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Objectives: study aims to provide a descriptive overview about the magnitude and frequency of dispensing the unprescribed antibiotics UABs. It furthermore aims, to specify the most dispensed UAB types, the most common infections, signs and symptoms that require dispensing the UABs in community pharmacies of Duhok city and its districts. Methods: A cross sectional cohort study had been conducted from September to October 2022, private community pharmacies of Duhok province were included in this study. A standardized questionnaire platform was utilized to complete the survey, it included 2 sections, the first of which was related to demographic data and the second part included details of the dispensing unprescribed antibiotics UABs like: what are the most common dispensed UABs, what are the most common illness and symptoms of patients who require dispensing UABs. Results: One hundred fifty pharmacies have been included in this study. The majorities were from Duhok city 46%, and Zakho 28.7%. The prevalence of dispensing UABs was 100%, the three most common dispensed UABs were Amoxicillin 77%, followed by azithromycin 16% and cefixime 7%. The most infections and conditions requiring dispensing UABs were tonsilitis (69.3%), followed by flu and common cold (58.7%), and lower respiratory tract infection (48.7%). Conclusion: This study concluded that dispensing UABs is a frequent practice in Duhok community pharmacies. Viruses are the most common cause of upper respiratory tract infections; hence, antibiotics must be avoided and OTC medicines should be encouraged to alleviate the symptoms. Continuing medical education through training pharmacists on dispensing antibiotics by adhering to the regulations of antibiotic stewardship is crucial.

BACKGROUND: In patients who have undergone retrograde endoscopic choledocholithoextraction, technical difficulties are frequently encountered when performing laparoscopic cholecystectomy, which is associated with the development of destructive changes in the gallbladder wall. However, no studies on the assessment of morphological changes occurring in the gallbladder wall at different terms after endoscopic retrograde bile duct interventions are currently available in the literature. The relevance and insufficient knowledge of the research area prompted this study. AIM: This study aimed to determine the optimal terms of laparoscopic cholecystectomy after endoscopic bile duct decompression performed for cholelithiasis complicated by choledocholithiasis based on morphological changes in the gallbladder wall. MATERIALS AND METHODS: A comparative analysis of the pathological examination of 198 gallbladders removed surgically on different days after endoscopic bile duct decompression performed for cholelithiasis complicated by choledocholithiasis is presented. RESULTS: In group 1, cholecystectomy after endoscopic bile duct decompression was performed on days 13. Gallbladder wall changes were observed in 10 (12.8%) patients. In group 2, cholecystectomy was performed on days 47. Inflammatory changes were revealed in 13 (37.1%) preparations. Pathological examination of the surgical specimens of the patients in group 3 who underwent cholecystectomy on days 1430 revealed changes in the gallbladder wall in 48 (56.4%) cases. CONCLUSIONS: Laparoscopic cholecystectomy after endoscopic bile duct decompression within the first 72 h is the most optimal.

BACKGROUND: According to the Federal Clinical Guidelines, patients with severe persistent allergic rhinitis and/or severe exacerbation who failed to respond to third-line pharmacotherapy (antihistamines, leukotriene receptor antagonists, nasal corticosteroids) are advised to consider the administration of omalizumab. However, there is a lack of practical recommendations guiding the regimens and duration of the omalizumab therapy in the severe exacerbation of seasonal allergic rhinitis. AIMS: To assess the efficacy of omalizumab additional therapy in patients with severe exacerbation of allergic rhinitis during the pollen season, and to determine the optimal regimen and duration of treatment. MATERIALS AND METHODS: This is an open observational uncontrolled prospective single-center study. 10 adult patients with severe exacerbation of seasonal allergic rhinitis due to birch pollen were selected for the study. All of them received the third-line of therapy according to Federal Clinical Guidelines and had absence or incomplete control: Total nasal symptom score 2. All of them were treated with omalizumab. The dose and regime were prescribed according to instructions that took into account the overall IgE level, as well as the patients weight. Daily symptom diaries and the need for rescue medication levels were evaluated. The primary endpoint had a decrease in the Combined Medical and Symptom Score mean. RESULTS: The additional omalizumab treatment improved allergic rhinitis control for all patients and also reduced the rescue medication (TNSS 1.8 [95% CI 1.562.04]; р 0.001, and CMSS 2.12 [95% CI 1.742.5]; р 0.001, by the end of 1 week after the first omalizumab injection; TNSS 2.53 [95% CI 2.053.01]; р 0.0001, and CMSS 5.22 [95% CI 4.745.7]; р 0.001, by the end of four weeks, respectively). It was noted that the omalizumab effect realization occurs for some time (37 days). Due to short-season pollen for birch (12 months), the duration of treatment in our study did not exceed one month, so we managed to achieve complete control over the symptoms in all patients by the omalizumab with a small multiplicity of injections (12 injections). No adverse events were registered during the study. CONCLUSION: Omalizumab additional therapy in patients with severe exacerbation of allergic rhinitis allows control of all symptoms. Taking into account the mechanism of its action, omalizumab should be administered at least a week before the expected pollen season in patients with severe exacerbation (according to the previous seasons) who did not complete their allergen-specific immunotherapy on time, and continue therapy till the end of the pollen season.

Conjugated molecules with phenylethynyl building blocks are usually characterised by torsional disorder at room temperature. They are much more rigid in the electronic excited state due to conjugation. As a consequence, the electronic absorption and emission spectra do not present a mirror-image relationship. Here, we investigate how torsional disorder affects the excited state dynamics of 9,10-bis(phenylethynyl)anthracene in solvents of different viscosities and in polymers, using both stationary and ultrafast electronic spectroscopies. Temperature-dependent measurements reveal inhomogeneous broadening of the absorption spectrum at room temperature. This is confirmed by ultrafast spectroscopic measurements at different excitation wavelengths. Red-edge irradiation excites planar molecules that return to the ground state without significant structural dynamics. In this case, however, re-equilibration of the torsional disorder in the ground state can be observed. Higher-energy irradiation excites torsionally disordered molecules, which then planarise, leading to important spectral dynamics. The latter is found to occur partially

The spin dynamics of radical pairs from ion-pair complexes between viologen and tetraarylborate compounds have been investigated in the presence of microwave (μw) radiation, using steady-state electron paramagnetic resonance to follow the radical pair dynamics.

BACKGROUND: COVID-19 is a disease which course depends on a number of factors, including genetic ones, among which the genes of the innate immune system receptors TLR (toll-like receptors), which play a central role in the development of innate immunity reactions, are of particular interest. The SARS-CoV-2 virus structure includes, in addition to the nucleocapsid, a protein-lipid membrane envelope, which determines the recognition of virus components by different TLRs, including TLR2 subfamily receptors (TLR1, 6, 10), which genetic polymorphisms occur with different frequencies in different human populations and affect not only the functional activity of the innate immunity but also determine the quality of the adaptive immune response. AIM: The study aimed to determine the association of polymorphisms of toll-like receptor genes TLR1, TLR6 and TLR10 with the severity of coronavirus infection (COVID-19) in the Russian population of the Chelyabinsk region. MATERIALS AND METHODS: The study included 86 patients from COVID-departments of hospitals in Chelyabinsk with a diagnosis of bilateral pneumonia with a degree of severity: moderate (M-BLP, n = 36) or severe (S-BLP, n = 50). The control group consisted of 100 healthy individuals from the register of the Chelyabinsk regional hemotransfusion station (Control). All the individuals studied belonged to the Russian ethnic group. Polymorphisms 1805TG of TLR1 gene, 745CT of TLR6 gene and 721AC of TLR10 gene were determined using polymerase chain reaction with restriction fragment length polymorphism. The analysis of the association between genotypes and the status of individuals was carried out using the correspondence analysis and the Monte Carlo method. RESULTS: It was revealed that the differences between the studied groups are completely determined by TLR1 genotypes. The GG genotype with statistical significance is more often detected in the Control group compared to M-BLP and S-BLP (p 0.001, OR = 12.94) and can be assessed as protective in relation to the development of bilateral pneumonia in COVID-19. The TT genotype can be considered as predisposing to the development of a severe form of bilateral pneumonia in COVID-19 (p = 0.022): the TT genotype is significantly less common (OR = 0.20) in the M-BLP group compared to S-BLP. CONCLUSIONS: It can be assumed that the genetic variant 1805*G of the TLR1 gene, which provides a moderate pro-inflammatory response and predominates in European populations, gives an advantage to its owners, preventing the development of complicated conditions in COVID-19 infection.

AIM: The aim of this study was to investigate the features of the course of pregnancy, childbirth and the postpartum period in women with cerebrovascular pathology and to assess the choice of the optimal method of delivery and perinatal outcomes. MATERIALS AND METHODS: This study assessed ten cases of pregnancy and delivery in women with cerebrovascular pathology (arteriovenous malformation (50%), cavernous malformation (30%), and arterial aneurysms (20%)). All women were followed up, treated and delivered at the Obstetrics and Gynecology Clinic (Academician I.P. Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia) between 2018 and 2019. RESULTS: In eight out of ten women with cerebrovascular pathology, the course of pregnancy was complicated by the threat of premature birth, chronic placental insufficiency, and severe preeclampsia. In one case, the pathology of the cerebral blood vessels (cavernous malformation) manifested itself as a general hemorrhagic disturbance of the cerebral blood circulation during this pregnancy; in all other cases, cerebrovascular pathology was diagnosed before pregnancy. When analyzing the timing of delivery, it should be noted that only in one case with severe preeclampsia, the pregnancy was completed at 34 weeks and 1 day (emergency childbirth). The average delivery time for the remaining patients was 38 weeks 3 days (planned childbirth). The analysis of delivery methods showed that in 90% of cases (n = 9), pregnant women were delivered by caesarean section. Vaginal delivery occurred in one patient with a history of arteriovenous malformation of the left frontal lobe after subtotal embolization. The course of the postpartum period in all the patients was uneventful. During the next year, a planned consultation with a neurologist took place in three cases. CONCLUSIONS: It is required that a multidisciplinary team should develop tactics for pregravid preparation, pregnancy and postpartum management, with an assessment of long-term consequences in pregnant women with cerebrovascular disease, which will improve the efficiency of medical care and will contribute to the further implementation of reproductive functions in such patients. It is necessary to develop rehabilitation plans with the selection of personalized rehabilitation methods aimed at reducing complications associated with pregnancy and childbirth.

Background. 4-Nitrosopyrazoles have become widespread in the pharmaceutical industry and in chemistry due to their high reactivity and biological activity. However, the interaction of 3,5-substituted 4-nitroso-1H-pyrazoles with diene hydrocarbons has not been studied to date. Purpose. Study of diene condensation of tetraphenylcyclopentadienone with 3,5-dimethyl-4-nitroso-1H-pyrazole and 3(5)-methyl-4-nitroso-5(3)-phenyl-1H-pyrazole; proof of the structure of the obtained compounds; prediction of potential positive biological activity. Materials and methods. Research methods include: directed organic synthesis, thin-layer chromatography, chromato-mass spectra, prediction of biological activity using the PASS-online web-resource. Results. Substituted oxazines, pyrazoles and but-2-en-1-ones were synthesized. Fragmentation decays based on the mass spectrum of the obtained compounds confirm their molecular weight and structure. The PASS-online program predicts potential biological activity. Conclusion. Substituted oxazines, pyrazoles and but-2-en-1-ones were obtained for the first time by the Diels-Alder reaction, the structure of which was proved by HPLC/MS. Based on the output data of the PASS-online program, the synthesized substances are taurine dehydrogenase inhibitors and exhibit antitumor effect.

BACKGRAUND: Cytochrome P450 is an enzyme involved in the metabolism of phase I xenobiotics, toxins, endogenous hormones and pharmaceuticals. AIM: Is studying the polymorphism of the CYP1A1 gene (Ile462Val, rs1048943) in the Turkic-speaking populations of the central part of the North Caucasus Region (Balkars and Karachays). MATERIALS AND METHODS: We analyzed DNA isolated from leukocytes of peripheral venous blood of a total of 177 unrelated Balkars and Karachays (104 Balkars, 73 Karachays). RESULTS: The ethnicity of the studied individuals was established, indicating their ancestors up to the third generation. The method of genotyping was performed by real-time PCR using competing TaqMan probes. As a result: the frequency of the 462Val variant in the sample of Balkars was 8,6% (95% CI 5,2113,33), slightly above the frequency range found in European populations. In the sample of Karachays, the frequency of the 462Val allele was 7,5% (95% CI 9,8213.08), which is the upper limit of values typical for European populations. CONCLUSION: In the Turkic-speaking populations of the central part of the North Caucasus, the CYP1A1 462Val allele occurs with a frequency characteristic of the Near Eastern and European populations.

This article discusses the improvement of the work of an enterprise in the production sphere of LLC "TETA FOOD", which consists in increasing the efficiency of employees of the enterprise by reducing the time for the formation of a full package of documents (UPD) for submission to the tax office for the purpose of refunding VAT to the exporting enterprise. In the analytical part, the features of the VAT refund to the exporting company are analyzed in detail. To formalize and describe business processes, the notation IDEF0 and IDEF3 was chosen. In the design part, the ―AS IS‖ model was analyzed and the main problems of the model were identified. A strategy for the future strategy based on the IDEF0 methodology was developed.

Among the great variety of anti-cancer therapeutic strategies, boron neutron capture therapy (BNCT) represents a unique approach that doubles the targeting accuracy due to the precise positioning of a neutron beam and the addressed delivery of boron compounds. We have recently demonstrated the principal possibility of using a cell-specific 2′-F-RNA aptamer for the targeted delivery of boron clusters for BNCT. In the present study, we evaluated the amount of boron-loaded aptamer inside the cell via two independent methods: quantitative real-time polymerase chain reaction and inductive coupled plasma–atomic emission spectrometry. Both assays showed that the internalized boron level inside the cell exceeds 1 × 109 atoms/cell. We have synthesized closo-dodecaborate conjugates of 2′-F-RNA aptamers GL44 and Waz, with boron clusters attached either at the 3′- or at the 5′-end. The influence of cluster localization was evaluated in BNCT experiments on U-87 MG human glioblastoma cells and normal fibroblasts and subsequent analyses of cell viability via real-time cell monitoring and clonogenic assay. Both conjugates of GL44 aptamer provided a specific decrease in cell viability, while only the 3′-conjugate of the Waz aptamer showed the same effect. Thus, an individual adjustment of boron cluster localization is required for each aptamer. The efficacy of boron-loaded 2′-F-RNA conjugates was comparable to that of 10B-boronophenylalanine, so this type of boron delivery agent has good potential for BNCT due to such benefits as precise targeting, low toxicity and the possibility to use boron clusters made of natural, unenriched boron.

BACKGROUND Some ischemic complications due to giant cell arteritis (GCA) are rare and underdiagnosed. We describe the clinical features and outcomes of patients with GCA presenting with rare ischemic complications. CASE REPORT Our single-center retrospective database of patients with GCA was reviewed from 1994 to 2020. We describe 3 cases of rare ischemic complications secondary to GCA. We review the literature regarding ischemic complications due to GCA and their outcomes. All 3 cases met the American College of Rheumatology criteria for GCA. All patients experienced rare ischemic complications due to GCA. In case 1, the patient presented with a sixth cranial nerve palsy. In case 2, the patient presented with tongue and scalp necrosis, and with permanent visual loss due to anterior ischemic optic neuropathy. In case 3, the patient presented with scalp necrosis. In all 3 cases, the patients received glucocorticoids either intravenously and/or orally, which led to improvement. They all improved within the course of their followup visits. A literature review was performed to identify similar cases and outcomes. CONCLUSIONS Ischemic complications due to GCA can be part of the initial presentation of the vasculitis, making confirmation of the diagnosis more difficult. Physicians should be aware of these rare complications since rapid diagnosis and initiation of glucocorticoids may alter the course of the disease.

Antimicrobial resistance is a global threat. The use of biologically active natural products alone or in combination with the clinically proven antimicrobial agents might be a useful strategy to fight the resistance. The scientific hypotheses of this study were twofold: (1) the natural humic substances rich in dicarboxyl, phenolic, heteroaryl, and other fragments might possess inhibitory activity against β-lactamases, and (2) this inhibitory activity might be linked to the molecular composition of the humic ensemble. To test these hypotheses, we used humic substances (HS) from different sources (coal, peat, and soil) and of different fractional compositions (humic acids, hymatomelanic acids, and narrow fractions from solid-phase extraction) for inhibiting serine β-lactamase TEM-1. Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) was used to characterize the molecular composition of all humic materials used in this study. The kinetic assay with chromogenic substrate CENTA was used for assessment of inhibitory activity. The inhibition data have shown that among all humic materials tested, a distinct activity was observed within apolar fractions of hymatomelanic acid isolated from lignite. The decrease in the hydrolysis rate in the presence of most active fractions was 42% (with sulbactam-87%). Of particular importance is that these very fractions caused a synergistic effect (2-fold) for the combinations with sulbactam. Linking the observed inhibition effects to molecular composition revealed the preferential contribution of low-oxidized aromatic and acyclic components such as flavonoid-, lignin, and terpenoid-like molecules. The binding of single low-molecular-weight components to the cryptic allosteric site along with supramolecular interactions of humic aggregates with the protein surface could be considered as a major contributor to the observed inhibition. We believe that fine fractionation of hydrophobic humic materials along with molecular modeling studies on the interaction between humic molecules and β-lactamases might contribute to the development of novel β-lactamase inhibitors of humic nature.

Acetylene derivatives of 1,2,4-oxadiazoles, i.e., 5-(2-arylethynyl)-3-aryl-1,2,4-oxadiazoles, have been obtained, for the first time reported, from 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles by their bromination at the carbon–carbon double bond followed by di-dehydrobromination with NaNH2 in liquid NH3. The reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed.

Introduction. Occupational asthma is a complex and heterogeneous disease. Development of personalized treatment and prevention tactics becomes feasible due to phenotyping, which means identifying of markers to combine cases of occupational asthma with similar manifestations (clinical, instrumental, laboratory) and prognosis to phenotypes. The study aims to determination and comparative analysis of spirographic and immunological parameters for different phenotypes of occupational asthma. Materials and methods. In this study, we included 170 patients with different phenotypes of occupational asthma and 50 participants in control group. The spirographic examination was performed using computer spirograph with determination of the following parameters: forced vital capacity (FVC), forced expiratory volume during the first second (FEV1), Tiffeneau-Pinelli index (FEV1/FVC), peak expiratory flow (PEF), maximal expiratory flow at 75%, 50%, 25% of the forced vital capacity (MEF75%VC, MEF50%VC, MEF25%VC). Quantification of the immunoglobulins IgA, IgM, and IgG in human serum was conducted by Mancini method; levels of IgE, C-reactive protein and fibronectin were determined using a solid-phase enzyme immunoassay. Fibrinogen concentration in plasma was measured by an automatic coagulometer. Haptoglobin concentration in serum was determined by spectrophotometry. Results. According to spirometry and laboratory results obtained, there is a strong evidence, that the phenotype "occupational asthma - occupational chronic obstructive pulmonary disease" has the lowest values in pulmonary function tests and the most significant changes in immunoglobulins, fibronectin and acute phase proteins levels among other studied phenotypes of occupational asthma. Conclusions. Dynamic determination of spirometric, immunological parameters, fibronectin and proteins of the acute phase of inflammation in workers at risk for the formation of occupational bronchial asthma may be recommended to be carried out once every 6 months, followed by the isolation of disease phenotypes. This will optimize diagnostics, therapeutic and preventive tactics, as well as predict the course of this pathology.