Recent scientific advancements have significantly improved the understanding of the molecular mechanisms underlying the pathogenesis of atherosclerosis. However, there remains a need to systematize this data. Numerous factors act as inducers of the inflammatory process in atherosclerosis, including endothelial aging, metabolic dysfunctions, autoimmune factors, and, in some cases, infectious damage. In the clinical picture of atherosclerosis, it is crucial to timely diagnose signs of destabilization of atherosclerotic plaques, as unstable plaques are prone to rupture, which can lead to life-threatening complications (such as stroke, myocardial infarction, etc.). Therefore, the search for and identification of molecular markers and instrumental methods reflecting the processes associated with plaque destabilization are particularly relevant for patients with asymptomatic disease progression.

Obesity is currently recognized as a pandemic of modernity and a serious medical and social problem that brings significant economic damage to society. This is largely due to the increase and younger onset of obesity-related morbidity, accompanied by cardiovascular pathology, which worsens quality of life, leading to early temporary and permanent loss of working capacity and premature death. This review presents an analysis of current understanding of the risks and mechanisms of cardiovascular system damage in obesity, the role of insulin resistance, the hormonal activity of adipose tissue, and the prognostic significance of different types of obesity. Along with traditional cardiovascular risk factors, obesity is associated with a range of metabolic and hormonal disorders, the development of systemic inflammation, and oxidative stress, leading to specific myocardial damage—lipotoxic cardiomyopathy. This pathological condition significantly contributes to the development of myocardial dysfunction (heart failure, urgent arrhythmias with the risk of sudden cardiac death) even in the absence of ischemic heart disease. The review provides current data on the features of myocardial remodeling in obesity, the mechanisms of its development and progression, and methods of diagnosis. It emphasizes that the problem of diagnosing myocardial dysfunction, as well as adequate treatment of this pathology—including non-drug interventions, surgical procedures, and the use of weightloss medications—is far from being resolved. This necessitates in-depth research into this pathology and the search for new, optimal, effective, and safe methods for prevention and treatment.

This article discusses modern non-invasive methods for diagnosing melanoma and its prevention. The use of contemporary non-invasive diagnostic techniques significantly improves the accuracy of clinical diagnosis, which facilitates the early detection of malignant skin tumors and reduces the need for unnecessary surgical interventions. The focus is on advanced technologies that allow for the detection of the disease at early stages, which substantially increases the chances of successful treatment and decreases the risk of mortality.

Objective. The aim of this work is to analyze and evaluate the effectiveness of modern non-invasive methods for diagnosing melanoma and preventive measures aimed at reducing the frequency of late diagnoses and increasing public awareness of the risks of the disease.

Material and methods. The article analyzes methods such as dermatoscopy, confocal microscopy, optical coherence tomography, and other innovative techniques like quantitative infrared thermography.

The results of the study show that the application of non-invasive diagnostic methods significantly enhances the accuracy of melanoma detection at early stages, contributing to a reduction in mortality and a decrease in unnecessary surgical interventions.

Conclusion. Late diagnosis of melanoma often leads to diagnostic errors by specialists in various fields and to the ineffectiveness of the therapy provided. Preventive measures, including primary and secondary prevention methods, are crucial aspects of reducing the risk of melanoma occurrence and increasing public awareness of possible protective measures.

This review of foreign literature addresses the pressing issue of preventing venous thromboembolic complications in the practice of modern oncogynecologists. It emphasizes the connection between the severity of the oncological process and the frequency of thromboembolic complications, the presence of which predetermines an unfavorable outcome. The review discusses methods for the prophylactic use of anticoagulants, their role in comprehensive therapy, and their interaction with other treatment methods. This work also discusses laboratory techniques for determining markers of oncological diseases and monitoring the treatment being administered. The prospect of a multidisciplinary approach involving geneticists, immunologists, biochemists, and laboratory diagnostics specialists to address issues of prevention and treatment of oncogynecological diseases is considered.

One of the priority areas in reducing mortality from acute ischemic stroke (IS) with acute occlusion of a major cerebral vessel is the search for active methods to restore cerebral blood flow. In recent years, the use of thrombolytic therapy and endovascular thrombectomy (EVT) has gained recognition. At the stage of actively implementing new methods of brain revascularization, predicting the outcomes of drug and mechanical recanalization of cerebral vessels is a pressing issue.

Objective. To scientifically justify and develop methods for predicting the outcomes of endovascular treatments for large-vessel cardioembolic and atherothrombotic subtypes of ischemic stroke.

Material and methods. The study included 324 patients treated for acute largevessel IS. Of these, 163 operated patients were included in the main “Group 1,” while 28 operated patients made up the control “Group 2.” “Group 0” consisted of 133 patients who received only medical therapy. Each group was divided into subgroups with cardioembolic (CEI) and atherothrombotic (ATI) subtypes of strokes. A multifactorial analysis was performed assessing clinical signs (neurological deficit according to the National Institutes of Health Stroke Scale (NIHSS), functional outcome according to the modified Rankin scale), hemodynamic parameters before and after surgery, echocardiography data, laboratory indicators, neuroimaging data before and after thrombectomies, and analysis of surgical techniques to identify factors contributing to favorable and unfavorable stroke outcomes.

Results. The significance of clinical and instrumental predictor signs for EVT outcomes in IS was determined. Based on discriminant analysis, a decision rule was obtained for predicting likely favorable and unfavorable outcomes after EVT in patients with cardioembolic and atherothrombotic subtypes of IS, demonstrating sensitivity and specificity exceeding 90%. Preventive tactics for emergency brain revascularizations and early therapeutic rehabilitation measures in a number of patients with an unfavorable prognosis allowed mortality to be reduced to 14.3% and achieved better functional outcomes in 60% of patients (NIHSS < 4 points, mRS 0–2).

Objective. To determine the role of bacterial infection in the development of recurrent exacerbations of chronic obstructive pulmonary disease (COPD) and to assess the adequacy of antibiotic therapy for COPD exacerbations during initial and repeat hospitalizations.

Material and methods. Analysis of 423 medical records of patients hospitalized in a therapeutic department due to COPD exacerbation over a period of 4 years. 276 cases were hospitalized once within a year (control group), while 147 were hospitalized repeatedly (main group).

Results. 36.9% of patients in the control group complained of cough with purulent sputum, compared to 25.2% in the main group (p < 0.05). 31.5% of patients in the control group and 17% in the main group reported fever (p < 0.05). A high level of C-reactive protein (CRP) was found in 62.8% of the control group and 49.1% of the main group (p < 0.05), while an increased level of leukocytes in sputum was observed in 47.1% of the control group and 28.6% of the main group. In 90% of cases, patients in both groups received antibiotic therapy, with some patients receiving the same antibiotic during their second and third consecutive hospitalizations. Patients in the main group had extremely severe obstructive disorders twice as often. The degree of respiratory failure increased twofold by the third hospitalization. The main group also had a higher prevalence of arterial hypertension and stage II chronic heart failure.

Conclusion. The severity of obstruction, comorbidity, and overall patient condition may have a more significant impact on the recurrence of exacerbations requiring repeated hospitalizations than bacterial infection. Therefore, a strict differentiated review of indications for initial antibiotic therapy and consideration of the peculiarities of bacterial etiology of exacerbations at the hospital stage is necessary.

The article presents the results of a study aimed at examining the relationship between arterial stiffness (AS), pulmonary hypertension (PH), and epicardial fat thickness (EFT) in patients with ischemic heart disease (IHD) and arterial hypertension (AH) combined with emphysematous and bronchitic phenotypes of chronic obstructive pulmonary disease (COPD).

Material and methods. The study included 68 patients with IHD, AH, and bronchitic phenotype of COPD (Group 1) and 55 patients with emphysematous phenotype of COPD (Group 2); 22 patients with IHD and AH without COPD (Group 3).

Results. The study revealed higher AS indicators (pulse wave velocity, augmentation index, central systolic and central pulse arterial pressure) associated with increased PH and EFT, as well as diastolic heart dysfunction in patients with IHD, AH, and bronchitic variant of COPD. It also identified key directions for etiopathogenetic therapy for these patients with frequent comorbid conditions.

Conclusion. In complex cases of comorbid pathology involving IHD and AH, it is important to clarify the COPD phenotype to prescribe appropriate etiopathogenetic therapy.

Objective. To study respiratory outcomes and identify predictors of respiratory failure development in patients undergoing surgical myocardial revascularization after COVID-19.

Material and methods. The study analyzed clinical data from 121 patients who underwent elective surgical myocardial revascularization from 2018 to 2022. The first group included 52 patients who had COVID-19 prior to surgery, on average 3.3 ± 2.3 months before the operation, while the second group consisted of 69 patients without a history of COVID-19. Indicators of mechanical ventilation and gas composition of arterial blood were studied during the intraoperative and early postoperative periods, the frequency of respiratory failure (RF) was assessed, and predictors of its development were identified.

Results. Patients who had COVID-19 showed significantly lower oxygenation index compared to those without the infection, both in the intraoperative period — 258 [184.6; 301] vs. 384.4 [335; 435] respectively (p = 0.0002), and in the early postoperative period — 228 [174.6; 303.5] vs. 407.5 [351.4; 462.5] respectively (p = 0.0019) during coronary artery bypass grafting on a beating heart. Patients with a history of COVID-19 developed RF 6.6 times more often — 23.1% vs. 4.3%; Odds Ratio (OR) 6.6; 95% Confidence Interval (CI) 1.76–24.82; p = 0.0038. Predictors of RF development included: severity of COVID-19 (p = 0.0016), lung involvement during COVID-19 (p = 0.0083), RF during COVID-19 (p = 0.0061), and duration of stay in the Intensive Care Unit (ICU) during COVID-19 (p = 0.0002). One (0.02%) fatal outcome was recorded the day after surgery in a patient with COVID-19 due to acute respiratory distress syndrome (ARDS).

Conclusions. Patients who have had COVID-19 exhibit respiratory impairments and a high risk of developing respiratory failure during surgical myocardial revascularization on a beating heart. Predictors of RF development are associated with the clinical course of COVID-19. Undiagnosed COVID-19 may contribute to the development of ARDS in the early postoperative period.

The article presents an analysis of changes in the platelet component of the hemostatic system in patients with paroxysmal and persistent forms of atrial fibrillation while taking direct oral anticoagulants. This group of medications is used for the prevention of ischemic stroke and other systemic thromboembolic events. The number of platelets involved in aggregates was within normal limits; however, there is a tendency toward an increase in active forms of platelets in these patients.

Currently, rheumatic diseases are classified as a group of immune-inflammatory disorders, in which endothelial dysfunction plays a significant role in their pathogenesis. The aim of the study was to present the heterogeneous pathogenesis of immune inflammation, to trace the links of pathogenesis, and to highlight the role of endothelial dysfunction in immune-inflammatory rheumatic diseases.

Material and methods. A total of 144 patients were examined: 80 with rheumatoid arthritis (RA) and 64 with systemic lupus erythematosus (SLE). The study involved the determination of rheumatoid factor (RF) IgG, C-reactive protein (CRP), soluble vascular cell adhesion molecule (sVCAM-1), von Willebrand factor antigen (vWF Ag), endothelin-1 (ET-1), and the number of desquamated endothelial cells (DEC) counted using a Goryaev chamber.

Results. Signs of endothelial dysfunction were identified in patients with RA and SLE, as evidenced by significant differences in endothelial activation markers compared to the control group. The level of ET-1 was lower in patients with RA at 2.54 [0.09; 3.51] fmol/ ml, compared to 5.96 [0.20; 9.54] fmol/ml in patients with SLE, and 0.46 [0.34; 0.56] fmol/ml in the control group, p < 0.05. The level of sVCAM-1 in RA was 1929 [1297.6; 2739.6] ng/ml, in the SLE group it was 1497.3 [919.6; 2348.6] ng/ml, and in the control group it was 750 [250; 890] ng/ml, p < 0.01. The number of DEC was significantly higher. An increase in IL-8 levels was noted in the RA group at 414.2 [285; 541] pg/ml, in the SLE group at 335.2 [280; 398.6] pg/ml, and in the control group at 208 [206; 211] pg/ml, p < 0.01. There was an increase in CRP levels in RA up to 19.67 [4.2; 27] mg/l, and in SLE up to 16.5 [10; 22], which significantly exceeded the control group value of 2.6 [2.2; 3.3], p < 0.01. In patients with RA and SLE, markers of endothelial activation positively correlated with the level of RF IgG and indicators of immune inflammation: with increasing values of CRP and ESR, rising concentrations of sVCAM-1, vWF Ag, and the number of DEC, p < 0.01.

Conclusion. Endothelial dysfunction plays a significant role in the pathogenesis of rheumatic diseases, and its correction may lead to the development of new therapeutic targets and help prevent complications in this patient category.

In the presented work, based on the research of Academician of the Russian Academy of Sciences G.P. Stupakov, the significance of the persistence of pathogens of viral, bacterial, and fungal nature that cause immunodeficient, immunopathological, and autoimmune reactions in the human body is demonstrated. This leads to chronic inflammatory, destructive, and other changes in organs and systems, revealing the causality of chronic disease development and substantiating the position that a wide range of chronic diseases in humans represents an organ-distributed, polysystemic, tropically-fixed chronic infectious process. To clarify the prevalence of persistent viral infections, 210 practically healthy college and university students aged 15 to 23 years (random sampling) were examined. The method of electronic organometry (electropuncture diagnostics according to R. Foll’s method) was used for diagnosis. The mechanisms of pathological changes formation are presented within the etiological and pathogenetic unity and multifaceted clinical manifestations, and etiotropic treatment aimed at pathogen elimination and normalization of innate immune function is justified, with the additional application of pathogenetic treatment.

Inflammation is intimately associated with atherosclerotic disease, including in patients with chronic heart failure (CHF), and high-sensitivity C-reactive protein (hsCRP) levels play a key role in determining severity and outcome.

Objective: to study the potential of serum hsCRP for predicting the outcome of ischemic heart failure in the presence of chronic kidney disease (CKD).

Material and methods. Clinical signs and 5-year outcomes of patients with CHF (n = 517), including those in combination with CKD (n = 207), were studied.

Results and conclusions. The phenotype of CHF in combination with CKD was characterized by female gender, older age, a higher prevalence of arterial hypertension, diabetes mellitus, previous myocardial infarction and coronary intervention, lower cardiorespiratory endurance, higher levels of hsCRP (p = 0.005), low-density lipoprotein cholesterol (p = 0.021), non-high-density lipoprotein cholesterol (p = 0.015). Patients with CHF with hsCRP > 3 mg/L have a higher 5-year risk of death from any cause, cardiovascular death, and achieving the composite endpoint (CCT). An increase in hsCRP for every 1 mg/l in CHF increases the risk of death from all causes (HR = 1.1; 95% CI 0.99–1.21), cardiovascular death (HR = 1.11; 95% CI 1.01–1.23). Death from any cause and cardiovascular death with CHF, incl. in the presence of CKD, hsCRP > 3.07 mg/l was predicted. Achieving CCT was predicted in patients with CHF with hsCRP > 2.69 mg/l, in patients with a combination of CHF and CKD — with hsCRP > 2.5 mg/l.

Objective of the study. To determine the indications for distal hybrid reconstruction of the lower leg arteries based on the severity of atherocalcinosis in the lower leg arteries.

Material and methods. A prospective controlled non-randomized study involved 28 patients suffering from critical limb ischemia (CLI) who underwent hybrid arterial reconstruction at the vascular surgery department of CCH No. 29. All patients were divided into two groups. The first group (n = 14) consisted of patients who underwent restoration of the main blood flow at the level of the iliac-femoral arterial segment using a hybrid method. The control group (second group, n = 14) included patients who underwent simultaneous proximal and distal hybrid surgery, ensuring main blood flow through the “key” artery of the lower leg. Intraoperatively, all patients underwent intravascular laser photoluminescence spectroscopy using an authorial method. The plaques obtained from endarterectomy were subjected to mass spectrometry to determine their calcium content. Subsequently, the correlation between the intensity of calcium luminescence in the plaques, its concentration, and postoperative outcomes was assessed. Statistical analysis was performed using SPSS Statistics 17.0 software.

Results. A strong positive correlation was found between the amplitude of luminescence at a frequency of 380 nm and the quantitative calcium content in the plaque structure determined by mass spectrometry (r = 0.85; p < 0.001). In the second group, revascularization in the “key” artery could not be performed in 2 patients due to severe atherocalcinosis. In these patients, luminescence intensity was measured at 4.01 ± 0.11 × 10⁵. No thrombotic complications were recorded in the first group, while three cases were observed in the second group, with an average signal intensity of 2.18 ± 0.11 × 10⁵ photons, which significantly differed from both technically unsuccessful revascularization cases in the lower leg arteries (p < 0.05) and from cases with an uncomplicated postoperative period in this group (p < 0.001). In the early postoperative period, no bleeding or formation of perivascular hematomas were observed in either group. When assessing the average length of hospital stay and intraoperative blood loss, these parameters were comparable between groups.

Conclusion. The method of intraoperative luminescent spectroscopy is an effective way to determine the feasibility of distal hybrid reconstruction in the absence of hemodynamically significant lesions of the profunda femoris artery.

In recent years, the periodic literature suggests dividing peritonitis based on the speed of its development into primary peritonitis (PP) and secondary peritonitis (SP). The significance of the speed of development of purulent peritonitis has not been studied yet.

The aim of the study was to assess the impact of the rates of peritonitis development on treatment outcomes in patients with purulent peritonitis.

Materials and Methods: A total of 113 patients with purulent peritonitis were analyzed. The incidence of peritonitis with varying rates of development, its etiological structure, and treatment outcomes were studied.

Results: The PP group included 56 (49.6%) patients, while the SP group included 57 (50.4%) patients. In the PP group, 64.3% of cases had pathology of the upper gastrointestinal tract as the source of peritonitis. In 35.7% of cases, the source of abdominal cavity contamination was the lower gastrointestinal tract and structures localized outside the digestive tract. In the SP group, 70.1% of patients had the lower gastrointestinal tract as the source of peritonitis. In 29.9% of cases, the source was identified as the upper gastrointestinal tract and structures localized outside the digestive tract. The postoperative mortality rate in the PP group reached 62.5%, which correlated with a frequency of somatic complications of 69.4%. Mortality in the SP group was 35.1% (p < 0.05), with somatic complications recorded in 40.3% of cases (p < 0.05).

Conclusion: The rates of development of purulent peritonitis have a significant impact on treatment outcomes for patients.

The paper identifies the main groups of patients in vitro fertilization (IVF) programs. The characterization of the unexpected (paradoxical) response and its association with the polymorphism of the FSHR gene is given. A comparative characteristic of СOS protocols with the original follitropin alpha and its domestic biosimilar is presented.

The aim of the study is to increase the effectiveness of IVF programs in patients with an unexpected response by developing a differentiated approach to ovarian stimulation.

Material and methods. At the 1st stage, 920 case histories were studied; at the 2nd, 197 patients were included — a characteristic of patients with an unexpected response and its association with FSHR gene polymorphism was given; at the 3rd, an algorithm for a differentiated approach to СOS was tested in 22 patients.

Results. The main groups differ in age, efficacy, and the amount of gonadotropins. The frequency of the unexpected response was 42.8%. When comparing the original follitropin alpha and its domestic biosimilar, the effectiveness was 36.46 and 40.59% (p = 0.0511), respectively. Genotype G/A of the FSHR gene polymorphism is associated with a normal response; genotype A/A with a poor response; genotype G/G with a high response (p < 0.0001). The frequency of repeated unexpected response was 21.3%, the efficiency per cycle was 39.1% according to the results of testing the algorithm.

Conclusion. Three main groups of IVF patients have been identified to calculate the required doses of gonadotropins. An unexpected ovarian response reduces the effectiveness of IVF programs by 8.5%. Polymorphism of the FSHR gene is a significant predictor of a repeated unexpected response. The developed algorithm of the differentiated approach to the СOS makes it possible to increase the effectiveness of IVF programs.

The presented article discusses the risk factors for occurrence of large and giant gastric ulcers (in particular, the use of immunosupressants, nonsteroidal anti-inflammatory drugs, infectious etiology), the need for differential diagnosis between benign ulcers and infiltrative ulcerative form of gastric cancer, as well as its other tumor lesions), the features of the course of such ulcers (tendency to bleeding, perforation, penetration).

Benign metastatic leiomyoma is a rare lung tumor. There are just over 200 cases of this disease reported in the global literature.

This article presents a clinical observation by the authors, describing a case of multiple leiomyomas located in the lungs of a young woman who had previously undergone a supravaginal hysterectomy due to a similar tumor.

Case Description: Patient R., 42 years old. Five years ago, the patient underwent surgical treatment in the form of a supravaginal hysterectomy for myoma. There was no history of malignant diseases. During a routine examination, computed tomography of the chest revealed multiple solid lesions in the lungs. Comprehensive examinations, including esophagogastroscopy, fiber colonoscopy, fiber bronchoscopy, and positron emission tomography, did not reveal other tumor pathologies (besides the lung lesions). For morphological study of the tumor foci, a thoracoscopic atypical resection of the lower lobe of the left lung was performed. Histological conclusion: benign metastatic leiomyoma of the lung. No malignant tumor growth was found in the examined material.

Conclusion: Benign metastatic pulmonary leiomyoma is a rare tumor that lacks distinct criteria for reliable preoperative differential diagnosis. Benign metastatic leiomyomas occur predominantly in women with uterine leiomyoma, especially after surgical treatment for this pathology, although isolated cases of this disease in men have been reported. Typically, multiple solid foci are detected in the lungs during radiological examination.

A rare case of fatal outcome in Celen–Gellerstedt syndrome with the development of microhemorrhages in the lungs after reinfection with SARS-CoV-2 is presented. The morphological changes in lung tissue and their correlation with clinical, laboratory, and instrumental study data are described. Multiple hemorrhages with areas of pneumonia were found in the lung tissue. The interalveolar septa exhibited fibrinoid disorganization, diffuse infiltration, and scattered multinucleated cells containing hemosiderin. A distinctive feature of this case is that the fatal outcome occurred at a young age, with no thickening of the alveoli, fibrosis of lung tissue, right heart hypertrophy, or somatic pathology, but with pronounced morphological changes in the form of fibrinoid disorganization of the vessel walls, diffuse cellular infiltration, and significant hemorrhagic exudate in the alveolar lumens. Multiple hemorrhages with an abundance of macrophages and hemosiderin granules were observed, and cells in the interalveolar septa showed karyolysis. Ruptures of small and medium-sized pulmonary vessels and small thrombi in some of them were noted. Thus, the hereditary insufficiency of elastic fibers in the small and medium-sized pulmonary vessels, characteristic of Celen–Gellerstedt syndrome, likely contributed to their dilation, increased permeability, blood stasis, ruptures, and hemorrhages in lung tissue. It is particularly noteworthy that small thrombotic masses were identified specifically in these vessels. The trigger was reinfection with SARS-CoV-2.

In the course of the discussion, the article discusses terminological issues that define the “doctor-patient” relationship and the concepts of “medical care” or “medical service” from both, a universal and legal perspective.

This article outlines the key milestones in the life and work of the outstanding master of European surgery, Professor Johann Mikulich-Radetsky. It analyzes his career progression and scientific achievements during various periods of his life. The osteoplastic resection of the foot was proposed by I. Mikulich in 1873 for tuberculosis of the ankle joint and tumors of the heel. The operation involves the removal of the talus and calcaneus bones along with the distal part of the tibia and fibula at the level of the arch of the ankle joint. It should be noted that V.D. Vladimirov’s priority in this bone-plastic operation was established in surgery due to the intervention of Professor N.V. Sklifosovsky, who spoke on this matter in print (1882, nine years after I. Mikulich’s operation) and at a medical congress in Copenhagen (1884). It is noted that I. Mikulich was the first to use iodoform for wound disinfection in practice. He proposed using thread gloves with an external seam, which he changed several times during surgery. Additionally, I. Mikulich invented an original method for preparing a surgeon’s hands before surgical intervention. He is considered the founder of oncological resections of the stomach. It is shown that he was the first to successfully suture a perforated gastric ulcer and developed a technique for pyloroplasty, which is still used today. The scientific ideas of Johann Mikulich-Radetsky have been widely disseminated and developed in the works of his students.

In 2024, it will be 170 years since the birth of the outstanding physician and obstetrician-gynecologist Georgy Yermolaevich Rein. Academician G.E. Rein made a tremendous contribution to the development of the Department of Obstetrics and Gynecology at the Imperial Medical and Surgical (Military Medical) Academy, leaving a significant mark not only in the history of the academy but also in civil medicine in Russia and around the world. Under his leadership, new modern clinics were built both in Russia and abroad. G.E. Rein actively participated in the life of the country: in 1912, he authored a project for healthcare reform in Russia, and in 1916, he became the first Minister of Health of Russia. The name G.E. Rein is known worldwide: he was an honorary member of obstetric societies and academies of sciences in 16 countries across Europe and America.