Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry.

Modern humans appeared in Europe by at least 45,000 years ago1-5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.

Initial Upper Palaeolithic Homo sapiens from Bacho Kiro Cave, Bulgaria.

The Middle to Upper Palaeolithic transition in Europe witnessed the replacement and partial absorption of local Neanderthal populations by Homo sapiens populations of African origin1. However, this process probably varied across regions and its details remain largely unknown. In particular, the duration of chronological overlap between the two groups is much debated, as are the implications of this overlap for the nature of the biological and cultural interactions between Neanderthals and H. sapiens. Here we report the discovery and direct dating of human remains found in association with Initial Upper Palaeolithic artefacts2, from excavations at Bacho Kiro Cave (Bulgaria). Morphological analysis of a tooth and mitochondrial DNA from several hominin bone fragments, identified through proteomic screening, assign these finds to H. sapiens and link the expansion of Initial Upper Palaeolithic technologies with the spread of H. sapiens into the mid-latitudes of Eurasia before 45 thousand years ago3. The excavations yielded a wealth of bone artefacts, including pendants manufactured from cave bear teeth that are reminiscent of those later produced by the last Neanderthals of western Europe4-6. These finds are consistent with models based on the arrival of multiple waves of H. sapiens into Europe coming into contact with declining Neanderthal populations7,8.

Fine-grained differences in gender-cue strength affect predictive processing in children: Cross-linguistic evidence from Russian and Bulgarian.

We tested predictive gender agreement processing in adjective-noun phrases by 45 4- to 6-year-old Russian- and Bulgarian-speaking children using the visual world eye-tracking paradigm. Russian and Bulgarian are closely related languages that have three genders but differ in the nature and number of gender cues on adjectives. Analysis of the proportion and time course of looks to the target noun showed that only Bulgarian children used gender cues to predict the upcoming noun. We argue that the cross-linguistic difference in the gender cue strength is revealed through the operation of economy, transparency, and interdependence in a gender complexity matrix. The documented advantage for Bulgarian children in gender agreement processing and acquisition underscores the need for a comparative language acquisition approach to typologically close languages.

Malnutrition in Institutionalized and Non-Institutionalized Neurologically Impaired Children in Bulgaria.

INTRODUCTION: The nutritional status of children with neurological impairment affects their health and quality of life. Bulgaria has many abandoned disabled children in residential homes. Lack of parental care puts them at risk for poor growth, suboptimal nutrition, and physical and mental development. Our study aims to identify factors associated with poor nutrition in Bulgarian children with neurological impairment living in different environments. METHODS: From January to December 2017, a cross-sectional study was conducted in northeastern Bulgaria. We recruited 109 residential and nonresidential children. The study included demographics, medical history, anthropometric measurements, biochemical tests, nutritional assessment, and gastrointestinal signs and symptoms. Data were analyzed with Jamovi 2.2.5 at a 0.05 significance level. Logistic regression was used to predict wasting in both environmental settings. RESULTS: About 70% of the neurologically impaired children living in residential settings have malnutrition based on weight-for-age Z-score, compared to 25% of the non-residential children. Prematurity, low gross motor function (as measured by the gross motor function classification system), pureed food consumption, birth before 37 weeks, and living in residential care homes are linked to poor nutrition. CONCLUSION: Neurologically impaired children have a poor nutritional state, especially those living in residential homes. The study underscores the pressing need for the allocation of additional nutrition resources to effectively address the nutritional and developmental needs of children with neurological disabilities in Bulgaria.

Which factors influence health services utilization in Bulgaria? Results of a cross-sectional survey.

BACKGROUND: Research on the factors influencing health care services utilization in Bulgaria does not apply a particular model to analyze these determinants. To fill this gap, we apply the Andersen's Behavioural Model, a commonly used framework, to determine the factors that impact the utilization of health care services in our country. METHODS: Data are collected in an online survey conducted in Bulgaria in 2023 among consumers. The standardized questionnaire includes questions on the utilization of health care services used by the respondent during the preceding 12 months. We apply binary logistic regressions to analyze predictors of visits to general practitioners and medical specialists, as well as hospitalizations. RESULTS: The results of the regression analysis show that the factors of self-reported health status and the presence of a chronic disease influence the utilization of health care services except for general practitioner visits. Greater trust in general practitioners and hospitals is associated with an increased probability of undergoing examinations and hospitalizations. Predisposing and enabling characteristics appear as significant determinants of health care utilization. CONCLUSION: The study confirms the relevance of the Behavioural Model for the use of health care services in the Bulgarian context. Further research on health outcomes and their impact on utilization can help determine the most efficient level and appropriateness of the use of health care services.

Addressing chronic diseases: a comparative study of policies towards type-2 diabetes and hypertension in selected European countries.

BACKGROUND: Type-2 diabetes (T2D) and hypertension (HTN) are two of the most prevalent non-communicable diseases (NCDs): they both cause a relevant number of premature deaths worldwide and heavily impact the national health systems. This study illustrates the impact of HTN and T2D in four European countries (Albania, Bulgaria, Greece and Spain) and compares their policies towards the monitoring and management of HTN and T2D and the prevention of NCDs as a whole. This analysis is conducted throughout the DigiCare4You Project (H2020)-which implements an innovative solution involving digital tools for the prevention and management of T2D and HTN. METHODS: The analysis is implemented through desk research, and it is enriched with additional information directly provided by the local coordinators in the four countries, by filling specific semi-structured forms. RESULTS: The countries exhibit significant differences in the prevalence of HTN and T2D and available policies and programs targeted to these two chronic conditions. Each country has implemented strategies for HTN and T2D, including prevention initiatives, therapeutic guidelines, educational programs and children's growth monitoring programs. However, patient education on proper disease management needs improvement in all countries, registries about patients affected by HTN and T2D are not always available, and not all countries promoted acts to contain the increasing rates of risk factors related to NCDs. CONCLUSIONS: While political awareness of the risks associated with HTN, T2D and NCDs in general is growing, there is a collective need for countries to strengthen their policies for preventing and managing these chronic diseases.

First detection of a cefiderocol-resistant and extensively drug-resistant Acinetobacter baumannii clinical isolate in Bulgaria.

Cefiderocol (CFDC) is a first-in-class siderophore cephalosporin with potent activity against multidrug-resistant Gram-negative bacteria including carbapenem-resistant Acinetobacter baumannii. The present study aimed to explore the CFDC resistance mechanisms of an extensively drug-resistant A. baumannii isolate from Bulgaria. The A. baumannii Aba52 strain (designated Aba52) was obtained in 2018 from a blood sample of a critically ill patient. The methodology included antimicrobial susceptibility testing, whole-genome sequencing (WGS), reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), multilocus sequence typing, and phylogenomic analysis. The isolate demonstrated high-level resistance to CFDC (MIC = 64 mg L-1), resistance to carbapenems, aminoglycosides, fluoroquinolones, sulfamethoxazole-trimethoprim, and tigecycline, as well as susceptibility only to colistin. WGS-based resistome analysis revealed the existence of blaOXA-23, blaOXA-66 and blaADC-73. Seven non-conservative missense mutations affecting iron transport-related genes were detected: exbD4 (p.Ser61Pro), tonB2 (p.Ala268Val), bauA (p.Thr61Ala), ftsI (p.Ala515Val), piuA (p.Gly216Val), and feoB (p.Ser429Pro and p.Thr595Ala). A variety of virulence factors associated with adherence, biofilm formation, enzyme production, immune invasion, iron uptake, quorum sensing, and two-component regulatory systems were identified, suggesting a significant pathogenic potential of Aba52. The performed RT-qPCR analysis showed diminished (0.17) and absent expression of the pirA and piuA genes, respectively, encoding TonB-dependent siderophore receptors. Aba52 belonged to the widespread high-risk sequence type ST2 (Pasteur scheme). To the best of our knowledge, this is the first documented case of CFDC-resistant A. baumannii in Bulgaria even though, CFDC has never been applied in our country. The emerging resistance highlights the crucial need for nationwide surveillance targeting the implementation of novel antibiotics.

Genomic insights into NDM-1-producing Pseudomonas aeruginosa: Current status in a Bulgarian tertiary hospital and on the Balkans.

The present study aimed to explore the genomic characteristics of eight New Delhi metallo-ß-lactamase-1 (NDM-1)-producing carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from a Bulgarian tertiary hospital (2021-2023) in comparison to blaNDM-1-positive strains originating from the Balkans. Antimicrobial susceptibility testing, phenotypic assays for carbapenemase activity, PCR screening, whole-genome sequencing (WGS), and phylogenomic analysis were performed. Seven of the CRPA isolates investigated (Minimum inhibitory concentration values of imipenem and meropenem >32 mg L-1) were also resistant to piperacillin-tazobactam, ceftazidime, ceftazidime-avibactam, cefepime, ceftolozane-tazobactam, amikacin, tobramycin, ciprofloxacin, and levofloxacin, but were susceptible to colistin (0.5-2 mg L-1) and cefiderocol (0.25-1 mg L-1). The P. aeruginosa Pae57 isolate (designated Pae57) remained susceptible to aminoglycosides as well. WGS uncovered the co-existence of blaNDM-1 and blaGES-1. The isolates belonged to the ST654 high-risk clone, except for Pae57 (ST611). Alignment against reference sequences revealed the presence of a Tn21 transposon harboring bleMBL-blaNDM-1-ISAba125. It was similar to that found in the P. aeruginosa ST654 NDM1_1 strain (GCA_020404785.1) from Serbia. Phylogenomic analysis of our isolates indicated that seven of them (ST654) differed from each other in no more than 44 single-nucleotide polymorphisms (SNPs). Pae57 (ST611) was strikingly different (>21,700 SNPs) compared to all Balkan strains. In conclusion, to our knowledge this is the first report of blaNDM-1-positive P. aeruginosa ST611 isolation, which indicates the transmission dynamics of this determinant between high-risk and potentially high-risk P. aeruginosa clones. Obtained results unveil the dissemination of clonally related NDM-1-producing P. aeruginosa strains in the monitored hospital for approximately a 2-year period.

The acoustics of Contemporary Standard Bulgarian vowels: A corpus study.

A comprehensive examination of the acoustics of Contemporary Standard Bulgarian vowels is lacking to date, and this article aims to fill that gap. Six acoustic variables-the first three formant frequencies, duration, mean f0, and mean intensity-of 11 615 vowel tokens from 140 speakers were analysed using linear mixed models, multivariate analysis of variance, and linear discriminant analysis. The vowel system, which comprises six phonemes in stressed position, [ε a ɔ i ɤ u], was examined from four angles. First, vowels in pretonic syllables were compared to other unstressed vowels, and no spectral or durational differences were found, contrary to an oft-repeated claim that pretonic vowels reduce less. Second, comparisons of stressed and unstressed vowels revealed significant differences in all six variables for the non-high vowels [ε a ɔ]. No spectral or durational differences were found in [i ɤ u], which disproves another received view that high vowels are lowered when unstressed. Third, non-high vowels were compared with their high counterparts; the height contrast was completely neutralized in unstressed [a-ɤ] and [ɔ-u] while [ε-i] remained distinct. Last, the acoustic correlates of vowel contrasts were examined, and it was demonstrated that only F1, F2 frequencies and duration were systematically employed in differentiating vowel phonemes.

Seroprevalence of hepatitis D virus in Bulgarian outpatients with history of liver dysfunction.

The aim of this research was to define the prevalence of antibodies against hepatitis D virus (anti-HDV Ab) in a group of 26 outpatients with liver dysfunction in northeastern Bulgaria. Serum samples were obtained from April 2022 to December 2023 in the "Status" Medical Diagnostic Laboratory, Varna, Bulgaria. We found seroprevalence of anti-HDV Ab in 15.4% (CI: 4.3-34.8%) of the target population. Age and gender had no significant role in HDV seropositivity.

Etiological structure and antibiotic resistance pattern of burn wound infections in hospitalized patients - a one-center study in Varna, Bulgaria.

In the present retrospective study, we have evaluated bacterial pathogens isolated from patients admitted to the Burn Care Unit at the Military Medical Academy, Varna, Bulgaria over a three-year period (January 2019 - December 2021). We also tried to summarize the corresponding antibiotic resistance pattern of the isolated infectious agents. A total of 1030 isolates were obtained from 1912 burn wound samples investigated. There were 553 Gram-positive (53.7%) and 477 Gram-negative (46.3%) isolates. The most common isolates for the study period were coagulase-negative staphylococci (CoNS) (25%), Pseudomonas aeruginosa (17.7%), Staphylococcus aureus (16.6%), Acinetobacter baumannii (7.7%), Enterobacter spp. (7.1%), Escherichia coli (4.4%), Proteus spp. (3.4%), and Klebsiella spp. (2.9%). Glycopeptide antibiotics and linezolid were the most effective drugs against gram-positive isolates, followed by amikacin (for synergistic combinations), whereas colistin, imipenem, meropenem, cefoperazon/sulbactam, and piperacillin/tazobactam were the most active drugs against Gram-negative isolates, and colistin, ampicillin/sulbactam - against A. baumannii.

An integrative approach highlights the discrepancy in the genetic, phenotypic, and presumptive taxonomic structure of Phoxinus (Actinopterygii, Leuciscidae, Phoxininae) in Bulgaria.

The present drainage network of Bulgaria is the result of a complex Neogene and Quaternary evolution. Karst, which has developed on 23% of the territory, further complicates the hydrological pattern. Fresh waters of Bulgaria drain into the Black Sea and the Aegean Sea basins and can be roughly divided into the Danube (Middle and Lower Danube), non-Danube Black Sea, East Aegean, and West Aegean hydrological regions. Phoxinus, a small leuciscid fish, has a mosaic distribution in all four of these regions, inhabiting small mountainous and semi-mountainous streams. Based on morphology, it was identified as three species, Phoxinus phoxinus in the Danube, Phoxinus strandjae in the non-Danube, and Phoxinus strymonicus in West Aegean region. Later, molecular data revealed Phoxinus csikii and Phoxinus lumaireul in the Middle Danube and P. csikii in the Lower Danube. Phoxinus has been the focus of many studies, showing a high molecular and morphological diversity, which is not entirely consistent with previous morphology-only-based taxonomic concepts. In this study, molecular (a mitochondrial marker and a nuclear marker) and morphological data from both historical and recently sampled collections were analysed to assess the applicability of the integrative approach in Phoxinus. The results showed a significant influence of the complex paleo- and recent hydrology on the currently observed genetic structure of the considered populations and species. Furthermore, the study also demonstrated a strong influence of phenotypic plasticity on the morphological analysis of Phoxinus and the lack of a clear differentiation between P. csikii and P. strandjae. A barcoded specimen was designated as neotype to fix the species named P. strandjae in the current taxonomic concept. Finally, a significant discordance between genetically delimited clades and phenotypic groups did not allow a proper delineation of the species distributed in Bulgaria, demonstrating that more molecular markers are needed for further taxonomic study of the Phoxinus complex.

A Comparison between Bulgarian Tanacetum parthenium Essential Oil from Two Different Locations.

Tanacetum parthenium L. (Asteraceae) is a perennial herbaceous plant with a long-standing historical use in traditional medicine. Recently Tanacetum parthenium L. essential oil has been associated with a promising potential for future applications in the pharmaceutical industry, in the cosmetics industry, and in agriculture. Investigations on the essential oil (EO) have indicated antimicrobial, antioxidant, and repellent activity. The present study aimed to evaluate the chemical composition of Bulgarian T. parthenium essential oil from two different regions, to compare the results to those reported previously in the literature, and to point out some of its future applications. The essential oils of the air-dried flowering aerial parts were obtained by hydrodistillation using a Clevenger-type apparatus. The chemical composition was evaluated using gas chromatography with mass spectrometry (GC-MS). It was established that the oxygenated monoterpenes were the predominant terpene class, followed by the monoterpene hydrocarbons. Significant qualitative and quantitative differences between both samples were revealed. Camphor (50.90%), camphene (16.12%), and bornyl acetate (6.05%) were the major constituents in the feverfew EO from the western Rhodope Mountains, while in the EO from the central Balkan mountains camphor (45.54%), trans-chrysanthenyl acetate (13.87%), and camphene (13.03%) were the most abundant components.

Chemical Composition and Lipid Bioactive Components of Centaurea thracica Dwelling in Bulgaria.

Centaurea thracica (Janka) Hayek is a plant common in southern Bulgaria. The inflorescences were collected during June and September 2021, while their seeds were obtained in September 2021. The chemical and lipid composition of the inflorescences during the vegetation process of the plant were established. A significant decrease in total proteins (from 8.7 to 7.4%), glyceride oils (2.0-1.7%), and ash (4.5-4.2%) content was observed, while the amount of carbohydrates (72.3-77.2%) and fibers (28.7-35.8%) increased. During the vegetation of the plant, the content of oleic and linoleic acids increased up to 2-3 times, while the level of palmitic acid decreased. The lipids from the seeds were rich in oleic (53.0%) and palmitic (36.2%) acids. The tocopherol content in the oils of the inflorescences during vegetation increased from 58 to 110 mg/kg, and the content in the oil from the seeds was 260 mg/kg. The phospholipid content decreased during vegetation, and differences were observed in the composition between the inflorescences and the seeds. The high content of oleic acid, linoleic acid, tocopherols, and phospholipids determine the nutritional and biological value of the oils isolated from Centaurea thracica, and contribute to their potential use in various directions.

History of development of undergraduate public health education in Bulgaria.

OBJECTIVE: The study aims to present a historical review and analysis of the establishment and development of undergraduate public health (PH) education in Bulgaria from 1878 until 2019. METHODS: А search and selection of historical documents was performed, including laws, rules, regulations, government plans, programmes, scientific publications from periodical medical press, journals, specialized monographs, and books. A retrospective analysis of the normative documents related to the organization of the sanitation and public health activities, and to the provision of professional undergraduate education of the public health workforce in Bulgaria has been carried out. The required competences and tasks of the specialists exercising public health control services were extracted. RESULTS: The development in the public health educational activities were followed in three consecutive periods: the newly independent state (1878-1944); the socialist state (1945-1990); the democratizing state (1990-2019). The development of organized PH activities began after the liberation of Bulgaria in 1878. The historical analysis reveals a direct link between the major socioeconomic changes in the country and the organization of PH undergraduate education which passed through dynamic transformations. The professional education in the sphere of PH started with the training of feldshers, followed by sanitary feldsher and sanitary health inspectors performed in secondary vocational medical schools during the socialist period, reaching the stage of undergraduate university PH education provided by medical colleges associated with universities in the third period. CONCLUSION: Despite the continuous development in the organization of undergraduate PH education in Bulgaria, its content is still not fully compatible with the basic European PH services and actions. There is a growing need for wider standardization and integration of undergraduate PH education in the EU so that the specialty can reach the status of a regulated health profession similar to medicine, nursing, and others.

Are the elements zinc, copper, magnesium, and rubidium related to nutrition and iodine deficiency in pregnant Bulgarian women from iodine deficient region?

OBJECTIVE: Trace elements are essential for the biochemistry of the cell. Their reference values have been found to differ considerably in pregnant women stratified by age, place of residence, anthropometric status, and length of pregnancy. In optimal amounts, these elements reduce the risk of pregnancy complications. Subclinical hypothyroidism in pregnancy is associated with adverse maternal and neonatal outcomes. The aim of the study was to determine the effects of zinc (Zn), copper (Cu), magnesium (Mg), and rubidium (Rb) on pregnant women in an iodine deficiency region and find the relationship with the thyroid status and nutrition. METHODS: We evaluated the iodine status of 61 healthy pregnant women from an iodine deficient region in Bulgaria. Thyroid stimulating hormone (TSH) and thyroxin free (FT4) levels were measured using ELISA. RESULTS: We found elevated levels of copper that differed the most between the first and second trimesters; Cu and TSH were found to be positively correlated (р < 0.05). Lower Cu levels were found in pregnant women consuming pulses more than 2-3 times a week (р = 0.033). The women consuming fish more than 2-3 times a week had higher levels of Rb. We found a pronounced iodine deficiency in more than half of the examined women in the first to third trimesters, without any effect of pregnancy on the ioduria (р=0.834). All second and third trimester cases were associated with severe ioduria (< 150 µg/L). CONCLUSION: The high Cu levels were associated with subclinical hypothyroidism (SCH) and less pulse consumption during pregnancy in an iodine deficiency endemic area. SCH was found in 24% of the pregnant women in such an area while in 13% of them SCH had progressed to overt hypothyroidism.

Defining Trimester-Specific Reference Intervals for Thyroid Hormones: Insights from a Bulgarian Monocenter Study.

Background and Objectives: Pregnancy introduces various interfering factors that, alongside individual variations, impact the assessment of thyroid function tests. This underscores the necessity of defining trimester-specific reference intervals for thyroid-stimulating hormone (TSH) levels. Differences in population characteristics, including ethnicity, socio-economic factors, iodine prophylaxis, and obesity, emphasize the need to establish trimester-specific TSH ranges for women of reproductive age in the respective region or center. The aim of the present study was to establish first- and second-trimester-specific reference intervals for TSH and free thyroxine (FT4) in a relevant pregnant population. Materials and Methods: A retrospective monocenter analysis utilized the electronic database of Ob/Gyn Hospital "Dr. Shterev", Sofia, Bulgaria. The analysis involved data from 497 pregnant and 250 non-pregnant women, all without evidence of thyroid dysfunction or a family history thereof, no indication of taking medication interfering with thyroid function, no evidence of levothyroxine treatment, and no history of sterility treatment. To establish the limits of the TSH reference range, the percentile method was applied using a bootstrapping procedure following the recommendations of the International Federation of Clinical Chemistry (IFCC). Results: Trimester-specific reference intervals for TSH and FT4 in our center were established as follows: first trimester-0.38-2.91 mU/L, FT4-12.18-19.48 pmol/L; second trimester-0.72-4.22 mIU/L and 9.64-17.39 pmol/L, respectively. We also established the normal reference range for the non-pregnant control group, which is similar to that applicable in our laboratory. Conclusions: Our results differ from the fixed limits recommended by the American Thyroid Association, European Thyroid Association, and Endocrine Society Guidelines. Following the relevant established intervals would significantly impact timely diagnosis and therapy requirements for a substantial proportion of pregnant women.

Patients' perspectives on the use of artificial intelligence and robots in healthcare.

OBJECTIVE: We aimed to evaluate the opinions of individuals aged 18 and above in our country regarding the use of artificial intelligence (AI) and robots in the field of healthcare. BACKGROUND: The growing population and patient load, coupled with increasing data, can expedite the diagnosis and treatment process for patients through faster, easier, and more accurate interpretation of information. METHODS: The study encompasses voluntary participants aged 18 and above, who have either undergone surgery in a hospital or have accompanied a family member during a surgical procedure and possess internet access as well as the capability to participate in online surveys. RESULTS: A total of 725 individuals participated in our study 61% (n=442) of respondents expressed trust in the operation of AI and robots in the hospital setting. 64.1% (n=465) of participants expressed trust in AI's contribution to disease diagnosis and laboratory tests. The confidence in AI's use in radiological examinations and its contribution reached 71.6% (n=519). CONCLUSION: This study demonstrates that the use of AI and robots in healthcare services is accepted by our society and would be appropriate in our society (Tab. 5, Fig. 1, Ref. 24).

Evaluation of disease-specific quality of life and its influencing factors in Bulgarian patients with Graves' orbitopathy.

PURPOSE: Graves' orbitopathy (GO) profoundly affects patients' quality of life (QoL). Our aim was to assess QoL in patients with different forms of GO and to search for predictors of QoL. METHODS: This was a cross-sectional study involving 221 consecutive unselected GO patients (77.4% females, mean age 52 ± 11.6) referred to our clinic in the period 2017-2021. Detailed medical history was obtained from all patients, followed by hormonal and immunological testing and comprehensive ocular status. QoL was assessed by a disease-specific questionnaire (GO-QoL), consisting of two scales-one related to visual functioning (QoL-VF) and the other-to physical appearance (QoL-AP). The results were calculated by formula and expressed as percentages. RESULTS: Mild GO patients had significantly higher scores on both scales of GO-QoL compared to moderate-to-severe and sight-threatening GO patients (82.0 vs. 54.6% and 27.3% for QoL-VF; 70.1 vs. 54.4% and 36.9% for QoL-AP). Patients with active GO had significantly poorer QoL-VF (56.6 vs. 76.6%) and QoL-AP (53.1 vs. 67.5%) in comparison to patients with inactive GO. The stepwise linear regression analysis showed that the variables with major predictive value for QoL-VF were: CAS, diplopia score, visual acuity and severity of the symptoms (R2 = 0.44), whereas gender, CAS, diplopia score and proptosis best predicted QoL-AP (R2 = 0.39). CONCLUSIONS: The impact of GO on patients' QoL depends on the severity and activity of the disease. The clinical predictors of the impairment of QoL should be taken into account when considering the optimal adjunctive treatment approaches aiming to improve patients' QoL.

Low prevalence of influenza viruses and predominance of A(H3N2) virus with respect to SARS-CoV-2 during the 2021-2022 season in Bulgaria.

Social distancing, mask-wearing, and travel restrictions during the COVID-19 pandemic have significantly impacted the spread of influenza viruses. The objectives of this study were to analyze the pattern of influenza virus circulation with respect to that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Bulgaria during the 2021-2022 season and to perform a phylogenetic/molecular analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of representative influenza strains. Influenza infection was confirmed using real-time reverse transcription polymerase chain reaction in 93 (4.2%) of the 2193 patients with acute respiratory illness tested wherein all detected viruses were subtyped as A(H3N2). SARS-CoV-2 was identified in 377 (24.3%) of the 1552 patients tested. Significant differences in the incidence of influenza viruses and SARS-CoV-2 were found between individual age groups, outpatients/inpatients, and in the seasonal distribution of cases. Two cases of coinfections were identified. In hospitalized patients, the Ct values of influenza viruses at admission were lower in adults aged ≥65 years (indicating higher viral load) than in children aged 0-14 years (p < 0.05). In SARS-CoV-2-positive inpatients, this association was not statistically significant. HA genes of all A(H3N2) viruses analyzed belonged to subclade 3C.2a1b.2a. The sequenced viruses carried 11 substitutions in HA and 5 in NA, in comparison to the vaccine virus A/Cambodia/e0826360/2020, including several substitutions in the HA antigenic sites B and C. This study revealed extensive changes in the typical epidemiology of influenza infection, including a dramatic reduction in the number of cases, diminished genetic diversity of circulating viruses, changes in age, and seasonal distribution of cases.