Abstract Metabolic syndrome (MetS) and ulcerative colitis (UC) are widespread health conditions characterized by chronic, low-grade inflammation. Galectin-1 (Gal-1), an immunomodulatory peptide mainly secreted from adipose tissue, could potentially play a crucial role in mitigating these conditions. This cross-sectional study explores the involvement of Gal-1 in MetS and UC within a cohort of 75 patients, newly diagnosed with UC. The MetS subgroup displayed increased fecal Gal-1 levels compared to those without MetS. Furthermore, Gal-1 showed predominance over pro-inflammatory cytokines, including TNF-α, IL-6, and IL-17, in these subjects. These findings emphasize the potential involvement of Gal-1 in the pathophysiology of UC and MetS, presenting it as a promising diagnostic biomarker and therapeutic target for these conditions.

Abstract In breast cancer therapy, as the leading cause of death in women, besides chemo-radiotherapy, immunotherapy has been increasingly used. PD-1/PD-L1 axis blockade primarily acts on T lymphocytes, the main effectors of acquired immune response. NK cells, which are part of the innate immune response, also play a role in the anti-tumor response through the blockade of this signaling pathway. The study was conducted to examine the effects of anti-PD-1 therapy on NK and T cells in mouse breast cancer. Female BALB/c mice were used, divided into two groups, one with induced breast cancer and one treated with anti-PD-1 antibody. Breast cancer cell line was used to induce the cancer, and the anti-PD-1 antibody was applied intraperitoneally. Cell populations in spleen and tumor microenvironment were examined using flow cytometry. Data were statistically analyzed using SPSS. The percentage of NK cells expressing FasL, NKG2D, and IFN-γ is significantly higher in spleen and tumor-infiltrating NK cells upon anti-PD-1 therapy, while the expression of inhibitory markers Foxp3 and IL-10 in regulatory NK cells is significantly lower. The percentage of T lymphocytes expressing CD107a and IL-17 is significantly higher in the spleen, while a higher number of T lymphocytes expressing CD69 is present in the tumor microenvironment. The study suggests that anti-PD-1 therapy can activate NK and T cells, and improve anti-tumor immune response in breast cancer. Further research is needed to understand the interplay between these cells during PD-1 blockage.

Abstract Periodontal disease is inflammatory pathological conditions in the gingiva and dental support structures that usually results in extracellular matrix and connective tissue destruction. During periodontitis, inflammatory cells facilitate collagen and connective tissue loss, affects the number and activity of fibroblasts and its production of local collagen networks. Aim of this study was to evaluate collagen density and accumulation of collagen producing fibroblast and macrophages in affected tissue of periodontal disease. Histological and immunohistochemical analyzes were performed on paraffin embedded tissue sections of gingival biopsies, obtained from 30 patients with diagnosis of periodontal disease and 10 healthy donors. Tissue sections of gingival of patients with periodontal disease had significantly decreased collagen volume density and visible fragmentation and lysis of the collagen fibers, decreased number of fibroblasts, accompanied with increased accumulation of macrophages. Presented data implicate that macrophages accumulation may be the cause of enzyme mediated collagen destruction

Background: Pleural disorders in novel coronavirus disease 2019 (COVID-19), responsible for the deaths of more than 6.7 million people worldwide, are relatively uncommon and underappreciated findings. The severity of the pleural disease in these patients correlates with the treatment outcome and overall prognosis. Objective: We aim to review our experience with treatment modalities and prognosis in 45 patients with COVID-19, who were treated at our Clinic between April 2020 and October 2021. Methods: We conducted a retrospective, single-center, cross-sectional study. Demographic data, the type of thoracosurgical intervention(s), and treatment outcome for 45 patients included in this study were recorded for every patient. We analyzed the type and number of treatment modalities according to the pleural disorder, and the outcome of the treatment. Results: Pneumothorax was the most common COVID-19-related pleural disorder, followed by the pleural effusion. Tube thoracostomy was the mainstay of treatment, performed in 84.4% of patients with unilateral pleural complications. In total, 20% of our patients were on mechanical ventilation, and all of them had a fatal outcome. We found statistical significance in comparison to the percentage of fatal outcomes between patients treated with and without mechanical ventilation (p=0.000). Conclusion: COVID-19-related pleural disorders are prognostic markers of disease progression. Mechanically ventilated patients who require tube thoracostomy have an unfavorable prognosis.

Introduction. Acute appendicitis is the most common cause of the acute abdomen. Based on the idea that appendicitis is a progressive disease eventually leading to perforation, removal of the appendix is the gold standard of treatment. Material and Methods. The objective of the study is to determine if there is any difference in the occurrence of postoperative complications, and if hospitalization differs depending on the appendicitis surgery method used with the patients. A retrospective analysis was made using the data from the hospital sample of patients admitted to the University Hospital in Foca in the period from January 2019 to December 2021. Results. In the period that was retrospectively analyzed, 107 patients diagnosed with acute appendicitis were operated on. There was no statistically significant difference between the treated groups in relation to the degree of appendicitis, type and duration of symptoms, diagnostic procedures and the time that had elapsed from admission to surgery. The Alverado Score in the probable appendicitis group was 41.1%. The most common symptoms were palpation sensitivity in the inguinal region (84.1%), and pain in the right lower quadrant (69.1%), intraoperative findings of uncomplicated appendicitis 58%, and 25.2% intraoperative findings inconsistent with the pathohistological ones. Conclusion. Acute appendicitis is one of the most common emergency surgical conditions, which requires surgical intervention if not treated in time, and causes life-threatening consequences. Surgical treatment with selected techniques for faster establishment of the gastrointestinal tract function, shorter stay in the hospital, faster recovery and return to daily activities.

Introduction: Pleural complications in coronavirus disease 2019 (COVID-19) are relatively uncommon findings. Pleural involvement in these patients may directly correlate to disease severity and overall prognosis. We aimed to review clinical features and treatment approaches for pleural complications (accumulation of fluid/air inside the pleural cavity) in 45 patients with COVID-19, who were treated at our institution between April 2020 and October 2021. Methods: Our study was designed as single-center, observational, cross-sectional study of 45 patients with COVID-19 and at least one radiologically verified pleural complication. Demographic data, radiological findings, as well as type and number of thoracosurgical intervention(s) were recorded for every patient. We included patients of both genders and various age groups, with positive RT-PCR assay for COVID-19 and radiologic features of pleural complications, which required single or multiple thoracosurgical interventions. Results: Unilateral pleural complications were more common, right-sided pleural complications were found in 44.4% of patients. Right-sided pneumothorax was reported in 26.7% of patients. Almost one-fourth of our patients required invasive mechanical ventilation. Tube thoracostomy was performed in 84.4% of patients with unilateral pleural complications. A fatal outcome was most common in patients over 60 years old. More than half of patients with bilateral pleural complications died in our study. Conclusions: Pleural complications are a rare finding in patients with COVID-19. Tube thoracostomy is the mainstay of treatment for most symptomatic patients with pleural complications. Future research should be directed toward investigation of long-term pulmonary consequences in patients with COVID-19.

Abstract Some recent findings suggest that metformin, an oral antidiabetic drug, may have antitumor properties. Studies have shown that metformin can alter cell metabolism, both tumor and immune cells, which can greatly influence disease outcome. In this review, we discuss the potential mechanisms in which metformin can directly induce apoptosis of tumor cells as well as mechanisms in which metformin can elicit or enhance antitumor immune response.

Abstract Surgical treatment and formation of a stoma can be lifesaving for colorectal cancer patients. However, the quality of life is often impaired in patients with stoma. The goal of this study is to determine the quality of life of patients with stoma and cancer, and the relationship between the quality of life and characteristics of these patients. The study was conducted from 2018 to 2020 and included a total of 64 patients of both sexes with colorectal cancer and temporary or permanent stoma. The European Organization for Research and Treatment of Cancer with Quality of Life Questionnaire (EORTC QLQC29-30) and the anonymous WHO Quality of Life Questionnaire SF-36 were used for self-assessment of quality of life. Our study included 39 (61.0%) men and 25 (39.0%) women. 24 patients (37.5%) had colostomy, 14 patients (21.9%) had ileostomy, and 26 patients (40.6%) underwent surgery for resection of colorectal cancer without stoma. A significant number of women were in the group of patients with a permanent stoma (p = 0.01). There was no statistically significant difference in the assessment of general health (p = 0.680) and quality of life (p = 0.721) during the past month in relation to gender. Patients without a stoma rated their general health better compared to those with stoma and the difference reached statistical significance (p = 0.035). There was no statistically significant difference in the assessment of quality of life between the group of patients with stoma and without stoma, as well as between the patients of different age groups. Patients with stoma rated their general health as worse, but not their quality of life.

Introduction. Visual-motor integration (VMI) is defined as the degree to which visual perception (VP) and finger-hand movements are well coordinated. The VMI consists of two components: VP and motor coordination (MC). The main goal of our research was to determine whether there are differences in age and gender categories in VMI, VP and MC scores, as well as whether there is a correlation between VMI and school success of younger school-aged children. Methods. Out of 103 student respondents, 52 were female (50.5%), aged 6 to 11 years (8.05 ± 1.44 years), divided into two groups according to age: 6-8 years (first, second and third grade) and 9-11 years (fourth to fifth grade). Data on the level of VMI were obtained by applying the following tests: Beery-Buktenica Developmental Test of VMI, VP test and MC test. Results. In the older age group of subjects, a significant difference was observed in the mean values of the score on the VMI (12.67 ± 1.92), VP (23.69 ± 3.21) and MC (24.34 ± 3.23) tests comparing to the younger group of subjects (9.98 ± 2.12; 20.80 ± 3.2; 19.65 ± 3.82) (p < 0.001), while the difference in the mean values of scores in relation to gender was not observed. A significant, positive and strong correlation was observed between the scores on the VMI, VP and MC test with the success of second to fifth grade students (p < 0.050). Conclusion. Given such a strong correlation between VMI and the success of younger students, we conclude that it is important that VMI disabilities are identified in time, so that these students can be referred for further assessment and receive the necessary support.

Speech is a way of communication formed by rhythmic units of syllables, words and sentences, and as such is inherent in man, the only being whose organs and psyche are trained for this process. Delayed speech is defined as a phenomenon in which a child does not start speaking on time, or there are errors in the speech pattern that are not appropriate in relation to a given age. It is known that significant risk factors for the development of delayed speech in preschool children are physical, and most often social and emotional in nature. For the normal development of speech, it is necessary that the child is in a human environment, and therefore the circle of people with whom children come into contact should always be expanded. The aim of this study is to review the existing literature on studies examining the impact of social isolation during the COVID-19 pandemic on preschool children, as well as the speech and language development in preschool children. The recent pandemic of corona virus infection (COVID-19) has led to a state of emergency, quarantine, closure of public institutions, and preschools, kindergartens and schools in 172 countries. These epidemiological measures have led to social isolation and the need for children to learn from home, which has manifested itself in the emergence of difficulties in the development of speech and language. Research has shown that during the pandemic, children spent significantly more time watching television and computer screens than before pandemic, and less in play and physical activity.

Objective. Diabetes mellitus and arterial hypertension are chronic, mass non-communicable diseases that are global health problems with characteristics of epidemiology where complications of these diseases are the common reason for visual handicap and disability in the work productive population. The primary aim of this paper was to analyze the frequency of visual dysfunction, and behavioral habits in diabetic and hypertensive patients and the second aim was to analyze the occurrence of work disability in patients with these diseases. Methods. The research is a cross-sectional study made in two Health Centers in the City of Eastern Sarajevo in a period of July 2018 to July 2019 (12 months). 192 patients with diabetes and 100 patients with hypertension were selected using the random sampling method. A special questionnaire was created for this purpose, and statistic analysis was made by SPSS (IBM, Chicago version 19). Statistical significance was tested with ch2 test. Results. Diabetic patients significantly have more visual disturbances than hypertensive patients according to subjective assessment (ch2=14.21, p< 0.001). Worsening of visual acuity is presented more in diabetic than in hypertensive patients (ch2=6.17, p<0.001). There is no significant difference in behavioral habits between diabetic and hypertensive patients for smoking (ch2=1.778, p=0.411) and alcohol consumption.( ch2=2.158, p=0.142). Patients with diabetes are more frequent in the status of work disability than those with hypertension (ch2=13,46, p<0,001). Conclusion. Mass non-communicable diseases are a common cause of visual dysfunction. Diabetes mellitus is the main reason for visual disability in the adult population from the region of Eastern Sarajevo. Behavioral habits like smoking and alcohol consumption have a serious impact on the prognosis of those patients.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity. Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed. Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1β, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1β, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1β, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1β, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven. Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

Background Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients. Methods Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia). Results CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients. Conclusions Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

Background/Aim. Reactive thrombocytosis, as a paraneoplastic syndrome, is often observed in cancer patients. A variety of tumor-related humoral factors and cytokines con-tribute to tumor-stimulated thrombopoiesis. However, the exact role of these cytokines in the pathogenesis of thrombocytosis remains unclear. The aim of this study was to analyze systemic values of cytokines and clinical-pathological characteristics in colorectal carcinoma (CRC) patients with and without thrombocytosis. Methods. Fifty nine CRC patients were involved in this study and divided into two groups according to the number of platelets. We recorded and analyzed the data about: age, gender, size of the cancer, localization, metastasis, vascular or lymph vessel invasion, nuclear grade, histological differentiation rate, tumor, nodus, metastasis (TNM) stage and concentration of cytokines [interleukin (IL)-1, IL-33, IL-12, IL-17 and interferon (IFN)-?] in both groups. Results. CRC patients with thrombocytosis had significantly higher nuclear grade of the cancer (p = 0.002); higher percentage of detectable metastatic lesions in the liver (p = 0.002), lung (p = 0.001), peritoneal carcinomatosis (p = 0.001), detectable invasion of blood (p = 0.012) and lymph vessels (p = 0.010). Concentrations of tumor markers [alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9)] and se-rum values of IL-1 a nd I L-33 were significantly higher in CRC patients with thrombocytosis. IL-1/IL-12 (p = 0.016), IL-1/IFN-? (p = 0.007), IL-1/IL-17 (p = 0.006), IL-33/IL- 12 (p = 0.001), IL-33/IFN-? (p = 0.001), IL-33/IL-17 (p = 0.002), and IL-33/IL-1 (p = 0.006) ratios were significantly higher in CRC patients with thrombocytosis in comparison to CRC patients without thrombocytosis. Analysis of Receiver Operating Characteristic (ROC) curves showed that values of IL-1 [area under curve (AUC) = 0.718; 95% confidence interval (CI): 0.567?0.868; sensitivity 69.2%, specificity 62.9%] and IL-33 (AUC = 0.763; 95% CI: 0.614? 0.911; sensitivity 84.6%, specificity 65.7%)], could be serve as possible markers for paraneoplastic thrombocytosis in CRC patients. Conclusion. IL-1 a nd I L-33 significantly correlated to high thrombocyte number in patients with more aggressive CRC.