Prevention of Postoperative Urethral Strictures by Irrigation with 5-Fluorouracil via a Modified Urinary Catheter.

Background and Objectives: Urethral strictures are the most common complications after surgical treatments of benign prostatic hyperplasia (BPH). Despite various preventive measures, the search for medications with antiproliferative activity and the development of surgical procedures to prevent the development of urethral strictures are still relevant. We evaluated the preventive efficacy of 5-fluorouracil against urethral strictures in patients undergoing surgery for BPH. Materials and Methods: A non-randomized clinical trial including 246 male patients with an average age of 70.0 ± 8.0 years was conducted. The main study group included 124 patients who, in addition to the standard treatment, received lavage with a 5-fluorouracil solution (1000 mg/20 mL per 500 mL of 0.9% isotonic saline) using a modified three-way urethral catheter. The monitoring of clinical, laboratory, and instrumental parameters was carried out 10 days, 3 months, and 6 months after surgery. Results: The evaluation of severity for dysuria symptoms in patients using the IPSS scale throughout the entire follow-up period showed a statistically significant decrease in ischuria and stranguria, prolongation of the interval between urinations, a decrease in intermittent urination, urinary incontinence, and straining before urination in the main group in comparison with the control patients. The patients of both study groups noted an improvement in the quality of life. It was found statistically significant decrease in the maximum urinary flow rate in the main group (p < 0.001). In the control group, after three months, four cases of urethral strictures and stenosis were recorded; after six months, this rate reached nine cases (7.3%), while in the main group, only one patient with infravesical obstruction was found (0.8%) (χ2 = 3.855, p < 0.05). Conclusions: The results of our study could indicate the effectiveness of the antiproliferative drug 5-fluorouracil in combination with use of a modified catheter in relation to the development of postoperative urethral strictures.

A global survey in the developmental landscape of possible vaccination strategies for COVID-19.

The development of COVID-19 vaccines was promptly regulated to ensure the best possible approach. By January 2022, 75 candidates reached preclinical evaluation in various animal models, 114 vaccines were in clinical trials on humans, and 48 were in the final testing stages. Vaccine platforms range from whole virus vaccines to nucleic acid vaccines, which are the most promising in prompt availability and safety. The USA and Europe have approved vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNa1273). So far, Pfizer-BioNTech, Moderna, Johnson & Johnson, AstraZeneca-University of Oxford, Sinopharm, Sinovac Biotech Gamaleya, Bharat Biotech, and Novavax have documented effective vaccines. Even with technological advances and a fast-paced development approach, many limitations and problems need to be overcome before a large-scale production of new vaccines can start. The Key is to ensure equal and fair distribution globally through regulatory measures. Recent studies link Bacillus Calmette-Guérin (BCG) vaccination programs and lower disease severity.

Phosphocalcic metabolism and the role of vitamin D, vitamin K2, and nattokinase supplementation.

Calcium is involved in bone metabolism, regulation of nerve signaling, and release of neurotransmitters. Phosphorus is a structural component of ATP, participates in metabolic energy regulation, and ensures stability to biological membranes and cells. Vitamin D and vitamin K are important for intestinal absorption and renal excretion of calcium and phosphorus. Vitamin D plays a regulatory role in bone formation, carbohydrate metabolism, immune responses, and cardiovascular regulation. Research has linked vitamin D deficiency to the development of diabetes mellitus, hypertension, cancer, and osteoporosis. Vitamin K has been associated with a reduced risk of osteoporosis, cancer, and cardiovascular diseases (due to improved vascular elasticity). This review highlights the importance of vitamins D and K in the metabolism of calcium and phosphorus and explores various molecular mechanisms that help maintain the system's mineral homeostasis. Moreover, the paper reviews the enzyme nattokinase's role in thrombotic prevention due to its fibrinolytic activity.

Epidemiology of stroke and transient ischemic attacks in the population of the territories adjacent to the former Semipalatinsk Nuclear Test Site, Kazakhstan.

The issue of radiation exposure as a potential cause of cerebrovascular disease raises many concerns. The aim of the present study was to investigate the epidemiology of stroke and transient ischemic attacks (TIA) along with the associated risk factors among the population of East Kazakhstan exposed to ionising radiation from the former Semipalatinsk Nuclear Test Site (SNTS) in comparison with the unexposed population of the same region. This 5-year retrospective cross-sectional study included the data on 10,970 patients, of whom the majority (62.3%) suffered from ischemic stroke, 11.7% had hemorrhagic stroke and the remaining 26.0% had TIA. At the moment when stroke/TIA happened, exposed patients were younger than the unexposed (mean age 63 years versus 64 years, p < 0.001) and showed higher rates of nearly all associated comorbidities, which commonly were more severe. Besides, exposed patients showed a higher risk of stroke lethality in contrast with the unexposed. The observed features might indicate that people residing in the vicinity of the SNTS are vulnerable to cerebrovascular disease and thus, this study contributes to timely recognition of this public health problem. In addition, a longitudinal study has to be envisaged to clarify whether there is any cause-effect relationship between exposure to radiation from the SNTS and the development of stroke or transient ischemic attacks.

Neurotransmitters Regulation and Food Intake: The Role of Dietary Sources in Neurotransmission.

Neurotransmitters (NTs) are biologically active chemicals, which mediate the electrochemical transmission between neurons. NTs control numerous organic functions particularly crucial for life, including movement, emotional responses, and the physical ability to feel pleasure and pain. These molecules are synthesized from simple, very common precursors. Many types of NTs have both excitatory and inhibitory effects. Neurotransmitters' imbalance can cause many diseases and disorders, such as Parkinson's disease, depression, insomnia, increased anxiety, memory loss, etc. Natural food sources containing NTs and/or their precursors would be a potential option to help maintain the balance of NTs to prevent brain and psychiatric disorders. The level of NTs could be influenced, therefore, by targeting dietary habits and nutritional regimens. The progressive implementation of nutritional approaches in clinical practice has made it necessary to infer more about some of the nutritional NTs in neuropsychiatry. However, the importance of the intake of nutritional NTs requires further understanding, since there are no prior significant studies about their bioavailability, clinical significance, and effects on nerve cells. Interventional strategies supported by evidence should be encouraged.

COVID-19 and New Onset IgA Vasculitis: A Systematic Review of Case Reports.

INTRODUCTION: Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19. COVID-19 has not been formally established in literature as a trigger for immunoglobulin A vasculitis. However, a main pathogenetic mechanism of COVID-19 is vascular damage, which makes it likely that vasculitis associated with COVID-19 (ie, COVID-19-mediated immunoglobulin A vasculitis) could be biologically plausible, with serious implications, especially for adults. The purpose of this review is to assist emergency nurses in gaining knowledge on the pathophysiology, symptoms, and treatment of COVID-19-mediated immunoglobulin A vasculitis. METHODS: A systematic search for case reports of COVID-19-associated immunoglobulin A vasculitis was conducted in the PubMed and Scopus electronic databases. The search terms used were COVID-19, coronavirus 2019, SARS COVID-19, and IgA vasculitis, case reports. The following were the inclusion criteria: publication dates between December 1, 2019, and December 1, 2021; full-text article, clinical case studies, and letters to the editor available electronically in English. The following were exclusion criteria: a summary of reports and newspaper publications. RESULTS: Only 13 clinical cases met the inclusion criteria. The median age of patients described in the case reports were 38.1 years. Of them, 3 children were less than 5 years old. Twelve patients were male. In 7 of 13 cases of immunoglobulin A vasculitis, renal involvement was found. DISCUSSION: The analysis of published clinical cases showed that COVID-19-associated immunoglobulin A vasculitis affected mostly adults and was characterized by a more severe course because of renal involvement. COVID-19 may be a possible trigger for immunoglobulin A-related disorders. More research is needed to better understand the relationship between immunoglobulin A vasculitis and COVID-19.

Interrelations between COVID-19 and other disorders.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory tract virus that causes Coronavirus disease (COVID-19). The virus originated in Wuhan, China, in December 2019 and has spread across the globe to-date. The disease ranges from asymptomatic carriers to symptoms such as fever, sore throat, cough, lung infections, and in severe cases, acute respiratory distress syndrome, sepsis, and death. As many as 50% of patients reported having at least one comorbidities with COVID-19 upon hospital admission. Hypertension, diabetes, chronic obstructive pulmonary disease, obesity, and cardiovascular diseases are among the most commonly reported. Comorbidities are contributing to acute disease prognosis and increased risk of severe symptoms. Around 70% of patients who require ICU care have been observed to have comorbidities. This review intends to understand how some of these comorbidities affect the disease's prognosis and how severe the outcome can be expected.

Depleted uranium and Gulf War Illness: Updates and comments on possible mechanisms behind the syndrome.

Indications of proximal tubule effects have been observed in recent surveillance study of Gulf War veterans exposed to depleted uranium (DU). This gives some support for the suspicion that DU may represent one of the causes for the so-called Persian Gulf syndrome. Proposed effects may be especially harmful if the toxicity hits the mitochondrial DNA since the mitochondria lack the nucleotide excision repair mechanism, which is needed for repairing bulky adducts that have been associated with DU. It is a plausible working hypothesis that a significant part of the symptoms from various organs, which have been observed among veterans from Gulf War 1 and that have been grouped under the name of the Persian Gulf syndrome, may be explained as a consequence of mitochondrial DNA damage in various cell types and organs. Interpretation of observations, on military personnel and civilians after Gulf War 1, is associated with difficulties because of the abundance of potential confounding factors. The symptoms observed on veterans from Gulf War 1 may be attributed to a multiplicity of substances functioning directly or indirectly as mitochondrial mutagens. A concise analysis of the cascade of toxic effects initiated by DU exposure in the human body is the subject of this article.

Uranium in drinking water: a public health threat.

Uranium (U) has no known essential biological functions. Furthermore, it is well known for its toxicity, radioactivity, and carcinogenic potency. Impacts on human health due to U exposure have been studied extensively by many researchers. Chronic exposure to low-level U isotopes (radionuclides) may be interlinked with cancer etiology and at high exposure levels, also kidney disease. Other important issues covered U and fertilizers, and also U in soils or human tissues as an easily measurable indicator element in a pathophysiological examination. Furthermore, phosphate fertilization is known as the important source of contamination with U in the agricultural land, mainly due to contamination in the phosphate rock applied for fertilizer manufacture. Therefore, long-term usage of U-bearing fertilizers can substantially increase the concentration of U in fertilized soils. It should also be noted that U is an active redox catalyst for the reaction between DNA and H2O2. This review is aimed to highlight a series on various hydro-geochemical aspects in different water sources and focused on the comparison of different U contents in the drinking water sources and presentation of data in relation to health issues.

Epidemiological Characteristics and Forecast of COVID-19 Outbreak in the Republic of Kazakhstan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic entered Kazakhstan on 13 March 2020 and quickly spread over its territory. This study aimed at reporting on the rates of COVID-19 in the country and at making prognoses on cases, deaths, and recoveries through predictive modeling. Also, we attempted to forecast the needs in professional workforce depending on implementation of quarantine measures. METHODS: We calculated both national and local incidence, mortality and case-fatality rates, and made forecast modeling via classic susceptible-exposed-infected-removed (SEIR) model. The Health Workforce Estimator tool was utilized for forecast modeling of health care workers capacity. RESULTS: The vast majority of symptomatic patients had mild disease manifestations and the proportion of moderate disease was around 10%. According to the SEIR model, there will be 156 thousand hospitalized patients due to severe illness and 15.47 thousand deaths at the peak of an outbreak if no measures are implemented. Besides, this will substantially increase the need in professional medical workforce. Still, 50% compliance with quarantine may possibly reduce the deaths up to 3.75 thousand cases and the number of hospitalized up to 9.31 thousand cases at the peak. CONCLUSION: The outcomes of our study could be of interest for policymakers as they help to forecast the trends of COVID-19 outbreak, the demands for professional workforce, and to estimate the consequences of quarantine measures.

Increased prevalence of essential hypertension in areas previously exposed to fallout due to nuclear weapons testing at the Semipalatinsk Test Site, Kazakhstan.

This study examines the association between environmental radiation exposure and essential hypertension in a series of investigated geographical districts adjacent to the Semipalatinsk nuclear test site in Kazakhstan. The sample consists of 2000 volunteers participants in screening examinations in three administrative districts close to the nuclear test site, which was carried out as part of the Government Programs on Environmental Health Hazard. The cross-sectional study compares prevalence ratios in a population sample with long-term exposure in the low and intermediate dose range. Age-adjusted odds ratios for hypertension were found significantly increased with higher exposure groups. After accounting for main cardiovascular risk factors into the model and stratifying by gender, the prevalence odds ratios for radiation remained significantly increased, with a significant dose-response effect observed for some but not all subgroups. The results support existing evidence of cardiovascular health effects of radiation exposure and of persisting environmental health issues that require attention in both epidemiological surveys and healthcare provision.

Paramedic To Provider Consultation Challenges in the Emergency Department in Kazakhstan: An Online Survey.

Objective: Consultation is an important and necessary aspect of patient care in the emergency department. We prospectively examined difficulties during the consultation process between paramedics and providers in emergency departments in Kazakhstan. Methods: The paramedics were interviewed using various platforms and face-to-face meetings. Questionnaires were administered to paramedics to gather feedback on the current consultation process. In our survey, 202 paramedics of ambulance from the cities of Semey, Pavlodar, and Ust-Kamenogorsk, located in the North and East of Kazakhstan took part. Results: Serious barriers to effective consultation were identified during consultations with cardiologists, pediatricians, and traumatologists. Weekends, as well as nighttime, are associated with more consultation difficulties. The most common problems for paramedics are non-attendance of the consultant, refusal of hospitalization by the consultant, and referral to other specialists and departments. More than 40% of the respondents noted the desire to share responsibility for the patient with medical consultants, which indicates uncertainty in their own knowledge due to the limited work experience of the majority of respondents. Conclusion: Barriers that arise during the consultation process of patients with emergency conditions can lead to unfavorable outcomes. Strategies to address these barriers are needed to improve the quality of patient care. This review aims to understand and evaluate the issues that arise during the consultation process.

Restenosis of Coronary Arteries in Patients with Coronavirus Infection: Case Series.

Introduction: Coronavirus infection is a risk factor for vascular thrombosis. This is of particular importance for patients undergoing myocardial revascularization since this infection can be a trigger for the formation of restenosis in the area of a previously implanted coronary stent. Understanding the risk factors for stent thrombosis and restenosis is of particular importance in individuals at risk for adverse outcomes. The rarity of such situations makes the present study unique. Objective: Studying the peculiarities of restenosis and thrombosis of the coronary arteries in patients after coronavirus infection. Methods: The study was performed in the Department of Cardiovascular Surgery of Emergency Hospital, Semey City, in 2021. We have examined the medical records of 10 consecutive patients with restenosis of coronary arteries after coronavirus infection and 10 matched-by-age patients with similar restenosis of coronary arteries who did not have coronavirus infection as a comparison group. To determine statistically significant differences between independent samples, we calculated the Mann-Whitney U test. Results: The average age of patients was 65.7 years. Only one case was classified as early restenosis (within 8 days of previous revascularization), two cases represented late restenosis, and seven cases were very late restenoses. In 70% of cases, restenosis was localized in the left anterior descending artery, in 30% of cases, it was in the right coronary artery, and in 40% of cases, it was in the left circumflex artery. In comparison with patients who did not have a coronavirus infection, there were statistically significant differences regarding IgG (P < 0.001) and fibrinogen (P=0.019). Conclusion: Patients with myocardial revascularization in the past have a higher risk of stent restenosis against the background of coronavirus infection due to excessive neointimal hyperplasia, hypercoagulability, increased inflammatory response, and endothelial dysfunction.

Post-conflict acute stress reactions in Kazakhstan in the aftermath of January 2022 unrests: A national survey.

Background: In January 2022 Kazakhstan experienced unprecedented nationwide protests that quickly turned to violent riots. Although the number of individuals affected physically by the disturbances were cited, the emotional toll of the events remains undetermined. The aim of this study was to evaluate the comparative rates of acute stress reactions in Kazakhstan in the aftermath of the unrests. Methods: A cross-sectional, population-based online survey was conducted one month after the start of the disturbances. The study questionnaire were completed anonymously and included the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) and the General Anxiety Disorder-7 (GAD-7), as well as socio-demographic and event exposure information. Results: Of the 7021 people who initially agreed to participate, 6510 were able to complete the full survey. For a cut-off of ≥3 on the PC-PTSD-5, 14.8 % of the study participants exhibited symptoms. With a cut-off of ≥4, this percentage reduced to 4.6 %. Participants from Almaty city and Almaty region who experienced the most extensive disturbances showed a doubled prevalence compared to the national level (30.0 % for a cut-off of ≥3, and 10.1 % for a cut-off of ≥4). At the national level, the prevalence of anxiety symptoms, defined as a score of ≥10 on the GAD-7, stood at 10.9 %. This prevalence decreased to 4.2 % when considering a cut-off of ≥15. Conclusion: Health authorities of riot-affected areas ought to be aware of the population level mental health impact of the civil conflict and consider provision of targeted interventions to mitigate the long-term consequence of these lifespan disorders, while also seeking for the peaceful resolution of the ensuing conflicts.

Autoimmune polyendocrine syndrome type 1: Clinical manifestations, pathogenetic features, and management approach.

Autoimmune polyendocrine syndrome type 1 (APS-1) is an autosomal recessive hereditary pathology that develops with endocrine and non-endocrine manifestations in childhood. The classic triad of APS-1 includes chronic candidiasis of the skin and mucous membranes, adrenal insufficiency, and hypoparathyroidism. APS-1 is often accompanied by hypogonadism, type 1 diabetes, autoimmune thyroiditis, vitiligo, alopecia, asplenia, pneumonitis, gastritis, pernicious anemia, and intestinal dysfunction, nephritis, and hepatitis. The prevalence rate is highest in genetically isolated populations (up to 1:6500-1:9000). APS-1 occurs because of mutations in the autoimmune regulator (AIRE) gene, leading to a disrupted mechanism of normal antigen expression, the formation of abnormal clones of immune cells, and autoimmune damage to various organs. Analysis of the AIRE gene is the main diagnostic method for early detection of APS-1 and the choice of methods for its treatment. Timely genetic counseling makes it possible to identify the disease early, prescribe appropriate treatment and prevent serious complications. This paper analyzes scientific information characterizing clinical manifestations of autoimmune polyendocrine syndrome type 1 in association with its pathogenetic features, epidemiology, and current management.

Obesity and Insulin Resistance: Associations with Chronic Inflammation, Genetic and Epigenetic Factors.

BACKGROUND: Obesity is known to be a multifactorial disease. In its pathogenesis, different factors such as chronic inflammation, oxidative stress, insulin resistance, genetic factors, environmental effects, vegetative disturbance, and unbalanced nutrition play a significant role. METHODOLOGY: This study describes the association of obesity and insulin resistance with chronic inflammation, genetic, and epigenetic factors. Previous literature has been reviewed to explain the relation of obesity with those factors involved in chronic low-grade inflammation and insulin. RESULTS: Obesity is associated with a decrease in ghrelin secretion, elevated plasma leptin levels, oxidative stress, increased macrophage phagocytic activity, and the induction of proinflammatory synthesis of cytokines and interferon-gamma. Obesity is linked to decreased levels of cytochrome P450 (CYP) enzymes and impaired detoxification processes. Deficiency of vitamins and minerals can also play a significant role in the development of oxidative stress and chronic inflammation in obesity. There is evidence of associations between a genetic predisposition to obesity in children with elevated levels of certain miRNAs. CONCLUSION: The purpose of the present review is an analysis of the multiple factors associated with obesity.

Relationship between Gut Microbiota, Gut Hyperpermeability and Obesity.

Intestinal hyperpermeability is a complex metabolic process mediated by different pathways in close relation to the gut microbiota. Previous studies suggested that the gut microbiota is involved in different metabolic regulations, and its imbalance is associated with several metabolic diseases, including obesity. It is well known that intestinal hyperpermeability is associated with dysbiosis, and the combination of these two conditions can lead to an increase in the level of low-grade inflammation in obese patients due to an increase in pro-inflammatory cytokine levels. Inflammatory bowel syndrome often accompanies this condition causing an alteration of the intestinal mucosa and thus reinforcing the dysbiosis and gut hyperpermeability. The onset of metabolic disorders depends on violations of the integrity of the intestinal barrier as a result of increased intestinal permeability. Chronic inflammation due to endotoxemia is responsible for the development of obesity. Metabolic disorders are associated with dysregulation of the microbiota-gut-brain axis and with an altered composition of gut flora. In this review, we will discuss the mechanisms that illustrate the relationship between hyperpermeability, the composition of the gut microbiota, and obesity.

Iron Deficiency in Obesity and after Bariatric Surgery.

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass-RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects' iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation.

Follow-up after bariatric surgery: A review.

Bariatric surgery is becoming increasingly popular in the treatment of severely obese patients who failed to lose weight with the help of non-surgical interventions. Such patients are at increased risk for premature death, type 2 diabetes, high blood pressure, gallstones, coronary heart disease, dyslipidemia, some cancers, anxiety, depression, and degenerative joint disorders. Although bariatric surgery appears to be the most effective and durable treatment option for obesity, it is associated with a number of surgical and medical complications. These include a range of conditions, of which dumping syndrome and malnutrition due to malabsorption of vitamins and minerals are the most common. To achieve better surgery outcomes, a number of postsurgical strategies must be considered. The aim of this review was to describe possible complications, ailments, and important moments in the follow-up after bariatric surgery. Adequate lifelong monitoring is crucial for the achievement of long-lasting goals and reduction of post-bariatric complications.

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS. Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS. This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.