. Early detection is crucial for improved outcomes in these rare malignancies. While surgery remains the primary treatment, outcomes vary, emphasizing the need for research on standardized protocols. Enhanced awareness and interdisciplinary collaboration are vital for effective management. Comprehensive guidelines are essential for optimizing patient prognoses in urachal adenocarcinomas.

Abstract Background Ankylosing spondylitis (AS) and Behçet's disease (BD) are distinct inflammatory disorders, but their coexistence is a rare clinical entity. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors. Case Presentation A 42‐year‐old woman presented with a decade‐long history of lower back pain, nocturnal spinal discomfort, recurrent eye issues, oral and genital ulcers, hearing loss, pus formation in the left eye, and abdominal pain. Multidisciplinary consultations and diagnostic tests confirmed AS (HLA‐B27 positivity and sacroiliitis) and BD (HLA‐B51). Elevated acute‐phase markers were observed. Conclusion This case fulfills diagnostic criteria for both AS and BD, emphasizing their coexistence. Notably, treatment with upadacitinib exhibited promising efficacy, underscoring its potential as a therapeutic option in patients with contraindications for conventional treatments. Our findings illuminate the intricate management of patients presenting with these two diverse systemic conditions and advocate for further exploration of JAK inhibitors in similar cases.

IntroductionBottleneck events are crucial for the strength of genetic drift, selection and speed of evolution. They are believed to play a particularly prominent role for parasitic infrapopulations, inhabiting single host individuals, which are often established by very few parasite individuals during transmission. In vector-borne pathogens, the bottlenecking effects can even be serialized through repeated filtering of parasitic stages at different tissues and organs of the vector. Using qPCR we aimed to quantify the number of potentially transmittable sporozoites of the hemosporidian blood parasite Haemoproteus columbae in the specialized vector louse flies Pseudolynchia canariensis which transmit these parasites between house pigeon hosts Columba livia.ResultsBased on qPCR measurements of organ-derived DNA of individual louse flies, we estimate that the midgut of these vectors contains on average 20 parasites, the hindgut and other intestines ca. 50 parasites and the salivary glands ca. 5 parasite cells. Nearly one third of all vector individuals appeared to lack parasite DNA, despite having only infected hosts as blood meal sources. The magnitude of parasite numbers in midgut and salivary glands tended to correlate positively.DiscussionOur results indicate, potential severe bottlenecking of parasite populations during individual transmission events and a probable effect of individual vector immunity on this variable. However, this may be partly alleviated by the coloniality of house pigeons, the frequency of louse flies and their daily feeding events in most populations, leading to repeated transmission opportunities, decreased quasi-vertical transmission between parents and offspring and probable panmixia of Haemoproteus columbae lineages. Many of these mechanisms might not apply in other host-vector systems. We propose several additional molecular and microscopical tools to improve the accuracy of estimating parasite population sizes in vectors and call for more estimations in different vector species to better understand the co-evolution between malaria-like blood parasites and their avian and insect hosts.

The discovery of new peptides and their derivatives is an outcome of ongoing efforts to identify a peptide with significant biological activity for effective usage as a possible therapeutic agent. Spinorphin peptides have been documented to exhibit numerous applications and features. In this study, biologically active peptide derivatives based on novel peptide analogues of spinorphin conjugated with 5,5′-dimethyl (Dm) and 5,5′-diphenyl (Ph) hydantoin derivatives have been successfully synthesized and characterized. Scanning electron microscopy (SEM) and spectral methods such as UV-Vis, FT-IR (Fourier Transform Infrared Spectroscopy), CD (Circular Dichroism), and fluorimetry were used to characterize the microstructure of the resulting compounds. The results revealed changes in peptide morphology as a result of the restructuring of the aminoacidic sequences and aromatic bonds, which is related to the formation of intermolecular hydrogen bonds between tyrosyl groups and the hydantoin moiety. Electrochemical and fluorescence approaches were used to determine some physicochemical parameters related to the biological behavior of the compounds. The biological properties of the spinorphin derivatives were evaluated in vivo for anticonvulsant activity against the psychomotor seizures at different doses of the studied peptides. Both spinorphin analog peptides with Ph and Dm groups showed activity against all three phases of the seizure in the intravenous Pentylenetetrazole Seizure (ivPTZ) test. This suggests that hydantoin residues do not play a crucial role in the structure of spinorphin compounds and in determining the potency to raise the seizure threshold. On the other hand, analogs with a phenytoin residue are active against the drug-resistant epilepsy test (6-Hz test). In addition, bioactivity analyses revealed that the new peptide analogues have the potential to be used as antimicrobial and antioxidant compounds. These findings suggest promising avenues for further research that may lead to the development of alternative medicines or applications in various fields beyond epilepsy treatment.

The globally endangered saker falcon (Falco cherrug) is currently being re-introduced in Bulgaria, where the falcons are bred in captivity and released through the hacking method. We relied on the birds’ pedigree when forming the breeding pairs from 2011. In 2021-2022, we had the opportunity to evaluate our captive population via DNA tests. We performed the first genetic assessment of the sakers in the WRBC through a genome evaluation of the most important founders (n = 12) and, in 2022, we executed a microsatellite analysis on 30 saker falcons from the programme. We compared the results with the known pedigree and history of the saker falcons. The genetic tests helped to assign relatedness to some birds with missing or incomplete pedigrees, indicating the test can complement that information and lead to better management of the captive group. One pair was separated as a precaution as it was indicated by one the tests that the two birds are more closely related than expected. The research could be beneficial to other raptor captive breeding programmes dealing with a similar group composition.

Abstract Background The major histocompatibility complex (MHC), which encodes molecules that recognize various pathogens and parasites and initiates the adaptive immune response in vertebrates, is renowned for its exceptional polymorphism and is a model of adaptive gene evolution. In birds, the number of MHC genes and sequence diversity varies greatly among taxa, believed due to evolutionary history and differential selection pressures. Earlier characterization studies and recent comparative studies suggest that non-passerine species have relatively few MHC gene copies compared to passerines. Additionally, comparative studies that have looked at partial MHC sequences have speculated that non-passerines have opposite patterns of selection on MHC class I (MHC-I) and class II (MHC-II) loci than passerines: namely, greater sequence diversity and signals of selection on MHC-II than MHC-I. However, new sequencing technology is revealing much greater MHC variation than previously expected while also facilitating full sequence variant detection directly from genomic data. Our study aims to take advantage of high-throughput sequencing methods to fully characterize both classes and domains of MHC of a non-passerine bird of prey, the common buzzard (Buteo buteo), to test predictions of MHC variation and differential selection on MHC classes. Results Using genetic, genomic, and transcriptomic high-throughput sequencing data, we established common buzzards have at least three loci that produce functional alleles at both MHC classes. In total, we characterize 91 alleles from 113 common buzzard chicks for MHC-I exon 3 and 41 alleles from 125 chicks for MHC-IIB exon 2. Among these alleles, we found greater sequence polymorphism and stronger diversifying selection at MHC-IIB exon 2 than MHC-I exon 3, suggesting differential selection pressures on MHC classes. However, upon further investigation of the entire peptide-binding groove by including genomic data from MHC-I exon 2 and MHC-IIA exon 2, this turned out to be false. MHC-I exon 2 was as polymorphic as MHC-IIB exon 2 and MHC-IIA exon 2 was essentially invariant. Thus, comparisons between MHC-I and MHC-II that included both domains of the peptide-binding groove showed no differences in polymorphism nor diversifying selection between the classes. Nevertheless, selection analysis indicates balancing selection has been acting on common buzzard MHC and phylogenetic inference revealed that trans-species polymorphism is present between common buzzards and species separated for over 33 million years for class I and class II. Conclusions We characterize and confirm the functionality of unexpectedly high copy number and allelic diversity in both MHC classes of a bird of prey. While balancing selection is acting on both classes, there is no evidence of differential selection pressure on MHC classes in common buzzards and this result may hold more generally once more data for understudied MHC exons becomes available.

Endosymbiotic organelles, such as mitochondria and plastids, contain own remnant genomes (nucleoids), whose variable abundance in cells may be adaptive to the physiological necessities and functions of the cells. Unicellular apicomplexan parasites contain one mitochondrium and one apicoplast with variable genome copy numbers. We measured the abundance of mitochondrial, apicoplast and nuclear genome copies in a set of avian blood samples infected with haemosporidian blood parasites, belonging to the three main genera Plasmodium, Haemoproteus and Leucocytozoon. We designed general primers suitable for qPCR, amplifying fragments of the mitogenome, plastome and nuclear genomes of avian malaria and related haemosporidian parasites. We measured the amplification of these fragments in 153 samples of 23 avian host species and infected with 33 parasitic lineages. We estimate on average several hundred mitochondrial genome copies and several tens of apicoplast copies per haploid gametocyte cell with substantial variation among samples. Host species appeared to differ in their mitogenome abundance while parasitic lineages differed in plastome abundance per cell (per nuclear copy signal). We did not find consistent differences between parasite genera or higher avian taxa. Parasite lineages and host bird species did not differ consistently in infection intensity, estimated from parasite to host nuclear signals, which may indicate that samples were taken at different stages of infection. However, this and similar results remain to be cross-validated with in-situ imaging techniques. The novel molecular tools introduced here offer avenues for the characterization of nucleoid abundance of haemosporidian parasites over environmental conditions and parasitic developmental stages. Such measures will improve our understanding of parasite physiology, ecology, the coadaptation and coevolution with hosts and suggest possible augmentations to standard methods in the research field.

Introduction: Descending necrotizing mediastinitis is one of the most lethal forms of acute mediastinitis. It originates from an odontogenic or deep neck infection, which descends to the mediastinum through the fascial planes. It is a rare condition, but mortality rates remain high, especially in the presence of comorbidities or predisposing factors. Delay in diagnosis has been shown to be one of the most important factors for the disease outcome. Therefore, early diagnosis and treatment by a multidisciplinary team are of utmost importance. Case series: Four healthy young males with descending necrotizing mediastinitis were treated at our institution. None of them had any comorbidities, but all of them waited between 3 and 4 days before seeking medical help. Upon their arrival at the hospital, in addition to the presence of a severe neck infection, the presence of mediastinitis was also found. Despite the timely surgical treatment of both the source of the infection and the mediastinitis, three of the four cases had a fatal outcome. Conclusion: We believe that the time factor is of greater importance for the outcome of acute descending mediastinitis than the factors of age and presence of accompanying diseases. Proper and rapid treatment by a multidisciplinary team is essential, even for young and healthy people.

Background and objectives: This review aims to delve into the role of artificial intelligence in medicine. Ulcerative colitis (UC) is a chronic, inflammatory bowel disease (IBD) characterized by superficial mucosal inflammation, rectal bleeding, diarrhoea and abdominal pain. By identifying the challenges inherent in UC diagnosis, we seek to highlight the potential impact of artificial intelligence on enhancing both diagnosis and treatment methodologies for this condition. Method: A targeted, non-systematic review of literature relating to ulcerative colitis was undertaken. The PubMed and Scopus databases were searched to categorize a well-rounded understanding of the field of artificial intelligence and its developing role in the diagnosis and treatment of ulcerative colitis. Articles that were thought to be relevant were included. This paper only included articles published in English. Results: Artificial intelligence (AI) refers to computer algorithms capable of learning, problem solving and decision-making. Throughout our review, we highlighted the role and importance of artificial intelligence in modern medicine, emphasizing its role in diagnosis through AI-assisted endoscopies and histology analysis and its enhancements in the treatment of ulcerative colitis. Despite these advances, AI is still hindered due to its current lack of adaptability to real-world scenarios and its difficulty in widespread data availability, which hinders the growth of AI-led data analysis. Conclusions: When considering the potential of artificial intelligence, its ability to enhance patient care from a diagnostic and therapeutic perspective shows signs of promise. For the true utilization of artificial intelligence, some roadblocks must be addressed. The datasets available to AI may not truly reflect the real-world, which would prevent its impact in all clinical scenarios when dealing with a spectrum of patients with different backgrounds and presenting factors. Considering this, the shift in medical diagnostics and therapeutics is coinciding with evolving technology. With a continuous advancement in artificial intelligence programming and a perpetual surge in patient datasets, these networks can be further enhanced and supplemented with a greater cohort, enabling better outcomes and prediction models for the future of modern medicine.

The naturally occurring compounds ecdysterone and turkesterone, which are present in plants, including Rhaponticum carthamoides Willd. (Iljin), Spinacia oleracea L., Chenopodium quinoa Willd., and Ajuga turkestanica (Regel) Briq, are widely recognized due to their possible advantages for both general health and athletic performance. The current review investigates the beneficial biological effects of ecdysterone and turkesterone in nutrition, highlighting their roles not only in enhancing athletic performance but also in the management of various health problems. Plant-based diets, associated with various health benefits and environmental sustainability, often include sources rich in phytoecdysteroids. However, the therapeutic potential of phytoecdysteroid-rich extracts extends beyond sports nutrition, with promising applications in treating chronic fatigue, cardiovascular diseases, and neurodegenerative disorders.

Background: The aim of this review is to explore the role of artificial intelligence in the diagnosis of colorectal cancer, how it impacts CRC morbidity and mortality, and why its role in clinical medicine is limited. Methods: A targeted, non-systematic review of the published literature relating to colorectal cancer diagnosis was performed with PubMed databases that were scouted to help provide a more defined understanding of the recent advances regarding artificial intelligence and their impact on colorectal-related morbidity and mortality. Articles were included if deemed relevant and including information associated with the keywords. Results: The advancements in artificial intelligence have been significant in facilitating an earlier diagnosis of CRC. In this review, we focused on evaluating genomic biomarkers, the integration of instruments with artificial intelligence, MR and hyperspectral imaging, and the architecture of neural networks. We found that these neural networks seem practical and yield positive results in initial testing. Furthermore, we explored the use of deep-learning-based majority voting methods, such as bag of words and PAHLI, in improving diagnostic accuracy in colorectal cancer detection. Alongside this, the autonomous and expansive learning ability of artificial intelligence, coupled with its ability to extract increasingly complex features from images or videos without human reliance, highlight its impact in the diagnostic sector. Despite this, as most of the research involves a small sample of patients, a diversification of patient data is needed to enhance cohort stratification for a more sensitive and specific neural model. We also examined the successful application of artificial intelligence in predicting microsatellite instability, showcasing its potential in stratifying patients for targeted therapies. Conclusions: Since its commencement in colorectal cancer, artificial intelligence has revealed a multitude of functionalities and augmentations in the diagnostic sector of CRC. Given its early implementation, its clinical application remains a fair way away, but with steady research dedicated to improving neural architecture and expanding its applicational range, there is hope that these advanced neural software could directly impact the early diagnosis of CRC. The true promise of artificial intelligence, extending beyond the medical sector, lies in its potential to significantly influence the future landscape of CRC’s morbidity and mortality.

AbstractThe number of stem cell lines worldwide grows steadily, including disease-specific lines and lines derived from specific tissues. The proportion of stem cell lines that were established in strictly xeno-free conditions is rapidly increasing, but it is still unclear whether these lines may be maintained in vitro for prolonged periods of time with satisfactory survival rates and minimal loss of their ‘stemness’ properties. The efficiency of repair of DNA damage has recently emerged as an important factor for maintenance of stem cells in culture with minimal genomic changes and preservation of the undifferentiated state. In this study we investigated the individual capacity for repair of DNA damage/maintenance of genomic integrity and additional markers in one human embryonic stem cell (hESC) line derived in Bulgaria from a discarded embryo and two of the human T-leukaemia cell lines commonly used for research purposes (T-1301 and Jurkat E6-1). Knowledge about the status of the studied cancer cell lines may be valuable for research purposes. Data about the individual repair capacity and the genetic risk for common late-onset diseases of newly established hESC lines as well as hESC lines currently in use may become a valuable tool in the assessment of the applicability of pluripotent human cell lines for research purposes, clinical trials and, potentially, clinical applications.

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs’ diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

Avian haemosporidian parasites (order Haemosporida, phylum Apicomplexa) are blood and tissue parasites transmitted by blood-sucking dipteran insects. Three genera (Plasmodium, Haemoproteus and Leucocytozoon) have been most often found in birds, with over 270 species described and named in avian hosts based mainly on the morphological characters of blood stages. A broad diversity of Haemoproteus parasites remains to be identified and characterized morphologically and molecularly, especially those infecting birds of prey, an underrepresented bird group in haemosporidian parasite studies. The aim of this study was to investigate and identify Haemoproteus parasites from a large sample comprising accipitriform raptors of 16 species combining morphological and new molecular protocols targeting the cytb genes of this parasite group. This study provides morphological descriptions and molecular characterizations of two Haemoproteus species, H. multivacuolatus n. sp. and H. nisi Peirce and Marquiss, 1983. Haemoproteus parasites of this group were so far found in accipitriform raptors only and might be classified into a separate subgenus or even genus. Cytb sequences of these parasites diverge by more than 15% from those of all others known avian haemosporidian genera and form a unique phylogenetic clade. This study underlines the importance of developing new diagnostic tools to detect molecularly highly divergent parasites that might be undetectable by commonly used conventional tools.

Leucocytozoonosis is a vector-borne infection of birds, caused by members of the haemosporidian genus Leucocytozoon. The clinical presentation may range from asymptomatic to severe disease. Consequences of Leucocytozoon infection on blood profiles remain to be described, especially for different host species in the wild. In the current study, the prevalence of Leucocytozoon infection was determined in wild nestlings of three European raptor species, the common buzzard (Buteo buteo, n = 464), red kite (Milvus milvus, n = 46) and northern goshawk (Accipiter gentilis, n = 18). Among 528 nestlings, 51.9% (n = 274) were infected with Leucocytozoon spp., whereby the highest prevalence was found in common buzzards (54.9%), followed by red kites (32.6%) and northern goshawks (22.2%). For a subset of 87 individuals (50 common buzzards, 29 red kites, 8 northern goshawks), a detailed analysis of differential leukocyte counts and several blood chemistry parameters in response to infection was conducted: AP (alkaline phosphatase), AST (aspartate aminotransferase), GLDH (glutamate dehydrogenase), LDH (lactate dehydrogenase), GGT (gamma glutamyl transferase), CK (creatine kinase), BuChE (butyrylcholinesterase), BA (bile acids), ALB (albumin) and TP (total protein). Even though in the physiological range, infected nestlings displayed significantly increased levels of heterophils, aspartate aminotransferase, lactate dehydrogenase, bile acids and butyrylcholinesterase, but decreased lymphocyte and monocyte values compared to uninfected ones. Furthermore, significant species differences with regard to blood parameters, but no sex differences were found. Overall, obtained results show a high prevalence, but a low pathogenicity of Leucocytozoon spp. in wild raptor chicks, presumably resulting from coevolutionary adaptation, but show signatures of infection in the haematological and blood chemistry profiles.

The general aim of the project is to enhance our knowledge of Nicopolis ad Istrum city plan outside of the fortification wall. At present the immediate surroundings of the Roman civitas are under meadows. Thus geophysical survey is one of the most extensive ways to investigate the extramural urban planning. The total area covered by geomagnetic survey in 2021 is 9.09 ha (101 quadrants of the square grid), while the resistivity survey was conducted over 1.11 ha. The surveyed areas are on the two banks of the Nikyupsko dere Creek, to the northwest and to the north of the Roman city. Not all of the registered anomalies are clear for interpretation due to the character of the building materials used in Antiquity, the search and extraction of spolia, and the depth of the structures. Potential pottery kilns and workshops have been registered along the creek. Extramural continuations of streets, or cardines and decumani cut off by the fortification wall (built circa 175 AD) from the initial urban planning, are visible in the geophysics results. Building foundations have also been registered. In addition to the Western aqueduct, information from previous field surveys suggests two more northwestern aqueducts that supplied the city with water. Some of the registered anomalies could be identified with one of those structures.

The area of Coastal Dobrudzha in NE Bulgaria is well known for its richness of vagrants. A long-term research project was started at a location at Durankulak Lake, on the northern Black Sea Coast, aiming to obtain data on the characteristics of autumn migration of passerine birds and on the presence of vagrants there. A total of 20 mist nets with an overall length of 200 meters were set between August and October in two different habitats - reed bed and broad-leaved forest. In 2019, a total of 9344 birds of 84 species were caught and ringed. In 2020, the number of the birds caught increased to 13786 of 93 species. Vagrants such as dusky warbler (Phylloscopus fuscatus), yellow-browed warbler (Phylloscopus inornatus) and red-flanked bluetail (Tarsiger cyanurus) were captured in 2020. Detailed information about these findings is given in the present work.

Abstract Background The feeding behavior of bloodsucking insects determines the transmission, distribution, host spectrum and evolution of blood parasites in the wild. Conventional wisdom suggests that some vector groups (e.g. black flies, family Simuliidae) are consistently exophagous daytime biters. We aimed to understand more about the exceptions to this pattern by combining targeted trapping and molecular identification of parasites in vectors. Methods In this study, we collected black flies in nest boxes used by European rollers Coracias garrulus in southeastern Spain. We molecularly analyzed 434 individual insects, identifying the black fly species caught in the nest boxes, their potential vertebrate blood meals, and the haemosporidian parasite lineages that they carried. Results Only one black fly species, Simulium rubzovianum, appeared to enter the nest boxes of rollers. Among the trapped specimens, 15% contained vertebrate DNA, which always belonged to rollers, even though only half of those specimens were visibly engorged. Furthermore, 15% of all black flies contained Leucocytozoon lineages, indicating previous feeding on avian hosts but probably not on infected adult rollers. The known vertebrate hosts of the recorded Leucocytozoon lineages suggested that large and/or abundant birds are their hosts. Particularly represented were cavity-nesting species breeding in the vicinity, such as pigeons, corvids and owls. Open-nesting species such as thrushes and birds of prey were also represented. Conclusions Our data strongly suggest that S. rubzovianum bites uninfected roller nestlings and infected individuals of other species, potentially incubating adults, inside nest boxes and natural cavities. This simuliid does not appear to have a strong preference for specific host clades. Contrary to the general pattern for the group, and possibly enhanced by the harsh environmental conditions in the study area, this black fly appeared to intensively use and may even have a preference for confined spaces such as cavities for feeding and resting. Preferences of vectors for atypical microhabitat niches where hosts are less mobile may enable social and within-family transmission and parasite speciation in the long term. At the same time, a lack of host preference in concentrated multispecies communities can lead to host switches. Both processes may be underappreciated driving forces in the evolution of avian blood parasites. Graphical abstract

The Schӧnlein-Henoch vasculitis is an IgA-mediated inflammation of small vessels. The main clinical manifestation is palpable purpura without thrombocytopenia, manifested by bilateral symmetrical distribution on both lower limbs, abdominal pain, often accompanied by blood in the stools, hematuria with / or without proteinuria. Historically, the disease has been known since 1832. In Bulgaria, although that later HenochSchӧnlein purpura (HSP) aroused scientific interest, several publications focused on the pathogenic nature, clinical variations, and potential complications of the disease, as well as options for therapeutic intervention. Modern knowledge about the etiology and pathogenesis of the disease has given new light, respectively a basis for early diagnosis, reduction of complications and recurrences, as well as the avoidance of polypragmatism. It turned out that in HSP there are genetic factors and new aspects, binding until now accepted concept that there are no changes in the coagulation system. The role of factor XIII, as a prognostic indicator of the severity of clinical manifestations and von Willebrand factor (vWF), as a reliable index of the degree of vascular wall damage, has been demonstrated. Plasma imbalance in the Th1 / Th2 ratio was also found and a percentage of NK cells, respectively their immune function, were reduced. This new knowledge about the pathogenic nature of HSP is the basis for a change in the concept of therapeutic behavior, which is aimed at the severity of the clinical course, and not only at the treatment of the disease, which is itself symptomatic.

Summary: Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression. In adulthood, monocyte recruitment dominates adrenal gland macrophage maintenance in female mice. Adrenal gland macrophage sub-tissular distribution follows a sex-dimorphic pattern, with MHC class IIlow macrophages located at the cortico-medullary junction. Macrophage sex dimorphism depends on the presence of the cortical X-zone. Adrenal gland macrophage depletion results in altered tissue homeostasis, modulated lipid metabolism, and decreased local aldosterone production during stress exposure. Overall, these data reveal the heterogeneity of adrenal gland macrophages and point toward sex-restricted distribution and functions of these cells.

First encountered in the 2019 COVID-19 virus has a high transmission capacity, and children are not spared. Therefore, we set a goal, referring to the experience of the countries in which the infection spread the earliest and widest, to make a summary of the characteristics of COVID-19 in the pediatric population. Of course, the most significant thing is the variation in the clinical manifestation, the correct assessment of the clinical risk of lung damage, as well as the laboratory and imaging methods of examination that support a reliable diagnosis. The therapy section of the article describes all the possible strategies for therapeutic behavior. Despite the rapidly growing theoretical information and shared clinical experience, the article could be a foundation on which to add and expand theoretical and practical knowledge.

Abstract Background The behaviour of blood-sucking arthropods is a crucial determinant of blood protozoan distribution and hence of host-parasite coevolution, but it is very challenging to study in the wild. The molecular identification of parasite lineages in vectors can be a useful key to understand the behaviour and transmission patterns realised by these vectors. Methods In this study, we collected blackflies around nests of three raptor species in the upper forest canopy in central Europe and examined the presence of vertebrate DNA and haemosporidian parasites in them. We molecularly analysed 156 blackfly individuals, their vertebrate blood meals, and the haemosporidian parasite lineages they carried. Results We identified nine species of Simulium blackflies, largely belonging to the subgenera Nevermannia and Eusimulium. Only 1% of the collected specimens was visibly engorged, and only 4% contained remains of host DNA. However, in 29% of the blackflies Leucocytozoon lineages were identified, which is evidence of a previous blood meal on an avian host. Based on the known vertebrate hosts of the recorded Leucocytozoon lineages, we can infer that large and/or abundant birds, such as thrushes, crows, pigeons, birds of prey, owls and tits are the main targets of ornithophilic blackflies in the canopy. Blackfly species contained similar proportions of host group-specific parasite lineages and thus do not appear to be associated with particular host groups. Conclusions The Leucocytozoon clade infecting thrushes, crows, and pigeons present in most represented blackfly species suggests a lack of association between hosts and blackflies, which can increase the probability of host switches of blood parasites. However, the composition of the simuliid species differed between nests of common buzzards, goshawks and red kites. This segregation can be explained by coinciding habitat preferences between host and vector, and may lead to the fast speciation of Leucocytozoon parasites. Thus, subtle ecological preferences and lack of host preference of vectors in the canopy may enable both parasite diversification and host switches, and enforce a habitat-dependent evolution of avian malaria parasites and related haemosporidia.