Chronic Form Research Articles

A Case of Adult-onset Still’s Disease Complicated with Macrophage Activation Syndrome and Diffuse Alveolar Hemorrhage

Adult-onset Still’s Disease (AOSD) is a rare inflammatory disease of unknown etiology characterized by high fever, skin rash, arthritis, elevated ferritin and organ involvement. Macrophage Activation Syndrome (MAS) can be seen as a rare, potentially fatal complication in AOSD. Here, we presented a case who was diagnosed with MAS due to general condition disorder, increased ferritin and cytopenia while being followed up with the diagnosis of chronic articular form ESH, and then developed diffuse alveolar hemorrhage (DAH) after a short time. We aimed to draw attention to rare complications after AOSD with this case report that showed a dramatic response to corticosteroid and tocilizumab treatment.

Superoxide dismutase and glutathione peroxidase content in children with type 1 diabetes mellitus

Type 1 diabetes mellitus (T1D) is one of the most frequently diagnosed chronic diseases of childhood. Oxidative stress (OS) is considered as one of the possible mechanisms of its development and complications. The aim of the study was to analyze the content of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GP) in children and adolescents with adequately controlled T1D.Material and methods. A total of 58 children were examined, including 34 children with type 1 diabetes (study group) and 24 conditionally healthy children (control group). The content of glycated hemoglobin, blood plasma glucose per day, post-prandial glucose, total protein, creatinine and urea were determined by conventional methods, as well as the level of SOD and GP in the blood serum by ELISA.Results and discussion. A significant decrease in the content of both enzymes was found in type 1 DM patients compared to conditionally healthy children. In patients with the chronic form of the disease, SOD and GP level was significantly lower than in patients with incident T1D. An inverse correlation was revealed between the antioxidant enzymes level on the one hand and age, duration of the disease, and the number of episodes with a poor glucose history on the other hand. The decrease in SOD and GP concentration was associated with an increase in glycated hemoglobin and plasma glucose level over a 24-hour period in patients with chronic type SD 1. The decrease in SOD concentrations was associated with an increase in glycated hemoglobin in patients with T1D chronic type. The discovered abnormalities indicate that decreased antioxidant enzyme level represent a manifestation of OS in patients with adequately controlled type 1 DM.Conclusions. Content of antioxidant enzymes in children with T1D provides an important criterion for the assessment of OS manifestations in this disease.

CXCR5 and TIM-3 expressions define distinct exhausted T cell subsets in experimental cutaneous infection with Leishmania mexicana.

T-cell exhaustion is a key stage in chronic infections since it limits immunopathology, but also hinders the elimination of pathogens. Exhausted T (Tex) cells encompass dynamic subsets, including progenitor cells that sustain long-term immunity through their memory/stem like properties, and terminally-differentiated cells, resembling the so-called Tex cells. The presence of Tex cells in chronic leishmaniasis has been reported in humans and murine models, yet their heterogeneity remains unexplored. Using flow cytometry, we identified Tex cells subtypes based on PD-1, CXCR5 and TIM-3 expressions in draining lymph nodes (dLNs) and lesion sites of C57BL/6 mice infected with L. mexicana at 30-, 60- and 90-days post-infection. We showed that infected mice developed a chronic infection characterized by non-healing lesions with a high parasite load and impaired Th1/Th2 cytokine production. Throughout the infection, PD-1+ cells were observed in dLNs, in addition to an enhanced expression of PD-1 in both CD4+ and CD8+ T lymphocytes. We demonstrated that CD4+ and CD8+ T cells were subdivided into PD-1+CXCR5+TIM-3- (CXCR5+), PD-1+CXCR5+TIM-3+ (CXCR5+TIM-3+), and PD-1+CXCR5-TIM-3+ (TIM-3+) subsets. CXCR5+ Tex cells were detected in dLNs during the whole course of the infection, whereas TIM-3+ cells were predominantly localized in the infection sites at day 90. CXCR5+TIM-3+ cells only increased at 30 and 60 days of infection in dLNs, whereas no increase was observed in the lesions. Phenotypic analysis revealed that CXCR5+ cells expressed significantly higher levels of CCR7 and lower levels of CX3CR1, PD-1, TIM-3, and CD39 compared to the TIM-3+ subset. CXCR5+TIM-3+ cells expressed the highest levels of all exhaustion-associated markers and of CX3CR1. In agreement with a less exhausted phenotype, the frequency of proliferating Ki-67 and IFN-γ expressing cells was significantly higher in the CXCR5+ subset within both CD4+ and CD8+ T cells compared to their respective TIM-3+ subsets, whereas CD8+CXCR5+TIM-3+ and CD8+TIM-3+ subsets showed an enhanced frequency of degranulating CD107a+ cells. In summary, we identified a novel, less-differentiated CXCR5+ Tex subset in experimental cutaneous leishmaniasis caused by L. mexicana. Targeting these cells through immune checkpoint inhibitors such as anti-PD-1 or anti PD-L1 might improve the current treatment for patients with the chronic forms of leishmaniasis.

Epigallocatechin Gallate Adjuvant Immunomodulatory Therapy for Hypersensitivity Pneumonitis

The current research aims to investigate the management of Hypersensitivity Pneumonitis (HP), a respiratory ailment affecting the lung parenchyma, particularly the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic response. Various factors, such as microbial agents, animal and plant proteins, organic and inorganic compounds, and environmental substances, can contribute to respiratory issues. The inflammatory reaction in the alveolar mucosa is a hypersensitive response of type-3 (immune-complex-mediated) or type-4 (T-lymphocytes-mediated) that plays a role in the development of HP. Depending on the frequency and intensity of exposure to the causative antigens, the disease is categorized into acute, subacute, and chronic forms. The research shows the success for subacute and chronic forms of the disease as an alternative to corticosteroids. Although corticosteroids can provide relief for subacute and chronic HP as well as acute symptoms, they do not appear to alter the disease's long-term progression. As corticosteroids are only suitable for certain patients, there is a pressing need for an alternative treatment option to advance patient care. Sea Buckthorn is known to exhibit various beneficial effects, such as antioxidative, cytoprotective, wound-healing, immunomodulatory, and cardioprotective properties, among others. In contrast, Epigallocatechin gallate (EGCG) possesses antioxidant properties and can also mitigate the production of inflammatory cytokines, which are responsible for inducing inflammation in the body. The study postulates that incorporating EGCG alongside deciduous plant extracts could serve as a supplementary agent for HP treatment. Consequently, the research confirms the efficacy of the test medications in managing HP. It is essential to continue exploring alternative treatments and novel therapies to address the multifaceted aspects of HP and improve patients' overall quality of life. By broadening our understanding of the disease and potential treatment approaches, medical professionals can develop more personalized and effective interventions tailored to each patient's needs. Further investigations into the interplay between various therapeutic agents and their mechanisms of action will undoubtedly pave the way for more advanced and comprehensive strategies for combating HP. The study focuses on the Toluene di-isocyanate induced Hypersensitivity Pneumonitis rats with the prophylactic as well as therapeutic dose of the Sea Buckthorn berries extract along with the Epigallocatechin gallate for around 2.5 months. The paper also shows the various parameters on which the research has been successfully conducted. The research confirms the effectiveness of the test medications in modern HP treatment. This gives a basis for replacing the steroid therapy and opt for the better prolonged lifestyle.

Targeting Anaerobic Respiration in Pseudomonas aeruginosa with Chlorate Improves Healing of Chronic Wounds.

Objective: Pseudomonas aeruginosa is an opportunistic pathogen that can establish chronic infections and form biofilm in wounds. Because the wound environment is largely devoid of oxygen, P. aeruginosa may rely on anaerobic metabolism, such as nitrate respiration, to survive in wounds. While nitrate reductase (Nar) typically reduces nitrate to nitrite, it can also reduce chlorate to chlorite, which is a toxic oxidizing agent. Therefore, chlorate can act as a prodrug to specifically eradicate hypoxic/anoxic, nitrate-respiring P. aeruginosa populations, which are often tolerant to conventional antibiotic treatments. Approach: Using a diabetic mouse model for chronic wounds, we tested the role that anaerobic nitrate respiration plays in supporting chronic P. aeruginosa infections. Results: P. aeruginosa forms biofilm deep within the wound where the environment is anoxic. Daily treatment of P. aeruginosa-infected wounds with chlorate supported wound healing. Chlorate treatment was as effective as a treatment with ciprofloxacin (a conventional antibiotic that targets both oxic and hypoxic/anoxic P. aeruginosa populations). Chlorate-treated wounds showed markers of good-quality wound healing, including well-formed granulation tissue, reepithelialization and microvessel development. Loss- and gain-of-function experiments showed that P. aeruginosa requires nitrate respiration to establish a chronic wound infection and form biofilms. Innovation: We show that the small molecule chlorate, kills the opportunistic pathogen, P. aeruginosa, by targeting a form of anaerobic metabolism called nitrate respiration. Conclusion: Chlorate holds promise as a treatment to combat diverse bacterial infections where oxygen is limiting and/or where pathogens grow as biofilms because many other pathogens possess Nar and survive using anaerobic metabolism.

Characteristics of the phagocyte effector indexes and effect of local cytokine therapy on their parameters in inflammatory diseases of the maxillofacial region

Odontogenic inflammatory diseases and injuries take a leading place in the structure of surgical dental pathology. They often proceed with inflammatory complications. The aim of the present work was to analyze the effector indexes of phagocytic cells at the local area of inflammation (secretions from purulent wounds, tooth socket and mixed saliva), and to evaluate the effect of topical cytokine therapy on the studied parameters in patients with inflammatory dental diseases (chronic periodontitis, odontogenic phlegmon) complicated by mandibular fractures. As a part of a two-stage research, 236 people were comprehensively examined, divided into groups depending on their clinical disease and method of treatment. This group included 74 patients (classified as K 04.5 K 04.9), divided into subgroups by the types of periodontitis (chronic fibrous, granulating and granulomatous form); 102 patients with phlegmon (classified as L03.2, K12.2), who, at the second stage of basic therapy, received topical cytokine treatment with betaleukin (recombinant IL- 1) and roncoleukin (recombinant IL-2). Fifty patients with fractures of the lower jaw (classified as S 02.6) underwent immunotherapy with betaleukin at the second stage of treatment. Examination of patients with inflammatory dental diseases at the first stage of study and analysis of the effector indexes of neutrophilic granulocytes and macrophages from the local inflammatory foci revealed some immunological predictive signs of lacking efficiency of the inflammatory response, manifesting as aberrant functional activity of phagocytes, e.g., inhibition of all studied parameters along with sufficiently reduced functional reserve of phagocytic cells in the patients with phlegmon; high ability to produce reactive oxygen species with a decreased functional reserve of neutrophils in the patients with fractures, and signs of activated chronic inflammation in the patients with periapical lesions. The second stage of our research associated with topical therapy with recombinant cytokines and analysis of the obtained data, ebabled us to detect different effects of drugs on the studied parameters and register the integral effect of immunotherapy, which represents normalization of altered functional indexes. Hence, the data obtained may indicate that, in patients with inflammatory processes in the maxillofacial region, a higher adaptive effector potential of phagocytes was formed at the affected focus following the topical cytokine therapy.

Serological Biomarkers of Chronic Migraine.

Chronic migraine (CM) is a chronic form of migraine that differs from episodic migraine (EM) in terms of prevalence, comorbidities, response to treatment, and biomarkers. The aim of this review was to summarize the recent findings on serological biomarkers of CM. Neuronal, inflammatory, and vascular markers have been investigated to assess their diagnostic and prognostic ability and treatment effectiveness. Several markers showed significant alterations according to disease status and treatment response in CM. Calcitonin gene-related peptide (CGRP), glutamate, and adiponectin appear to be the most promising blood biomarkers for CM. Most studies have shown altered ictal and interictal levels of these markers in CM compared with those in EM and controls. Additionally, they showed a significant association with treatment outcomes. Total adiponectin and high-molecular-weight adiponectin levels were less studied as biomarkers of CM than CGRP and glutamate levels but showed promising results. The development of suitable biomarkers could revolutionize the diagnosis and treatment of CM and ultimately decrease the disability and societal costs of the disease.

The prevalence of chronic and episodic loneliness and social isolation from a longitudinal survey

Loneliness and social isolation, experienced more long-term, has been shown to increase mortality and lead to poorer health outcomes in specific cohorts. However, it is unclear what the prevalence of chronic loneliness and social isolation is, and which demographic groups are most at risk of reporting more chronic forms. A psychometrically validated classification system was used to identify people who met criteria for episodic and chronic loneliness and social isolation using the Household Income and Labour Dynamics in Australia (HILDA) survey waves 14–18. The prevalence of loneliness (overall 34%; 21% episodic, 13% chronic) far exceeded that of social isolation (overall 17%; 13% episodic, 4% chronic). There was consistency in the demographic characteristics (from age, sex, household type, income) of those who experienced loneliness and social isolation. However, people with a long-term health condition had an elevated risk of episodic loneliness (AOR 1.24, 95% CI 1.11–1.39) and a markedly higher risk of chronic loneliness (AOR 2.01, 95% CI 1.76–2.29), compared with those without a long-term health condition. Loneliness, both episodic and chronic subtypes, is more prevalent than social isolation. However, both chronic loneliness and social isolation remains neglected and poorly targeted within current practice and policy.

Serological and Bacteriological Surveillance of Glanders Among Horses in Central Region of Iran.

Glanders is the oldest and very contagious disease among horses caused by Burkholderia mallei. The disease occurs as a chronic form in horses. Hence, because of the prolonged shedding, numerous horses can potentially get infected by one horse with glanders. Glanders is endemic in Iran and this causes occasional occurrence in horse population of the country. The aim of this study was to determine the incidence of B.mallei infection in horses in two central provinces of Iran. A total of 517 serum samples were collected from stable horses in Tehran and Alborz provinces. Among the studied horses, seven presented fever, anorexia, dyspnea, subcutaneous abscesses, nasal and cutaneous discharges, emaciation, and lymphadenopathy. Nasal and ocular discharges and subcutaneous abscesses were sampled for bacterial culture and PCR. The sera were examined by means of complement fixation test (CFT) and indirect enzyme-linked immunosorbent assay (iELISA). Seropositive cases were further examined by Mallein test. The results derived from the present study indicated that only 1.35% of the studied horses were positive in CFT, iELISA and Mallein test, of which only in 42.85% B.mallei was successfully cultured on blood agar and glycerinated nutrient media and confirmed by PCR. Periodic serological tests along with quarantine can benefit reduction of the occurrence of the disease in horses in Iran.

BIOCHEMICAL CHANGES OF CHRONIC GENERALIZED PERIODONTITIS IN CHRONIC VIRAL HEPATITIS B, C AND MIXED INFECTIONS

Viral hepatitis (VH) belongs to the category of infectious diseases of the human body that develop under the influence of viruses, which are diverse in nature, in the ways of their spread and transmission from a patient to a healthy person and have one identical attribute - liver damage. VG is an atroponous infection, which means that their pathogens in natural conditions can only be present in the human body. In hepatitis of viral origin, pathogens have a selective similarity (tropism) to liver cells. For this reason, the early location of viruses and their replication (reproduction) are manifested mainly in the liver tissue, primarily in liver cells (hepatocytes). According to the nature and duration of development, hepatitis of viral origin is divided into acute and chronic. The threshold among these two types of disease is relatively taken into account 6 months from the onset of the disease or in certain patients from the onset of infection (if the disease does not develop) and up to 6 months - acute hepatitis B or acute virus carrier, after 6 months - chronic hepatitis or chronic virus carrier. [4; 8]. According to WHO, in different countries of the world more than 2 billion people are infected with viral hepatitis (VH), while about 350 million are carriers of hepatitis B and 500 million of hepatitis C [3; 5]. All known hepatitis viruses are present in the CIS countries. In relation to parenteral infections of viral hepatitis, the CIS countries belong to the region with a moderate incidence rate (35.2 cases per 100,000 people). In Tatarstan, the share of viral hepatitis "B" and "C" in the total number of viral hepatitis is 80%. According to some authors [1], the number of so-called "virus carriers" of infection is growing in our republic, more than 10,000-12,000 primary carriers of hepatitis B and C viruses are registered annually. However, the registered incidence is only a part of the true incidence and only the visible part of the "iceberg". This is due to the fact that most cases of hepatitis B occur outside the scope of medical diagnosis, without jaundice and with minor clinical symptoms. However, the anicteric form of parenteral hepatitis is less dangerous than the icteric form in terms of infection and consequences [10]. Viral hepatitis B and C belong to the group of viral hepatitis with a parenteral transmission mechanism. These pathogenic viruses are taxonomically distinct. Common features are the parenteral transmission mechanism and the obligatory circulation of the virus in the blood [7]. Viral hepatitis B is a strictly parenteral infection caused by the IIBV virus, including CMV; IIBV is highly resistant to cold, heat, chemical and physical attack. It persists for 3 months at room temperature and 25 years in dried plasma; a direct correlation has been demonstrated between IIBV duration and blood levels. [6]. The source of transmission of the virus (HBV) can be all forms of acute and chronic HBV, as well as virus carriers. More important as the main source of infection for the epidemic potential are chronic forms of HBV infection than acute ones. An important role is played by chronic carriers of HbsAg and patients with clinically icteric form of IIBV; the ability of IIBV to persist for a long time, often for life, in the human body is considered as an ecological form of its existence [3; 5]. The most fully studied artificial (artifacial) ways of HBV infection as a result of various parenteral therapeutic, diagnostic, therapeutic and non-medical manipulations, leading to a violation of the integrity of the mucous membranes and skin. The source of infection can be contaminated blood products, medical equipment and instruments, transplanted organs and tissues; transfusion of blood or blood products containing HBV can also cause infection (post-transfusion hepatitis) [8; 11]. In addition to medical procedures, non-medical parenteral injections are of paramount importance in the transmission of IIBV infections. This is especially true of intravenous administration of drugs, which has become widespread in recent years. According to a number of authors [2], it has been shown that in recent years there has been a rapid increase in the number of patients with acute viral hepatitis "B", which is associated with the use of intravenous drugs, and a quantitative increase in the incidence is observed among young men aged 15 to 30 years. . Below is a list of the most common causes of acute viral hepatitis B. The purpose of this study is to substantiate the functional features of periodontal tissues in chronic hepatitis B, C and mixed infection B + C.

ANALYSIS OF THE EFFECTIVENESS OF USING A LASER PHOTODYNAMIC SYSTEM FOR THE TREATMENT OF CHRONIC APICAL PERIODONTITIS. CLINICAL CASES SERIES

Background/Aim: The objective of study analysis of the effectiveness of using a laser photodynamic system for the treatment of chronic apical periodontitis. Materials and Methods: The study included 66 patients aged 18 to 60 years with a diagnosis of chronic apical periodontitis in whom 90 root canals were treated. The diagnosis was established on the basis of the patient's complaints, clinical and instrumental studies, X-ray data. The patients were divided equally into two groups and underwent endodontic treatment. In the root canals of patients of the first group, disinfection was carried out by the method of photodynamic therapy. Then the canal was obturated with gutta-percha pins and sealer, the tooth was restored. In patients of the 2nd group, after instrumental and medical treatment, the root canals were sealed with a temporary material "Kalasept" (Sweden) based on calcium hydroxide, and the tooth was restored with a temporary glass ionomer cement "Vitremer" (3M ESPE). process of the rarefaction focus. Results: The evaluation of the results of treatment was carried out in terms of 1-14 days, 6 and 12 months after the final filling of the root canals. positive dynamics in a short time was observed in 93.9% of patients. cases in patients of the 1st group and in 72.7% in patients of the 2nd group. Complications arose in patients of the 1st group in 6.1% of cases. In the 2nd group in 27.3% of cases, which is almost 4.5 times more than in the 1st group. When comparing 2 methods of treatment after 6 months, clinical well-being was observed in patients of the 1st group in 96.9% and in the 2nd group in 81.8% of cases. The percentage of complications that occurred was 3.1% in patients of the 1st group and 18.2% in the 2nd group. Complete healing of the focus in the bone tissue was observed in 84.8% of cases in patients of the 1st group and in 66.6% of cases in patients of the 2nd group. Partial healing of the bone tissue focus was observed in 18.1% and 15.1% of cases in the 1st and 2nd groups. Conclusion: The use of laser radiation in preparing the root canal for obturation in the treatment of chronic forms of periodontitis made it possible to reduce the number of complications by almost 1.5 times and accelerate the healing process of the rarefaction focus.

Coxiellosis in Livestock: Epidemiology, Public Health Significance, and Prevalence of Coxiella burnetii Infection in Ethiopia.

Coxiellosis is a zoonotic disease that is prevalent globally and can pose significant challenges, especially in less developed countries like Ethiopia. Coxiella burnetii is responsible for causing an infection called Q fever in humans and coxiellosis in ruminants. Pneumonia and endocarditis are the only signs that characterize the acute and chronic forms of Q fever, respectively. Ruminants exhibit symptoms such as abortion during the later stages of pregnancy, impaired fertility, perinatal death, premature delivery, and reduced birth weight. C. burnetii infection typically spreads among healthy cattle via tick bites and exposure to infected cattle or their bodily secretions. The primary source of human infection is through the ingestion of contaminated milk and milk products, but transmission through aerosols and dust generated during livestock operations is also common. Cattle, sheep, camels and goats are the primary sources of human infection, and the bacterium can be found in various bodily fluids of infected animals. Several factors, including host characteristics, environmental conditions, and management practices, can potentially affect the occurrence of C. burnetii infection in livestock, such as cattle, camels, sheep, and goats. Coxiellosis is prevalent in Ethiopia's pastoral and mixed cattle management systems, as individuals frequently interact with cattle and are therefore more prone to exposure to the C. burnetii bacterium. Vaccination and biosecurity measures are effective techniques for managing C. burnetii infection. Therefore, it is crucial to implement appropriate mitigation strategies, raise awareness about the spread of C. burnetii infection, and conduct further studies on C. burnetii infection in high-risk groups.

Insights into Magnetic Resonance Imaging Findings in Central Nervous System Paracoccidioidomycosis: A Comprehensive Review.

Paracoccidioidomycosis (PCM) is a infection caused by the thermodimorphic fungus Paracoccidioides spp. (P. lutzii and, mainly, P. brasiliensis). This infection predominantly affects rural male workers aged between 30 and 50 years old who deal with soil on daily activities. Clinically, the disease is classified as acute/subacute phase, which evolves rapidly, secondary to dissemination of the fungus through to the phagocytic-mononuclear system, leading to fever, weight loss, and anorexia, associated with hepatosplenomegaly and lymphadenopathy, which can be complicated with suppuration and fistulization; and chronic phase, which corresponds to 74% to 95% of symptomatic cases, with a common pulmonary involvement. Central nervous system involvement is almost always a characteristic of the chronic form. Inhalation is the most common route of primary infection, usually affecting the lungs, forming the primary complex. From the primary complex, hematogenic dissemination can occur to any organ, including the brain and spinal cord. Although PCM of the central nervous system diagnosis is usually based on histopathological analysis and the imaging features are not specific for PCM, computed tomography and magnetic resonance imaging can demonstrate evidences of granuloma, abscess, meningitis, or a combination of these lesions, contributing to a preoperative diagnosis, especially when considered in conjunction with epidemiology. In this article, we review the pathophysiology, clinical manifestations and imaging aspects of neuro-PCM.

Towards the sustainable elimination of gambiense human African trypanosomiasis in Côte d'Ivoire using an integrated approach.

Human African trypanosomiasis is a parasitic disease caused by trypanosomes among which Trypanosoma brucei gambiense is responsible for a chronic form (gHAT) in West and Central Africa. Its elimination as a public health problem (EPHP) was targeted for 2020. Côte d'Ivoire was one of the first countries to be validated by WHO in 2020 and this was particularly challenging as the country still reported around a hundred cases a year in the early 2000s. This article describes the strategies implemented including a mathematical model to evaluate the reporting results and infer progress towards sustainable elimination. The control methods used combined both exhaustive and targeted medical screening strategies including the follow-up of seropositive subjects- considered as potential asymptomatic carriers to diagnose and treat cases- as well as vector control to reduce the risk of transmission in the most at-risk areas. A mechanistic model was used to estimate the number of underlying infections and the probability of elimination of transmission (EoT) was met between 2000-2021 in two endemic and two hypo-endemic health districts. Between 2015 and 2019, nine gHAT cases were detected in the two endemic health districts of Bouaflé and Sinfra in which the number of cases/10,000 inhabitants was far below 1, a necessary condition for validating EPHP. Modelling estimated a slow but steady decline in transmission across the health districts, bolstered in the two endemic health districts by the introduction of vector control. The decrease in underlying transmission in all health districts corresponds to a high probability that EoT has already occurred in Côte d'Ivoire. This success was achieved through a multi-stakeholder and multidisciplinary one health approach where research has played a major role in adapting tools and strategies to this large epidemiological transition to a very low prevalence. This integrated approach will need to continue to reach the verification of EoT in Côte d'Ivoire targeted by 2025.

Biocenosis of the vagina and modern approaches to the correction of vaginal dysbiosis (Literature review)

In the modern world it is important to understand the interaction of macro- and microorganisms in normal conditions and during illness. It is the biotope of the vagina that plays an extremely important role in a woman’s organism and it reflects the general state of woman’s health. Urogenital endogenous microflora is not static, it is a constantly changing macropopulation. In this population the number of specific types of microorganisms fluctuates within the limits of changes in the conditions of their environment. The microflora of the vagina changes during different periods of a woman’s life, namely during perinatal, late neonatal, prepubertal, pubertal, reproductive and postmenopausal periods, as well as the menstrual cycle, daily and hourly. The ability of commensal microorganisms to protect the region from the invasion of their own microflora from other cavities and the microflora of the sexual partner is unique. Considering the general global trend towards the increase in prevalence, virulence and resistance of microorganisms to traditional methods of antiseptic therapy, as well as the appearance of new types of microorganisms, a steady trend towards an increase in infectious diseases, including sexually transmitted infections, is determined. Dysbiosis is considered qualitative and quantitative violations of the corresponding biotope of the normal flora. According to official statistics, the prevalence of bacterial vaginosis is 10-35% among all patients with pathological vaginal discharge. The variability of the vaginal microbiome is widely studied in the world and depends on many factors, namely the hormonal background of a woman’s organism, her diet, the characteristics of urination and defecation, menstruation, hygienic procedures and infections. One of the key links in the pathogenesis of vaginal infectious diseases is the ability of bacteria to form biofilms, which are microbial associations. Infections caused by film-forming strains of pathogenic and opportunistic microorganisms are characterized by an atypical course, insufficient effectiveness of antibiotic therapy, and often transition to a chronic form or carriage. Therefore, understanding the mechanisms of formation, structure and regulation of vital activities of biofilms helps in solving problems related to human health. The World Health Organization recommends evaluating the vaginal microbiome according to the Hay – Ison criteria. Determining the pH of vaginal secretions also helps to establish the type of vaginal dysbiosis. Clinical therapy includes two main stages of treatment: antiseptic measures and restoration of one’s own vaginal microbiome. Often, these two stages of therapy are carried out simultaneously. Correcting the pH of the vaginal secretion is also important.

Epidemiological and genetic analysis of Cetacean Morbillivirus circulating on the Italian coast between 2018 and 2021.

Cetacean morbillivirus (CeMV) has caused several outbreaks, unusual mortality events, and interepidemic single-lethal disease episodes in the Mediterranean Sea. Since 2012, a new strain with a northeast (NE) Atlantic origin has been circulating among Mediterranean cetaceans, causing numerous deaths. The objective of this study was to determine the prevalence of CeMV in cetaceans stranded in Italy between 2018 and 2021 and characterize the strain of CeMV circulating. Out of the 354 stranded cetaceans along the Italian coastlines, 113 were CeMV-positive. This prevalence (31.9%) is one of the highest reported without an associated outbreak. All marine sectors along the Italian coastlines, except for the northern Adriatic coast, reported a positive molecular diagnosis of CeMV. In one-third of the CeMV-positive cetaceans submitted to a histological evaluation, a chronic form of the infection (detectable viral antigen, the absence of associated lesions, and concomitant coinfections) was suspected. Tissues from 24 animals were used to characterize the strain, obtaining 57 sequences from phosphoprotein, nucleocapsid, and fusion protein genes, which were submitted to GenBank. Our sequences showed the highest identity with NE-Atlantic strain sequences, and in the phylogenetic study, they clustered together with them. Regarding age and species, most of these individuals were adults (17/24, 70.83%) and striped dolphins (19/24, 79.16%). This study improves our understanding on the NE-Atlantic CeMV strain in the Italian waters, supporting the hypothesis of an endemic circulation of the virus in this area; however, additional studies are necessary to deeply comprehend the epidemiology of this strain in the Mediterranean Sea.

Evaluation of methods of drug administration for the treatment of cows with subclinical endometritis

The article presents the results of studies on the spread of various forms of endometritis in cows. Clinical acute and chronic forms of endometritis occurred in 15.17 and 8.99% of cows, respectively. The data obtained indicate the dominant distribution of subclinical endometritis in cows (32.02%). To conduct research, two experimental and one control groups of cows were formed. Animals of the first experimental group were injected intrauterine with the drug Metricef, the second experimental group - intramuscularly with the drug amoxicillin 150. The cows of the control group were not treated. The results of the studies showed the effectiveness of the use of amoxicillin 150. The method of intramuscular use of the amoxicillin preparation is much simpler and makes it possible to achieve fertilization of cows by 5.26% more compared to the intrauterine administration of the metricef preparation.

REHABILITATION AND PREVENTION OF THE MEDIAL TIBIAL STRESS SYNDROME IN MILITARY PERSONNEL

Abstract.Medial tibial stress syndrome is an injury that occurs as a result of cumulative and chronic damage to the lower extremities during excessive physical exertion. It is manifested by pain in the posterior medial part of the tibia, which is caused by microtraumas of the shin muscles and overstrain of their attachment sites, as well as tibial periostitis progressing to a stress fracture. It is most often found among athletes and military personnel and can significantly limit their ability to perform professional physical activities. The risk of receiving this injury is especially high among military personnel in their first year of service, which includes cadets of higher military educational institutions. Persons who have developed medial tibial stress syndrome are prone to relapses of the disease, and without proper treatment and rehabilitation, its chronic form may develop, which leads to deterioration of functioning. In addition, medial tibial stress syndrome is considered a precursor to a tibial stress fracture, requiring longer treatment and recovery.
 Based on the results of the analysis of the existing methodical approaches to physical therapy of people with medial tibial stress syndrome in Ukraine, a small number of publications dealing with this problem were found. Also, complex physical therapy programs for servicemen with injuries from heavy workload were not developed and implemented.
 Aim. The aim of the research is to analyze approaches to the rehabilitation and prevention of medial tibial stress syndrome among military personnel.
 Materials and methods. The publications selected on the basis of a search in the databases PubMed, PEDro, Cochrane Library, Google Scholar, and Vernadsky National Library of Ukraine were analyzed.
 Results. It was found that almost all physical therapy methods used in the treatment of the syndrome were part of an individual (standard) treatment program for military personnel with stress syndrome, which also included medication and surgical intervention as indicated. In only one research, after treatment of an acute period of the disease, patients were offered a multidisciplinary rehabilitation program based on therapeutic exercises, which were used to reduce symptoms, improve endurance, and return servicemen to duty.
 It has been established that therapeutic exercises, as the main means of physical therapy, are ineffective in the rehabilitation and prevention of medial tibial stress syndrome without combination with other interventions. The insufficient effectiveness of the treatment of the syndrome by combining therapeutic exercises with means of physical therapy was determined.
 It has been found that gait retraining in combination with therapeutic exercises accelerates recovery and prevents the occurrence of medial tibial stress syndrome in military personnel.
 Conclusions. The data obtained in the analyzed scientific researches, a significant difference in the organization of research, rehabilitation programs, and research methods make it impossible to draw certain conclusions about optimal approaches to therapy and prevention of medial tibial stress syndrome in military personnel. This makes it necessary to continue research on this issue.
 Since the results of the research did not reveal a consensus regarding effective physical therapy programs for the prevention and rehabilitation of medial tibial stress syndrome, as well as the lack of relevant research in Ukraine, it is important to continue studying this issue.

Ferroptosis induces detrimental effects in chronic EAE and its implications for progressive MS

Ferroptosis is a form of lipid peroxidation-mediated cell death and damage triggered by excess iron and insufficiency in the glutathione antioxidant pathway. Oxidative stress is thought to play a crucial role in progressive forms of multiple sclerosis (MS) in which iron deposition occurs. In this study we assessed if ferroptosis plays a role in a chronic form of experimental autoimmune encephalomyelitis (CH-EAE), a mouse model used to study MS. Changes were detected in the mRNA levels of several ferroptosis genes in CH-EAE but not in relapsing–remitting EAE. At the protein level, expression of iron importers is increased in the earlier stages of CH-EAE (onset and peak). While expression of hemoxygenase-1, which mobilizes iron from heme, likely from phagocytosed material, is increased in macrophages at the peak and progressive stages. Excess iron in cells is stored safely in ferritin, which increases with disease progression. Harmful, redox active iron is released from ferritin when shuttled to autophagosomes by ‘nuclear receptor coactivator 4’ (NCOA4). NCOA4 expression increases at the peak and progressive stages of CH-EAE and accompanied by increase in redox active ferrous iron. These changes occur in parallel with reduction in the antioxidant pathway (system xCT, glutathione peroxidase 4 and glutathione), and accompanied by increased lipid peroxidation. Mice treated with a ferroptosis inhibitor for 2 weeks starting at the peak of CH-EAE paralysis, show significant improvements in function and pathology. Autopsy samples of tissue sections of secondary progressive MS (SPMS) showed NCOA4 expression in macrophages and oligodendrocytes along the rim of mixed active/inactive lesions, where ferritin+ and iron containing cells are located. Cells expressing NCOA4 express less ferritin, suggesting ferritin degradation and release of redox active iron, as indicated by increased lipid peroxidation. These data suggest that ferroptosis is likely to contribute to pathogenesis in CH-EAE and SPMS.

Application of StyleGAN Architecture for Generating Venous Leg Ulcer Images.

Leg ulcers caused by impaired venous blood return are the most typical chronic wound form and have a significant negative impact on the lives of people living with these wounds. Thus, it is important to provide early assessment and appropriate treatment of the wounds to promote their healing in the normal trajectory. Gathering quality wound data is an important component of good clinical care, enabling monitoring of healing progress. This data can also be useful to train machine learning algorithms with a view to predicting healing. Unfortunately, a high volume of good-quality data is needed to create datasets of suitable volume from people with wounds. In order to improve the process of gathering venous leg ulcer (VLU) data we propose the generative adversarial network based on StyleGAN architecture to synthesize new images from original samples. We utilized a dataset that was manually collected as part of a longitudinal observational study of VLUs and successfully synthesized new samples. These synthesized samples were validated by two clinicians. In future work, we plan to further process these new samples to train a fully automated neural network for ulcer segmentation.