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Introduction. Infertility affects tens of millions of men and women across the globe. In approximately half of cases, male factors are the cause of infertility. In recent decades, there has been a significant decline in the quality of male ejaculate, which is characterized by reduced sperm concentration and motility. The insufficient diagnostic and prognostic value of routine semen analysis results highlights the challenge of developing effective diagnostic tools and searching for reliable biomarkers of male infertility. One of the most promising approaches may be assessing sperm microRNA expression.Objective. To study the role of sperm exosomal microRNAs miR-34a and miR-210 in the development of male infertility.Materials & methods. The retrospective study included 150 men aged 25 – 49 years; of these, 96 patients were diagnosed with idiopathic infertility. The comparison group consisted of 54 fertile men. To assess the structure and motility of sperm, the results of a standard ejaculate study (WHO, 2021) and computer data analysis using MMC Sperm (MMCSoft, St. Petersburg, Russia) software were used. The degree of DNA fragmentation was assessed using the TUNEL method. To analyze the expression of miR-34a and miR-210, quantitative real-time PCR was performed using the miRCURY LNA SYBR Green PCR Kit («Qiagen» GmbH, Hilden, Germany) and the Rotor-Gene Q PCR product detection system («Qiagen» GmbH, Hilden, Germany).Results. The study of ejaculate using the Computer Assisted Sperm Analysis System (CASA) method revealed a statistically significant relationship between the level of DNA fragmentation of sperm and indicators of the speed of their movement: rectilinear (VSL) (r = -0.522726; p < 0.01), curvilinear (VCL) (r = -0.499096; p < 0.01), along the middle path (VAP) (r = -0.429533; p < 0.01), as well as with the amplitude of lateral head displacement (ALH) (r = -0.294779, p < 0.01), the linearity of their curvilinear path (LIN) (r = -0.385796; p < 0.01), the degree of straight-line movements (STR) (r = -0.268248; p < 0.05) and their progressive mobility (r = -0.411547; p < 0.01). A study of the level of microRNA expression in sperm exosomes revealed a statistically significant decrease in its miRNA-34a pool (p = 0.0116). According to the Chaddock scale, the strength of the correlation between miR-210 expression and the effectiveness of ART programs was moderate (0.437993). The inverse relationship between miR-34a expression and IVF and ICSI results was weak (0.135314).Conclusion. The analysis of exosomal microRNA-34a and microRNA-210, which are involved in the regulation of spermatogenesis, reveals a direct correlation between their variations and changes in the kinetic and morphological parameters of gametes. It also indicates a relationship with the state of DNA fragmentation. These findings suggest varying levels of gene expression among infertile patients, men with proven fertility, and those undergoing assisted reproductive technology (ART) treatments, both with successful and repeated unsuccessful outcomes.

This study analyzes how medical educational programs are evolving to address the digital transformation in healthcare. Surveys, curriculum analysis, and faculty interviews were utilized to examine technology integration. Findings indicate electronic medical records are considered the most significant digital achievement, though only 4% of beginner faculty emphasized telemedicine. Curriculum analysis revealed increasing modifications related to technology, informatics, and data analytics, especially in certain specialties like biochemistry and biophysics. Interviews provided insights into digital integration opportunities and challenges. A key theme was re-evaluating pedagogical strategies as students rely more on technology. Interviewees also envisioned emerging innovations enabling personalized, immersive learning, but cautioned against over-dependence on technology impeding development of clinical skills and humanism. Overall, while core medical fundamentals remain unchanged, curriculum content is adapting to incorporate new competencies like digital literacy. However, strategic integration remains crucial to balance technology's benefits and drawbacks. Challenges like technical difficulties, costs, and over-reliance must be addressed. The outlook is increased technology utilization, with solutions like AI-enabled adaptive learning on the horizon. However, investing in infrastructure and faculty development will be vital. Medical schools must leverage technology to elevate learning while retaining humanistic values. This study provides timely insights into medical education's digital transformation, laying groundwork for further research on optimizing technology integration while upholding the human core of medicine.

Objective: To review the signs and symptoms of Wernicke encephalopathy (WE) after bariatric surgery based on 2 case reports and a literature data analysis. Methods: We present two case reports of WE. In these patients, thiamine deficiency developed due to bariatric gastric surgery, which was performed to treat class III obesity, formerly known as morbid obesity. The patients underwent comprehensive physical and neurological examinations; clinical, laboratory, and instrumental data were collected from medical records and analyzed. The researchers also performed a computerized search using the keywords "Wernicke encephalopathy after bariatric surgery" to find relevant publications in the PubMed/Medline, Scopus, and Web of Science databases. Results: The presented acute neurological condition related to vitamin B1 deficiency in two patients after undergoing a weight loss surgery, specifically a mini-gastric bypass. The clinical picture in one patient was dominated by memory impairment, ataxic, and polyneuritic syndrome, while in the other, it was only polyneuritic syndrome. Conclusion: The initial symptoms of WE are often overlooked, leading to the progression of the disease with the development of severe neurological deficits. To prevent the progression of encephalopathy, it is necessary to begin treatment with high doses of parenteral thiamine replacement therapy as early as possible.

Introduction Brick-and-mortar vape shops specialize in the sale of e-cigarettes and remain a primary source for purchasing emerging e-cigarette products. New regulatory policies have been implemented at local-, state- and federal-level; the retail environment at vape shops and product preferences among vape shop customers shifted accordingly. Methods From 2019 to 2023, we collected anonymous interview data from vape shop customers (n=572) from 83 vape shops in Southern California. We aggregated the data by month and treated each month as the unit of analysis to document changes in recruitment efforts among the vape shops in relation to major policy implementations over 4 years. We also examined the systematic fluctuations and trends in customers’ e-cigarette product preferences and nicotine content in these products. Results The monthly average shop-level consent rate was 52.9% (SD=8.7), with an overall decreasing trend over time. It was necessary for our data collection team to approach a greater number of vape shops to obtain consent with implementation of various state and federal tobacco regulations and following COVID-19. We observed an increase in the purchase of disposable products and nicotine concentrations in the products, while the average use frequency remained the same. Conclusions Our findings demonstrated that user preferences, product characteristics and challenges in research involving vape shops are closely associated to changes in regulations. We documented a dramatic increase in nicotine concentration in products. Future policies restricting the amount of nicotine in tobacco products at the federal level are necessary to protect consumers from further nicotine addiction. This study provides documentation over time of the drastic increases in nicotine concentration among e-cigarette users as a result of the fluctuations in the product market. Regulating nicotine content in tobacco products could safeguard against further unsafe modifications in e-cigarettes and other types of tobacco products.

This study is devoted to assessing the weighted average distances between the regions of Russia according to different metrics – the shortest distances on the sphere, as well as distances by railways and highways. Such aggregated estimates are necessary for researchers of interregional processes (from migration to cargo transportation), but these estimates are not publicly available. The article fills this gap. We describe the methods for estimating distances using various metrics (relying on the Russian Railways data on ‘tariff distances’ between railway stations, information on cities’ coordinates and population, and web-services for calculating inter-city distances). The proposed metrics can be considered as an economic distance metric developed in the context of gravitational interaction studies. We estimate the distances between Russian regions using recent and highly detailed data (the distances between 2840 railway stations, the population data gathered for about 10,000 settlements). For scientific and practical purposes, the open access to resulting estimates is provided. We discuss and interpret the cases of significant discrepancies in the estimates of distances between Russian regions according to different metrics. We demonstrate that, for a number of regions, location of transport infrastructure determines the need to choose the metric of interregional distance carefully, depending on the task. We estimate the weighted distance between all regions of Russia with an account for changes in regional structure of population; on this basis, we show that since 1990s migration has been directed to regions with greater relative transport connectivity

Introduction JUUL is a high-nicotine pod-based vaping device that is popular among adolescents and young adults. On 23 June 2022, the US Food and Drug Administration (FDA) denied authorization to market JUUL, and ordered JUUL Labs to remove products from the US market. The next day, a US federal appeals court temporarily suspended the ban. The mixed public discourse surrounding the FDA ban warrants further investigation. Methods This study examined Twitter data to describe public reaction to these announcements. Posts containing terms ‘JUUL’ and/or ‘#JUUL’ (N=97548 unique tweets) were collected from 23 June to 3 July 2022, from Twitter’s Streaming Application Programming Interface (API). After removing retweets, we used an inductive approach to become familiar with the data, generated a codebook, and conducted a content analysis on a random sample of n=4000 tweets. Results A total of 2755 (68.9%) tweets discussed JUUL in the context of the FDA ban. News (n=1425/2755; 51.7%) about the JUUL ban, government distrust (n=588; 21.3%), and individual rights (n=253; 9.2%) were the most prevalent themes. Less commonly discussed themes included inconsistencies between policies (n=174; 6.3%), mentions of switching to other products (n=162; 5.9%), smoking cessation (n=99; 3.6%), and craving for JUUL (n=94; 3.4%). Sentiment analysis of JUUL ban-related posts (n=2755) demonstrated that 1989 (72.2%) tweets were categorized as neutral, while anti-ban posts (n=566; 20.5%) were more prevalent than pro-ban posts (n=200; 7.3%). Conclusions Besides straightforward announcements of the JUUL ban and its suspension, Twitter posts discussed government distrust, individual rights, and policy inconsistencies. While most posts conveyed neutral sentiments, anti-ban posts were almost three times more prevalent than pro-ban posts. Our findings suggest that text-based social media platforms like Twitter may be an effective instrument to understand opinions, attitudes, and beliefs regarding the FDA’s JUUL ban.

A new physics-based compact model, which makes it possible to simulate in a unified way the neutrons and protons of cosmic ray-induced SEU cross-sections, including the effects from nuclear reaction products and from direct ionization by low-energy protons, has been proposed and validated. The proposed approach is analytical and based on explicit analytical relationships and approximations with physics-based fitting parameters. GEANT4 or SRIM numerical calculations can be used as an aid to adjust or refine the phenomenological parameters or functions included in the model, taking into account real geometrical configurations and chemical compositions of the devices. In particular, explicit energy dependencies of the soft error cross-sections for protons and neutrons over a wide range of nucleon energies were obtained and validated. The main application areas of the developed model include space physics, accelerator studies high energy physics and nuclear experiments.

IntroductionE-cigarette users typically initiate vaping with flavoured e-liquids. People who vape flavours tend to underestimate the harm of vaping. We examined the inter-relationship between flavour preference, vaping for cessation purposes, e-cigarette dependence, e-cigarette harm perception and purchase/use intention, given a hypothetical flavour ban. We hypothesised that non-tobacco flavour preference and vaping for cessation would be negatively associated with harm perception of e-cigarettes and intention to continue vaping if a flavour ban occurred and that these effects would be mediated by e-cigarette dependence.MethodsFrom July 2019 to March 2020, we conducted intercept interviews with 276 customers at 44 vape shops in California. The predictor variables were flavour preference and vaping for cessation. The outcome variables were harm perception of e-cigarettes and intention to purchase/use, given a hypothetical flavour ban. Multilevel structural equation modelling tested whether e-cigarette dependence mediates the effects of flavour preference on hypothetical continued vaping and purchase.ResultsThose who preferred flavours showed significantly lower intention to purchase e-liquids (β=-0.28, p

Background We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance.Methods Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed.Results We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively.Conclusions Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.

Objective: Synthetic nicotine (SN) e-cigarettes emerged on the market as an alternative to tobacco-derived nicotine (TDN) vaping products. It is critical to understand the harm perceptions, purchase, and use of SN vs. TDN e-cigarettes. Methods: From November 2021 to February 2023, we conducted intercept interviews with 263 adult customers at 37 vape shops in Southern California. Self-reported use and harm perceptions towards SN vs TDN e-cigarettes were examined. A qualitative analysis of researcher-obtained photographs of vaping items just purchased by customer participants was conducted. Results: Past 30-day SN e-cigarette use was reported by 44 (16.7 %) customers. Past 30-day SN e-cigarette users vs. non-users reported vaping on more days in the past month (29.3 vs. 26.1 days, p = 0.02). Overall, 23.8 % of participants perceived SN e-cigarettes as less harmful than TDN ones; never-smoking vapers and dual users perceived SN e-cigarettes as less harmful than salt-based TDN e-cigarettes. Among 44 customers who purchased SN products (verified through qualitative analysis of photographs), only 13 (29.6 %) self-reported using SN products in the past month, while 5 (11.4 %) indicated they were not aware of the existence of SN products. Most SN vaping products (71.4 %) displayed a modified “tobacco-free” warning label. Conclusions: Misperceptions about SN e-cigarettes were documented in this study, including the perception that SN is either less or more harmful than TDN. Further, some customers may be unknowingly purchasing and using SN e-cigarettes. Regulating “tobacco-free nicotine“ terminology in SN vaping products marketing is suggested. SN product labeling should not imply that SN is safe/safer than TDN.

Ensuring a high quality of teaching mathematics to students is inextricably linked with teaching how to solve creative mathematical problems. These problems traditionally include tasks of high educational, developmental and diagnostic value. Teaching how to solve such problems allows training graduates with the highest level of the subject knowledge. The problem under study is relevant due to the need to form students' ability to solve problems with parameters in order to achieve high results in mathematics, intellectual and personal growth. The problem has a new meaning during temporary distance learning, emphasizing the need to create educational and methodological materials that allow students to organize self-education on complex topics in mathematics. The purpose of this research is to develop and describe a teaching methodology for solving problems with parameters based on the allocation of basic (key) problems. The authors have developed a methodology for constructing a system of tasks based on systematizing the theoretical and task material, highlighting students' basic knowledge and skills, describing the intra- and inter-subject connections of the topic "Equation of a circle in tasks with parameters". This methodology includes a typology of problems with parameters containing the equation of a circle, a substantiated description of the system of basic (key) problems, the role and content of the propaedeutic stage of teaching. The materials have passed multi-stage approbation and shown their consistency in achieving high results in mathematics. They can help teachers to prepare lessons and extracurricular activities, authors to provide teaching aids for students and teachers, and serve as the basis for a special course for students of pedagogical universities.

Abstract Background In the evolution from unicellular to multicellular life forms, natural selection favored reduced cell proliferation and even programmed cell death if this increased organismal fitness. Could reduced individual fertility or even programmed organismal death similarly increase the fitness of colonies of closely-related metazoan organisms? This possibility is at least consistent with evolutionary theory, and has been supported by computer modelling. Caenorhabditis elegans has a boom and bust life history, where populations of nematodes that are sometimes near clonal subsist on and consume food patches, and then generate dauer larva dispersal propagules. A recent study of an in silico model of C. elegans predicted that one determinant of colony fitness (measured as dauer yield) is minimization of futile food consumption (i.e. that which does not contribute to dauer yield). One way to achieve this is to optimize colony population structure by adjustment of individual fertility. Results Here we describe development of a C. elegans colony fitness assay, and its use to investigate the effect of altering population structure on colony fitness after population bust. Fitness metrics measured were speed of dauer production, and dauer yield, an indirect measure of efficiency of resource utilization (i.e. conversion of food into dauers). We find that with increasing founder number, speed of dauer production increases (due to earlier bust) but dauer yield rises and falls. In addition, some dauer recovery was detected soon after the post-colony bust peak of dauer yield, suggesting possible bet hedging among dauers. Conclusions These results suggest the presence of a fitness trade-off at colony level between speed and efficiency of resource utilization in C. elegans. They also provide indirect evidence that population structure is a determinant of colony level fitness, potentially by affecting level of futile food consumption.

The consequences of stroke are often severe and result in the need for rehabilitation of different regions in the body for a defined period. Rehabilitation exercises are often monotonous and quickly become boring, therefore serious games try to include gaming aspects into the rehabilitation process, which was previously shown can support the overall process. To support wrist and hand rehabilitation, the authors propose a new and innovative serious game, which relies only on the Leap Motion Controller together with a PC combining cognitive and physical rehabilitation. The development was based on a user-centred design approach divided into 3 consecutive phases focusing on the therapeutical point of view. In Phase 1, requirements for such a solution were identified and validated in cooperation with one therapist. Phases 2 and 3 pose additional changes gathered from interviews together with four more therapists and one stroke patient to develop a highly sophisticated and flexible prototype. Different and easily adaptable levels were developed in which the patient needs to perform specific movements with one or two hands and wrists to control the avatar throughout a jump-and-run game. Additionally, it includes memory aspects for additional and combined cognitive training. In the end, overall 44 requirements were identified and the gathered feedback during the iterations showed a positive acceptance and massive potential of the proposed solution. These requirements should also pose a good starting point for the development and research of new serious games in that domain as well.

ObjectiveThe 2016 FDA's "Deeming Rule" prohibited free samples of vaping products. The purpose of this study was to investigate compliance with or adaptation to this newly established FDA policy.MethodsVape shops were recruited in Southern California between November 2017 and December 2018. Data collectors interviewed 121 vape shop employees who responded to questions pertaining to the sampling protocol at their shop. Nicotine levels used for sampling were also assessed for consideration of future policy adoption.ResultsOnly 7.4% of shops were non-compliant to federal sampling rules. The remaining shops either: 1) charged a fee for samples (58.7%); 2) deducted the fee from the final purchase price (5.8%); or 3) eliminated product sampling (28.1%). Of the shops that charged for sampling (including membership fees), 94.4% initiated a minimal cost protocol (≤$1) for sampling. Half (50.0%) the shops that allowed sampling offered nicotine-containing samples.ConclusionThere was high compliance (92.6%) to the change in policy among vape shops. However, minimal modification of sampling protocol was observed due in part to the lack of specificity on parameters of compliance, which lessened the potential impact of the policy. To further protect consumers, policymakers must develop unambiguous and comprehensive policies to achieve intended results and true compliance. At minimum, future tobacco product sampling policies should consider standardized pricing; alternatively, total elimination of tobacco product sampling is suggested.

Research objectives: The objective of this study is to determine the causes and circumstances surrounding the death of Grand Duke Yaroslav Vsevolodovich. His demise occurred during his presence at the headquarters of Turakina and in the presence of the Great Khan Guyuk. Research materials: The research draws from a complex of Russian chronicle sources, monuments of ”hagiographic” literature from Ancient Rus’, Plano Carpini’s “The History of the Mongols,” Rashid al-Din’s “The Collection of Chronicles,” Juvayni Ata-Malik’s “The History of the Conqueror of the World,” and acts of diplomatic correspondence. Results and novelty of the study: Through a critical and comparative analysis of written sources, examined in the context of the political landscape within the Mongolian Empire leading up to and during the Kurultai of 1246, the authors of this article conclude that Plano Carpini’s account of the poisoning of Russian Prince Yaroslav Vsevolodovich by Turakina khatun is unreliable. Utilizing a methodology akin to the natural sciences, the study ultimately attributes Yaroslav Vsevolodovich’s death to natural causes, specifically complications arising from an acute toxicoinfective disease. This conclusion is drawn considering the absence of qualified medical care, weakened immunity, and the advanced age of the ruler of Northeastern Russia.

Background. Allergic rhinitis is caused by grass pollen is a common problem in the world. The symptoms of this disease can varied on the age of the patient. Aim: to identify the etiology and analyze the clinic of allergic rhinitis in adolescents. Methods. An allergic examination was carried out in 96 patients with allergic rhinitis signs who were treated at MEGI MC, which included the study of an allergic history and setting of scarification tests, determination of IgE, comparison of clinical manifestations and detection of sensitization to pollen of various plants in adolescents with allergic rhinitis. Results. The prevailing share of girls was 65.4 %. The etiological factors were tree pollen in 28.6 % of cases (in 27 patients), weeds – 12.4 % (12 people), meadow grasses – 10.6 % (10 people), meadow and weeds – 8.3 % (8 people), a combination of trees, meadow and weeds – 6.4 % (6 people) and trees and meadow grasses – 4.7 % (4 people). Conclusion. Typical clinical manifestations consist of light and middle rhinitis – 71 people (94 %), conjunctivitis – 45 people (58.8 %), rhinosinusitis – 22 people (28.6 %), bronchial asthma – 10 people (10.4 %).