Central Clinical Hospital

Background. Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, which collectively impair fertility. Insulin-sensitizing agents have emerged as a key therapeutic strategy to improve metabolic, hormonal, and reproductive outcomes in this population. Aim. This review critically evaluates current evidence on insulin-sensitizing agents in women with PCOS, addressing both their mechanisms of action at the metabolic and ovarian levels and their effects on reproductive outcomes. Material and Methods. A review of randomized controlled trials, meta-analyses, and high-quality observational studies published up to 2025 evaluated the effects of metformin, myo-inositol, and berberine on reproductive outcomes in women with PCOS. Results. Insulin-sensitizing agents improve metabolic dysfunction and ovulatory outcomes in PCOS. Metformin increases ovulation and clinical pregnancy rates, particularly in women with insulin resistance or higher BMI, though its effect on live birth is inconsistent. Myo-inositol and berberine show beneficial effects on metabolic parameters and ovulatory function, but evidence for live birth and miscarriage remains limited. Conclusions. Insulin-sensitizing therapies support reproductive function in women with PCOS, particularly in metabolically compromised phenotypes. Metformin has the strongest evidence base, whereas myo-inositol and berberine are promising adjunctive or alternative options. Future high-quality randomized trials focusing on live birth and miscarriage outcomes, standardized reporting, and precise patient stratification are needed to optimize the clinical use of these agents in PCOS-related infertility.

Background. The gut microbiota plays a key role in metabolic regulation and is increasingly recognized as a mediator of lifestyle-related health outcomes. Physical activity has emerged as a potential modulator of microbial composition and function. Aim. This narrative review aims to summarize current evidence on the relationship between physical activity and the gut microbiota and to evaluate its implications for metabolic health. Materials and Methods. A PubMed search of English-language studies published over the last 10 years was conducted to assess the effects of physical activity on the gut microbiota and metabolic health. Additional studies were identified through reference screening. Results. Regular moderate physical activity is associated with increased microbial diversity and a higher abundance of beneficial bacteria, including short-chain fatty acid producers. These changes are linked to improved glucose metabolism, reduced inflammation, and enhanced intestinal barrier function. However, excessive or prolonged high-intensity exercise may induce adverse effects, such as increased gut permeability and dysbiosis. The observed effects are strongly influenced by diet and individual factors. Conclusions. The gut microbiota represents an important mediator of exercise-induced metabolic adaptations. Combined lifestyle interventions, particularly physical activity and a fiber-rich diet, may provide synergistic benefits. Further research is needed to develop personalized strategies targeting the gut microbiota in metabolic disease prevention.

The rabies virus is responsible for one of the most severe diseases transmitted from animals to humans. Rabies is associated with an almost 100% case-fatality rate once clinical symptoms develop. The aim of this study is to present the principal routes of rabies virus transmission to humans and to discuss strategies for limiting viral spread through preventive measures, based on the available literature concerning the pathogenesis, epidemiology, and prophylactic methods applied in both animals and humans. The primary route of transmission to humans is a bite from an infected animal. However, other, less common routes of infection are also possible, including contact of secretions from an infected animal with mucous membranes or damaged skin. Extremely rare cases of transmission have also been reported through aerosol exposure or through organ transplantation from an infected donor. In Europe, wild animals constitute the main reservoir of the rabies virus, with particular emphasis on foxes, highlighting the critical role of oral vaccination programs targeting these species. Vaccination of domestic animals, as well as pre-exposure and post-exposure prophylaxis in humans, also remain essential components of rabies prevention. A multidisciplinary approach to rabies control, integrating the efforts of veterinary and medical services through infection control in animal populations, improved access to vaccines and rabies immunoglobulin, and increased public awareness regarding the disease, its transmission routes, and preventive measures, may ultimately contribute to the complete elimination of human rabies in the future.

This article presents a case of a mine blow shrapnel wound to the chest with shell fragment fixation in the interventricular septum. The patient underwent several evacuation stages in stable condition and then underwent surgery. Under cardiopulmonary bypass, the foreign body was removed with a neodymium magnet through a transaortic approach. The operation necessitated a significant expansion of the surgical procedure to explore and suture the removed fragment bed in the interventricular septum. The postoperative period and rehabilitation were uneventful. This article provides historical and statistical information related to the heart gunshot wounds, and discusses aspects of diagnosis and treatment strategies.

Gene expression silencing is one of the key tools in molecular biology and is widely applied in in vitro studies to investigate gene function and the mechanisms regulating cellular processes. The dynamic development of molecular techniques has resulted in the availability of numerous strategies that enable either transient or permanent reduction of gene activity at different stages of gene expression. The aim of this work is to review and compare gene expression silencing methods used in in vitro models, with particular emphasis on their mechanisms of action, efficiency, durability of the effect, and experimental limitations. The article discusses classical approaches based on RNA interference, including the use of siRNA, shRNA, and microRNA modulation, as well as strategies employing antisense oligonucleotides. Special attention is given to technologies based on the CRISPR system, including CRISPRi as a tool for reversible transcriptional repression and CRISPR–Cas9, which enables permanent disruption of gene function. Issues related to the delivery of molecular tools into cells, validation of silencing efficiency, and the importance of appropriate experimental controls are also addressed. Analysis of the literature indicates that the choice of an appropriate method should be tailored to the research objective, the characteristics of the gene under investigation, and the planned duration of the experiment. Increasingly, a complementary approach—combining different gene silencing strategies is recommended, as it enhances the reliability of results obtained in in vitro studies.

Concerns about antiretroviral therapy failure are growing among people with HIV receiving two-drug regimens, as these schemes include fewer active agents, while the prevalence of transmitted resistance in HIV-1 continues to increase. Therefore, we aimed to assess the epidemiology of HIV-1 drug resistance mutations to the most commonly used two-drug regimens, consisting of oral dolutegravir plus lamivudine and injectable cabotegravir plus rilpivirine. In a multicenter, cross-sectional study conducted from January 2023 to March 2024, the frequency of HIV-1 resistance mutations to antiretrovirals was evaluated. Analyses were performed for drugs used in two-drug regimens, separately in treatment-naïve and treatment-experienced patients. In a total of 333 patients included, 82% were treatment-naïve and sub-subtype A6 was responsible for 49.8% of infections. In treatment naïve patients, the frequency of transmitted major mutations to at least one agent ranged from 1.5% for dolutegravir plus lamivudine to 4.4% for cabotegravir plus rilpivirine. In treatment-experienced individuals with antiretroviral failure or who interrupted the treatment, the frequency of acquired major mutations to at least one agent was 6.7% for cabotegravir plus rilpivirine and 11.7% for dolutegravir plus lamivudine. In the latter subgroup, the frequency of any acquired resistance mutations (major and accessory) reached 16.7-23.3%. The integrase genotyping provides wide insight in a variable infection epidemiology and new therapeutic schemes. In our cohort, transmitted resistance to two-drug regimens in treatment-naïve individuals appears uncommon, with the frequency of 0.7-4.4%. However, in patients who interrupted the treatment or who experienced virological failure, all acquired resistance mutations are present in almost one-fourth of individuals, thus selective pressure from antiretroviral therapy warrants continuous surveillance. NCT06661317.

This manuscript comprehensively reviews psilocybin-assisted therapy for major depressive disorder and treatment-resistant depression. It aims to synthesize current understanding regarding its mechanisms, efficacy, safety, costs, and accessibility, comparing it with conventional antidepressant and ketamine treatments. The methodology involved a narrative synthesis of academic literature, drawing from systematic reviews, meta-analyses, and clinical trials identified through targeted database searches. Key findings indicate that psilocybin therapy demonstrates rapid, robust, and sustained antidepressant effects, with high response and remission rates, often after one or two sessions. Its safety profile is generally favorable, with transient and mild adverse events. Mechanistically, psilocybin primarily acts on serotonin 5-HT2A receptors, modulating brain networks and enhancing neuroplasticity. However, significant challenges exist in terms of high costs, limited accessibility due to the intensive therapeutic model, and regulatory hurdles. In conclusion, psilocybin-assisted therapy offers a promising alternative for depression, particularly where standard treatments fail, by providing rapid and durable symptom reduction through unique neurobiological pathways. Future research should focus on optimizing treatment protocols, exploring long-term outcomes, identifying predictors of response, and addressing systemic barriers to accessibility and cost-effectiveness to facilitate its integration into broader mental healthcare.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disorder whose diagnosis and differentiation from asthma remain challenging. The aim of this review was to present current biomarkers used in the diagnosis of COPD and to highlight promising directions for future research. A literature analysis covering the years 2020–2025 included biomarkers assessed in blood, urine, sputum, as well as genetic and molecular markers. The findings indicate that peripheral blood eosinophil counts and the neutrophil-to-lymphocyte ratio (NLR) are useful in predicting the risk of exacerbations and response to therapy. Serum proteomic and metabolomic analyses, together with urinary biomarkers, enable non-invasive patient phenotyping and early detection of exacerbations. Genetic and transcriptomic studies have identified key genes and inflammatory pathways relevant to disease pathogenesis, while the composition of the airway microbiome correlates with symptom severity and lung function. Integration of molecular, immunological, and microbiological data allows for precise patient phenotyping, supports personalized therapeutic strategies, and improves clinical outcomes. Biomarkers are becoming an important source of information in the differential diagnosis of COPD and asthma–COPD overlap (ACO), as well as in targeted treatment approaches.

Background/Objectives: Cardioneuroablation (CNA) is used to treat reflex syncope by parasympathetic denervation of the cardiac conduction system. Respiratory heart rate variability (RespHRV) constitutes an important physiological mechanism that optimizes lung perfusion. The impact of CNA on various components of RespHRV remains unclear. Methods: Eleven subjects (36.8 ± 14.1 years) undergoing CNA for the treatment of cardioinhibitory, vagally mediated syncope were enrolled. For the RespHRV assessment, we used continuous respiratory flow measurement and an electrocardiogram. RespHRV analysis included the following: (a) amplitude, reflecting the overall magnitude of changes in RR interval during the respiratory cycle (RespHRVpv, ms); and (b) efficiency, defined as the percentage of inspirations accompanied by RR shortening (short-RRi inspirations, %), and expirations accompanied by RR prolongation (long-RRi expirations, %). Baroreflex sensitivity (BRS, ms/mmHg) was assessed with a sequential method using a noninvasive hemodynamic monitor. Both RespHRV and BRS were captured 48 h apart, before and after CNA. Results: A significant reduction was observed in RespHRVpv (57 [30–131] vs. 13 [7–16] ms, p = 0.003), short-RRi inspirations (97.0 [77.8–100.0] vs. 36.0 [14.3–63.2] %, p = 0.003), and long-RRi expirations (88.0 [78.1–97.6] vs. 31.1 [21.4–65.8] %, p = 0.008). Moreover, we found a strong relationship between ΔBRS and ΔRespHRVpv (r = 0.77, p = 0.005) following CNA. Conclusions: Our results indicate a substantial role of the cardiac parasympathetic system in RespHRV development, including both its amplitude and efficiency. The marked decrease in key RespHRV measures after CNA highlights the need for further research into its long-term clinical effects.