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Kawasaki disease (KD) is an acute systemic vasculitis that affects medium-sized vessels, particularly the coronary arteries. KD predominantly affects children under 5 years of age. Main symptoms include fever, bilateral conjunctivitis, polymorphous exanthema, oropharyngeal mucous membranes changes, palmar and/or plantar erythema and edema, and cervical lymphadenopathy. KD can present with a few clinical features, which might lead to a delayed diagnosis, particularly in infants. When the therapy is delayed, the diagnosis is missed or in refractory cases, there is a higher risk of coronary artery aneurysms to be formed. We report a clinical case of a 3-month-old male who presented initially with fever and cervical lymphadenopathy in whom a bacterial infection was suspected and treatment with antibiotics was started. In the course of the disease erythema of the palms and soles and generalized erythematous rash developed. The diagnosis of KD was made on the 11th day of onset of symptoms and despite the treatment with two doses of intravenous immunoglobulin, high-doses corticosteroids and infliximab, during follow-up the infant developed giant coronary artery aneurysms. A comprehensive review of the literature concerning KD in infants is included. Clinical suspicion is required to diagnose KD in the youngest patients, as they are more likely to present with few features of the disease.

BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p

Light-emitting diodes (LEDs) have become an alternative light source to the fluorescent lamp (FL) for the maintenance of plant tissue cultures due to their low heat emission, low power consumption and the ability to fine-tune the light spectrum. In this study, the effect of LEDs on the growth and leaf stomata features of in vitro cultivated raspberries (Rubus idaeus L. 'Lloyd George') was examined. The plantlets were grown in vitro under a lighting system based on the Philips GreenPower LED research module. Four groups of LEDs emitting white (W), red (R), blue (B), and mixed (W:R:B: far red = 1:1:1:1) lights and FL (control) were used. As a second control (marked as EV), plants grown in the multiplication and rooting stage under fluorescent lamps and then acclimatized ex vitro in a greenhouse for 90 days in natural light were included. Relative growth rate (RGR), protein content as well as stomata morphology and density of the plantlets were analysed after three passages under corresponding light treatment. The results show that different LEDs specifically affect the growth and size of leaf stomata and density of in vitro cultured raspberry plants and can be applied as an effective modulator of morphogenesis during micropropagation. The combination of white, blue, red and far red LED stimulated the accumulation of biomass and proteins, as well as the formation of a higher number of stomata on the lower surface of the leaves, which would be a prerequisite for more effective control of water loss from plantlets during the ex vitro acclimatization.

Aims. The present study aimed to assess vitamin D status and serum concentrations of pro-inflammatory cytokines IL-17, Il-23, and IL-18 in patients with chronic plaque psoriasis and their association with various demographic and clinical characteristics. Methods. The study was conducted during the autumn/winter period on 48 patients with chronic plaque psoriasis and 48 controls. Total serum 25(OH)D level was determined with Roche Elecsys® 2010 Vitamin D total assay. Commercial ELISA kits were used for quantifying the serum levels of IL-17A, IL-18, and IL-23. Results. Serum 25(OH)D had a median value of 16.95 ng/mL (IQR 10.8-23.50) for patients with psoriasis and 18.80 ng/mL (IQR 15.45-25.85) for the control group (P=0.09). A moderate negative correlation was found between PASI score and 25(OH)D levels (rs=-0.34; P=0.02). The serum levels of IL-17 (P=0.001), IL-23 (P=0.01) and IL-18 (P=0.02) were significantly higher in the patient group compared to controls. IL-17 concentrations were higher in patients with moderate to severe psoriasis compared to patients with mild psoriasis (P=0.003). No significant correlations were detected between the serum concentrations of 25(ОH)D and IL-17, IL-23, and IL-18. Conclusion. It was confirmed that IL-17 serum level is associated with psoriasis severity. Measurement of 25(OH)D serum concentration can be useful in patients with moderate to severe psoriasis with or without comorbidities. A direct association between 25(OH)D serum concentration and the serum concentrations of IL-17, IL-23, or IL-18 was not identified in this study.

The objective of this study was to compare the motility, morphology, and levels of DNA fragmentation of spermatozoa subjected to conventional swim-up or cumulus matrix (CM) sperm selection. Semen samples were collected from 60 normozoospermic men at a private hospital between December 2021 and March 2022. After liquefaction, semen samples were separated into two portions – one part was subjected to conventional swim-up preparation, and the remaining spermatozoa were subjected to CM selection. The CM was obtained by mechanical isolation from healthy donor oocytes. Semen analysis and evaluation of sperm were performed according to the WHO 6th Edition Laboratory Manual and Kruger’s strict criteria, respectively. Sperm DNA fragmentation (SDF, %) of the two preparations was evaluated using the Halosperm G2 detection Kit (Halotech, Madrid, Spain). Wilcoxon rank-sum test was used to compare the characteristics of spermatozoa obtained by the two preparations. Spermatozoa selected by CM showed significantly better rapidly progressive motility (43.5% vs 30.6%, respectively, P < 0.001), a higher percentage of morphologically normal forms (14.0% vs 9.0%, respectively, P < 0.05), and lower levels of SDF (26.0% vs 45.0%, P < 0.05) compared to those prepared by conventional swim-up. Moreover, the incidence of multiple sperm defects was considerably lower in the samples that underwent CM selection compared to those that did not (30.0% vs 49.0%, respectively, P < 0.05).The selection by CM significantly increases sperm motility and reduces morphologically abnormal spermatozoa and DNA fragmentation rates compared to the conventional swim-up preparation. The application of this selection technique may increase the chances of successful IVF outcomes.

Vegetation productivity is a critical indicator of global ecosystem health and is impacted by human activities and climate change. A wide range of optical sensing platforms, from ground-based to airborne and satellite, provide spatially continuous information on terrestrial vegetation status and functioning. As optical Earth observation (EO) data are usually routinely acquired, vegetation can be monitored repeatedly over time, reflecting seasonal vegetation patterns and trends in vegetation productivity metrics. Such metrics include gross primary productivity, net primary productivity, biomass, or yield. To summarize current knowledge, in this paper we systematically reviewed time series (TS) literature for assessing state-of-the-art vegetation productivity monitoring approaches for different ecosystems based on optical remote sensing (RS) data. As the integration of solar-induced fluorescence (SIF) data in vegetation productivity processing chains has emerged as a promising source, we also include this relatively recent sensor modality. We define three methodological categories to derive productivity metrics from remotely sensed TS of vegetation indices or quantitative traits: (i) trend analysis and anomaly detection, (ii) land surface phenology, and (iii) integration and assimilation of TS-derived metrics into statistical and process-based dynamic vegetation models (DVMs). Although the majority of used TS data streams originate from data acquired from satellite platforms, TS data from aircraft and unoccupied aerial vehicles have found their way into productivity monitoring studies. To facilitate processing, we provide a list of common toolboxes for inferring productivity metrics and information from TS data. We further discuss validation strategies of the RS data derived productivity metrics: (1) using in situ measured data, such as yield; (2) sensor networks of distinct sensors, including spectroradiometers, flux towers, or phenological cameras; and (3) inter-comparison of different productivity metrics. Finally, we address current challenges and propose a conceptual framework for productivity metrics derivation, including fully integrated DVMs and radiative transfer models here labelled as “Digital Twin”. This novel framework meets the requirements of multiple ecosystems and enables both an improved understanding of vegetation temporal dynamics in response to climate and environmental drivers and enhances the accuracy of vegetation productivity monitoring.

The Bulgarian research landscape, presented mainly by the research institutes that are part of the Bulgarian Academy of Sciences and the Agricultural Academy, needs diversification to match the research and innovation potential of the other European Union (EU) countries. This article describes the establishment of the Center of Plant Systems Biology and Biotechnology (CPSBB), a new innovative type of independent research organization that is changing the research landscape in Bulgaria. Supported by the EU Commission, Bulgarian Government, and Plovdiv Municipality, CPSBB has quickly become the leading plant science institute in Bulgaria, creating knowledge in diverse fields such as bioinformatics, biotechnology, genetics and genomics, metabolomics, and systems biology. We outline the organizational structure of CPSBB, the development of its infrastructure, and its scientific productivity. Finally, we compare CPSBB with other similar research establishments in Europe and we conclude that such new types of institutes have a bright future in Bulgaria due to their operational flexibility, productivity, and connections with academia and industry.

This review explores the intricate relationship between interleukin-6 (IL-6) and sarcopenia, a prevalent condition characterized by progressive skeletal muscle loss, particularly in aging populations. Emphasizing the rising prevalence and health challenges posed by sarcopenia, the paper delves into the multifunctional roles of IL-6 in immune response, inflammation and inflammaging associated with sarcopenia. Significantly elevated in sarcopenic individuals, IL-6 prompts an exploration of its molecular impact on muscle wasting. The review critically assesses IL-6 as a potential biomarker for sarcopenia diagnosis and prognosis while also examining therapeutic interventions targeting IL-6 signaling pathways, offering a foundation for future research and the development of targeted therapeutic strategies to alleviate the impact of this debilitating condition.

Abstract Background In yeast, recombinant membrane proteins including viral scaffold proteins used for the formation of enveloped Virus-like particles (eVLPs) typically accumulate intracellularly. Their recovery is carried out by mechanical disruption of the cells, often in combination with detergent treatment. Cell permeabilization is an attractive alternative to mechanical lysis because it allows for milder and more selective recovery of different intracellular products. Results Here, we present a novel approach for extraction of integral membrane proteins from yeast based on cell envelope permeabilization through a combination of pulsed electric field and lytic enzyme pretreatment of the cells. Our primary experiments focused on Hansenula polymorpha strain #25-5 co-expressing the integral membrane small surface protein (dS) of the duck hepatitis B virus and a fusion protein of dS with a trimer of a Human papillomavirus (HPV) L2-peptide (3xL2-dS). Irreversible plasma membrane permeabilization was induced by treating the cell suspension with monopolar rectangular pulses using a continuous flow system. The permeabilized cells were incubated with lyticase and dithiothreitol. This treatment increased the cell wall permeability, resulting in the release of over 50% of the soluble host proteins without causing significant cell lysis. The subsequent incubation with Triton X-100 resulted in the solubilization and release of a significant portion of 3xL2-dS and dS from the cells. By applying two steps: (i) brief heating of the cells before detergent treatment, and (ii) incubation of the extracts with KSCN, an 80% purity on the protein level has been achieved. Experiments performed with H. polymorpha strain T#3-3, co-expressing dS and the fusion protein EDIIIWNV-dS consisting of dS and the antigen from the West Nile virus (WSV), confirmed the applicability of this approach for recovering dS. The treatment, optimal for solubilization of 3xL2-dS and a significant part of dS, was not effective in isolating the fused protein EDIIIWNV-dS from the membranes, resulting in its retention within the cells. Conclusions This study presents an alternative approach for the recovery and partial purification of viral membrane proteins expressed in H. polymorpha. The factors influencing the effectiveness of this procedure and its potential use for the recovery of other integral membrane proteins are discussed.

Purpose: The aim of this report is to measure and analyse the isometric and isokinetic (concentric) peak torque (PT) of knee extensors and flexors of the involved and uninvolved limb of twin professional football players over one year post anterior cruciate ligament reconstruction (ACLR). To calculate the unilateral and bilateral asymmetry indexes and compare the athlete's PT values with sport-specific and position-specific data. Case description: Strength measurements of the knee extensors and flexors were conducted on two ACLR football players (twins) on the involved and uninvolved limbs in isometric and concentric modes of muscle contractions, and unilateral/bilateral asymmetry indexes were calculated. Results: The peak torque isometric data indicated that the strength characteristics of the involved leg extensors in both patients were significantly lower compared to the uninvolved limb and were indicators of higher secondary injury risk. The first athlete's concentric peak torque values showed relatively good return-to-sport results, while the second football player returned to sport having not met the recovery criteria. Both athletes require additional specific muscle strength exercises on the extension and flexion muscle groups to reach the ACL reconstruction recovery targets. Conclusions: In this case report, the possibilities of isokinetic dynamometric testing in an isometric and concentric mode of football players to more accurately assess the extent of the muscle strength deficiency and asymmetry are demonstrated. This more precise information allows to the creation of correct training and therapeutic program to recover the knee muscle groups' strength and unilateral/bilateral strength balance to avoid reinjury.

With the advancement of artificial intelligence and machine learning methods, autonomous approaches are recognized to have great potential for performing more efficient scattering experiments. In our view, it is crucial for such approaches to provide thorough evidence about respective performance improvements in order to increase acceptance within a scientific community. Therefore, we propose a benchmarking procedure designed as a cost-benefit analysis that is applicable to any scattering method sequentially collecting data during an experiment. For a given approach, the performance assessment is based on how much benefit, given a certain cost budget, it is able to acquire in predefined test cases. Different approaches thus get a chance for comparison and can make their advantages explicit and visible. Key components of the procedure, i.e., cost measures, benefit measures, and test cases, are made precise for the setting of three-axes spectrometry (TAS) as an illustration. Finally, we discuss neglected aspects and possible extensions for the TAS setting and comment on the procedure’s applicability to other scattering methods. A Python implementation of the procedure to simplify its utilization by interested researchers from the field is also provided.

Adenomyosis and endometriosis are distinct gynecological disorders characterized by ectopic growth of endometrial tissue. Their etiology remains unclear, but stem cells have been implicated in both. The aim of this study was to investigate and compare the quantity of NOTCH1+ and CD117+ stem cells in endometriosis and adenomyosis lesions. Immunohistochemical staining of ectopic endometrium biopsies using antibodies against NOTCH1 and CD117 was performed. The quantity and spatial distribution of endometrial stromal cells positive for these markers were determined and compared between endometriosis and adenomyosis lesions. Additionally, their quantities were compared between endometriosis lesion types. Mann–Whitney U test showed that the median percentages of both NOTCH1+ and CD117+ cells in the endometriosis lesions were significantly higher than those in the adenomyosis lesions (2.26% vs. 0.13%, p = 0.002 and 0.44% vs. 0.26%, p = 0.016, respectively). Spearman’s test showed a positive correlation between NOTCH1+ and CD117+ cells in endometriosis lesions (R = 0.45, p = 0.027) but no significant correlation in adenomyosis lesions (R = −0.11, p = 0.69). The quantity of both stem cell types was highest in extragenital endometriotic lesions. Unlike adenomyosis, endometriosis lesions are associated with higher quantities of NOTCH1+ and CD117+ stem cells and a coordinated increase in their number. These findings support the distinct origin of the two conditions.

The most common primary cardiac tumors are myxomas, while cardiac hamartomas are rare. Cardiac hamartomas may constitute manifestation of a genetic disorder such as tuberous sclerosis, or could be diagnosed independently as a solitary lesion. We present two rare cases of primary cardiac tumors detected via diagnostic imaging and subsequent histopathology examination. The first described case is that of a male preterm foetus with multiple rhabdomyomas in the heart, discovered during foetal echocardiography. The finding was later confirmed by autopsy, which also revealed presence of cortical tubers with typical balloon cells constituting well known epileptogenic lesions in the foetal brain. The second case describes an even rarer benign cardiac lesion – a hamartoma of mature cardiomyocytes – which was discovered by chance in a 49-year old female patient during echocardiography. The performed CT scan revealed a 37 x 16 x 12 mm tumor in the right atrium obstructing the superior vena cava inlet. The malformation was surgically removed and examined histologically revealing disorganized hypertrophic mature cardiomyocytes, partly separated by fibrous strands and admixed with mature adipocytes. Differential diagnosis was performed to rule out other benign tumors with myocyte differentiation – cardiac rhabdomyoma, histiocytoid cardiomyopathy and adult cellular rhabdomyoma.

Abstract Neutron scattering experiments at three-axes spectrometers (TAS) investigate magnetic and lattice excitations by measuring intensity distributions to understand the origins of materials properties. The high demand and limited availability of beam time for TAS experiments however raise the natural question whether we can improve their efficiency and make better use of the experimenter’s time. In fact, there are a number of scientific problems that require searching for signals, which may be time consuming and inefficient if done manually due to measurements in uninformative regions. Here, we describe a probabilistic active learning approach that not only runs autonomously, i.e., without human interference, but can also directly provide locations for informative measurements in a mathematically sound and methodologically robust way by exploiting log-Gaussian processes. Ultimately, the resulting benefits can be demonstrated on a real TAS experiment and a benchmark including numerous different excitations.

Accurate disease severity assessment is critical for plant breeders, as it directly impacts crop yield. While hyperspectral remote sensing has shown promise for disease severity assessment in breeding experiments, most studies have focused on either leaf or canopy levels, neglecting the valuable insights gained from a combined approach. Moreover, many studies have centered on experiments involving a single disease and a few genotypes. However, this approach needs to accurately represent the challenges encountered in field conditions, where multiple diseases could occur simultaneously. To address these gaps, our current study analyses a combination of diseases, yellow rust, brown rust, and yellow leaf spots, collectively evaluated as the percentage of the diseased leaf area relative to the total leaf area (DA) at both leaf and canopy levels, using hyperspectral data from an ASD field spectrometer. We quantitatively estimate overall disease severity across fifty-two winter durum wheat genotypes categorized into early (medium milk) and late (late milk) groups based on the phenophase. Chlorophyll content (CC) within each group is studied concerning infection response, and a correlation analysis is conducted for each group with nine vegetation indices (VI) known for their sensitivity to rust and leaf spot infection in wheat. Subsequent parametric (linear and polynomial) and nonparametric (partial least squares and kernel ridge) regression analyses were performed using all available spectral bands. We found a significant reduction in Leaf CC (>30%) in the late group and Canopy CC (2 of 0.63 and 0.42 for the cross-validation and test datasets, respectively. Canopy CC retrieval required separate models for each group: the late group achieved R2 of 0.61 and 0.37 (cross-validation and test), while the early group achieved R2 of 0.48 and 0.50. Similar trends were observed for canopy DA, with separate models for early and late groups achieving comparable R2 values of 0.53 and 0.51 (cross-validation) and 0.35 and 0.36 (test), respectively. All of our models had medium accuracy and tended to overfit. In this study, we analyzed the spectral response mechanism associated with durum wheat diseases, offering a novel crop disease severity assessment approach. Additionally, our findings serve as a foundation for detecting resistant wheat varieties, which is the most economical and environmentally friendly management strategy for wheat leaf diseases on a large scale in the future.

Crop phenology data offer crucial information for crop yield estimation, agricultural management, and assessment of agroecosystems. Such information becomes more important in the context of increasing year-to-year climatic variability. The dataset provides in-situ crop phenology data (first leaves emergence and harvest date) of major European crops (wheat, corn, sunflower, rapeseed) from seventeen field study sites in Bulgaria and two in France. Additional information such as the sowing date, area of each site, coordinates, method and equipment used for phenophase data estimation, and photos of the France sites are also provided. The georeferenced ground-truth dataset provides a solid base for a better understanding of crop growth and can be used to validate the retrieval of phenological stages from remote sensing data.

Хроничната злоупотреба с райски газ сред юношите се превръща в сериозен проблем, тъй като води до функционален дефицит на витамин В12 с последващи миелоневропатии. Представяме кохорта от 5 пациента на възраст от 15 до 18 г. с анамнестични данни за хронична злоупотреба на райски газ до 10-12 пълнителя на ден – един до два пъти седмично за период между 3 месeца и 2 г. При всички пациенти се установяват парестезии по дистален тип, сензорна атаксия, а при една болна и силно смутена походка. Електроневрографското изследване е с данни да смесен тип полиневропатия, по-изразена в долните крайници. Серумните нива на витамин В12 са намалени при 4/5, докато нивата на хомоцистеин и метилмалонова киселина са увеличени над 7 пъти над нормата при всички. Магнотнорезонансната томография е с данни за хиперинтензни лезии, засягащи задните стълбци на гръбначния мозък при една болна. Пациентите са лекувани с витамин В12 с различна степен на подобрение. Хроничната злоупотреба с райски газ води до обратима подост ро прогресираща миелоневропатия. Преустановяването на приема и приложението на витамин В12 е с добър ефект.

BackgroundDizziness is a common leading symptom in bilateral vestibulopathy (BVP) and functional dizziness (FD), with significant negative effects on functional ability and quality of life. Vertigoheel is a widely used non-prescription drug for the treatment of vertigo. In order to generate systematic data for Vertigoheel in BVP and FD, we conducted a non-interventional study assessing vertigo symptoms.MethodsThis study was conducted as an open-label, prospective, monocentric, non-interventional case series (ClinicalTrials.gov identifier NCT05897853). Patients with BVP and FD received Vertigoheel according to market approval for an observational period of 2 months. Change from baseline after 2 months was assessed for the following endpoints: Dizziness Handicap Inventory (DHI) as the primary endpoint, quality of life (QoL) by EQ-5D-5L, and body sway by static posturography. Patients with FD were additionally assessed for depression and anxiety by PHQ-9 and GAD-7 questionnaires. Patients with BVP were assessed for vestibular function by video head impulse testing and caloric testing. Adverse events and other safety-related observations were evaluated.ResultsOf 41 patients with FD and 13 with BVP, two with FD and none with BVP dropped out before the follow-up visit. Both patient groups showed significantly improved disability caused by dizziness after 2 months: In BVP, the DHI decreased on average by 13.2 points from 45.4 to 32.2 (p

PURPOSE. To evaluate the incidence of urticarial adverse drug reactions (ADRs) to ACE inhibitors and beta-blockers, patient demographics, drug causality, and treatment outcome. METHODS. An epidemiological study including 154 patients with urticarial ADRs, out of a total of 3554 hospitalized patients in the Clinic of Dermatology and Venereology, for a 7-year period. ADRs were defined according to the WHO and the Naranjo algorithm was used for case drug causality assessment. RESULTS. Urticarial ADRs were found in 4,1% of the study population (≥ 18 years), the average age was 50,2 years, and female prevalence was established. Concomitant cardiovascular diseases were found in 45,2% of the patients and 30,1% declared using ACE inhibitors and/or beta-blockers. The suspected drug was withdrawn, and alternative therapy was recommended by a cardiologist. The Naranjo algorithm showed 4.5% “definitive”, 45,5% “possible”, and 50% “probable” urticarial ADRs. Systemic antihistamines were administered to all patients and single short corticosteroid courses were added in 81,8%. Clinical recovery was achieved in 59% of the patients and improvement in 41%. CONCLUSIONS. The need for drug therapy and hospitalization in severe cases of urticarial ADRs to ACE inhibitors and beta-blockers are factors contributing to the overall socio-economic burden of ADRs.

Purpose: The study aims to examine the use of dietary supplements (DSs) in patients with chronic dermatological diseases, as well as, the patients' views of the safety and benefit of DSs. Methods: A crosssectional study of patients hospitalized in the Clinic of Dermatology and Venereology at the University Нospital "Prof. Dr Stoyan Kirkovich" - Stara Zagora from March 2019 to March 2020 was performed. A specially designed and validated questionnaire was used to collect data. Descriptive statistics was performed to analyze the results. Results: Overall 250 patients were involved in the study. The intake of DSs was established in 174 (69.6%) of the participants. Commonly used DSs were vitamins/minerals (41.2%) and herbal supplements (8.2%). Most of the respondents (59.2%) were ignorant about adverse reactions to DSs and 44.4% perceived DSs as completely safe. The majority of DSs consumers (59%) declared satisfaction with the effect of DSs and were convinced (62.4%) of their benefits. Conclusions: DSs are widely used in patients with chronic skin diseases. Most of the patients are ignorant about the risk associated with DSs intake. Physicians' awareness of DSs use in hospitalized patients is important for the rational use of DSs and their safe combination with drugs.

Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are oral antidiabetic agents commonly used for the treatment of type 2 diabetes mellitus. More than ten years of clinical experience with this group of drugs provides evidence of their efficacy and good tolerability especially in patients at risk of hypoglycemia. DPP4 inhibitors act by increasing the levels of the incretins glucagon-like peptide-1 (GLP-1) and glucosedependent insulinotropic peptide (GIP) and thus augmenting glucose-induced insulin secretion. The enzyme DPP-4 degrades plenty of substrates including chemokines, cytokines, and neuropeptides. Thus the inhibition of DPP-4 may affect many biological and pathological processes. Although rarely DPP-4 inhibitors have been reported to induce the development of infections, heart failure, liver injury and pancreatitis. The longterm effects of DPP-4 inhibition on the immune function are still not clarified. The close monitoring of polymorbid patients using DPP-4 inhibitors, and the reporting of possible adverse reactions associated with these drugs is warranted.

Objectives: The aim of this research is to examine the effects of fructose-drinking on the plasma levels of appetite-regulating hormones insulin, leptin and ghrelin in male and female rats. Methods: Mature Wistar rats were divided as follows: two control groups - male (CM) and female (CF); two fructose-drinking groups - male (FDM) and female (FDF), received 15% fructose solution. The experiment lasted 11 weeks. At the end, insulin, leptin and ghrelin levels as well as lipid and glucose profile were assessed. Results: Plasma concentrations of the examined hormones were elevated in fructose-drinking groups. However, in the FDM group only the leptin levels were significantly increased compared to the control. In the FDF group, all three appetite-regulating hormones showed the highest concentrations in comparison to the other groups. Conclusion: Sex hormones may affect the appetite-regulation signals and could be a factor contributing to degree of metabolic changes caused by long-term fructose overconsumption.

Based on the study on the composition of the tabanid fauna of the Sredna Gora Mountains and the summarized reference data 54 species and 2 subspecies of 10 genera have been identified: Silvius (1 species), Chrysops (4 species), Atylotus (4 species), Therioplectes (2 species and 1 subspecies), Hybomitra (5 species), Tabanus (23 species and 1 subspecies), Heptatoma (1 species), Haematopota (10 species), Dasyrhamphis (2 species) and Philipomyia (2 species). For the first time, data on the tabanid fauna of the Ihtimanska and Sashtinska Sredna Gora Mountains have been reported. For the Ihtimanska Sredna Gora Mountains 17 species of 4 genera have been identified: Atylotus (1 species), Tabanus (12 species), Haematopota (2 species) and Philipomyia (2 species), and for Sashtinska - 20 species of 6 genera: Chrysops (2 species), Atylotus (2 species), Hybomitra (1 species), Tabanus (12 species), Haematopota (2 species), and Philipomyia (1 species). The species Atylotus latistriatus Brauer in Br. & Bergenstamm, 1880, Tabanus spodopterus Meigen, 1820 and Philipomyia aprica (Meigen, 1820), registered in the Ihtimanska and the Sashtinska Sredna Gora Mountains have been reported for the first time for the fauna of the Sredna Gora Mountains.

AbstractPlatelet-rich plasma (PRP) is used for successful regeneration of female reproductive tissues. However, little is known about the effect of ovarian PRP treatment on oocyte and embryo quality. The objective of our study was to assess the role of autologous ovarian PRP treatment on ovarian reserve and number and quality of oocytes and embryos in women with poor ovarian response (POR) undergoing in-vitro fertilization cycles. A total of 66 women with POR were treated with ovarian PRP injection in two subsequent menstrual cycles. The antral follicle counts, serum anti-Mullerian hormone, follicle-stimulating hormone levels, fertilization rate, number and quality of oocytes, and embryos were assessed and compared between the cycle before and after PRP treatment. Ovarian PRP treatment resulted in insignificantly lower follicle-stimulating hormone levels, significantly higher antral follicle count, anti-Mullerian hormone, number of retrieved oocytes, and insignificantly higher fertilization rate. However, the mean number of Day 5 embryos (2.19 ± 1.45 vs. 1.58 ± 1.30, p = 0.01), the percentage of high-quality oocytes (45.29% ± 42.40% vs. 15.21% ± 30.24%, p

AbstractWe report a clinical case of a 4-year-and-10-month-old boy whose first symptoms (fever and tachypnoea) were noticed at the age of 6 months. In the upcoming months, skin acral violaceous plaques developed. Failure to thrive and growth impairment were detected. In the journey to find the correct diagnosis, a lot of diseases were suspected. The final diagnosis was suggested after more than 2 years since the first symptoms had appeared. A multi-detector computed tomography of the chest with low radiation dose protocol showed signs of interstitial lung disease (ILD). Next-Generation Sequencing was done, and it revealed a pathogenic heterozygous N154S mutation (NM_198282.4 (Stimulator of IFN genes STING1):c.461A > G (p.Asn154Ser)) in STING1 gene. Treatment with JAK-inhibitor baricitinib was started at the age of 3 years and 10 months. The presence of cutaneous vasculopathy, lung involvement, laboratory signs of inflammation, recurrent fevers and failure to thrive should indicate STING1 gene analysis. STING-associated vasculopathy of infantile-onset (SAVI) is one of the newly identified type I interferonopathies. SAVI is characterized by systemic inflammation via the overproduction of type I IFN due to heterozygous gain-of-function mutations in STING1. The onset of the symptoms of SAVI is usually early in infancy with recurrent fevers accompanied by increased acute phase reactants and ulcerating skin lesions.

The leaf anatomy and chloroplast ultrastructure of Nepeta nuda L. plantlets regenerated in vitro from cryopreserved shoot apical meristem and in vitro-micropropagated plantlets were studied comparatively to assess whether cryoprocedure affected leaf morphogenesis. Both postcryo and in vitro plantlets failed to develop a distinguishable palisade layer, making the mesophyll appear homogeneous. Significant damage to the chloroplast envelope and substantial thylakoid ruptures were also observed. We assumed that the specific in vitro conditions more likely affected the structures than the cryotreatment itself. Light and transmission electron microscopy observations were also carried out on newly formed leaves of ex vitro-adapted plants. The examined leaf features were similar to those in the in situ plants – bifacial leaf lamina, double-layered palisade parenchyma, loosely arranged spongy parenchyma cells, and chloroplasts with intact envelope and evenly distributed throughout the stroma internal membrane system. The obtained histological and ultrastructural results revealed the retained morphogenetic potential of N. nuda plants and proved cryopreservation as a suitable method for long-term storage.

It is an acknowledged fact that SARS-CoV-2 exhibits tropism for the human placenta. A possible mechanism of SARS-CoV-2 entry into host cells is via angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in trophoblasts, endothelial cells, and macrophages. The present study describes a case of spontaneous miscarriage in the 20th gestational week after maternal SARS-CoV-2 infection. The placenta and various fetal organs were examined for structural alterations and expression of the viral nucleocapsid protein and several immune cell markers via immunohistochemistry (IHC). Histopathological examination of the placenta revealed acute chorioamnionitis, acute subamnionic placentitis, multiple intervillous thrombi, increased fibrinoid deposition, and necrotic changes of the chorionic villi. Immunohistochemistry confirmed the presence of SARS-CoV-2 nucleocapsid protein regions predominantly in the syncytiotrophoblast. Staining of the placental tissue for different markers helped elucidate the distribution of immune cells. Pathomorphological examination of the fetal organs demonstrated changes in microcirculation with the presence of sludge phenomenon and diapedesis haemorrhages, mostly in the lungs, brain, and myocardium. IHC staining of fetal organs revealed expression of SARS-CoV-2 nucleocapsid protein, which was detected to the highest extent in the brain, lungs, and liver. The findings of the present report support the hypothesis of possible vertical transmission of SARS-CoV-2 from mother to fetus.

Anorexia nervosa is an eating disorder with a multisystemic nature, affecting female adolescents predominantly. The disease is potentially fatal with cardiac complications being the leading cause. We present a clinical case of a 16-year-old girl with anorexia nervosa after a mental trauma, hospitalized in our Clinic in an extremely severe, pre comatose state with weight 26 kg, BSA – 1.12 m2 and BMI – 10.4. On the background of severe abnormalities in homeostasis, bradycardia with left ventricular extrasystoles in bigeminy and episodes of tachycardia with a frequency of 238/min. Echocardiography revealed reduce in the heart size and the left ventricular muscle mass, MI – I + degree and a small, apical pericardial effusion. During the echocardiographic follow-up, there was signifi cant hypertrophy of the left ventricle with obstruction in the outfl ow tract, with a reduction in ventricular size, without signifi cant change in left ventricular muscle mass. As a result of long-term, comprehensive treatment, with the participation of a team of specialists, the patient achieved true behavioural criticality, improved food tolerance, weight gain up to 46 kg with BMI - 18.4 and normalization of cardiac anatomy. Cardiac complications of anorexia nervosa are common, varied, and potentially lethal and require targeted cardiac monitoring and treatment. Left ventricular hypertrophy with obstruction in the ventricular outfl ow tract, fi rst described in 2006, is a rare but potentially fatal cardiac complication in patients with the disease.

Thalassemias are a group of inherited disorders, that require regular lifelong blood transfusions, which are vital for the normal development and life of the patients. With time, complications occur due to iron deposition in internal organs with subsequent chronic hemochromatosis development and predominantly affecting the heart, the liver and the endocrine glands. Despite the absence of clinical symptoms in young patients, enough data are supporting the fact that early myocardial iron deposition occurs. This necessitates the introduction of suffi ciently reliable methods and techniques for the detection and follow-up of early heart disorders before the onset of symptoms. Evaluation of myocardial iron deposition by the T2* MRI technique is established as a reliable, non-invasive method with good reproducibility and a low percentage of variability. Echocardiography as a method does not give information concerning the iron deposition in the heart but is easily applicable, safe and widespread for screening and follow up of patients. The use of new technique such as longitudinal strain makes the method almost comparable for the assessment of early subclinical myocardial damage. Although still in the fi eld of research, the identifi cation of specifi c miRNAs associated with cardiac stroke, fi brosis and remodeling is emerging as a new, potential biomarker for myocardial damage that could support the overall cardiovascular assessment of patients. This review will focus on current manifestations of cardiac complications in young patients with beta-thalassemia major, as well as the noninvasive methods for assessing cardiac function described above.

A study was conducted on the dynamics of tabanids daily activity in the Central Balkan Mountains in the 2011-2013 period. Tabanids have been found to fly 11 hours a day, with a peak in activity around 11:00. Their mass activation is in the temperature range 18-23°С and at 26°С maximum activity has been reported. In the present study a new, minimum temperature threshold for activation of T. quatuornоtatus Mg. in Bulgaria was registered (13°С).

The aim of this prospective study was to compare the endometrial microbiome between pregnant and non-pregnant women after frozen embryo transfer (FET) with euploid embryos. Endometrial biopsies were collected from 30 women during the mid-luteal phase in a natural cycle. FET was performed with euploid embryos up to 3 months after the biopsy. Endometrial microbiota composition was analysed using 16S rRNA (v4-v5 region) next generation sequencing (NGS). The analysis of different clinical outcomes after the biopsy (no pregnancy (n = 14), and ultrasound confirmed pregnancy (n = 16)) revealed differences in the endometrial microbiome composition. In total, 271 distinct bacterial species and 668 bacterial genera were identified. The number of unique species found in non-pregnant women was 62 (22.88%), while in the patients who became pregnant after FET it was 39 (14.39%). Among them, bacteria with high frequency of occurrence such as Bacteroides spp., Cutibacterium granulosum, Isoptericola spp., Acetomicrobium spp., Marivivens spp. and Syntrophomonas spp. were found only in non-pregnant patients, while Bosea spp. was present only in pregnant women. The analysis of bacteria relative abundance revealed that Lactobacillus genus was not significantly different between the studied groups. In contrast, Serratia marcescens, Staphylococcus spp., Glutamicibacter spp. and Delftia spp. were significantly enriched in the non-pregnant group. In conclusion, specific bacteria taxa had higher relative abundance in the endometrium of patients with implantation failure after FET with euploid embryos. We hypothesize that an appropriate treatment for optimization of endometrial microbiome content in women with diagnosed microbiome dysbiosis could be beneficial for improvement of pregnancy rates.