Friend or foe? Contextualizing Bacteroides through the lens of niche remodeling.

To evaluate the incidence of failure of trabeculectomy versus tube shunt (TS) glaucoma surgery in eyes of patients with uveitis. Multicenter retrospective cohort study. Among 356 eyes of 288 patients with noninfectious inflammatory eye disease undergoing first incisional glaucoma surgery using one of the techniques, 244 eyes had TSs, and 112 eyes had trabeculectomy augmented with mitomycin-C (Trab-MMC). A standardized chart review was used to collect clinical data over time retrospectively. Cox regression analyses with adjustment for propensity score and intereye correlations were performed to compare the incidence of failure of glaucoma surgery between TS and Trab-MMC. Failure of glaucoma surgery of the first 5 years postoperatively, defined as the following: (1) intraocular pressure (IOP) ≤ 5 or > 21 mmHg at 2 consecutive visits at least 90 days apart beginning 3 months after surgery; or (2) reoperation; or (3) complete blindness (no light perception). The median age was 40.3 years (interquartile range [IQR], 13.4-57.3 years) in the TS group and 44.2 years (IQR, 29.0-58.9 years) in the Trab-MMC group. The median preglaucoma surgery IOP was 30.0 mmHg (IQR, 21-35.5 mmHg) in the TS group and 30.5 mmHg (IQR, 20-38 mmHg) in the Trab-MMC group. Anterior uveitis was the most common location of primary inflammation in both the TS (52.5%) and Trab-MMC 55.4%) groups. Failure was observed in the TS group in 23.5%, 27.1%, and 30.8% cumulatively through 12, 24, and 36 months, respectively, versus 16.1%, 25.6%, and 30.0%, respectively, in the Trab-MMC group. In the propensity score-adjusted Cox regression analysis, there was no significant difference in failure incidence rate between the TS and Trab-MMC groups (adjusted hazard ratio, 1.08; 95% confidence interval, 0.65-1.78; P = 0.77). Success without the requirement for IOP-lowering medicines was observed more frequently in the Trab-MMC group. Tube shunt and Trab-MMC fail frequently with similar incidences when done as the first glaucoma surgery among eyes with uveitis over 5 years of follow-up, but there were more complete successes in the Trab-MMC group than in the TS group at 12, 24, and 36 months. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Introduction. The most important preventive measure for occupational diseases (OD) is the diagnosis of their early manifestations during periodic medical examinations (PME).The purpose of the study. To investigate the effectiveness and quality of PME to assess their role in the prevention system of OD among workers in a number of subjects of the Volga Federal District between 2021 and 2023.Materials and methods. We have analyzed the reporting forms of the centers of occupational pathology (COP) in 4 regions of the Volga Federal District: the Republics of Bashkortostan, Tatarstan, Samara and Orenburg regions between 2021 and 2023. To assess the effectiveness and quality of PME, the following indicators are calculated: the coverage of employees by periodic medical examinations, the detection of diseases, and primary disability. The detection of chronic non-infectious diseases (CNID) using the χ2 criterion and its reliability (p) with multiple comparisons of groups and reliability p < 0.05 has been analyzed. Statistical processing was carried out using Microsoft Excel software.Results. Over the studied period, the PFO revealed an increase in the number of employees covered by PMO. There was a low proportion of employees subject to PME in the COP (2.1–4.2% in Bashkortostan during 2021–2023; 1.7% in the Samara Region in 2023). Low rates of OD detection were identified in Bashkortostan — 17.6%, high ones in Tatarstan — 82.0% and Orenburg Region — 91.2%. An increase in primary disability of workers with OD was recorded — 2.8 — 3.8 — 12.2%. In 2023, the detection of NICD decreased, especially neoplasms (χ2 = 153.6; p = 0.001), diseases of the genitourinary system (χ2 = 710.2; p = 0.001). The COP reports do not contain information on the number of workers with early signs of OD based on the PME results.Research limitations. The study is limited to data on examinations of workers in the Volga Federal District.Conclusions. Obtaining reliable and objective information for the purpose of analyzing the effectiveness and quality of PME based on the reports of the COP is difficult. The qualitative indicators of PME based on the example of several subjects of the Volga Federal District indicate to their low effectiveness in the system of prevention of OD.Compliance with ethical standards. The study does not require the submission of the conclusion of the biomedical ethics committee or other documents.Contribution of the authors: Valeeva E.T., Shaikhlislamova E.R. — research concept and design, writing the text, compilation of the list of literature, statistical data processing; Shastin A.S., Akhmetshina V.T., Babanov S.A., Galimova R.R., Basyrova A.R. — collection and processing of material; Distanova A.A. — writing the text, statistical data processing, editing. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.Funding. The study had no sponsorship.Conflict of interest. The authors declare no conflict of interest.Received: July 4, 2024 / Revised: February 18, 2025 / Accepted: June 24, 2025 / Published: October 31, 2025

Background. Bronchial asthma is one of the most common chronic non-infectious inflammatory diseases of the respiratory tract, affecting people of all ages and characterized by respiratory symptoms resulting from variable airflow limitation and bronchial hyperresponsiveness. Severe bronchial asthma is registered in 5-10% of patients. This course of asthma remains uncontrolled, despite adequate therapy, including high doses of inhaled glucocorticosteroids, long-acting B2 agonists, long-acting anticholinergic drugs. This variant of the course of asthma requires either continuous therapy with high doses of inhaled glucocorticosteroids/long-acting B2 agonists/long-acting anticholinergic drugs, and in some cases, the appointment of systemic glucocorticosteroids. Severe bronchial asthma patients have the highest incidence of lack of control and development of exacerbations. Results. The article presents a clinical case illustrating the possibility of using genetically engineered biological drugs in patients with severe bronchial asthma. Conclusion. For patients with high T2-inflammation (T2-asthma) severe bronchial asthma (allergic or late eosinophilic) in recent years, biological therapy has become available using genetically engineered biological drugs aimed at suppressing excessive immune signaling pathways associated with T2 cytokines (IL-5 and IL-5R, IL-4/IL-13) or immunoglobulin E (IgE). With the right approach to choosing patient management and a biological drug option, this therapy proves to be highly effective, leading to control of severe bronchial asthma, a decrease in the frequency or complete absence of exacerbations, and a reduction in the dose of systemic glucocorticosteroids.

Currently, the problem of obesity and metabolic syndrome, which are part of the group of chronic non-infectious diseases, has acquired serious medical and social significance and a global scale due to the steady worldwide increase in prevalence, which forces scientists to look for the reasons for such negative epidemiological trends. In recent years, the concept of early programming, which is based on the postulate that the origins of most chronic diseases in adults are formed in childhood, has become one of the most interesting issues discussed in the medical community. This review presents current scientific evidence supporting the concept of the early origins of chronic diseases, with a focus on obesity and metabolic syndrome. The authors consider the key factors that determine the characteristics of metabolic processes that underlie the formation of human health or predispose to the development of metabolic diseases, especially in the early periods of development, focusing on risk factors for obesity and possible areas of preventive interventions.

Asthma, a prevalent noninfectious chronic disease characterized by type II inflammation, features airway hyperreactivity, bronchoconstriction, and airway remodeling, ultimately causing widespread airway narrowing. Hydrogen has been shown to exhibit antioxidant and anti-inflammatory properties that are beneficial for a range of diseases. This study initially investigated the ameliorative effects of hydrogen gas inhalation on lung inflammation in mice with asthma induced by ovalbumin (OVA). The mice were first sensitized with OVA and subsequently exposed to nebulized 1% OVA via the airway to induce an asthma model. Hydrogen was inhaled for 7 consecutive days as a therapeutic intervention to detect changes in various indicators. Compared with the control treatment, hydrogen inhalation significantly mitigated OVA-induced airway hyperreactivity and inflammation. Hydrogen inhalation attenuated the immune response; decreased the levels of IL-4, IL-5 and IL-13; and further increased the mRNA expression levels of Treg-associated cytokines, namely, IL-10 and TGF-β1, thereby bolstering the body's inflammatory resistance mechanisms. In addition, it also reduced total serum IgE levels and malondialdehyde (MDA) production and increased superoxide dismutase (SOD) secretion in lung tissue. The histological analysis of lung tissues revealed that OVA induced prominent inflammatory cell infiltration and cell proliferation in the alveolar wall, which were markedly ameliorated in the hydrogen-treated group, indicating reduced pathological damage. These findings indicate that hydrogen inhalation effectively suppresses OVA-induced asthma, leading to a substantial improvement in associated lung inflammation, and that the inhalation of hydrogen may be a more feasible approach for future asthma treatment strategies.

Introduction . Type 2 diabetes mellitus occupies a leading position in the structure of non-infectious diseases in the world. The development of severe vascular complications of the disease, including diabetic foot syndrome, requires complex treatment and is an economically costly process accompanied by high disability and mortality of patients. Objective . To evaluate the association of polymorphic markers A1298C of the MTHFR gene with changes in the microcirculatory bed during the development of diabetic foot. Materials and methods . At the 1st stage of the study, the distribution of genotypes of the A1298C polymorphism of the MTHFR gene was studied in 198 patients with uncomplicated type 2 diabetes mellitus and 199 patients with diabetic foot. At the 2nd stage of the study, 30 patients with a comparable percentage distribution of the frequencies of the studied polymorphism as at the 1st stage were selected from the general groups of patients, and their microcirculation was examined using laser Doppler flowmetry. At the 3rd stage of the study, microcirculation parameters were analyzed depending on the carriage of the genotype of the A1298C polymorphism of the MTHFR gene. Results. In patients with diabetic foot syndrome, who are carriers of the A/A and A/C genotypes, a decrease in the temporal variability of perfusion by 2 and 1.2 times was revealed at a remote point. Locally, in patients with the studied complication of type 2 diabetes mellitus and genotypes C/C, A/C, a deterioration in the general condition of the microcirculatory bed by 2 and 2.2 times was noted. A decrease in the variability of microcirculation at a point on the 1st toe in diabetic foot syndrome with carriage of the A/A and A/C genotypes by 2 and 1.8 times was recorded. Conclusion . Carriage of different genotype variants of the A1298C polymorphism of the MTHFR gene is associated with different pathways for the implementation of mechanisms of microcirculatory bed impairment.

Hypereosinophilia (HE) is a rare disease with complex and diverse causes. Therapeutic strategies for HE differ because of its diverse causes, demanding advanced diagnostic tools for accurate assessment. This study evaluated the role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in determining the etiology of HE. This retrospective single-center study consecutively included 78 patients with HE who underwent 18 F-FDG PET/CT examinations between 2011 and 2022. The diagnostic value of 18 F-FDG PET/CT in identifying the etiology of HE was assessed. Logistic regression analyses were conducted to determine the clinical and laboratory factors associated with 18 F-FDG PET/CT outcomes. Seventy-eight patients aged 44.58±17.01 years had different conditions: infectious diseases, n=9 [11.54%]; noninfectious inflammatory diseases, n=23 [29.49%]; solid tumors or hematological malignancies, n=16 [20.51%]; lymphocyte-variant HE, n=1 [1.28%]; and idiopathic HE or idiopathic hypereosinophilic syndrome, n=29 [37.18%]. 18 F-FDG PET/CT was used to identify the etiology in 48 patients (61.54%, true positive), whereas secondary causes were ruled out in 21 patients (26.92%), leading to a diagnosis of idiopathic HE. 18 F-FDG PET/CT achieved a diagnostic sensitivity of 92.31%, specificity of 80.77%, and accuracy of 88.46%. The presence of symptoms was positively correlated with true-positive PET/CT results (odds ratio: 2.940, 95% CI: 1.073-8.055), whereas immunoglobulin E level exhibited no association. 18 F-FDG PET/CT showed high sensitivity and accuracy in identifying the etiology of HE, making it a valuable tool for assessing elevated eosinophil counts.

The article analyzes modern principles of therapy for non-infectious liver diseases, with a focus on the use of hepatoprotectors. The pathogenetic mechanisms of key syndromes are examined: cytolysis, cholestasis, immune-inflammatory reactions, and hepatocellular insufficiency. A classification of hepatoprotectors (UDCA, ademetionine, essential phospholipids, silibinin, etc.) is presented, along with an evaluation of their effectiveness in correcting specific disorders. Special attention is paid to the rational combination of drugs and a staged treatment approach. Evidence-based data on the use of hepatoprotectors in comorbid patients and promising directions, including new drugs and mechanisms targeting fibrosis and cellular senescence, are discussed.

Cats are among the most popular pets in society due to their friendly and active nature. Scientifically known as Felis Silvestris Catus, cats are one of the most commonly kept pets by humans. In addition to being adorable animals, they are also known for their ability to adapt easily. Cats that are not properly cared for, however, are highly susceptible to various diseases. Diseases in cats are often caused by viruses, parasites, or bacteria that inhabit the cat’s body without the owner’s awareness. Several infectious diseases include Feline Panleukopenia (FPV), Feline Infectious Peritonitis (FIP), Feline Calicivirus (FCV), and Scabies. Meanwhile, non-infectious diseases include Hernia, Abscess, Kidney Failure, and Diabetes Mellitus. From these two categories of diseases, solutions to the problems can be determined by using an expert system. This study aims to develop an Android-based expert system application that can assist cat owners in diagnosing diseases quickly and practically. The method used is forward chaining, as it can trace the symptoms entered by users step by step until reaching a conclusion in the form of a disease diagnosis. The results of the testing show that the application is able to provide diagnoses with a fairly good level of accuracy.

Non-infectious diseases in various clinical forms are one of the most pressing problems among all diseases in modern livestock farms. This article presents monitoring of the most common non-communicable diseases of cattle for the first through fourth quarters of 2024 in agricultural organizations in St. Petersburg. The study established a seasonality of pathologies: the maximum number of sick animals is recorded in the autumn months and early winter (from October to December), while the minimum indicators are in the spring months and early summer (from April to June). The nosological profile is represented by diseases of the digestive and respiratory systems, metabolic disorders, and poisonings (including in young animals), with a determination of their proportional distribution by morbidity and mortality. It was revealed that of the 1,084 registered cases of non-communicable diseases of cattle, the majority were diseases of the digestive system (44.4%) and metabolic (24.7%). The most common forms are: dyspepsia, bronchopneumonia, osteodystrophy, and ketosis. The obtained data allows for the timely implementation of a range of veterinary and zootechnical measures aimed at preserving the health of animals and the products obtained from them.

HighlightsWhat are the main findings?•Children with obesity showed a multidimensional profile of health and fitness: balance, speed, functional strength, and agility were significantly impaired, while flexibility remained within the normal range and handgrip strength was above reference values.•Sex-related differences were observed: girls outperformed boys in half of the fitness tests, indicating gender-specific patterns in physical performance.What is the implication of the main finding?•Identification of specific strengths and weaknesses in physical fitness can guide the development of tailored rehabilitation and physical activity programs for children with obesity. Considering gender differences is crucial when designing personalized interventions to optimize effectiveness and engagement in pediatric obesity management. These results may have practical implications for designing personalized interventions aimed at improving physical fitness in children and adolescents with obesity.•The observed sex-specific patterns of motor performance in children with simple obesity suggest that biological maturation and the endocrine profile may modulate the impact of excess body weight on physical fitness. These findings highlight the need to consider developmental and hormonal factors when interpreting physical performance outcomes in pediatric populations with obesity.Objectives: The systematic increase in the number of overweight and obese people in recent years has led to the recognition of this condition as a chronic, non-infectious disease of civilization, declared a global epidemic by WHO in 1997. This phenomenon is particularly dangerous in children, because it negatively affects their later existence in the health, mental and social spheres. This phenomenon is particularly concerning in the pediatric population, as it may have long-term adverse effects on physical health, psychological well-being, and social functioning. Objective: The aim of this study was to assess anthropometric parameters and physical fitness using the EUROFIT test in children and adolescents diagnosed with obesity. Materials and Methods: The study group consisted of 123 pediatric patients attending the Endocrinology and Diabetology Clinic and Pediatric Rehabilitation IP-CZD aged 8–16 (64 boys—52% and 59 girls—48%) with diagnosed simple obesity. Obesity was diagnosed according to the CDC standard using percentile charts from the OLAF study. Physical fitness was assessed using the EUROFIT test using 8 samples, and body mass composition was examined using the bioimpedance method with the BC 418 Tanita analyzer. Results: The results of our own research obtained in this study were compared to population standards. The total results of the EUROFIT test in the study group were statistically significantly lower than the norm. The results of the balance, upper limb movement speed, jumping, trunk strength, functional strength and agility tests were lower than the norm, the flexibility result was within the norm, and only hand strength was higher than the norm. In 4 out of 8 fitness tests, girls achieved significantly better results than boys. Conclusions: Reduced physical fitness is characteristic of children and adolescents with simple obesity. Worse physical fitness shows significant correlations with the results of anthropometric measurements.

Staphylococcus aureus is an important human pathogen causing severe invasive infections. Pathogenesis is attributed to a wide array of virulence factors, including several potent exotoxins such as the pore-forming α-toxin. In this study, we found that patients with S. aureus respiratory tract infections had elevated CX3CL1 levels in airway fluid and plasma. Using human-organotypic lung models, we observed that stimulation of lung epithelium with α-toxin induces an intensified CX3CL1 expression apically in the epithelium as well as the release of CX3CL1. Blocking α-toxin or ADAM10 activity in organotypic lung using an α-toxin-blocking antibody or a specific ADAM10 inhibitor confirmed their role in modulating CX3CL1 cleavage and release. Analyses of CD14+ human monocytes in combination with a CX3CR1 inhibitor revealed that α-toxin-mediated CX3CL1 release induces CX3CL1-dependent chemotaxis. In line with these data, lung tissue from patients with S. aureus respiratory tract infection showed elevated CX3CL1 and CD14 staining as compared with tissue from patients with non-infectious lung diseases. Functional studies of monocytes showed that CX3CL1 released by lung models resulted in upregulated CD83 and downregulated CD86, as well as impaired killing of phagocytosed S. aureus. Furthermore, stimulation of monocytes with soluble CX3CL1 hampered their reactive-oxygen and nitric-oxide production. Taken together our data show that S. aureus triggers the release of lung epithelial CX3CL1, and we identify an immunomodulatory effect of α-toxin involving its cytotoxic and ADAM10-interacting properties, inducing CX3CL1 release leading to impaired monocyte effector function.IMPORTANCEExotoxins are essential virulence factors for the pathobiont S. aureus and contribute toward severe invasive infections such as pneumonia. S. aureus α-toxin is a pore-forming exotoxin that causes host cell lysis and severe lung pathology. We found that α-toxin drives the release of membrane-bound chemokine CX3CL1 by involving ADAM10-mediated proteolytic activity. Furthermore, the release of CX3CL1 modulated immune responses locally, as demonstrated by enhanced monocyte migration and reduced capacity of monocytes to kill ingested bacteria. CX3CL1-induced reduction in bacterial killing coincided with impaired production of reactive oxygen and nitric oxide species. This reveals a novel mechanism in the pathogenesis of S. aureus lung infections involving α-toxin-induced release of CX3CL1, leading to impaired bacterial killing by monocytes.

Rapid and accurate diagnostic testing is critical for effective management of infectious and non-infectious diseases, particularly in an era of emerging pathogens and antimicrobial resistance. Traditional methods such as microscopy, culture, and serology continue to serve as valuable tools; however, their limitations in speed and sensitivity have driven the evolution of advanced diagnostic techniques. Recent decades have seen the integration of molecular biology, immunology, proteomics, nanotechnology, and artificial intelligence (AI) into diagnostic platforms. Innovations including polymerase chain reaction (PCR), next-generation sequencing (NGS), CRISPR-based diagnostics, biosensors, and digital pathology are transforming laboratory medicine into a faster, more precise, and patient-centered discipline. These advancements are not only improving turnaround time but also enabling decentralized testing in remote and resource-limited settings, thereby expanding access to high-quality healthcare. Furthermore, rapid diagnostics have been shown to reduce healthcare costs by minimizing unnecessary hospital stays and ensuring timely initiation of targeted therapy. This review highlights key developments in diagnostic technologies, their clinical applications, challenges in global implementation, and future prospects for advancing personalized and precision medicine.

Rotavirus (RV) is one of the main etiologic agents associated with diarrheal diseases (DDs), being responsible for approximately 200 thousand deaths annually. Currently, there are still many aspects regarding the virus biology, cell cycle, and pathophysiology of RV that need further elucidation. Therefore, the present work aimed to investigate whether the triggering receptor expressed on myeloid cells 1 (TREM-1) might be associated with RV infection. This immune receptor has been observed as an amplifier of inflammatory responses in different infectious and non-infectious diseases, including inflammatory bowel disease and celiac disease. Initially, we searched for public transcriptomic data regarding RV infection and the expression of TREM-1 and its associated genes, which were significantly upregulated in infected mice and children. Then, we infected monocytes with the virus, with or without a TREM-1 inhibitor. The inhibition of the receptor’s activity resulted in a significant decrease in IL-1β production. We also observed a reduction in cytopathic effects when MA104 cells were treated with TREM-1 inhibitors and then infected with simian RV. To further elucidate the interactions between the virus and TREM-1, in silico tools were used to simulate interactions between the receptor and RV proteins. These simulations suggested the occurrence of interactions between TREM-1 and VP5*, a protein involved in viral attachment to target cells, and also between the receptor and NSP4, a viral enterotoxin with immunostimulant properties. Hence, our results indicate that TREM-1 is involved in RV infection, both as a mediator of inflammatory responses and as a player in the host–virus relationship.

Resistant starch (RS) is employed as a functional food component to prevent non-infectious diseases. Due to its generous amylose content, which ranges from 20.5% to 30.27%, arrowroot tuber is a potential source of RS. The RS content of tuber starch can be further enhanced through physical modifications, such as an autoclaving-cooling cycle to generate type III RS. This research aimed to determine the optimal autoclaving temperature and duration in order to produce arrowroot starch with the maximum RS content, as well as to characterize its properties. The arrowroot starch was autoclaved at temperatures of 105°C, 120°C, and 135°C for 20, 40, and 60 min, respectively. The autoclaving cooling modification was carried out over 5 cycles. Based on the findings, the arrowroot starch with the highest RS content (5.02%) was generated by autoclaving at 105°C for 40 min. This was higher than that of the native starch (1.24%). This modified starch with the highest RS comprised 10.49% moisture content, 86.75% starch content, 27.93% amylose content, and 58.82% amylopectin content. The modified starch had higher amylose content than native starch (25.43%). Additionally, it had a bulk density of 0.68 g/mL, 2.24 g/g swelling power, 1.82% solubility, 0.83 g/g water absorption, and 83.33 brightness value. The swelling power and the solubility of modified starch were lower than the native starch. Amylograph curves demonstrated that the autoclaving-cooling modification generated starch with a more stable pasting profile. These results show that the autoclaving-cooling method improved the amylose and RS content of the modified starch. However, the modified starch has a lower value of pasting properties. Lower values for these viscosity parameters may be desirable in a variety of food applications that require a less viscous, more stable, and less retrograded starch paste.

Asthma remains the most common chronic non-infectious respiratory disease in children, affecting about 14 – 15% of the global pediatric population. Current research shows that asthma is not a single disease, but a spectrum of different endotypes and phenotypes. Phenotypes describe the observed demographic and clinical characteristics of asthma, while endotypes reflect the underlying pathogenetic mechanisms of the disease. The aim. The review systematizes current data on clinical phenotypes (allergic and non-allergic asthma, preschool-age asthma, severe asthma) and inflammatory endotypes (T2-high and T2-low) of asthma in children. Results. Biomarkers used to identify endotypes and their clinical significance are analyzed. The main problems in determining phenotypes and endotypes of asthma in children are highlighted, including the possibility of combining several phenotypes in one patient, temporal instability of biomarkers, and the influence of comorbid conditions. Particular attention is paid to insufficient study of non-allergic asthma and T2-low endotype in children. Conclusion. It is shown that the determination of phenotypes and endotypes of asthma is critical for personalizing therapy and improving the prognosis of the disease. However, further studies of their stability over time and validation in prospective studies are needed for more effective use in clinical practice.

Genetic predisposition constitutes a well-established etiological factor in the pathogenesis of proliferative diseases of the mammary gland and uterus. Empirical evidence from cytogenetic and epidemiological studies substantiates a heritable component in the development of uterine hyperplastic processes (UHPP). Objective. The aim of our study was to investigate the significance of rs1138272 polymorphisms in the GSTP1 (Ala/Val) gene and rs5918 polymorphisms in the ITGB3 (T/C) gene in the mechanisms underlying the development of hyperplastic processes of the endometrium and/or myometrium, concomitant with benign breast dysplasia in perimenopausal women. Methods. A total of 82 patients with a confirmed diagnosis of endometrial and/or myometrial hyperplastic processes were enrolled. In addition to standard diagnostic protocols for uterine hyperplastic conditions, all study participants underwent genetic analysis. The study cohort was divided into a main group (n=50) of patients with UHPP and co-existing benign breast dysplasia, and a comparison group (n=32) of patients with UHPP without breast pathology. The control group consisted of 80 clinically healthy women. The principles of bioethics, approved by the Scientific Council of Samarkand State Medical University, are preserved and upheld in full compliance. To variationally estimate the frequency of genotypes of the studied rs 5918 polymorphism in the ITGB3 gene (T/C), the agreement was analyzed between the expected (Hexp) and observed (Hobs) frequencies of their distribution in the groups of patients with UHPP and controls, in accordance with the Hardy-Weinberg equilibrium (PXB, p>0.05). The work was carried out within the framework of the scientific project No. 012000260 "Development of promising technologies for the prevention, diagnostics, and treatment of infectious and non-infectious diseases of the human body that have social significance" in accordance with the research plan of Samarkand State Medical University. Results. In the main group, the expected (Hexp) and observed (Hobs) frequencies of the T/T, T/C, and C/C genotypes for rs5918 in the ITGB3 gene (T/C) were 0.85 and 0.86 (χ²=0.00), 0.15 and 0.14 (χ²=0.07), and 0.00 and 0.01 (χ²=0.44), respectively, with no statistically significant differences (p=0.45). In the control group, the frequencies were: 0.83 and 0.83 (χ²=0.01), 0.18 and 0.16 (χ²=0.12), and 0.00 and 0.10 (χ²=0.61), also without significant differences (p=0.37). Discussion. The findings suggest that the rs5918 polymorphism in the ITGB3 gene is not a principal driver mutation in the pathogenesis of hyperplastic diseases of the uterus and mammary glands. Furthermore, within the subgroup of patients with UHPP, no association was identified between this polymorphism and concomitant breast pathology. However, among patients who presented with abnormal uterine bleeding (AUB), the heterozygous T/C genotype was significantly more common. Conclusion. A solitary genetic polymorphism may exert a negligible effect on complex physiological systems; however, the aggregate effect of alterations in multiple genes can significantly disrupt systemic homeostasis and precipitate pathological states. Consequently, the investigation of genetic susceptibility to multifactorial diseases necessitates the evaluation of polygenic models or the analysis of multiple polymorphisms within pertinent gene pathways.

ABSTRACT Purpose To assess appeal outcomes and factors influencing those outcomes in insurance-mandated non-medical switching (NMS) from adalimumab (Humira®) to biosimilars in patients with uveitis and ocular inflammatory diseases. Methods This retrospective observational study reviewed the electronic medical records of patients receiving Humira® for non-infectious uveitis and ocular inflammatory diseases prior to pharmacy benefit manager (PBM) formulary changes effective April 1, 2024, at the University of Texas Southwestern Medical Center (UTSW) and University of Texas Health Austin (UTHA). Data collected included PBM assignment, treatment duration, remission status, incidence of NMS mandates, appeal outcomes, and final treatment status. Appeals at UTSW cited Texas Senate Bill 680, which allows exemptions from new step-therapy protocols. Logistic regression assessed associations between patient characteristics, PBM, and NMS outcomes. Results Of the 75 patients, 30 (40%) received NMS mandates. CVS Caremark patients were more likely to receive mandates for NMS (86.4% vs 20.8%; p < 0.01) and had a lower appeal success rate (14.3% vs 90.9%; p < 0.01) compared to non-CVS Caremark patients. Ultimately, 18 (24%) patients (94% CVS Caremark patients, p < 0.01) were forcibly switched. Median appeal time was 11 days (range 1–35), and processing biosimilar transitions added considerable administrative burden, even in the absence of appeals. Conclusion PBM-driven formulary changes disrupted treatment continuity for patients with non-infectious ocular inflammation. Enforcement of NMS mandates varied by PBM and often disregarded clinical stability and physician input, underscoring the urgent need for policy reform and uveitis-specific biosimilar outcome data.

Abstract Granulomatous inflammation involving the heart and intrathoracic or abdominopelvic lymph nodes presents a substantial diagnostic challenge; the differential spans infectious, inflammatory, and malignant conditions. Clinical features are often nonspecific, imaging patterns may overlap, and tissue samples can show mixed or evolving histologic findings. Cardiac involvement further complicates the picture, as both infectious and noninfectious granulomatous diseases can affect conduction pathways and structural integrity, sometimes with subtle or atypical presentations. We present a case of a middle-aged man with chronic constitutional symptoms, progressive conduction system disease, and fluorodeoxyglucose (FDG)-avid lymphadenopathy, whose evaluation required careful integration of clinical history, advanced imaging, and tissue diagnosis to arrive at the underlying cause.