Medical University of Sofia

The global rise in honey demand has been accompanied by increasing concerns over adulteration and synthetic substitutes, complicating quality control for regulators and importers. The quality and freshness of Apis mellifera honey are widely assessed using indicators such as 5-hydroxymethylfurfural (HMF) content and diastase activity. HMF increases with excessive heating and storage, while diastase activity declines under the same conditions. This study analyzed 140 honey samples from Panama (2022-2024), including artisanal and commercially available products. HMF quantification was performed using a validated solid-phase extraction (SPE) method coupled with ultra-high-performance liquid chromatography with diode array detection (UHPLC-DAD), following ICH guidelines. Diastase activity was measured with the Phadebas® enzymatic method. Validation confirmed excellent specificity, linearity (r2=0.9995), precision (RSD<2.5%), accuracy (98-102% recovery), and sensitivity (LOD = 0.15µg/mL; LOQ = 0.45µg/mL). Results showed that 50% of commercial honeys did not meet regulatory limits (HMF≤80mg/kg; diastase≥8 DN), suggesting inadequate storage, thermal abuse, or adulteration, while most artisanal honey samples complied with national and international standards. These findings provide essential evidence for honey quality monitoring in Panama and highlight the importance of enforcing regulations to safeguard consumers and support authentic local products.

Hereditary angioedema is a bradykinin-mediated, rare condition characterised by recurrent and potentially life-threatening attacks of subcutaneous and submucosal swelling. Bradykinin B2 receptor antagonism is a proven mechanism for on-demand treatment of attacks, but no evidence exists on its effects when used prophylactically. Deucrictibant is an investigational orally bioavailable bradykinin B2 receptor antagonist. We aimed to evaluate the efficacy, safety, and tolerability of two dose regimens of oral deucrictibant administered as prophylaxis against hereditary angioedema attacks. CHAPTER-1 was a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial conducted in two parts, a double-blind placebo controlled first part and an open-label second part, with only part 1 reported here. Part 1 recruited adults (aged 18-75 years) with hereditary angioedema type 1 or 2 from 37 sites (university hospitals and accredited angioedema centres) across North America, Europe, and Israel. Patients required a documented history of three or more attacks within the last 3 consecutive months before screening or two or more during the screening period (up to 8 weeks) to be eligible. An interactive response technology system randomised eligible patients 1:1:1 to receive oral deucrictibant 20 mg daily, 40 mg daily, or matching placebo for 12 weeks. Randomisation to treatment groups was stratified by the baseline attack rate. Patients, investigators, site personnel, and the sponsor were blinded to treatment assignment. Masking was achieved with identically appearing deucrictibant and placebo capsules. The primary endpoint was the time-normalised number of investigator-confirmed attacks per 4 weeks (monthly attack rate) from weeks 1 to 12 and was assessed using the intention-to-treat set. The endpoint was analysed by comparing each deucrictibant group with the placebo group using a Poisson generalised linear model with a log link function and Pearson's χ2 scaling of SEs to account for potential dispersion. The safety analysis set included all patients who were randomly assigned and who received one or more doses of study drug (deucrictibant or placebo). CHAPTER-1 is registered with ClinicalTrials.gov (NCT05047185) and is now complete. Between March 9, 2022, and June 19, 2023, 44 patients were screened. Of 34 patients who were randomly assigned, 11 patients received deucrictibant 20 mg, 12 patients received deucrictibant 40 mg, and 11 patients received the placebo, with a median follow-up of 85·0 days (IQR 84·0-86·0). 21 (62%) patients were female, 13 (38%) were male, and 34 (100%) patients were White. The least squares mean monthly attack rate (primary analysis) was 0·40 (95% CI 0·18-0·92) for deucrictibant 20 mg, 0·30 (0·11-0·81) for deucrictibant 40 mg, and 1·93 (1·30-2·88) for placebo; percent reduction in attack rate compared with placebo was 79·2% (95% CI 47·2-91·8) for deucrictibant 20 mg (p=0·0010) and 84·5% (95% CI 53·8-94·8) for deucrictibant 40 mg (p=0·0008). Treatment-related treatment-emergent adverse events were experienced by two (18%) patients receiving deucrictibant 20 mg, one (8%) patient receiving deucrictibant 40 mg, and one (9%) patient receiving the placebo; all were mild in severity (grade 1) and did not require dosing modification of the study drug. There were no serious adverse events or deaths in any treatment group. To the best of our knowledge, this trial provides the first clinical evidence and proof-of-concept for bradykinin B2 receptor antagonism as a therapeutic approach for the prevention of hereditary angioedema attacks and supports further investigation of oral deucrictibant for bradykinin-mediated angioedema. Pharvaris.

This study investigates the prerequisites and barriers to effective communication regarding seasonal influenza vaccination by examining the perspectives of general practitioners (GPs) in Bulgaria. GPs play a crucial role in providing primary healthcare services, including health information, promotion of health, disease prevention, and vaccination programs. However, they face significant challenges related to patient trust in social media and internet sources, patients' tendency to neglect their health, and administrative burdens that can hinder their ability to engage in preventive measures. The survey involved 368 GPs who completed an anonymous questionnaire assessing various aspects of their work and relationships with patients. Results indicate that most GPs believe patients heavily rely on potentially misleading information from social media, which complicates efforts to promote vaccinations. Additionally, many patients tend to neglect their health, making them less receptive to health promotion campaigns. Furthermore, GPs often feel overwhelmed by administrative tasks, limiting their capacity to participate in additional preventive programs. Despite these challenges, GPs recognize the importance of communication skills, with 94% considering them as vital as diagnostic and treatment skills. This highlights the need for ongoing training and development of communication skills to improve interactions with patients and enhance the effectiveness of vaccination programs. In conclusion, addressing misinformation, promoting patient responsibility, and reducing administrative burdens are essential steps towards improving communication and increasing vaccination rates among the Bulgarian population.

Infertility is a growing concern, with metabolic disorders such as type 2 diabetes mellitus (T2DM), obesity and polycystic ovarian syndrome (PCOS) being associated with it. Insulin resistance is seen to be the central feature of these conditions which ends up disrupting hormonal balance and also impairs fertility in both men and women. Hence, understanding the connection between new antidiabetic drugs and fertility can open new possibilities for fertility care. This review studies the role of antidiabetic drugs in improving reproductive outcomes by targeting insulin resistance and related metabolic dysfunctions. Metformin which is the most widely used insulin sensitizer has evidence to improve ovulation in women with PCOS and is seen to be enhancing sperm count, motility and hormone levels in diabetic males by reducing oxidative stress and inflammation. GLP-1 (Glucagon-like peptide-1) receptor agonists include liraglutide and exenatide which support weight loss, improve insulin sensitivity and show positive effects on testosterone levels, ovulation and menstrual regularity. Current growing agents like SGLT2 (Sodium-glucose cotransporter-2) inhibitors and DPP-4 (Dipeptidyl Peptidase-4 inhibitors) inhibitors are also being studied for their potential reproductive too. During pregnancy, glycemic control is critical where metformin and insulin are relatively well-studied, newer agents show variable placental transfer and safety profiles. Further research is required to create new treatment protocols and guidelines to fully understand their long-term reproductive effects in both sexes. Antidiabetic drugs that improve insulin sensitivity offer promising avenues for addressing infertility associated with metabolic disorders. However, gaps remain regarding their long-term preconceptional and postconceptional reproductive effects, underscoring the need for further targeted research.

Acute ischemic stroke is one of the leading causes of mortality and morbidity worldwide. The underlying inflammation process following the ischemic event arises as an important factor of great therapeutic interest. Recent research has showcased the roles of B- and T-lymphocytes in the acute post-stroke period, with various types of lymphocytes affecting differently the clinical outcome of the patient. Herein, we reviewed the literature and discussed the functional role of various subpopulations of lymphocytes in recovery and repair of the ischemic tissue as well as their influence on the final outcome of the patient. Additionally, we searched the literature regarding current knowledge on various drugs possibly affecting neuroinflammation or exhibiting a neuroprotective role in the acute post-stroke period.

Abstract In this study the synthesis of three new N-pyrrolyl azomethine derivatives comprising furan, substituted furan and indole residues is presented. A classical Paal-Knorr cyclization was used for synthesis of the initial N-pyrrolyl hydrazine and the final azomethines were obtained in a micro synthesis scale, assuring about 69–76% yields, low harmful emissions and reagent economy. The compounds were elucidated by IR, 1H NMR and 13C NMR spectral analyses and the obtained results were consistent with the assigned structures. The purity of the substances was proven by TLC characteristics and corresponding melting points. In addition, the neurotoxicity and possible MAO-A and MAO-B inhibitory effects were elucidated in vitro. The obtained results indicated that the target molecules are with low neurotoxicity and no MAOA/B enzyme inhibiting effects.

Abstract Carpal tunnel syndrome (CTS) stands as the most common entrapment neuropathy. The PMA, a transient embryonic vessel, is found in approximately 3-7% of the population, yet it is extremely rare to present as a possible symptomatic space-occupying lesion or a source of pulsatile compression within the carpal tunnel. Herein, we report a case of a 66-year-old female with CTS together with large PMA, surgically treated by simple open carpal tunnel release. Following meticulous surgical decompression and preservation of the artery in situ, the patient achieved complete symptomatic relief. Post-operative high-resolution sonography was utilized to confirm the vascular anomaly and document the successful decompression. This case underscores a critical diagnostic dilemma in orthopedic surgery: performing a blind carpal tunnel release in the elderly without prior imaging carries an inherent danger, as failure to detect such a variant preoperatively risks iatrogenic vascular injury.

Modern virtual high-throughput screening (VHTS) pipelines can be suboptimally validated, with no rigorous studies conclusively demonstrating that every one of their steps reliably adds increasing enrichment atop the baseline random hit rate. Moreover, what little benchmarking studies are available primarily focus on the docking aspect of the pipelines, which is usually only the beginning or near the beginning, and even there, authors tend to use flawed data sets that artificially inflate performance metrics. Herein, we present an alternative method to pipeline validation and data set generation that requires no additional experimental work and expenditure, yet offers vast amounts of negative data that can be used in VHTS pipeline validation. By randomizing ligands across published experimental structures and generating structural isomers of known binders, practically unlimited amounts of negative data can be generated. Such sets of positive and negative data points match closely in key molecular properties and are well suited to pipeline validation. Once such sets are generated, they are to be run through any proposed pipeline, assessing performance at every step. We stress the importance of using negative data of adequate quality and quantity in validation studies to definitively and verifiably demonstrate the utility of a given tool or workflow. Our goal is to help distinguish tools and pipelines that truly accelerate hit discovery and lead optimization from ones that promise to do so but actually do not, whereupon academia and industry can begin to tackle the many unaddressed medical needs of the 21st century.