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Abstract Aliphatic diols such as ethylene and propylene glycol are the key products in the chemical industry for manufacturing polymers. The synthesis of these molecules usually implies sequential processes, including epoxidation of olefins using hydrogen peroxide or oxygen with subsequent hydrolysis to glycols. Direct hydroxylation of olefins by cheap and green oxidants is an economically attractive and environmentally friendly route for the synthesis of diols. Here, we report a photocatalytic reaction for the dihydroxylation of ethylene and propylene to their glycols at room temperature using water as the oxidant. The photocatalyst contains Pd clusters stabilized by sub-nanometric polyoxometalate with TiO2 as the host material. Under light irradiation, it results in production rates of ethylene glycol and propylene glycols of 146.8 mmol·gPd −1·h−1 and 28.6 mmol·gPd −1·h−1 with liquid-phase selectivities of 63.3 % and 80.0 %, respectively. Meanwhile, green hydrogen derived from water is produced as another valuable product. Combined spectroscopy investigation suggests that the reaction proceeds via π-bonded adsorption of olefins over Pd clusters with hydroxylation by hydroxyl radicals formed by photocatalytic dissociation of water.

Night shift work and long working hours are associated with increased health risk. The aim of the study was to follow the effects of night shift work on morbidity of hospital healthcare workers (HCWs), determinants of ill health and mediating factors.

Abstract Objectives This data note contains updated characterization factors including the corresponding datasets for the integrated method to assess resource efficiency (abbreviated as ESSENZ) as well as its successor (ESSENZ+) utilized in assessing the criticality of 48 abiotic resources. The updated characterization factors enable life cycle-based case studies of product systems to determine criticality aspects as well as aspects related to compliance with social and environmental impacts. Underlying data is provided as it is needed for efficiently interpreting the results. Data description Data was collected from publicly available source, including i.e. the United States Geological Survey for abiotic resource production and reserves, the Fraser Institute for the Policy Perception Index, the World Economic Forum for the Enabling Trade Index, the World Bank for the Worldwide Governance Indicators and the German Mineral Resources Agency for price fluctuations. The compiled data has been reorganized and recalculated in accordance with the principles outlined in the published ESSENZ and ESSENZ + method, serving as a foundation for the calculation of the characterization factors for assessing criticality and compliance with social and environmental impacts.

The present study aimed to assess the pollution of Bulgarian brackish lakes based on their ability to accumulate the heavy metals Cd, Zn and Ni. Physicochemical parameters, including pH, electrical conductivity and salinity of the waters, were determined by potentiometric methods. The heavy metal content of the water and crustacean samples was determined by atomic absorption spectrophotometry. The highest pH in the investigated lakes (Atanasovsko Lake, Poda and Pomorie Lake) in the period May–September 2021 was found in the month of September, in the waters of Atanasovsko Lake (8.84). The concentrations of Cd measured in Atanasovsko Lake in the fall were in the order of 0.0125 µg/L—the highest value recorded for all the studied water bodies. The concentrations of zinc and nickel in the waters did not exceed the norms in Bulgarian legislation. The dynamics of biogenic elements (Zn and Ni) in crustaceans were inversely proportional to those found in the waters. The levels of the toxicant cadmium as well as the metals zinc and nickel in the species Gammarus spp. and Atremia spp., inhabiting all analyzed water bodies, were significantly lower than those specified in the Bulgarian and European legislation. The pH and electrical conductivity parameters of the tested waters, as well as the concentrations of the heavy metals, cadmium, zinc and nickel, were within the recommended values. High positive correlations were determined between the content of nickel, on the one hand, and cadmium and zinc, on the other, in the organism of the investigated crustaceans. A longer period of research is needed to accurately determine the degree of contamination of these waters.

The relevance of the research is in the need of observation and analysis of new phenomena in the Russian language, as well as the representation of grammatical information in terminological dictionary that contains nominations of the new subject area. The aim of the study is to identify the grammatical features of the Digital Society terminology in the Russian language of the XXI century. The research material consists of over 500 terms identified with a continuous sampling from official documents and news on the website of the Ministry of Digitalization of the Russian Federation and from media and scientific texts. The research method of empirical material is based on the traditional comprehensive analysis of a new linguistic unit: semantic, morphological, syntactic, word-formation. To confirm the variation of some terms, the author conducted a poll, and a survey of social networks and other new media with the help of parsing. Summarizing the results, the author follows the idea of linguocognitive correlation of linguistic phenomena and changes. The study revealed the terms used mostly in the plural form, so this form became the initial one; new cases and types of grammatical variation of terms in relation to the category of animate/inanimate ( otklyuchit' golosovogo pomoshchnika/golosovoi pomoshchnik ) are described; the causes and types of formal variation of compound terms ( neironnaya set’ - neiroset’ ) are described. The results of the research prove that it is advisable to reflect the grammatical features of a term in lexicographic description of forming terminology at its early stage. The prospects of the study are seen in research of the Digital Society terminology from the point of view of wordformation features and their connection with the grammatical and semantic characteristics of terms, as well as in studying the influence of the “graphics factor” (writing the term in Latin) on the grammatical “behavior” of the term.

Although antimicrobial peptides are considered one of the most promising alternatives to conventional antibiotics given the alarming increase in bacterial multidrug resistance, many aspects of their mechanism of action remain unclear, in particular the emergence and role of collective phenomena such as the spontaneous formation of nano-sized unstructured objects (clusters) and their effects on the biodynamics. We study this process using two novel peptides from the mucus of the garden snail Cornu aspersum as an example to reveal its dynamics and bioactivity implications through coordinated in silico and in vitro techniques — molecular dynamics simulations, UV–Vis and fluorescence spectroscopy, and antibacterial activity tests against two representative bacterial strains — one gram-negative (Escherichia coli 3458) and one gram-positive (Bacillus subtilis). The results obtained confirm the impact of the aggregation processes of the peptides on their biological activity and provide insight into possible synergies in their action.

In a 2019 New York Times article, Paul Krugman declared himself a “crypto skeptic” and shared his pessimistic predictions for cryptocurrencies. Nevertheless, unbacked cryptomoney is now very important in our societies and has revolutionized the monetary and financial landscape as exemplified by the increased pressure from competent regulators to monitor and regulate it. Cryptocurrencies are described by their high volatility that permits regulators to define them as non-safe financial assets when it comes to energy consumption. The anonymous property of cryptocurrencies opens the door to tax evasion, making it especially susceptible to avoiding environment-related taxes aimed at tackling negative impact of climate change. Against this background, the paper sets a twofold aim: to demonstrate that unbacked cryptomoney is volatile and it may pose a threat to financial and fiscal stability; and to develop the idea that, given their different degrees of anonymity and their decentralisation nature, cryptocurrencies could actively participate in the process of tax evasion and therefore incur high costs for countries. Given the general ecological condition and ensuing concerns, it is clear that avoiding eco-taxes represents a serious issue since money from eco-taxation could have been invested in environmental social and governance projects. Therefore, a clear and compelling legal framework should be implemented worldwide to reduce the tax evasion phenomena via cryptomoney channels.

Acetylcholine plays an important role as a neurotransmitter in the central and peripheral nervous systems. Its biosynthesis is catalyzed by choline acetyltransferase (ChAT). In mice, the ChAT gene has three 5′-noncoding (R, N, and M) and 14 coding exons, from which seven mRNA isoforms (M, N1, N2, R1, R2, R3, and R4) are transcribed. They differ in the 5′-noncoding ends and encode the same protein (common ChAT). An additional isoform that lacks coding exons from 5 to 8 encodes a smaller protein (peripheral ChAT). This research aimed to design and check the specificity of primers targeting R3, N1, N2, M, peripheral ChAT, and common ChAT isoforms. The optimal PCR conditions and specificity of the primers were tested in a series of PCR reactions. Specially designed DNA fragments or plasmids containing isoform-specific nucleotide sequences were used as templates. The appropriate annealing temperature, which yields sufficient specificity for each tested primer pair, was as follows: R3 – 60 °C; N1 – 63 °C; N2 – 65 °C; M – 65 °C; peripheral ChAT – 65 °C and common ChAT – 63 °C.

Metabolic syndrome (MS) is often associated with anxiety and depression. Chaenomeles japonica (Thunb.) Lindl, also known as Chaenomeles maulei or Japanese quince, is a medicinal plant with a long history of use forits health-promoting properties.

Summary: Chronic myelogenous leukemia (CML) is a pluripotent hemopoietic stem cell malignancy characterized by the presence of a BCR-ABL1 fusion gene derived from a balanced translocation between the long arms of chromosomes 9 and 22 [t(9;22) (q34; q11)] known as the Philadelphia (Ph) chromosome. CML is an acquired hematopoietic stem cell disease common to myelo- and lymphopoiesis, characterized by uncontrolled proliferation of granulopoiesis (Shuvaev et al. 2015; Yordanov and Varbanova 2019). Relevance and goals: Second-generation tyrosine kinase inhibitors (TKIs) (nilotinib, dasatinib, and bosutinib) have an advantage over imatinib (first-generation) in the frequency and speed of achieving cytogenetic and molecular responses in the treatment of chronic myelogenous leukemia (CML), but they cause severe adverse effects and are much more expensive than imatinib, especially if we compare them to the prices of the registered generic products of Imatinib and Dasatinib. “Novartis Tasigna® trial shows superior results to Glivec® in patients with early-stage chronic myeloid leukemia”, reported on 10/20/2021 by Pierre Perrin-Montlouis. In the first direct comparison of these two oral therapies back in 2009 (Тasigna (nilotinib) 2009), as first-line treatment for CML, the results of Tasigna showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blast phase, with responses achieved faster in the Tasigna group than in the Glivec group. Furthermore, in the last ten years, CML patients who have achieved a stable deep molecular response for at least 2 years have been included in clinical trials for the management of treatment-free remission (TFR) (Kim et al. 2013; Saußele et al. 2016). On the other hand, the ever-increasing costs of diagnosis, treatment and monitoring of the response of CML to the various therapeutic strategies require conducting pharmacoeconomic analyses of the cost-effectiveness and cost-utility types in order to evaluate which are the cost-effective strategies with a view to introducing them into therapeutic practice. The present study aims to analyze the pharmacoeconomic efficiency of the TKI inhibitors used by the patients with CML-CP in the first and second lines, treated in the hematology clinic at UMHAT “St. George”, MU- Plovdiv during the period 2018–2022. Methods: An economic analysis of the medicinal use of TKIs for a 5-year period (2018–2022) was performed at the national level according to data from the National Health Insurance Fund and the availability, accessibility, and usability of original and generic TKIs in Bulgaria were evaluated. The direct medical costs for the therapy of all patients were calculated, including the costs of the TKI therapy, laboratory tests, and monitoring of the molecular response for the entire treatment period from the appointment of the TKI therapy until the end of 2022. A comparative analysis was conducted to assess the cost-effectiveness of the different therapeutic strategies with TKIs on the first and second lines of treatment of patients with CML-CP in the hematology clinic at UMHAT “St. George” Medical University, Plovdiv, using the decision analysis method and conducting one-way and probalistic sensitivity analyses. Results: The sensitivity analyzes of all pharmacoeconomic models showed the robustness and reliability of the obtained results. The threshold limits of medical costs and the frequency of achieving a deep molecular response determining the choice of first- and second-generation tyrosine kinase inhibitors as first- and second-line therapy for patients with chronic myeloid leukemia in the chronic phase have been determined. Prescribing doctors prefer the original MPs to generic analogues, which is also assumed by the current regulations, according to which even for expensive MPs dispensing by protocols, the prescription is by trade and not by international non-proprietary names (INN), which is why the use of the much cheaper generic MPs is negligibly low compared to original MPs. A personalized approach to the patient’s therapy and monitoring the patient’s molecular response to it, as well as stopping therapy in 25–30% of patients suitable to stop it safely when in TFR phase with a probability of more than 50% of not having a relapse will save additional costs that, by improving the cost-effectiveness of therapy for patients with CML, will be directed towards the treatment of new patients with this or other diseases. Conclusion: These pharmacoeconomic models can be applied to improve diagnostic and therapeutic standards in clinical practice and for the efficient use of the very limited resources for health care in countries like Bulgaria. The conducted cost-effectiveness analyses confirmed that the hematologists at the University Center in Plovdiv adhere to the recommendations of Leukemia Net and the Bulgarian Medical Society of Hematology and achieve not only good therapeutic but also pharmacoeconomic efficiency in the treatment of CML-СР patients in first- and second- line therapy.

The issue of storage and protection of yilded seeds from storage pests is fundamental to seed science, the nutrition of people and animals as well as the maintenance of state reserves. During 2019-2021, in the experimental field of IASS "Obraztsov chiflik" - Rousse, in a long-term stationary fertilizer experiment, seeds of common bean variety Obraztsov chiflik 12 were obtained utilizing the following fertilization options: 1 - individual nitrogen fertilization; 2 - individual phosphorus fertilization; 3 - individual potassium fertilization; 4 – combined NP application; 5 – combined NK application; 6 – combined PK application; 7 – triple combination of NPK. An unfertilized control variant was maintained for comparison purposes. The study aims to entomologically evaluate seeds regarding damage by bean weevils after crop harvesting. Measurements of yield, 1000-seed weight, damaged seeds percentage, Index of infestation, as well as weight loss were taken. The combined application of NP demonstrated the greatest positive effect on the yield qualities of beans, however it lead to an intermediate position of the yield in terms of damage by bean weevil. The variant treated with combined NK fertilization resulted in the lowest percentage of damaged seeds and Index of infestation; it was followed by the variant with full mineral fertilization and the control variant. The individual application of N resulted in highest damaged seeds percentage as well as highest Index of infestation; it also ensured the highest weight loss on average for the studied period.

Abstract Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76–11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11–9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10–13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.

The specifics of the word formation reflecting the certain protest of a society part against the Digital Society concept implementation in the country are considered on the material of Russian-language media texts. The aim of the study is to determine the semantic dominants and pragmatic peculiarities of the new nominations as the interpretive language function realization. The analysis of the material is carried out in line with functional sociolinguistics using the methodology of establishing the cognitive conditionality of language processes. The research resulted in revealing the contents of nominations, which reflect the protest attitude towards the concept of Digital Society. According to the type of the referent the following groups of lexical units are identified: the nominations of digitalization members, of the process itself and its consequences, as well as the foreseen future. The word-building peculiarities of the protest nominations are noted, their role in the key term elements structure of the Digital Society language is emphasized. The ‘restriction of freedom’ has been revealed to be the common semantic dominant of the new nominations. The coining of the units under consideration is characterized by the use of label-words and word-building formants that are typical of protest nominations. The semantic modification of the Digital Society terms shifts towards the ideologisation of meaning. The language and rhetoric of the official Digital Society concept followers, using their own ideologemes and word markers, are opposed to the language of the anti-digital resistance. The research outlook is in the analysis of pseudo arranging Digital Society nominations, which disguise the actual state of affairs.

Multi-proxy analysis (spore-pollen, dinoflagellate cysts, other non-pollen palynomorphs (NPPs), radiocarbon dating and lithology) was performed on marine sediments from three new cores retrieved during the two cruise expeditions on board the Research Vessel “Akademik” in 2009 and 2011. The Varna transect comprises three cores extending from the outer shelf, continental slope and deep-water zone. The record spans the last 26000 years (all ages obtained in this study are given in calendar years BP (cal. yrs BP)). The pollen record reveals the spreading of steppe vegetation dominated by Artemisia and Chenopodiaceae, suggesting cold and dry environments during the Late Pleniglacial – Oldest Dryas (25903–15612 cal. yrs BP). Stands of Pinus and Quercus reflect warming/humidity increase during the melting pulses (19.2–14.5 cal. ka BP) and the Late Glacial interstadials Bølling and Allerød. The Younger Dryas (13257–11788 cal. yrs BP) coldest and driest environments are clearly demonstrated by the maximum relative abundance of Artemisia and Chenopodiaceae. During the Early Holocene (Preboreal and Boreal chronozones, 11788–8004 cal. yrs BP), Quercus appeared as a pioneer species and, along with other temperate deciduous arboreal taxa, formed open deciduous forests as a response to the increased temperature. The rapid expansion of these taxa indicates that they survived in Glacial refugia in the coastal mountains. During the Atlantic chronozone (8004–5483 cal. yrs BP), optimal climate conditions (high humidity and increased mean annual temperatures) stimulated the establishment of species-rich mixed temperate deciduous forests. During the Subboreal chronozone (5483–2837 cal. yrs BP), Carpinus betulus and Fagus expanded simultaneously and became more important components of mixed oak forests and probably also formed separate communities. During the Subatlantic chronozone (2837 cal. yrs BP to pre-industrial time), climate-driven changes (an increase of humidity and a cooling of the climate) appear to be the main drivers of the specific vegetation succession expressed by increased abundance of Alnus, Fraxinus excelsior and Salix along with lianas, suggesting formation of flooded riparian forests (so called ‘Longoz’) lining the river valleys along the Black Sea coast. The first indicators of farming and other human activities have been recorded since 7074 cal. yrs BP. The dinoflagellate cyst (dinocyst) assemblages have been analysed to assess the changes in the Black Sea environment over the last 26000 years in terms of fluctuation in paleoproduction and surface water conditions related to changes in climate, freshwater input and Mediterranean water intrusion. Two major dinocyst assemblages were distinguished: one dominated by stenohaline freshwater/brackish-water species and a successive one dominated by euryhaline marine species. The changes in the composition of the assemblages occurred at 7668 cal. yrs BP. The abrupt decrease of stenohaline freshwater/brackish-water species Pyxidinopsis psilata and Spiniferites cruciformis was followed upwards by a gradual increase in euryhaline marine species, such as Lingulodinium machaerophorum, Spiniferites belerius, S. bentorii and acritarch Cymatiosphaera globulosa. The first occurrence of euryhaline marine species took place synchronously with the onset of sapropel deposition. Modern marine conditions were established after 6417 cal yrs BP when an abundance of Mediterranean-related species, such as Operculodinium centrocarpum and Spiniferites mirabilis, along with other heterotrophic species, occurred. After the stable cold and dry environment during the Last Glacial Maximum, the phytoplankton record of core AKAD 11-17 shows that Pediastrum boryanum var. boryanum has a cyclical abundance associated with the deposition of four red-brown clay layers between 19.2 and 14.5 cal. ka BP. This event is associated with the major melting phase of European Ice drained by the Danube and Dnieper Rivers in response to climate warming observed after the end of the Last Glacial Maximum. During the Early Holocene, P. psilata, characterised by a preference to warmer temperatures, demonstrates its ecological optimum for growth concerning SST reaching maximum relative abundance of 94% between 11072 and 8638 cal. yrs BP. This maximum was interrupted by an abrupt significant short-term decrease in the relative abundance of P. psilata centred between 8500 and 8300 cal. yrs BP reflecting cold conditions similar to those of Younger Dryas. This finding, also confirmed by the rapid significant decrease of arboreal pollen, particularly of Quercus in the same studied core, is considered a regional expression of the well-known ‘8.2 ka cold event’ which is commonly linked to a meltwater-related perturbation of the Atlantic Meridional Overturning Circulation (AMOC) and associated collapse of oceanic northward heat transport. Our fossil pollen and dinocyst data confirm that the high amplitude temperature anomaly associated with ‘the 8.2 ka cold event’ may have also occurred in south-eastern Europe, at lower latitudes of the western Black Sea coastal area, most probably due to atmospheric transition and/or river discharge.

Background: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, axonal damage and loss of neurons. Its growing incidence has determined the need for more intensive research towards effective models for managing disease progression and evaluation of treatment response. Finding clinically relevant biomarkers has been a significant challenge. Purpose: This review aims to summarize the findings from current relevant literature sources on neurofilaments as a potential biomarker of diagnostic and prognostic value in patients with MS. Results: Recently, neurofilaments have been identified as the most promising and informative biomarkers of axonal damage and loss. Neurofilament concentration demonstrates a strong association with the disease course, activity and progression, disability accumulation and response to disease-modifying treatment. A significant correlation with future relapse rates, symptom worsening and risk of conversion from clinically isolated syndrome (CIS) to definite MS has also been established. Several MS therapies have demonstrated a substantial reduction in neurofilament levels upon treatment initiation. Conclusion: The results available from real-world studies and clinical trials regarding neurofilaments as a reliable predictor and indicator of MS disease course are encouraging. They have consistently proven to be of utility if integrated into the diagnostic and therapeutic algorithm of MS patients. This review encompasses undeniable data confirming the considerable potential of neurofilaments for becoming the first globally verified biomarker for MS. The accessibility, safety, low cost and possibility for serial evaluation make the neurofilaments the perfect component to be implemented in routine clinical tests for MS.

The main results of the work of the team of the Institute of Mathematics and Informatics at the Bulgarian Academy of Sciences on the research projects CLaDA-BG – the Bulgarian National Interdisciplinary Research e-Infrastructure for Resources and Technologies in Favor of the Bulgarian Language and Cultural Heritage, Part of the EU Infrastructures CLARIN and DARIAH and No KP-06-N50/4 30.11.2020 “Fourteenth Century South Slavonic Scribes and Scriptoria (Palaeographical Attribution and Online Repertorium)”, will be presented during the Information Day within the DiPP2024 conference. The main emphasis will be placed on developments and implementations of CultIS – a webbased software platform for intelligent digital management and presentation of large data sets and knowledge from the fields of culture, humanities, and social sciences.

The paper gives an overview on the current landscape and the activities on both national and institutional level regarding Open Science, Open Access to scientific information, Open Data, and the Bulgarian Open Science Cloud.

The paper presents the research, development, and some of the major implementations to date of the web-based platform for intelligent cultural content management CultIS. It is an innovative environment providing descriptive cataloging, subject indexing, intelligent data retrieval, curation and collection development aimed at meeting the functional needs associated with the growing expectations of users of cultural institutions such as libraries, museums and other providers of cultural and historical heritage. Based on the implementations of CultIS for different purposes and contexts, not only its effectiveness, stability and reliability are tested, but the results also serve for its constant development and improvement.

The structure verification of 5′-oxospiro-(fluorene-9,4′-imidazolidine)-2′-thione by NMR is reported. Toward this aim, 2D NMR techniques including 1H-1H COSY, HMQC, and HMBC experiments were used to assist with the assignment of the 1H and 13C chemical shifts for the corresponding structure. The mutual interpretation of the 1D and 2D NMR spectra ensured a complete and accurate 1H and 13C NMR data assignment for 5′-oxospiro-(fluorene-9,4′-imidazolidine)-2′-thione.

IntroductionFabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. Reduced or absent enzyme activity causes progressive lysosomal accumulation of globotriaosylceramide (Lyso-Gb3) in various cells throughout the body to trigger inflammation and fibrosis.Case descriptionWe present the first familial case of Fabry Disease in North Macedonia identified based on clinical manifestations and confirmed through enzyme, biomarker, and genetic tests. The index case in the family was a 45-year-old male undergoing hemodialysis therapy. He has had chronic burning uncontrolled limb pain since childhood, intermittent abdominal cramps, anhidrosis, and hypertension. The constellation of clinical presentations accompanied by similar symptoms in close family members prompted the enzyme, biomarker, and genetic analyses for Fabry disease. Genetic testing identified a known pathogenic GLA missense variant c.443G>A or p.(Ser148Asn) in the hemizygous state. Subsequent family studies allowed identification of another hemizygous male and five heterozygous female carriers affected by this X-linked disorder.ConclusionWe report identification of the first familial case of Fabry disease in North Macedonia and describe the phenotype associated with the Ser148Asn GLA variant. Greater awareness of this rare disease linked to continuous medical education is crucial for timely diagnosis and treatment.