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Актуальность. Миксома — наиболее распространенная доброкачественная опухоль сердца. В левом предсердии ее типичной локализацией является межпредсердная перегородка в области овальной ямки; любое другое расположение считается атипичным. Результаты хирургического лечения миксом достаточно изу­чены, однако нет данных о результатах лечения атипично локализованных миксом левого предсердия. Цель. Анализ результатов хирургического лечения атипично локализованных миксом левого предсердия с оценкой пред- и послеоперационных факторов риска, эмболических осложнений. Методы. Выполнен ретроспективный обзор результатов хирургического лечения атипично локализованных миксом левого предсердия (n = 52) в период с 2008 по 2022 г. Результаты. Нелетальные госпитальные осложнения развились у 15 пациентов (29 %). Госпитальная летальность составила 6 % (n = 3). Сравнительный анализ данных трансторакальной эхокардиографии перед операцией и на момент выписки продемонстрировал снижение конечного диастолического объема левого желудочка и уменьшение размеров левого предсердия к моменту выписки (p < 0,001). Факторы риска нелетальных осложнений на госпитальном этапе: хроническая сердечная недостаточность III функционального класса по классификации Нью-Йоркской ассоциации кардиологов (ХСН III ФК по NYHA) (p < 0,001), значение по шкале EuroSCORE II (p = 0,03). Факторы риска госпитальной летальности: пожилой возраст (p = 0,03), EuroSCORE II (p = 0,03). Выявлена связь между предоперационными эмболическими осложнениями и локализацией миксомы на задней стенке левого предсердия (p = 0,02), ворсинчатой формой миксомы (p

BackgroundModular (universal) CAR T-platforms were developed to combat the limitations of traditional CAR-T therapy, allowing for multiple targeting of tumor-associated antigens and the ability to control CAR-T cell activity. The modular CAR-T platform consists of a universal receptor (signaling module) that recognizes an adapter molecule on the soluble module, which is responsible for antigen recognition. Multiple platforms have been developed over the last 12 years, and some of them have entered the clinical trial phase. This systematic review seeks to evaluate the different parameters of modular CAR-T platforms performance in animal models.MethodsA systematic search of literature in the PubMed database and in Google Scholar and BASE (Bielefeld Academic Search Engine) search engines was performed according to predefined eligibility criteria. All studies conducted on xenograft mouse models with any variant of modular CAR-T platforms were included. Forest plots were generated for visual presentation of the extracted quantitative findings (standardized mean difference (SMD) and median survival rate (MSR)).ResultsA total of 33 studies employing 15 different modular CAR-T platforms were included. The platforms varied in terms of CAR-T cells, soluble module doses, and their frequency of administration. The studies showed a reduction in tumor burden and in tumor volume compared to the combined negative group. In comparison with the positive control group, there was no significant change in tumor burden or volume. In all the included studies the experimental group had a higher survival probability compared to the combined negative group at the study endpoint, with no significant difference in survival rate compared to the positive control group.ConclusionThe modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023443984.

Abstract Background The interdependence of cytokines and appetite‐modifying hormones implicated in cancer anorexia‐cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non‐inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes. Methods Clinical characteristics of 133 patients [61.7% male; mean age = 63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia‐Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex‐standardized skeletal muscle index (z‐SMI) and fat mass index (z‐FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite‐modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two‐step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan–Meier analysis. Results Patients had low z‐SMI (mean = −3.78 cm2/m2; SD: 8.88) and z‐FMI (mean = 0.08 kg2/m2; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F‐1) IFN‐γ, IL‐1β, Il‐4, IL‐6, IL‐10, IL‐12, TGFβ1 (positive contribution), and IL‐18 (negative); (F‐2) IL‐8, IL‐18, MCP‐1, TGFβ1, TNF‐α (positive), and ghrelin (negative); and (F‐3) TRAIL and leptin (positive), and TGFβ1 and adiponectin (negative). RFS‐1 was associated with cachexia (P = 0.002); RFS‐2, with higher CRP (P

Background. Cancer is the leading cause of disease-related death among children of more than 1 year of age. However, childhood cancer risk factors and etiology are yet to be fully understood. The goal of this study is to identify geographic variation among children and adolescents diagnosed with pediatric tumors between 2001 and 2018 in the province of Quebec. Methods. We analyzed pediatric patients less than 15 years of age from the Cancer in Young People in Canada (CYP-C) surveillance system who were diagnosed between 2001 and 2018 with cancer in the province of Quebec. The age-standardized age-adjusted incidence rates (AAIR) per 100,000 person years were calculated for all childhood cancers by cancer subgroups, Quebec Health regions, and age groups. Results. Overall, 3904 pediatric patients less than 15 years old were diagnosed with cancer in the province of Quebec in 2001–2018. The overall incidence rate (IR) in the province of Quebec was 16.14 (95%CL [15.56–16.73]) per 100,000 person years. For childhood cancers, regions that presented a higher AAIR were Chaudière-Appalaches and Capitale-Nationale with 18.2 and 17.5 per 100,000 person years, respectively. The incidence rates (IRs) in Chaudière-Appalaches (95% CI 1.0439–1.3532) and in Capitale-Nationale (95% CI 1.0124–1.2942) were statistically higher than the incidence in the province of Quebec (p = 0.0090 and p = 0.0310, respectively). When comparing the AAIR of the CNS tumor subgroup in Chaudière-Appalaches and in Capitale-Nationale, with the provincial average, we noticed a statistically higher incidence in Chaudière-Appalaches and a trend for Capitale-Nationale (p < 0.0001 and p = 0.0602, respectively). Conclusion. There is evidence of spatial clusters in Chaudière-Appalaches and Capitale-Nationale as areas for all childhood cancers. Further studies should be performed to investigate potential risk factors in these regions.

Degenerative spinal stenosis is the most common type of degenerative and dystrophic spine disease. The clinical picture of stenosis, which may include axial pain syndrome, leg pain, intermittent claudication syndrome, weakness and loss of sensitivity in the legs, and impaired pelvic functions, can significantly worsen patients’ quality of life and reduce their ability to work and lead an active lifestyle. Degenerative spinal stenosis mostly affects the elderly. Therapeutic and neurological communities have stereotypes about spine surgery being too traumatic and invasive, and, therefore, they believe that their use should be contraindicated to and limited in elderly patients. However, surgeons are increasingly giving preference to minimally invasive interventions with high efficacy and safety together with a low risk of complications. We aimed at reviewing current treatment methods for degenerative lumbosacral spinal stenosis with an emphasis on surgical treatment methods.

In recent years, some illegal activities have emerged, enabling their owners to counterfeit billions of local and international currencies. Therefore, it is necessary to combat these activities by increasing insurance awareness among the public, and upgrading the level of the banknote and the elements included in its components and means of insurance. The problem of the research represented in the difficulty recognizing and distinguishing between original and counterfeit currencies for a large segment of Egyptian society and the absence of identifying the insurance components in Egyptian currencies and limiting them to a specific segment of specialists, whether in the field of their production or circulation, such as banks. The aim of the research is developing ways of dealing with the public through the Internet and smart phone applications, easily defining and educating the public about all insurance means, and identifying whether the currencies are valid or counterfeit. Raising public awareness of the visible and invisible insurance components in Egyptian currencies to support anti-counterfeiting and counterfeiting ways and devices through the application.

Abstract Brucellosis, a zoonotic disease impacting public health and economies, is prevalent in several countries, particularly low- and middle-income regions. This study centers on Armenia, where the Veterinary Department of the Food Safety Inspection Body employs a test-and-slaughter strategy to control the disease. A dynamic deterministic compartmental model was constructed using seropositive reported data from humans and livestock (cattle and sheep) from 2019 to 2021. The model simulates the effects of enhanced test-and-slaughter strategies from 2022 to 2031 on brucellosis transmission among sheep, cattle, and humans. The results suggest that an increase in testing and slaughter rates leads to a decrease in infected populations among both humans and livestock. Approximately 65% of the human brucellosis cases are a result of sheep-to-human transmissions. This reduction in infected populations is expected to subsequently lower the overall transmission rates in livestock and humans. However, even with the highest coverage levels (75% for sheep and 90% for cattle), infections in humans and livestock are projected to persist. The study highlights the need for a One Health approach that integrates mathematical modeling with public health intervention strategies. While the upgraded test-and-slaughter strategy could prove effective, an economic analysis of the predicted cumulative incidence in humans and livestock prevalence could guide decision making processes. Compensation for culled animals is a critical factor. The success of the intervention relies on collaboration between veterinary and public health sectors, community engagement, and awareness campaigns. One Health impact statement This study applied a mathematical model to investigate brucellosis transmission within the livestock population and from animals to humans. It assessed the impact of different test-and-slaughter coverage levels from 2022 to 2031 on disease burden and livestock populations. Although the research did not encompass the entire One Health spectrum, it shed light on the potential benefits of integrating human and animal health interventions. Local institutions (such as the Food Safety and Inspectorate Body and the National Centre for Disease Control in Armenia) and international collaboration among scientists contributed to a better understanding and controlling zoonotic diseases. The findings offer valuable insights for decision making, aiding Armenian policy makers in effectively managing brucellosis and enhancing public health, food safety, and monetary savings. Furthermore, the research provides a basis for further exploration in this field.

Abstract According to recent research, selective neuronal vulnerability in Parkinson’s disease (PD) results from several phenotypic traits, including calcium-dependent, feed-forward control of mitochondrial respiration leading to elevated reactive oxygen species and cytosolic calcium concentration, an extensive axonal arbor, and a reactive neurotransmitter. Therefore, antioxidant therapy is a promising direction in the treatment of PD. In vitro studies have indicated the survival-promoting activity of bacterial melanin (BM) on midbrain dopaminergic neuron cultures. It has been established that BM has a number of protective and anti-inflammatory properties, so there is a high probability of a protective effect of BM in the early stages of PD. In this study, PD was induced through the unilateral intracerebral administration of rotenone followed by bacterial melanin. Tissues (brain, lungs, and small intestine) from the observed groups underwent isolation and purification to extract isoforms of new thermostable superoxide (О2 −)-producing associates between NADPH-containing lipoprotein (NLP) and NADPH oxidase-Nox (NLP-Nox). The optical absorption spectral characteristics, specific amounts, stationary concentration of the produced О2 −, and the content of NADPH in the observed associates were determined. The optical absorption spectra of the NLP-Nox isoforms in the visible and UV regions in the experimental groups did not differ from those of the control group. However, compared with the control group, the specific content of the total fractions of NLP-Nox isoforms associated with PD groups was higher, especially in the small intestine. These findings suggest that the described changes may represent a novel mechanism for rotenone-induced PD. Furthermore, bacterial melanin demonstrated antioxidant properties and regulated membrane formation in the brain, lung, and small intestine. This regulation occurred by inhibiting the release of new membrane-bound formations (NLP-Nox associates) from these membranes while simultaneously regulating the steady-state concentration of the formed О2 −.

Abstract Background The primary objectives of this study were the evaluation of consumer self-medication practices, the assessment of pharmaceutical care provided by pharmacy employees, and the analysis of consumer satisfaction with such care. The research was also aimed at examining the main criteria that consumers consider important when selecting a pharmacy in Armenia. Methods The survey was based on an anonymous questionnaire and carried out between March 2020 and November 2021. It was aimed at providing a comprehensive assessment of pharmaceutical care services and consumer pharmacy choice by investigating two distinct groups: pharmacy consumers and pharmacy employees. Results The research reveals that many residents in Armenia engage in self-medication without consulting professional sources, which can lead to potential risks and result in dangerous consequences. This is partly due to a lack of trust in pharmacy employees, which is primarily due to their inability to provide adequate information and advice. This study highlights a significant need for improvement in the quality of service provided by pharmacy employees. Despite these challenges, the majority of consumers reported having a preferred pharmacy, and that employee knowledge is the most important criterion when choosing a pharmacy. Conclusions Consumer distrust, in this context, is based on the incomplete knowledge or incompetency of pharmacy employees. Collective actions should be taken to improve the role of pharmacy employees and consequently improve the public trust in them, which can ensure better control of self-medication and reduce the instances of mistreatment.

Background & Aims: Barrett’s esophagus is the precursor of esophageal dysplasia and esophageal adenocarcinoma. CDKN2A-p16 deletions were reported in 34%–74% of patients with Barrett’s esophagus who progressed to dysplasia and esophageal adenocarcinoma, suggesting that p16 loss may drive neoplastic progression. KRAS activation frequently occurs in esophageal adenocarcinoma and precancer lesions. LGR5+ stem cells in the squamocolumnar-junction (SCJ) of mouse stomach contribute as Barrett’s esophagus progenitors. We aimed to determine the functional effects of p16 loss and KRAS activation in Barrett’s-like metaplasia and dysplasia development. Methods: We established mouse models with conditional knockout of CDKN2A-p16 (p16KO) and/or activated KRASG12D expression targeting SCJ LGR5+ cells in interleukin 1b transgenic mice and characterized histologic alterations (mucous-gland hyperplasia/metaplasia, inflammation, and dysplasia) in mouse SCJ. Gene expression was determined by microarray, RNA sequencing, and immunohistochemistry of SCJ tissues and cultured 3-dimensional organoids. Results: p16KO mice exhibited increased mucous-gland hyperplasia/metaplasia versus control mice (P = .0051). Combined p16KO+KRASG12D resulted in more frequent dysplasia and higher dysplasia scores (P = .0036), with 82% of p16KO+KRASG12D mice developing high-grade dysplasia. SCJ transcriptome analysis showed several activated pathways in p16KO versus control mice (apoptosis, tumor necrosis factor-α/nuclear factor-kB, proteasome degradation, p53 signaling, MAPK, KRAS, and G1-to-S transition). Conclusions: p16 deletion in LGR5+ cell precursors triggers increased SCJ mucous-gland hyperplasia/metaplasia. KRASG12D synergizes with p16 deletion resulting in higher grades of SCJ glandular dysplasia, mimicking Barrett’s high-grade dysplasia. These genetically modified mouse models establish a functional role of p16 and activated KRAS in the progression of Barrett’s-like lesions to dysplasia in mice, representing an in vivo model of esophageal adenocarcinoma precancer. Derived 3-dimensional organoid models further provide in vitro modeling opportunities of esophageal precancer stages.

Abstract Background The muscle artifacts, caused by prominent muscle contractions, mimicking cardiac arrhythmias, might compromise the ECG signal quality and the implantable loop recorder memory capacity in patients with epilepsy. We developed an epileptic seizures clinical pattern-based implantable loop recorder manual activation algorithm, presenting its real-world efficacy here. Methods One hundred ninety-three patients (18–60 years) with drug-resistant focal epilepsy were consecutively enrolled and underwent a subcutaneous loop recorder implantation. Patients with focal onset-aware seizures and patients with focal impaired awareness seizures /bilateral tonic-clonic seizures without aura were recommended to use the activator once - just after the episode. Patients with focal impaired awareness seizures/bilateral tonic-clonic seizures with aura, the caregivers of patients experiencing status epilepticus, were advised to use the activator twice - during the aura and after the episode/ regaining consciousness. Results Six thousand four hundred ninety-four ECG traces (4826 - auto-triggered events, 1668 - person-activated events) were recorded and analyzed. The rate of true positive events in the person-activated group was statistically higher than in the autoactivation group (72.5% vs.19.4%, p

IntroductionThe localization, density but mostly the phenotype of tumor infiltrating lymphocytes (TIL) provide important information on the initial interaction between the host immune system and the tumor. Our objective was to assess the prognostic significance of T (CD3+), T regulatory (Treg) (FoxP3+) and T memory (Tmem) (CD45RO+) infiltrating lymphocytes and of genes associated with TIL in prostate cancer (PCa).MethodsImmunohistochemistry (IHC) was used to assess the infiltration of CD3+, FoxP3+ and CD45RO+ cells in the tumor area, tumor margin and adjacent normal-like epithelium of a series of 98 PCa samples with long clinical follow-up. Expression of a panel of 31 TIL-associated genes was analyzed by Taqman Low-Density Array (TLDA) technology in another series of 50 tumors with long clinical follow-up. Kaplan-Meier and Cox proportional hazards regression analyses were performed to determine association of these markers with biochemical recurrence (BCR), need for definitive androgen deprivation therapy (ADT) or lethal PCa.ResultsTIL subtypes were present at different densities in the tumor, tumor margin and adjacent normal-like epithelium, but their density and phenotype in the tumor area were the most predictive of clinical outcomes. In multivariate analyses, a high density of Treg (high FoxP3+/CD3+ cell ratio) predicted a higher risk for need of definitive ADT (HR=7.69, p=0.001) and lethal PCa (HR=4.37, p=0.04). Conversely, a high density of Tmem (high CD45RO+/CD3+ cell ratio) predicted a reduced risk of lethal PCa (HR=0.06, p=0.04). TLDA analyses showed that a high expression of FoxP3 was associated with a higher risk of lethal PCa (HR=5.26, p=0.02). Expression of CTLA-4, PD-1, TIM-3 and LAG-3 were correlated with that of FoxP3. Amongst these, only a high expression of TIM-3 was associated with a significant higher risk for definitive ADT in univariate Cox regression analysis (HR=3.11, p=0.01).ConclusionThese results show that the proportion of Treg and Tmem found within the tumor area is a strong and independent predictor of late systemic progression of PCa. Our results also suggest that inhibition of TIM-3 might be a potential approach to counter the immunosuppressive functions of Treg in order to improve the anti-tumor immune response against PCa.

Objective To compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases.Design A retrospective cohort study.Setting This study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays.Participants Inclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma.Main outcome measures The primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients.Results We included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)).Conclusions The incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.

Background: The aim of this study was to develop a patient-reported experience measure (PREM) for comparing the experience of care received by ambulatory patients with acute unexpected needs presenting in emergency departments (EDs), walk-in clinics, and primary care practices. Methods: The Ambulatory Patient EXperience (APEX) questionnaire was developed using a 5-phase mixed-methods approach. The questionnaire was pretested by asking potential users to rate its clarity, usefulness, redundancy, content and face validities, and discrimination on a 9-point scale (1 = strongly disagree to 9 = strongly agree). The pre-final version was then tested in a pilot study. Results: The final questionnaire is composed of 61 questions divided into 7 sections. In the pretest (n = 25), median responses were 8 and above for all dimensions assessed. In the pilot study, 63 participants were enrolled. Adjusted results show that access, cleanliness, and feeling treated with respect and dignity by nurses and physicians were significantly better in the clinics than in the ED. Conclusion: We developed a questionnaire to assess and compare experience of ambulatory care in different clinical settings.

The possibilities of increasing the ecological and technological efficiency of the innovative coal-watercoal cluster of housing and communal services, including the mechanics of coal destruction in a hydraulic shock installation, are considered. The creation of an experimental coal-watercoal cluster of housing and communal services involves the use of innovative coal-watercoal technology in boilers under construction or in operation, including the processing of solid coal fuels into innovative coal-water fuel suspension with subsequent combustion in specially equipped furnaces. The set tasks of managing environmental and technological qualities in the process of preparing an innovative coal-water fuel suspension based on statistical analysis of the granulometric composition correlate with the tasks of obtaining micro- and ultrafine coal-water suspensions in order to achieve high environmental and technological qualities. The control of an innovative coal-watercoal fuel technology based on automatic control of the granulometric composition using the natural fracturing of coal for the control action during the destruction of coal by the method of water hammer is proposed. Technological patterns of reducing the negative technogenic impact on the geospheres are revealed, including a method for managing the environmental and technological qualities of an innovative water-coal suspension based on automatic control of the granulometric composition during coal grinding by the hydraulic shock method.

AbstractThis research was set out to evaluate the specific energy consumption (SEC) in drying African oil bean seed using convective hot air and microwave oven dryers. The process parameters investigated in thin-layer drying were temperature (40, 50, 60, 70 °C), microwave power (450, 720, 900 W), slice thickness (2, 3, 5 mm) and treatment (untreated (UT), brine pretreated (BT) and sucrose pretreated (ST)). Response surface methodology (RSM) was used to evaluate the effect of oven temperature, microwave power, slice thickness, and treatment on the SEC of African oil bean seed. The result revealed that the SEC for African oil bean seed ranged from 21.12 to 57.33 k Wh kg−1 and 90.76 to 261.23 k Wh kg−1 for microwave and oven drying, respectively. The study also found that the SEC decreases with increase in slice thickness in both microwave and oven dryer. The microwave oven method reduced SEC of African oil bean seed by 22% compared to convective hot air oven drying method. The optimum SEC was obtained at 4 mm material thickness, 53.57 °C hot air oven temperature and 814.32 W microwave power. Among the treatments, BT sample is comparatively the best treatment for AOB in order to save drying energy consumption.

Background and Aim: Recently, viral diseases of honey bees (Apis mellifera) have presented an increasing threat to beekeeping. This study aimed to examine the presence of honey bee viruses in Apis and non-Apis bee species, the mite Varroa destructor, and pollinated plants in Armenia. Materials and Methods: Sampling was performed in Tavush Province, in the northeast of the Republic of Armenia, from August to November 2019. Overall, 200 A. mellifera bees, 50 V. destructor mites, and 20 wasps were collected (corresponding to three bees, five mites, and 2–11 wasps in each investigated sample) and homogenized for RNA isolation and detection of viruses. Ten pollinated plants were taken from each plant, and 2 g of each sample was used for homogenization. In each investigated case Apis mellifera, Varroa destructor, Vespula germanica and plants received percentages of the virus presence. Results: Six important honey bee viruses (acute bee paralysis virus [ABPV], deformed wing virus [DWV], A. mellifera norovirus [ANV], Lake Sinai virus-2 [LSV-2], Big Sioux River virus [BSRV], and A. mellifera filamentous virus [AmFV]) were detected in samples by polymerase chain reaction. Our results showed that DWV, ANV, and ABPV were the most common viruses in honey bees. All viruses were detected in wasps, but LSV-2 and ANV were present in almost all samples. Conclusion: Our results showed that almost all viruses were present in V. destructor. Although ANV is very common in honey bees, it did not appear in any mite samples. Our study indicates that viruses typically associated with honey bees were also actively infecting wasps. Our data suggest that the survival of viruses in plants can be an important source of seasonal transmission of viruses to bees. In addition, pollinated plants can potentially serve as reservoirs for honey bee viruses.

The authors would like to make the following corrections to this published paper [...]

Abstract Failure to direct axon regeneration to appropriate targets is a major barrier to restoring function after nerve injury. Development of strategies that can direct targeted regeneration of neurons such as retinal ganglion cells (RGCs) are needed to delay or reverse blindness in diseases like glaucoma. Here, we demonstrate that a new class of asymmetric, charge balanced (ACB) waveforms are effective at directing RGC axon growth, in vitro, without compromising cell viability. Unlike previously proposed direct current (DC) stimulation approaches, charge neutrality of ACB waveforms ensures the safety of stimulation while asymmetry ensures its efficacy. Furthermore, we demonstrate the relative influence of pulse amplitude and pulse width on the overall effectiveness of stimulation. This work can serve as a practical guideline for the potential deployment of electrical stimulation as a treatment strategy for nerve injury.

Abstract Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P

This work aimed to manufacture a highly sensitive hydrogen gas sensor based on Fe2O3:ZnO thin film. The Fe2O3:ZnO based sputtering target was synthesized by a solid-state synthesis method. Gas-sensitive thin films were deposited onto the alumina substrate by the high-frequency (RF) magnetron sputtering method. The thickness of the sensing film was measured and the morphology of the sensing layers was studied. The Fe2O3:ZnO sensor showed the highest hydrogen gas response at 100 ᵒC and the operating temperature of 150 ᵒC was selected as the optimum working temperature. The sensor showed sensitivity even to extremely low concentrations of hydrogen (100 ppm), where the response was 4.6. The sensing parameters of the fabricated sensor confirm that the Fe2O3:ZnO material may become an excellent nanostructure for the detection of low concentrations of hydrogen.

Objective: Non-alcoholic fatty liver disease (NAFLD) affects 1 in 3 adults and contributes to advanced liver injury and cardiometabolic disease. While recent evidence points to involvement of the brain in NAFLD, the downstream neural circuits and neuronal molecular mechanisms involved in this response, remain unclear. Here, we investigated the role of a unique forebrain-hypothalamic circuit in NAFLD. Methods: Chemogenetic activation and inhibition of circumventricular subfornical organ (SFO) neurons that project to the paraventricular nucleus of the hypothalamus (PVN; SFO→PVN) in mice were used to study the role of SFO→PVN signaling in NAFLD. Novel scanning electron microscopy techniques, histological approaches, molecular biology techniques, and viral methodologies were further used to delineate the role of endoplasmic reticulum (ER) stress within this circuit in driving NAFLD. Results: In lean animals, acute chemogenetic activation of SFO→PVN neurons was sufficient to cause hepatic steatosis in a liver sympathetic nerve dependent manner. Conversely, inhibition of this forebrain-hypothalamic circuit rescued obesity-associated NAFLD. Furthermore, dietary NAFLD is associated with marked ER ultrastructural alterations and ER stress in the PVN, which was blunted following reductions in excitatory signaling from the SFO. Finally, selective inhibition of PVN ER stress reduced hepatic steatosis during obesity. Conclusions: Collectively, these findings characterize a previously unrecognized forebrain-hypothalamic-ER stress circuit that is involved in hepatic steatosis, which may point to future therapeutic strategies for NAFLD.

Abstract Background NADPH oxidase (Nox) plays a crucial role in reactive oxygen spices (ROS) production and mediates different diseases’ development. Under aerobic conditions, the NADPH-containing protein component of the (NCP)-Fe (III) complex produces O2 − continuously and intensively. However, after the removal of Fe (III), the isolated NCP shows only antioxidant properties at the expense of NADPH composite. Based on the fact that the mentioned fruit juices are widely used in everyday life and also in biomedicine, it was aimed to use a universal method: 1. to obtain superoxide generating complex from available and relatively cheap raw materials without using any toxic substances; 2. to isolate, purify and study the components of prooxidant nature: the isoforms of O2 −—producing NCP-Fe (III) complexes obtained from Armenian fruits (raspberries, apricot, grapes), as well, grape seeds. Results Using a licensed method, for the first time isoforms of the superoxide (O2 −) producing a thermostable complex of the NCP component with Fe (III), (NCP-Fe (III)), were isolated and purified from Armenian fruits—raspberries, apricots, grapes, and grapes seeds. The process of isolation and purification of isoforms of these complexes included the following stages of processing: 1. alkaline hydrolysis at pH9,5; 2. their sedimentation at pH4.8; 3. Dissolving of the sediments in water at pH9.5, followed by ion-exchange chromatography on cellulose DE-52, and gel filtration on Sephadex G-100. Further, the heat treatment of the mentioned complexes was carried out. In a lyophilized state, under the anaerobic conditions, the isoforms of the given complexes, hybrid associates (hNCP-Nox), and NCP were stored practically without losing their activity in a mass of 1–1.5 g. Conclusions Isoforms of O2 − -producing complexes are new liquid-phase, thermo-stable prooxidant components found in raspberries, apricots, grapes, and grapes seeds.

Eastern European post-communist countries inherited pervasive corruption after the breakup of the USSR. Public trust was the crucial factor in tackling corruption and democracy building in these countries. This article takes Armenia as a case to study the antecedents and evolution of trust in Eastern European post-communist countries that went through a government coup in the 21st century. By comparing the corruption situation in Armenia before and after the Velvet Revolution 2018, we scrutinise how trust was and is critical to combating corruption and democracy building. We argue that in transition governments, one can distinguish two sources of creating public trust. The first wave generates when the government is newly established, and people trust the leader and his persona. Arguably, in this stage, the level of trust generated is based on expectations. The second wave of trust comes with the government’s actual performance, measured partly based on corruption perception.

Abstract We performed a mathematical analysis of functional connectivity in electroencephalography (EEG) of patients with obstructive sleep apnea (OSA) (N = 10; age: 52.8 ± 13 years; median age: 49 years; male/female ratio: 7/3), compared with a group of apparently healthy participants (N = 15; age: 51.5 ± 29.5 years; median age: 42 years; male/female ratio: 8/7), based on the calculation of wavelet bicoherence from nighttime polysomnograms. Having observed the previously known phenomenon of interhemispheric synchronization deterioration, we demonstrated a compensatory increase in intrahemispheric connectivity, as well as a slight increase in the connectivity of the central and occipital areas for high-frequency EEG activity. Significant changes in functional connectivity were extremely stable in groups of apparently healthy participants and OSA patients, maintaining the overall pattern when comparing different recording nights and various sleep stages. The maximum variability of the connectivity was observed at fast oscillatory processes during REM sleep. The possibility of observing some changes in functional connectivity of brain activity in OSA patients in a state of passive wakefulness opens up prospects for further research. Developing the methods of hypnogram evaluation that are independent of functional connectivity may be useful for implementing a medical decision support system.

Metric studies of teeth is a rapidly developing direction in odontological research, which is supported by means of corresponding imaging techniques for obtaining detailed digital reconstructions, and by application of image analysis methods. The current article presents methodological extension of teeth 3D models’ orientation tactics, which have been used in measurement techniques in dental, palaeoanthropological and palaeontological studies. Today image analysis has sufficient potential to perform orientation of teeth on the bases of their natural features; at the same time teeth possesses all necessary morphological structures for performing orientation on 3D reconstructions obtained by means of widely used today imaging techniques. Our aim is in providing an approach to orientation of teeth for its further use in morphologically relevant, accurate and applicable for various types of research, measurement techniques. The palaeoanthropological material presented in this paper, on which the proposed technique has been tested, is from territories of European part of Russian Federation and Republic of Armenia; it has been classified as related to the Middle Bronze Age, and is planned to be studied in a wider scope in the future. X-ray micro-focus tomography has been used for obtaining reconstructions of lower molars, which were segmented from semi-mandible 3D models. These teeth were used for setting vertical axis direction by means of surface curvature analysis and calculations based on points’ coordinates, which delineate functionally and morphologically important parts of teeth. This approach to accurate and morphologically relevant orientation of the studied teeth uses more than one structure at a time for choosing correct orientation according to aims of research and features of the studied material. This provides the proposed technique necessary potential to be applied for measurements of teeth and studies of their functional changes.

Photogrammetry is a non-destructive, three-dimensional modeling technique that has been widely adopted in archaeology. Archaeological monuments are particularly vulnerable to natural and anthropogenic activities, such as destruction, weathering, and erosion. Therefore, precise fixation and documentation of the monument are essential for preserving cultural layers for future generations. Digital technologies, especially photogrammetry, enable us to obtain better results for the photogrammetric survey. In recent years, this method has been employed in the excavation sites of Shengavit settlement and Verin Naver tombs, demonstrating its effectiveness in archaeological research. To obtain a better view of the stratigraphy of the site, the data was merged with archival drawings of previously collected information. This integration of data has allowed for a more comprehensive understanding of the site's history and evolution.

Abstract Background: NADPH oxidase 1 (Nox1), which is highly expressed in the colon, is thought to play a potential role in host defense as a physical and innate immune barrier against commensal or pathogenic microbes in the gastrointestinal epithelium. Diabetes can be caused by several biological factors, including insulin resistance is one of them. Alloxan is widely used to induce insulin-dependent diabetes in experimental animals. Alloxan increases the generation of reactive oxygen species as a result of metabolic reactions in the body, along with a massive increase in cytosolic calcium concentration. Methods Using a universal method, a superoxide radical (О2 −)-thermostable associate between NADPH-containing lipoprotein (NLP) and NADPH oxidase (Nox)- NLP-Nox was isolated and purified from the small intestine (SI) of control (C) and alloxan-induced diabetic (AD) albino rats. Results In comparison to the C indices, in AD in the SI, an increase in the specific content of NLP-Nox associate and a decrease in the stationary concentration of produced О2 − in liquid phase (in solution) and gas phase (during blowing by oxygen of the NLP-Nox solution) were observed. The NLP-Nox of SI associate in C and AD rats produced О2 − by an immediate mechanism, using NLP as a substrate. The phenomenon of the hiding of the optical absorption maxima of the Nox in oxidized states at pH10,5 was observed in the composition of these SI associates of the C and AD rat groups. The characteristic absorption maxima of the «hidden» Nox were observed under these conditions after reduction by potassium dithionite. Conclusion Thus, at AD, the decrease in the stationary concentration of produced О2 − in the solution and gas phase was compensated for by an increase in the specific amount of associate. In addition, the decrease in the stationary concentration of produced О2 − by NLP-Nox associates at AD can be linked to a decrease in the level of NADPH in NLP-Nox composition. This could be used as a new mechanism of AD pathogenesis.

Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which inhibits the production of ROS in complex I of the mitochondrial electron transport chain, prevent both mitochondrial lipid peroxidation and ferroptosis. SkQ1 and methylene blue also prevented accumulation of lipofuscin observed after 24 h incubation of cardiomyocytes with ferric ammonium citrate. Using isolated cardiac mitochondria as an in vitro ferroptosis model, it was shown that rotenone (complex I inhibitor) in the presence of ferrous iron stimulates lipid peroxidation and lipofuscin accumulation. Our data indicate that ROS generated in complex I stimulate mitochondrial lipid peroxidation, lipofuscin accumulation, and ferroptosis induced by exogenous iron.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to the low micrometric size range. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in the secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. In more detail, the dimer formation achieved by molecular self-docking showed two distinct poses, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

Abstract Background Metabolic dependencies of chronic lymphocytic leukaemia (CLL) cells may represent new personalized treatment approaches in patients harbouring unfavourable features. Methods Here, we used untargeted metabolomics and lipidomics analyses to isolate metabolomic features associated with aggressive CLL and poor survival outcomes. We initially focused on profiles associated with overexpression of the adverse metabolic marker glycosyltransferase (UGT2B17) associated with poor survival and drug resistance. Results Leukaemic B‐cell metabolomes indicated a significant perturbation in lipids, predominantly bio‐active sphingolipids. Expression of numerous enzyme‐encoding genes of sphingolipid biosynthesis pathways was significantly associated with shorter patient survival. Targeted metabolomics further exposed higher circulating levels of glucosylceramides (C16:0 GluCer) in CLL patients relative to healthy donors and an aggressive cancer biology. In multivariate analyses, C16:0 GluCer and sphinganine were independent prognostic markers and were inversely linked to treatment‐free survival. These two sphingolipid species function as antagonistic mediators, with sphinganine being pro‐apoptotic and GluCer being pro‐proliferative, tested in leukemic B‐CLL cell models. Blocking GluCer synthesis using ceramide glucosyltransferase inhibitors induced cell death and reduced the proliferative phenotype, which further sensitized a leukaemic B‐cell model to the anti‐leukaemics fludarabine and ibrutinib in vitro. Conclusions Specific sphingolipids may serve as prognostic markers in CLL, and inhibiting enzymatic pathways involved in their biosynthesis has potential as a therapaeutic approach.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level–dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.

This study evaluated the effects of drying temperature, slice thickness and pretreatment on the effective moisture diffusivity and activation energy of African oil bean seed in a hot-air convective oven dryer. Thin-layer drying of untreated, brine and sucrose pre-treated African oil bean seed slices was investigated under four oven temperatures (40, 50, 60, 70℃) and three slice thicknesses (2, 3, 5 mm) to determine the effective moisture diffusivity (Deff) and activation energy (Ea). Fick's second law of diffusion and the plot of ln(Deff) versus Ea were used to compute the moisture diffusivity and activation energy, respectively. The results showed that Deff for African oil bean seed is in the range of 0.637 × 10−10 to 13.870 × 10−10 m2s−1, whereas Ea ranged from 18.52 to 32.01 kJ mol−1. An increase in temperature, slice thickness and pre-treatment increased the diffusivity. Brine pretreatment was found to lower the activation energy of African oil bean seed whereas the reverse is the case for sucrose pretreatment. The moisture diffusivity is useful in understanding the rate of internal moisture movement during the processing and storage of African oil bean seed. The result of activation energy is important in selecting appropriate drying variables to ensure energy conservation during the drying of African oil bean seeds.

Our primary objective was to determine the proportion of trials that report the number of patients assessed for eligibility before randomization. We performed the systematic retrieval and analysis of all phase II, III, and IV RCTs published between 2013 and 2015 in four high-impact-factor journals in the field of clinical oncology. Among 456 RCTs reviewed, 236 trials (51.8%) reported the number of patients assessed for eligibility. Among the 236 trials that reported the entire enrollment process, the reasons for patient exclusion could be found in 184 trials (78%). A flow diagram was presented in 452 trials (99.1%), and 98 trials (21.5%) included a discussion on generalizability. Reporting the parameters of external validity in medical oncology RCTs is challenging. Improving adherence to the 2010 CONSORT guidelines concerning the enrollment process could help clinicians and health policymakers establish to whom trial results apply.

AbstractParkinson’s disease (PD) can affect speech as well as emotion processing. We employ whole-brain graph-theoretical network analysis to determine how the speech-processing network (SPN) changes in PD, and assess its susceptibility to emotional distraction. Functional magnetic resonance images of 14 patients (aged 59.6 ± 10.1 years, 5 female) and 23 healthy controls (aged 64.1 ± 6.5 years, 12 female) were obtained during a picture-naming task. Pictures were supraliminally primed by face pictures showing either a neutral or an emotional expression. PD network metrics were significantly decreased (mean nodal degree, p < 0.0001; mean nodal strength, p < 0.0001; global network efficiency, p < 0.002; mean clustering coefficient, p < 0.0001), indicating an impairment of network integration and segregation. There was an absence of connector hubs in PD. Controls exhibited key network hubs located in the associative cortices, of which most were insusceptible to emotional distraction. The PD SPN had more key network hubs, which were more disorganized and shifted into auditory, sensory, and motor cortices after emotional distraction. The whole-brain SPN in PD undergoes changes that result in (a) decreased network integration and segregation, (b) a modularization of information flow within the network, and (c) the inclusion of primary and secondary cortical areas after emotional distraction.

Abstract Background Single cell mRNA sequencing technologies have transformed our understanding of cellular heterogeneity and identity. For sensitive discovery or clinical marker estimation where high transcript capture per cell is needed only plate-based techniques currently offer sufficient resolution. Results Here, we present a performance evaluation of four different plate-based scRNA-seq protocols. Our evaluation is aimed towards applications taxing high gene detection sensitivity, reproducibility between samples, and minimum hands-on time, as is required, for example, in clinical use. We included two commercial kits, NEBNext® Single Cell/ Low Input RNA Library Prep Kit (NEB®), SMART-seq® HT kit (Takara®), and the non-commercial protocols Genome & Transcriptome sequencing (G&T) and SMART-seq3 (SS3). G&T delivered the highest detection of genes per single cell. SS3 presented the highest gene detection per single cell at the lowest price. Takara® kit presented similar high gene detection per single cell, and high reproducibility between samples, but at the absolute highest price. NEB® delivered a lower detection of genes but remains an alternative to more expensive commercial kits. Conclusion For the tested kits we found that ease-of-use came at higher prices. Takara can be selected for its ease-of-use to analyse a few samples, but we recommend the cheaper G&T-seq or SS3 for laboratories where a substantial sample flow can be expected.

Актуальность. Внутриартериальная радиочастотная ренальная денервация — единственный интервенционный метод лечения резистентной артериальной гипертензии, однако данная методика не обеспечивает стойкого длительного гипотензивного эффекта. Цель. Сравнить эффективность и безопасность лапароскопических механической и комбинированной ренальных денерваций с использованием радиочастотного зажима-электрода. Методы. Разделили 30 овец весом 93,00 ± 3,72 кг на две группы: I — механическая лапароскопическая ренальная денервация (n = 15), II — комбинированная лапароскопическая ренальная денервация с использованием радиочастотного зажима-электрода (n = 15). Период наблюдения — 6 мес. Оценили показатели: артериальное давление в ответ на высокочастотную электрическую стимуляцию из просвета сосуда, креатинин и мочевина, ятрогенные повреждения почечных артерий по результату ангиографии, степень разрушения нервных волокон по данным гистологического исследования. Результаты. Все животные были живы. Креатинин и мочевина были в норме. По ангиографии почечных артерий не выявили ятрогенных стенотических повреждений. Через 6 мес. в группе I отметили повышение артериального давления в ответ на высокочастотную электрическую стимуляцию (систолического — ∆ 66,73 ± 6,63 мм рт. ст., p < 0,001, диастолического — ∆ 47,27 ± 5,98 мм рт. ст., p < 0,001), а в группе II нет. После 6 мес. выводили животных из исследования с целью гистологии. В группе II отметили полное разрушение нервного волокна в виде демиелинизации, в группе I — отечность и вакуолизацию нервного волокна без признаков демиелинизации. Заключение. Лапароскопическая комбинированная ренальная денервация, в сравнении с лапароскопической механической, безопасна и эффективна и обеспечивает стойкий гипотензивный результат через 6 мес. на модели животных. Поступила в редакцию 30 марта 2022 г. Исправлена 5 декабря 2022 г. Принята к печати 9 декабря 2022 г. Финансирование Исследование не имело спонсорской поддержки. Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: Д.И. Башта, Л.И. Виленский, А.Б. Романов Сбор и анализ данных: Д.И. Башта, Ю.С. Кривошеев, А.А. Симонян Статистическая обработка данных: Д.И. Башта, Ю.С. Кривошеев Написание статьи: Д.И. Башта, Ю.С. Кривошеев Редактирование статьи: Л.И. Виленский, Ю.С. Кривошеев, А.Б. Романов Утверждение окончательного варианта статьи: все авторы

The proximate and microbial composition of cooking banana was determined after an active indirect solar drying experiment. The study was aimed at comparing the quality of dried cooking banana with similar products like banana and plantain. Fresh samples of the product were obtained from a local market in Umudike, Nigeria. The samples were washed, peeled, and sliced to the desired thickness (4 to 20 mm), before being loaded onto the dryer. The crude protein, crude lipid, carbohydrate content, ash content, and moisture content were determined after the drying experiment. The microbial load of the dried samples was also determined. The moisture content (10.20%), crude protein (7.18%), crude lipid (3.61%), and carbohydrate (85.61%) were higher than 6.00, 3.06, 2.80, and 82.90% respectively obtained for unripe banana. The ash content (2.21%) was lower than that of unripe banana (2.95%). A total of thirty-eight (38) bacterial isolates were observed from the sample and some of which were identified as Staphylococcus sp, bacillus subillus, and micrococcus sp. Eleven (11) molds (Fungal) were isolated from the dried samples, with Asperligillusniger and Absidia sp dominant. The frequency of occurrence was observed to had been higher in fungal than bacterial isolates.

Today, when digital technologies keep proliferating and integrating in different spheres of human activity, relations among entities, including economy and finance, are being transformed, which makes them more convenient and effective. Digital technologies extend communicative possibilities, simplify movement of information and finance flows and reveal a broad range of lines in further improvement of mechanisms providing better interaction between key entities of finance market, including credit consumer cooperatives. The principle goal of the research is to identify and substantiate the most promising directions of digitalization in functioning of self-regulating bodies of credit consumer cooperatives (CCC), to extend the number of mechanisms of raising extra investment into their work and to improve general finance accessibility in the Russian Federation. Fast development of Russian economy during the last decade, proliferation of digital, finance, banking services and technologies exercised a great impact on the system of cash circulation and credit relations, which shapes a modern outlook of the finance sector in Russia, including the sector of credit cooperation. The article demonstrates two key lines in introducing digital technologies into CCC work and depicts major vectors of their practical application: 1. Digitalization of CCC organization and management processes, as well as optimization of interaction between its members, executive body and selfregulating organization; 2. Use of advanced digital technologies in CCC functioning.

Abstract Background Childhood vaccination rates in Armenia are high. However, anecdotal evidence suggests that some health workers may advise against vaccination. The extent and reasons behind this are unknown. This study used the World Health Organization Tailoring Immunization Programmes approach to investigate medical specialists’ vaccination practices. Methods Face-to-face interviews were conducted with 30 medical specialists (paediatricians, immunologists, neonatologists, neurologists, gynaecologists). Interviews explored their vaccination practices (recommending/administering), knowledge, attitudes and confidence. Data were analysed using the Framework approach and COM (Capability, Opportunity, Motivation) factors. Findings Medical specialists were routinely consulted by parents about vaccination. They engaged in conversations, even if they did not administer vaccinations and lacked expertise. Vaccination recommendation was “selective”, influenced by their own vaccine hesitancy. Doctors administering vaccination used false contraindications to postpone vaccination. Multiple barriers and drivers to positive vaccination practices were evident, with differences between specialists administering/not administering vaccinations. Capability Drivers were knowledge of vaccination, vaccines, and vaccine-preventable diseases; with awareness and use of protocols for adverse events and contraindications (those with a vaccination role). Barriers were a lack of a detailed understanding of vaccination, vaccines, and vaccine-preventable diseases, especially amongst neonatologists and gynaecologists, and for HPV. Poor knowledge of adverse events and mixed knowledge of contraindications was evident, as was low confidence about conversations with parents declining vaccination. Opportunity Drivers were using “official“ guidance and professional information and feeling protected by the Government of Armenia should an adverse event occur. Conversely, barriers were a reliance on media/social media without considering credibility, peers not recommending vaccination, increasing parent demands and not feeling protected by the Government. Motivation Drivers were seeing vaccination as their responsibility (those who administer vaccinations); and generally supporting vaccination. Barriers were vaccine hesitancy, some anti-vaccination sentiments amongst neonatologists and gynaecologists and not seeing vaccination as their role (those who do not administer vaccinations). Conclusions Applying a theory-informed approach allowed us to identify critical issues and possible solutions. High vaccination coverage may disguise underlying issues, e.g. false contraindications. We addressed gaps in the literature, with our geographical focus and study of medical specialists advising parents on vaccination, a widely used practice in this sub-region.

Aim. To determine the incidence and predictors of cardiovascular events in onpump cardiac operations in modern practice.Material and methods. The study included 200 patients who underwent various elective cardiac surgical interventions. Cardiovascular events (CVEs) were determined within 30 days from the operation, according to medical records and autopsy protocols. We identified major CVEs (cardiovascular death, stroke, myocardial infarction) and minor CVEs (angina pectoris, significant ventricular arrhythmias, atrial fibrillation or flutter episodes, AV conduction disorders, etc.). A comprehensive preoperative examination was performed, including an extended echocardiography protocol and coronary angiography.Results. In 101 patients (50,05%), various CVEs were identified: 4,0% had major CVEs and 46,05% had minor CVEs and various non-cardiac complications, while perioperative mortality was 2,0%. Most ischemic CVEs, as well as most intracardiac conduction disorders, were registered during the first 3 days after surgery. In contrast, episodes of atrial fibrillation/flutter occurred 2-7 days after the intervention. There were following preoperative examination parameters with the highest prognostic value: history of heart failure, age >65 years, history of myocardial infarction, occlusion of at least one coronary artery, and diabetes.Conclusion. The data obtained indicate the high efficiency of current surgical and anesthetic technologies, which lead to relatively low risk of severe and fatal events. The parameters of the preoperative examination, which determine the increased risk of intervention, are highlighted.

Aim. To determine additional factors and sex differences associated with the intermediate probability of heart failure (HF) with preserved ejection fraction (HFpEF) in asymptomatic patients working in the Arctic on a rotating basis.Material and methods. In the polar village of Yamburg (68° 21' 40 "N), 99 men and 81 women with grade 1 and 2 hypertension (HTN) and normal blood pressure, comparable by age (p=0,450), length of service in the north (p=0,956), office systolic blood pressure (BP) (p=0,251), diastolic BP (p=0,579) were simultaneously examined. We performed echocardiography and assessed the risk of HFpEF by H2FPEF score (Heavy; Hypertensive; Atrial Fibrillation; Pulmonary Hypertension; Elder; Filling Pressure). A treadmill test, Baevsky index, 24-hour BP monitoring, and biochemical blood tests were performed.Results. Depending on H2FPEF score, participants were divided into groups: from 0 to 1 (group 1 — normal), from 2 to 5 (group 2 — intermediate probability of HFpEF). In men with intermediate probability of HFpEF, the Baevsky index (p=0,0048) and the incidence of resting body reserve dysaptation (p=0,0394) were higher, as well as a rapid BP increase during dosed exercise (p=0,0058) and a decrease in chronotropic reserve (p

Aim. To study dysfunctional types of eating behavior (EB) in relation to metabolic risk factors in workers in the Arctic, as well as to determine sex differences.Material and methods. In the polar village of Yamburg (680 21’ 40 "N), 99 men (M) and 81 women (W) with grade 1 and 2 hypertension (HTN) and normal blood pressure, comparable by age (p=0,450), length of service in the north (p=0,956), number of rotation work years (p=0,824), office systolic BP (p=0,251), diastolic BP (p=0,579). The Dutch Eating Behavior Questionnaire (DEBQ) and questionnaires on scales of general and occupational stress were used. We conducted daily monitoring of blood pressure, carotid artery (CA) ultrasound to determine plaques. Biochemical blood tests were carried out with the determination of lipid profile parameters, circulating markers of nonspecific inflammation, levels of homocysteine, C-peptide, insulin, and cortisol.Results. The body mass index in 77% of men and women was determined above the norm, while class 1 and 2 obesity was found in 46% of M and 42% of W and negatively correlated with impaired dietary control (DC) in M (r=-0,305, p=0,045). Men were less resistant to stress (p

Introduction Severe bronchopulmonary dysplasia (BPD) is a well-known factor consistently associated with impaired cognitive outcomes. Regarding reported benefits on long-term neurodevelopmental outcomes, the potential adverse effects of high-dose docosahexaenoic acid (DHA) supplementation on this short-term neonatal morbidity need further investigations in infants born very preterm. This study will determine whether high-dose DHA enteral supplementation during the neonatal period is associated with the risk of severe BPD at 36 weeks’ postmenstrual age (PMA) compared with control, in contemporary cohorts of preterm infants born at less than 29 weeks of gestation.Methods and analysis As part of an Australian–Canadian collaboration, we will conduct an individual participant data (IPD) meta-analysis of randomised controlled trials targeting infants born at less than 29 weeks of gestation and evaluating the effect of high-dose DHA enteral supplementation in the neonatal period compared with a control. Primary outcome will be severe grades of BPD (yes/no) at 36 weeks’ PMA harmonised according to a recent definition that predicts early childhood morbidities. Other outcomes will be survival without severe BPD, death, BPD severity grades, serious brain injury, severe retinopathy of prematurity, patent ductus arteriosus and necrotising enterocolitis requiring surgery, sepsis, combined neonatal morbidities and growth. Severe BPD will be compared between groups using a multivariate generalised estimating equations log-binomial regression model. Subgroup analyses are planned for gestational age, sex, small-for-gestational age, presence of maternal chorioamnionitis and mode of delivery.Ethics and dissemination The conduct of each trial was approved by institutional research ethics boards and written informed consent was obtained from participating parents. A collaboration and data sharing agreement will be signed between participating authors and institutions. This IPD meta-analysis will document the role of DHA in nutritional management of BPD. Findings will be disseminated through conferences, media interviews and publications to peer-reviewed journals.PROSPERO registration number CRD42023431063.Trial registration number NCT05915806.

In the work, the biological and agronomic evaluation studies of tomato varieties Lia, Titan, Orange, Eraz, Marine and Cherry Zeytun were carried out. The results of the study of biological and agronomic characteristics of tomato varieties showed that from seed germination to seedling took 5-7 days, from flowers - 65-74 days, seed germination from first harvest or biological maturity - 102-114. days. According to the research results, tomato yield: Lia (St) 701.25c/ha, Titan: 965.5 c/ha, Orange: 900.3 c/ha, Eraz (St): 853c/ha, Marine: 1055.55 c/ha. , Zeytun was 32.5 c/ha. Titan, Orange, Marine varieties stood out for their high yield, which surpassed the testers. The content of dry matter in tomato varieties Lia (St) was 7.3%, Titan: 7.5%, Orange: 7.2%, Eraz (St): 7.3%, Marine: 7.4%, Zeytun: 7.6%. Lia (St) sugar content was 4.8%, Titan: 4.9%, Orange: 4.1%, Eraz (St): 4.5%, Marine: 4.7%, Zeytun: 5.1% , vitamin C content: 35.65, 37.65, 35.75, 33.55, 33.65, 38.55 mg%, acidity - 0.45, 0.46, 0.51, 0.47, 0.48, 0.48%, respectively. Titan, Marine, Zeytun. The results of the cultivation of new varieties of tomatoes Titan, Orange, Marine, Zeytun, according to biological and agronomic assessment, are adaptive in the hot climate conditions of Armenia.

The production of electricity at thermal power plants using fossil fuels involves the use of such material resources, most of which are converted into waste that is released into the environment. Hrazdan Thermal Power Station is the largest power plant in Armenia, built and put into operation in the late 1960s. During the study, a comparative analysis of the concentration of some chemical elements in soil samples, including the Hrazdan Thermal Power Plant and the Hrazdan Cement Plant, was carried out. The analysis showed significant differences depending on the sampling location and season. This may be due not only to snow cover but also to the start of spring fieldwork and the application of fertilizers and pesticides to agricultural land, as well as the active period of power plant operation. Therefore, when using multi-criteria methods to assess the environmental impact of different types of power plants, it is necessary to consider the soil pollution coefficient as a separate correction factor.

The relevance of research is conditioned by the need to ensure efficient operation of the internal combustion engine ICE on NGV fuel at different altitudes above sea level, where there is atmospheric air rarefaction up to 20÷25%. This direction is dictated by the fact that when transferring the ICE operation from gasoline to gas-engine fuel, the engine power decreases from 5 to 15%, moreover, the atmospheric air rarefaction leads to an even greater reduction in engine power and ultimately reduces the performance of the vehicle. Due to violation of the process of combustion of gas-air charge in the cylinder is formed a large amount of carbon monoxide (CO). Research objective is to develop and propose a method of providing such a stoichiometric, fractional composition of the gas-air charge, which will ensure the restoration of the lost power of ICE and provide the optimal value of traction-dynamic characteristics of the car, without increasing toxic emissions. Research object: Variable crosssectional area of the intake manifold path (ICE), adjustable lumen for atmospheric air intake, atmospheric air pressure sensors adjustable diaphragm with stepper motor. Research methods: analytical modeling of the relationship of the aperture diameter depending on the altitude of the terrain above sea level, on the number of revolutions of the ICE, on the density and temperature of the ambient air. The process of combustion of the gas-air charge in the combustion chamber will be evaluated by the fractional composition of the exhaust, exhaust gases. Research results: Qualitative and quantitative assessment of the application of altitude corrector on the ICE operation mode, stability of the value of excess air ratio at different altitudes above sea level, formation of toxic gas, carbon monoxide, as well as carbon dioxide, hydrocarbon, oxygen, etc. is given.

The article raises a controversial topic of classifying business models of contemporary enterprises and justifies the necessity of their transformation, considering the factor of sustainability. The author analyzes various definitions of business models and proposes their own approach to interpretation. The article provides a traditional classification of enterprise business models, as well as the results of the author's scientific research in the field of sustainable economic growth. The paper highlights the advantages of platform-based business models over traditional models in terms of determining sustainability. It has developed a classification of digital enterprise business models based on various criteria and formulated the main directions for further development and improvement.

The article considers approaches to the concept of business model of business activity, considers its modern content in the context of taking into account the peculiarities and using the advantages of the digital economy. An analytical review of business models currently used by domestic and foreign companies with the allocation of e-commerce and innovation models is made. It is proven that the improvement of existing business models or the creation of new ones should be carried out through the re-engineering of their business processes. The classification of business processes according to various classification features which can be used in the process of reengineering, is given. Reengineering as a method of radical redesign of the company's business model, taking into account the main trends in the development of modern economy and the signals of key stakeholders is characterized in detail. Based on the results of the research, a conceptual model of hybrid reengineering for market adaptation of business models of Russian enterprises to the conditions of market economy is developed. Promising directions of its improvement were identified for all the main structural elements forming its integrity and synergetic character.

The article presents the researches on the morphological characteristics of seedlings, plants and fruits of several valuable Armenian tomato varieties intended for fresh consumption: Lia, Titan, Orange, intended for processing Marine and chery Zeytun, in the hot conditions of the Ararat Plain. The results of the study showed that the investigated varieties of tomato are distinguished from each other by morphological characteristics of plants, fruits of different size, shape, color, they are adaptive in the case of cultivation in the hot climatic conditions of the Ararat Plain. The results of the study allow to guarantee the cultivation of these new cultivars Titan, Orange, Marine, Zeytun in the farms of the zones with similar conditions.