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Mateusz Zarzecki,1 Iwona Obuchowska,1 Andrzej Ustymowicz,2 Joanna Konopińska1 1Department of Ophthalmology, Medical University of Bialystok, Bialystok, Poland; 2Department of Radiology, Medical University of Bialystok, Bialystok, PolandCorrespondence: Joanna Konopińska, Department of Ophthalmology, Medical University of Bialystok, Bialystok, Poland, Tel +48-857468372 ; +48-600471666, Fax +48-857468604, Email joannakonopinska@o2.plAbstract: Glaucoma is a common cause of blindness worldwide. This disease is characterised by increased intraocular pressure (IOP) and the concomitant disruption of ocular haemodynamic. Several studies have demonstrated that trabeculectomy is associated with changes in extraocular blood flow. In this study, we reviewed the available evidence on the use of colour Doppler imaging to evaluate and manage patients with open-angle glaucoma. We present the detailed anatomy of ocular blood flow to provide a background for the research findings. We also discuss the physiological foundations of ocular blood flow and detailed flow characteristics of specific extraocular vessels. Finally, we reviewed published studies that analysed the effects of glaucoma surgery on the blood flow parameters of the eye.Keywords: glaucoma, colour doppler, trabeculectomy, deep sclerectomy

Abstract Colorectal cancer (CRC) affects more than 1,000,000 people worldwide each year. Recently, the number of young patients with early-onset colorectal cancer has increased, and right-sided colorectal cancer is still often diagnosed only in advanced stages. The TNM classification is not perfect for CRC staging. This study aimed to perform, for the first time, simultaneous analysis of tumor-infiltrating immune cell density, presence of lymphoid follicles, and budding status in CRC tissue. Intraoperative samples of neoplastic tissue were collected from 195 consecutive patients who were admitted to the surgical ward for elective colorectal surgery. Histological parameters were assessed in the tissue samples: tumor budding foci, poorly differentiated clusters and areas of poorly differentiated components. Tumor-infiltrating immune cells (tumor-associated neutrophils and tumor-infiltrating lymphocytes) were detected in five randomly chosen, areas at the tumor center and at the invasive front. Additionally, the presence of lymphoid follicles in CRC tissue was assessed. Tumor budding parameters were positively correlated with colorectal cancer advancement or histologic (mucinous) type of CRC. The number of poorly differentiated clusters was higher in younger patients. Lower densities of CD3 and CD4 lymphocytes were seen in CRC with a greater depth of tumor invasion. Lower densities of CD3 and CD8 lymphocytes were found in CRC with metastases to the surrounding lymph nodes. The lower density of CD8 lymphocytes was observed in CRC with distant metastases. Lower densities of tumor-associated neutrophils and tumor-infiltrating lymphocytes (CD3 and CD8) were revealed in CRC without lymphoid follicles. The number of lymphoid follicles was higher in patients with less advanced CRCs. Three histopathology markers, such as high tumor budding, scanty lymphocyte infiltration, and the poverty of lymphoid follicles, complement each other, appear to be reliable indicators of colorectal cancer progression, and could be useful in everyday medical practice, but their widespread use requires further research. We propose to take into account these markers, in the assessment of colorectal cancer advancement, in addition to the TNM classification.

Justyna Dorf,1 Konrad Zaręba,2 Joanna Matowicka-Karna,1 Anna Pryczynicz,3 Katarzyna Guzińska-Ustymowicz,3 Anna Zalewska,4 Mateusz Maciejczyk5 1Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland; 2 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bialystok, Poland; 3Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland; 4Independent Laboratory of Experimental Dentistry, Medical University of Bialystok, Bialystok, Poland; 5Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, PolandCorrespondence: Justyna Dorf, Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15a St, Białystok, 15-269, Poland, Tel +48 85 8 31 87 16, Email justyna.dorf@umb.edu.plPurpose: Overproduction of reactive nitrogen species (RNS) causes the nitrosative stress, which plays a vital role in the development of metabolic, inflammatory, and cancerous diseases. However, the role of nitrosative and carbonyl stress in the biology of colorectal cancer (CRC) is still not well understood. Therefore, this study evaluated nitrosative stress, protein and DNA oxidation/glycoxidation, and pro- and anti-inflammatory cytokines in CRC patients compared with healthy controls.Patients and Methods: Fifty-five CRC patients (21 women, 34 men) and 55 healthy controls matched for sex and age were included in the experiment. Nitrosative stress parameters (nitric oxide (NO), peroxynitrite, S-nitrosothiols, and nitrotyrosine), protein oxidation (total thiols) and glycoxidation products (kynurenine N-formylkynurenine, dityrosine, Amadori products, and amyloid), and DNA damage markers (8-hydroxydeoxyguanosine (8-OHdG)), as well as levels of pro- and anti-inflammatory cytokines, were measured in serum or plasma samples.Results: The levels of NO, peroxynitrite, S-nitrosothiols, nitrotyrosine, total thiols, kynurenine, N-formylkynurenine, dityrosine, Amadori product, amyloid, and 8-OHdG, as well as IL1α, IL1β, IL6, IL10, and TNF-α, were significantly higher in CRC patients than in controls. Oxidation and glycoxidation products were positively correlated with pro-inflammatory (IL1α, IL1β, IL6, TNFα) and anti-inflammatory cytokines (IL10), indicating that redox damages may promote inflammation in CRC patients. Many redox biomarkers differentiate patients with CRC from healthy individuals with high sensitivity and specificity.Conclusion: Correlations of chosen oxidative products with pro-inflammatory (IL1α, IL1β, IL6, TNFα) and anti-inflammatory cytokines (IL10) suggest that redox damages may promote inflammation in CRC patients. Thus, our research is the first point for further clinical trials focusing on the evaluation of the diagnostic utility of nitrosative stress biomarkers in a larger group of CRC patients.Graphical Abstract: Keywords: nitrosative stress, cytokines, inflammation, colorectal cancer

Background/Objectives: Glaucomatous neuropathy, a progressive deterioration of retinal ganglion cells, is the leading cause of irreversible blindness worldwide. While elevated intraocular pressure (IOP) is a well-established modifiable risk factor, increasing attention is being directed towards IOP-independent factors, such as vascular alterations. Color Doppler imaging (CDI) is a prominent technique for investigating blood flow parameters in extraocular vessels. This prospective, nonrandomized clinical trial aimed to assess the impact of ab externo canaloplasty on ocular blood flow parameters in patients with primary open-angle glaucoma (POAG) at a three-month follow-up. Methods: Twenty-five eyes of twenty-five patients with early or moderate POAG underwent canaloplasty with simultaneous cataract removal. CDI was used to measure peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCAs) before and after surgery. Results: The results showed a significant reduction in IOP and improvement in mean deviation at three months post-surgery. Best corrected visual acuity and retinal nerve fiber layer thickness significantly increased at each postoperative control visit. However, no significant changes were observed in PSV, EDV, and RI in the studied vessels. Conclusions: In conclusion, while canaloplasty effectively reduced IOP and medication burden, it did not significantly improve blood flow parameters in vessels supplying the optic nerve at three months post-surgery. Careful patient selection considering glaucoma severity and vascular risk factors is crucial when choosing between canaloplasty and more invasive procedures like trabeculectomy. Further larger studies are needed to comprehensively analyze this issue. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer (PCa) is the second most common type of cancer diagnosed in men globally. Among PCa patients, approximately 65.8% present with metastases localized most commonly in vertebrae, long bones, local lymph nodes, lungs, and liver. Although a rare occurrence, PCa metastasis can also be found in the head and neck region including supraclavicular lymph nodes and cranial bones. Case Presentation: A 61-year-old man was diagnosed with prostate cancer, after presenting with increased PSA level and mild dysuric symptoms. After initial successful treatment, increases in PSA level led to discovery of rare asymptomatic metastases to the left cervical lymph nodes and sphenoid bone using an 18-F-FDG PET/CT scan. Conclusion: Diagnosis of head and neck prostate cancer metastases is a very rare finding that can be easily overlooked. PET/CT scan using tumorspecific agents proves to be a useful tool for the detection of early and unusual PCa metastases. [ABSTRACT FROM AUTHOR]

Introduction: Deep infiltrating endometriosis (DIE) can be diagnosed if endometrial-like tissue invades visceral organs deeper than 5 mm. DIE is mostly found in the rectum and can be misdiagnosed with colorectal cancer. Case presentation: A 43-year-old woman came to our clinic with suspected colorectal cancer, complaining about alternating diarrhea and constipation, tenesmus, and abdominal bloating. Colonoscopy and imaging test revealed around 3 cm lesion, and histopathology of the biopsy revealed low-grade dysplasia. Partial resection of the intestine with lesion was performed and the final diagnosis confirmed deep rectal endometriosis. Conclusion: Histopathological diagnosis can be difficult because of the possible coexistence of endometriosis and atypical glandular components in the intestines. DIE should be taken into consideration as one of the probable diagnoses in patients with a mass in the rectum. [ABSTRACT FROM AUTHOR]

Justyna Zi&nacute;czuk,1 Konrad Zar&eogon;ba,2 Joanna Kami&nacute;ska,1 Olga Martyna Koper-Lenkiewicz,1 Violetta Dymicka-Piekarska,1 Anna Pryczynicz,3 Katarzyna Guzi&nacute;ska-Ustymowicz,3 Bogu&lstrok;aw K&eogon;dra,2 Joanna Matowicka-Karna,1 Ma&lstrok;gorzata &Zdot;endzian-Piotrowska,4 Anna Zalewska,5 Mateusz Maciejczyk4 1Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Bia&lstrok;ystok, 15-269, Poland; 2 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bia&lstrok;ystok, 15-276, Poland; 3Department of General Pathomorphology, Medical University of Bialystok, Bia&lstrok;ystok, 15-269, Poland; 4Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bia&lstrok;ystok, 15-222, Poland; 5Independent Laboratory of Experimental Dentistry, Medical University of Bialystok, Bia&lstrok;ystok, 15-276, PolandCorrespondence: Justyna Zi&nacute;czukDepartment of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15a St., Bia&lstrok;ystok, 15-269, PolandTel +48 85 8 31 87 16Email justyna.zinczuk@umb.edu.plMateusz MaciejczykDepartment of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Mickiewicza 2c St., Bia&lstrok;ystok, 15-222, PolandTel +48 85 748 55 85Email mat.maciejczyk@gmail.comPurpose: In this study, we evaluated the total antioxidant capacity, nitrosative stress, and protein/DNA oxidation and glycoxidation products in patients with colorectal cancer regarding histopathological parameters associated with the tumour microenvironment, such as inflammatory infiltration and tumour budding and compare all determined parameters between tumours located in the right and left side of the colon and normal mucosa.Patients and Methods: Ferric reducing antioxidant power (FRAP), nitrosative stress (myeloperoxidase (MPO), nitrogen oxide (NO), peroxynitrite, and nitrotyrosine), protein oxidation products (protein carbonyls (PC), total thiols, and ischemia modified albumin (IMA)), protein glycooxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, Amadori product, advanced glycation end products (AGE)) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in homogenates from normal and cancerous tissue of 30 patients with colorectal cancer.Results: Levels of FRAP (p=0.0009), IMA (p=0.0002), kynurenine (p< 0.0001), N-formylkynurenine (p< 0.0001), dityrosine (p< 0.0001), Amadori products (p=0.0024), AGE (p< 0.0001), MPO (p< 0.0001), NO (p< 0.0001) and nitrotyrosine (p=0.0011) were increased, whereas PC (p=0.0004), tryptophan (p< 0.0001), 8-OHdG (p< 0.0001) and peroxynitrite (p=0.0003) were decreased in the left-side tumour compared to the right-side tumour and normal mucosa.Conclusion: Our results showed that colorectal cancer is related with disturbances in antioxidant defense and increased oxidative and nitrosative damages to proteins and DNA. These parameters may be useful for evaluation the progression and differentiation of the tumour location. We also demonstrated that redox indicators may depend on the histological type of the tumour and may influence tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion, inflammatory infiltration, and tumour budding, which are part of the tumour microenvironment.Keywords: oxidative stress, nitrosative stress, redox biomarkers, colorectal cancer

There is growing evidence that the body's energy expenditures constitute a significant risk factor for the development of most deadly diseases, including cancer. Our aim was to investigate the impact of basal metabolic rate (BMR) on the growth and progression of colorectal cancer (CRC). To do so, we used a unique model consisting of three lines of laboratory mice (Mus musculus) artificially selected for high (HBMR) and low (LBMR) basal metabolic rate and randomly bred individuals (non-selected, NSBMR). The experimental individuals were implanted with human colorectal cancer cells DLD-1. The variation in BMR between the lines allowed for testing the impact of whole-body metabolism on oxidative and antioxidant parameters in the liver throughout the cancerogenesis process. We investigated the dependence between metabolic values, reactive oxygen species (ROS) levels, and Kelch-like ECH-associated protein 1-based E3 ligase complexes (Keap1) gene activity in these animals. We found that the HBMR strain had a higher concentration of oxidative enzymes compared to the LBMR and NSBMR. Furthermore, the growth rate of CRC tumors was associated with alterations in the levels of oxidative stress enzymes and Keap1 expression in animals with a high metabolic rate. Our results indicate that a faster growth and development of CRC line DLD-1 is associated with enzymatic redox imbalance in animals with a high BMR. [ABSTRACT FROM AUTHOR]

Phloroglucinol (PHG), an analgesic and spasmolytic drug, shows promise in preventing high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG's efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG's full therapeutic potential. [ABSTRACT FROM AUTHOR]

Abstract Background Explanation of the pathogenesis and treatment of autism spectrum disorders (ASD) is one of the most significant challenges for scientists today. It is believed that a major pathogenetic factor of this condition is epigenetic changes caused by environmental factors, including toxic metals (cadmium (Cd), lead (Pb), mercury (Hg), aluminium (Al), and arsenic (As)). The nervous system may also be affected by deficiencies of both micro- and macroelements (e.g. calcium (Ca), zinc (Zn)). The aim of the study was to analyze the concentrations of Pb, As, and Ca in the hair of children with ASD and a control group. Methods The materials for the study comprised hair samples collected from 30 children diagnosed with ASD (case group) and 30 children randomly selected from the general population of Bialystok and surrounding region (control group). Concentrations of Pb, As, and Ca were tested with electron microscopy scanning method. Next, the content of the analyzed elements in the hair was assessed as well as their impact on autism development in the children and the mutual interactions between them. The obtained results were statistically analyzed with Statistica PL 12.5., using the Mann-Whitney U test, and Spearman correlation coefficient. Results Mean Ca level in the hair of the case group was lower than the mean level of this element in the control group. Mean As and Pb concentration in the hair of children with ASD was statistically significantly higher than the mean concentration of this element in the hair of children without neurological disorders. Statistically insignificant weak positive correlations between Ca and As content and negative between Ca and Pb in the hair of children from the case group were noted. Also, statistically significant mean positive correlations between Pb and As were observed. Conclusions In this small study, according to the observations, children diagnosed with ASD suffer from Ca deficiency and toxic metal overload (As and Pb). These abnormalities may play the main role, as an environmental factor, in the pathogenesis of the analyzed disorder.

Prostate cancer (PCa) is commonly associated with old age, but it can develop in patients under 40 years old. Furthermore, early occurrence of this cancer is associated with higher mortality and worse prognosis. Case presentation: A 32-year-old patient presented with lower back pain. CT, and MR Imaging tests revealed multiple enlarged lymph nodes in the pelvis and sacral bone remodeling. Later Histopathological and immunohistochemical examination of the lymph nodes revealed granular metastases, suspected of Prostate cancer. After a biopsy of the prostate and additional imaging tests, diagnosis of advanced adenocarcinoma prostate was confirmed. As the lesions were no longer operable, the patient received palliative treatment. Conclusion: Young patients may also suffer from Prostate cancer, so they should not be excluded from the differential diagnosis. Moreover, disseminated cancer lesions may manifest themselves with very non-specific symptoms. [ABSTRACT FROM AUTHOR]

Patients suffering from chronic kidney disease (CKD) are at a 20-fold higher risk of dying due to cardiovascular diseases (CVDs), primarily thrombosis following vascular injury. CKD is connected with retention of uremic toxins, especially indoxyl sulfate (IS), which are currently considered as a non-classical CKD-specific risk factor for CVDs. The present study aimed to examine the effect of chronic exposure to IS on the hemostatic system and arterial thrombosis in a model without greater interferences from the uremic milieu consisting of additional uremic toxins. Forty-eight male Wistar Crl:WI (cmdb) rats were divided into three groups: one control group and two experimental groups, which were exposed to 100 or 200 mg/kg of b.w./day of IS in drinking water for a period of 28 days. The control group received water without IS. At the end of the experiment, the induction of arterial thrombosis was performed. We investigated the impact of IS on thrombosis incidence, kinetics and strength of clot formation, platelet activity, aortic contents of sirtuin (SIRT) 1 and sirtuin 3 (SIRT3), hemostatic system, cardiorespiratory parameters, biochemistry of plasma and urine as well as histology of the thrombus, kidney, and liver. Obtained data revealed that chronic exposure to IS promotes arterial thrombosis via increased levels of complex tissue factor/factor VII, plasminogen activator inhibitor-1 (PAI-1), platelet activation, as well as decreased aortic levels of SIRT1 and SIRT3. Therefore, we hypothesize that IS enhances primary hemostasis leading to augmented formation of platelet plug with increased amounts of fibrin and affects secondary hemostasis through the influence on plasma coagulation and fibrinolysis factors, which results in the increased kinetics and strength of clot formation. The findings described may contribute to a better understanding of the mechanisms leading to increased thrombotic events in patients with CKD with elevated levels of IS.

[b][/b][b]Introduction. [/b]The most prevalent inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn’s disease (CD). Immune processes play a vital role in the etiopathogenesis of these conditions, involving both cellular and humoral response mechanisms. The aim of this study was to quantify CD40- and CD80-positive cells in the biopsy specimens of large intestinal mucosa from children with IBD. [b]Materials and method. [/b]The study comprised 38 children aged between 3–17 years (mean 11.5±3.7 years) – 20 boys (52.6 %) and 18 girls (47.4%). Eighteen patients were diagnosed with UC on the basis of clinical manifestation, endoscopic and histopathological findings. Mean age of this subgroup was 11.55±4.07 years. A group of 10 children (mean age 12.30±2.83) diagnosed with CD was also included. The control group comprised 10 IBD-free children (mean age 10.28±4.07 years). The surface expressions of CD40 and CD80 were analyzed in large intestine mucosa biopsy specimens, fixed in formaldehyde, embedded in paraffin, and cut with a microtome into 4 µm slices. [b]Results. [/b]The number of CD40- and CD80-positive cells in the large intestinal mucosa of children with Crohn’s disease and ulcerative colitis was significantly higher than in the controls. The highest number of CD40+ and CD80+ cells was observed in the caecal mucosal membrane of Crohn’s disease patients and in the rectal mucosa of individuals with ulcerative colitis. [b]Conclusion.[/b] IBD is characterized by elevated, segment-specific, expression of CD40 and CD80.

Aim: Ultrasound assessment of morphological parameters of the internal jugular veins and vertebral veins in healthy individuals as well as their dependence on the patient’s position. Material: The examinations were conducted in 185 healthy individuals (101 females and 84 males) aged 18–89. Ultrasound examinations were conducted with the use of a linear probe with the frequency of 5–9 MHz in the supine (0°) and sitting position (90°). Results: In 154 cases (83.2%) on the left side and in 150 cases (81.1%) on the right side, the jugular veins were completely closed in the sitting position. In 31 cases (16.8%) on the left side and in 35 cases (18.9%) on the right side, they were merely narrowed. By contrast with the jugular veins, the cross-sectional area (CSA) of the vertebral veins was greater in the sitting position than in the supine position in a statistically signifi cant way. The CSA values of the jugular veins in the supine position ranged from 0 cm2 to 4.3 cm2 . There were no statistically signifi cant differences in the CSA between men and women. The cross-sectional area of the right jugular vein in the supine position was greater in a statistically signifi cant way than that of the left jugular vein. In this study population, the ratio of the cross-sectional areas of the jugular veins on both sides amounted to 8.5:1. Conclusions: The width of the jugular and vertebral veins signifi cantly varies depending on the patient’s position. The range of the CSA values for the jugular veins is broad, which should be taken into account when interpreting imaging fi ndings. The internal jugular veins can show considerable asymmetry.