Expression Pattern of PDE4B, PDE4D, and SFRP5 Markers in Colorectal Cancer.

Background and Objectives: Colorectal cancer (CRC) is the most frequently diagnosed malignant disease of the gastrointestinal system, and new diagnostic and prognostic markers are needed to elucidate the complete tumor profile. Materials and Methods: We used CRC tumor tissues (Dukes' A-D) and adjacent noncancerous tissues of 43 patients. Immunohistochemistry was used to examine the expression of phosphodiesterase 4B (PDE4B), phosphodiesterase 4D (PDE4D), and secreted frizzled related protein 5 (SFRP5) markers. We also analyzed the expression levels of PDE4B, PDE4D, and SFRP5 in CRC tissues compared to control tissues using RNA-sequencing data from the UCSC Xena browser. Results: In CRC stages, the distribution of PDE4B-positive cells varied, with differing percentages between epithelium and lamina propria. Statistically significant differences were found in the number of PDE4B-positive epithelial cells between healthy controls and all CRC stages, as well as between different CRC stages. Similarly, significant differences were observed in the number of PDE4B-positive cells in the lamina propria between healthy controls and all CRC stages, as well as between different CRC stages. CRC stage Dukes' C exhibited a significantly higher number of PDE4B-positive cells in the lamina propria compared to CRC stage Dukes' B. Significant differences were noted in the number of PDE4D-positive epithelial cells between healthy controls and CRC stages Dukes' A, B, and D, as well as between CRC stage Dukes' C and stages A, B, and D. CRC stage Dukes' A had significantly more PDE4D-positive cells in the lamina propria compared to stage D. Significant differences were also observed in the number of SFRP5-positive cells in the lamina propria between healthy controls and all CRC stages, as well as between CRC stages Dukes' A and D. While the expression of PDE4D varied across CRC stages, the expression of SFRP5 remained consistently strong in both epithelium and lamina propria, with significant differences noted mainly in the lamina propria. The expression levels of PDE4B, PDE4D, and SFRP5 reveal significant differences in the expression of these genes between CRC patients and healthy controls, with notable implications for patient prognosis. Namely, our results demonstrate that PDE4B, PDE4D, and SFRP5 are significantly under-expressed in CRC tissues compared to control tissues. The Kaplan-Meier survival analysis and the log-rank (Mantel-Cox) test revealed distinct prognostic implications where patients with lower expression levels of SFRP5 exhibited significantly longer overall survival. The data align with our immunohistochemical results and might suggest a potential tumor-suppressive role for these genes in CRC. Conclusions: Considering significantly lower gene expression, aligned with our immunohistochemical data in tumor tissue in comparison to the control tissue, as well as the significantly poorer survival rate in the case of its higher expression, we can hypothesize that SFRP5 is the most promising biomarker for CRC out of the observed proteins. These findings suggest alterations in PDE4B, PDE4D, and SFRP5 expression during CRC progression, as well as between different stages of CRC, with potential implications for understanding the molecular mechanisms involved in CRC development and progression.

Personality Traits and Health Related Quality of Life in Patients with Irritable Bowel Sindrome and Inflammatory Bowel Disease.

BACKGROUND: Personality traits as alexithymia and type D personality may impair health related quality of life (HRQoL) in patients with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Aim of this study was to evaluate personality traits in patients with IBS and IBD and their impact on HRQoL. MATERIALS AND METHODS: The subjects (40 patients with IBS, 40 with IBD and 40 health control subjects) completed SF-36 questionnaire, TAS-20 and DS14 scale. RESULTS: Patients with IBS and IBD had higher results on TAS-20 and DS14 scale when compared with healthy controls. Also IBS patients had higher scores than IBD patients. Higher scores on TAS-20 and DS14 scales in IBS and IBD patients correlate with lower HRQoL. HRQoL was poorer in IBS and IBD patients than in healthy control subjects. CONCLUSIONS: Alexithymia and type D personality in IBS and IBD patients are associated with lower HRQoL and psychological interventions should be considered.

The Role of Family Physicians in the Prevention and Early Detection of Cancer in Herzegovina-Neretva and West-Herzegovina Canton.

BACKGROUND: This study aimed to investigate and analyze the role of general practitioners/family physicians (GPs/FPs) in counseling and encouraging early cancer prevention, their perception of value systems towards health and disease (especially malignant diseases), knowledge and experience with the national and local cancer early detection program. SUBJECTS AND METHODS: A cross-sectional observational study included 38 GPs/FPs from nine municipalities in the Hercegovina-Neretva and West Herzegovina canton. Data were collected by using an Individual questionnaire for all GPs/FPs which was prepared according to the Questionnaire for family physicians on implementing the Cancer Control Program, which is used in Croatia. RESULTS: Statistical analysis showed that most GPs/FPs carried out activities on primary cancer prevention (educating patients about smoking, alcohol, diet, physical activity, cancer education, and screening). The majority of respondents stated that it was not profitable to do screening for lung cancer and stomach cancer. Most GPs/FPs (73.7%) recommended mammography to women individually, sporadically, according to individual risk assessment. CONCLUSIONS: The scientific contribution and the results of this work can be applied in practice in local communities. Given its position in the health system, ongoing contact with the population that elected it, and its impact on the local community in which it operates, GP/FP plays an important role in the prevention of disease. Integration of preventive activities into the daily work of the doctor plays the most important role in achieving excellent results. Family medicine is primarily focused on primary and secondary prevention, which is carried out through a continuous approach and long-term management of patients.

The Use of Complementary and Alternative Medicine among Cancer Patients Undergoing Conventional Treatment: A Single-Centre Experience.

BACKGROUND: The alternative medicine is increasingly accepted by modern man. People realize that healing based on natural methods is much more affordable and not more aggressive than taking potent drugs of synthetic origin. The aim of this study was to collect data on the use of complementary agents and alternative medicine in cancer patients treated at the Oncology Clinic of the University Clinical Hospital in Mostar. SUBJECTS AND METHODS: We conducted a cross-sectional study that included 100 patients. Data were collected from a questionnaire compiled for this research, which comprised two groups of questions. The first group examined the sociodemographic characteristics of the respondents, and the second the modalities of using Complementary and Alternative Medicine (CAM), and health and conceptual reasons for use. RESULTS: A total of 72 patients (72.0%) had used a CAM during their anticancer treatment. Only 23% of patients had used CAM before the diagnosis of cancer. Among them, 26 (36.1%) previously discussed the topic with their oncologist. CAMs ranged from herbal medicine (58.3%), cannabinoid oil (19.4%) and different vitamins and minerals (22.2%). CAMs were mainly used to improve the health (40.3%). Among patients who used CAM only 25% find it financially demanding, 90.3% of patients were satisfied with effects of CAMs, and 78.1% would recommend it to other cancer patients. CONCLUSION: Our data showed that in our region, many patients used complementary and alternative methods of treatment. These results are very important because they provide information and give a clearer picture of the use of CAM among cancer patients and, accordingly, the right approach of the health practitioners to the patient, leading to optimized cancer therapy and increased safety.

Anxiety, Depression and Personality Types in Patients with Inflammatory Bowel Disease: Comparisons with Peptic Ulcer and the General Population.

BACKGROUND: To explore corellation of anxiety, depression ant type of personality in inflammatory bowel disease (IBD) and compare with peptic ulcer (PU). SUBJECTS AND METHODS: In this study, prevalence of anxiety, depression and type of personality was investigated in 362 cases divided into three groups: 112 of IBD patients, 122 of peptic ulcer patients and 128 of control group who didn't have any gastrointestinal or psychic complaints. IBD and peptic ulcer diagnosis were established by standard diagnostic procedures (anamnesis, clinical manifestations, laboratory, endoscopy and biopsy in IBD and upper endoscopy in peptic ulcer). Anxiety and depression were established by Hamilton anxiety rating scale (HAM-A) and Hamilton rating test for depression (HAM-D). Type of A/B personality was established by Bortner scale and D type of personality by Denollet scale (DS14). RESULTS: Anxiety was found in 47 (41.9%) and depression in 44 (38.3%) of a total of 112 IBD cases. In group with peptic ulcer anxiety was found in 40 (32.8%) and depression aalso in 40 (32.8%) of total 122 cases. In control group anxiety was diagnosed in 21 (16.4%) and depression in 20 (15.6%) of total 128 cases. Anxiety and depresson were significantly higher in both groups than in control group but anxiety and depression were significantly higher in IBD group than peptic ulcer group. D type of personality was statistically significant in peptic ulcer group. CONCLUSION: Anxiety and depression in IBD and peptic ulcer cases have a greater prevalence compared to the normal population and surprisingly are higher in IBD than peptic ulcer group. D type of personality is associated with peptic ulcer.

Pathophysiology of allergic drug reactions.

Adverse drug reactions (ADR) may be broadly divided into types A and B. Type A comprise the majority of reactions, can affect any individual, and are predictable from the known pharmacologic properties of a drug. Type B are less common, occur in susceptible patients and cannot be predicted. Allergic/immunologic drug reactions are a group of type B ADRs. Based on the time of onset allergic drug reactions can be divided into immediate and delayed and based on their underlaying immunologic mechanism, they can be further subdivided into 4 groups: immediate and mediated by IgE (1), delayed and caused by antibody facilitated cell destruction (2), delayed and caused by drug immune complex deposition and complement activation (3) and delayed and T cell mediated (4). Physicians should always insist on obtaining a thorough patient's history regarding drug allergy as well as on ascertaining details regarding the medication used, its route of administration, dosage and the treatment duration in order to properly assess risk of drug allergies and suggest further work-up in that regard.

Type of Cell Separator, Fenwal Amicus vs Fresenius Com Tec, May Influence the Corpuscular Elements Value of the Donor`s Blood.

INTRODUCTION: During the plateletpheresis procedure the number of thrombocytes in the donor's blood significantly decreases, and the levels of the hematocrit (HCT), hemoglobin (Hgb), and leukocyte (WBC) diminish as well. Influence of the cell separator is one of the factors that affects the levels of HCT, Hgb and WBC. In this study, the goal was to determine the value difference of HCT, Hgb, WBC, and platelets after the platelet pheresis process between performance on Fenwal AMICUS and on Fresenius Com Tec. DONORS AND METHODS: The criteria for participation: male in the age range of 25-45. We have formed two groups: for both groups - 180 separations were performed on 60 participants were the values of hematocrits, concentration of hemoglobin and number of leukocytes were established before and after separation using the double-needle continuous flow cell separation (DN-CFCS) on two different devices, Fenwal AMICUS device and the Fresenius Com Tec. device. To confirm the statistical differences we have used Student t-test for independent or dependent samples, as well as Mann-Whitney U test as non-parametric alternative. To compare differences between the values of four parameters (P1-P2) from two groups (using two devices - Fenwal AMICUS and Fresenius Com Tec) The possibility of errors were accepted for α<0.05, and the difference between groups as statistical relevant were accepted for p<0.05. RESULTS: Statistically significant lower values were noted for all researched parameters after separation on both devices. The statistically significant average values for Hct, Hgb and WBC obtained between two devices, were less than 0.05 (p=0.05). For the platelets (Plt) there was no statistical significant difference (p>0.05 - α=0.05), between average level obtained using either Fenwal AMICUS or Frazenius Com Tec. CONCLUSION: The type of cell separator had the influence on the decrease value of the observed parameters.

Correlation between biochemical and histopathological parameters in patients with chronic hepatitis C treated with pegylated interferon and ribavirin.

AIM: The main goal of this study was to compare the biochemical and histopathological findings in patients with sustained virological response (SVR) before and two years after the therapy with pegylated interferon α-2a and ribavirin in chronic hepatitis C. SUBJECTS AND METHODS: The study was conducted at the Department of Internal Medicine and the Clinic for Infectious Diseases of the Clinical Hospital Mostar. The study included 48 patients whose treatment for chronic hepatitis C with pegylated interferon α-2a and ribavirin was finished two years prior to the achieved SVR at the end of the treatment. The main criterion for inclusion was a negative result of HCV RNA, determined by the RealTime HCV assay. After taking a history, physical examination, laboratory tests: AST, ALT, GGT, a liver biopsy were performed with the help of the ultrasound. The assessment of necroinflamatory score was determined by histologic activity index (HAI) score, and the stage of fibrosis according to Knodell's numerical score. RESULTS: The values of AST and ALT levels were statistically significantly decreased after the successful treatment (p<0.001), as well as the value of HAI score (p=0.001) and the stage of fibrosis (p=0.010), in contrast to GGT (p=0.054). For the components of HAI score like focal necrosis (0.001) and portal inflammation (0.042) the result showed that they were significantly higher before the therapy, which was not true for the piecemeal (p=0.054) and confluated necrosis (p=0.078). The improvement of HAI score after therapy was found in 36 patients (75.0%), and 27 patients (56.2%) showed an improvement in the degree of fibrosis with the most common improvement of 1 degree (85.7%). One third of patients (31.3%) had the same result in the degree of fibrosis before and after the therapy. Before the treatment, a positive correlation was observed between ALT (p=0.039) and AST (p=0.04) with HAI, AST and the stage of fibrosis (p=0.04). In contrast, after the treatment the only correlation was observed between AST and the stage of fibrosis (p=0.042). CONCLUSION: Virological and biochemical responses in patients with SVR may not reflect the histopathological effects of the treatment and therefore these patients should be monitored for the possible development of the liver cirrhosis and hepatocellular carcinoma.

Diagnosis and treatment of chronic viral hepatitis B and C: doctrinary approach.

Association of Gastroenterologists and Hepatologists of Bosnia and Herzegovina based on the experiences of domestic and foreign centers operating in the field of hepatology and accepted guidelines of the European and the U.S. Association for Liver Diseases adopted the consensus for the diagnosis and treatment of chronic viral hepatitis B and C. The guidelines are intended for specialists in gastroenterology and hepatology, and infectious diseases physicians working in primary health care and family medicine, but also other physicians who are confronted with this disease in their practice, with the aim of facilitating and shortening the diagnostic and treatment protocols of patients with chronic viral hepatitis B and C. This ensures faster, more efficient, more rational and cost-effective care of patients with hepatitis, with an emphasis on stopping the deterioration of liver disease to liver cirrhosis and eventually hepatocellular carcinoma. Key words: Chronic hepatitis B and

IMP3 protein is an independent prognostic factor of clinical stage II rectal cancer.

Immunohistochemical level of IMP3-protein in patients with rectal cancer in clinical stage II (141), were correlated with sociodemographic, pathohistological and clinical indicators and duration of overall-survival and progression-free-survival. Vascular invasion was associated with IMP3-positive immunostaining (p < 0.001). Vascular invasion ratio in the group of poorly-differentiated-tumors was 21 times higher than in the group of well-differentiated-tumors. IMP3-positive patients lived 2.2 times shorter than negative (p < 0.001). Patients with well-differentiated-tumors lived 1.7 times longer than the subjects with poorly-differentiated-tumors (p < 0.001). Patients without vascular invasion lived 2.7 times longer than the subjects with vascular invasion (p < 0.001). The risk of mortality was 2.3 times higher for IMP3 positive patients (p = 0.027) and 10.4 higher for the patients with vascular invasion (p < 0.001). IMP3-negative participants had 2.3 times longer free interval without disease (p < 0.001). The free interval without disease was 3.6 times longer in the group without vascular invasion (p < 0.001). The risk of disease relapse in the IMP3 positive group was 5.3 times higher (p < 0.001) and with vascular invasion was 8 times longer (p < 0.001). The risk of disease relapse was 6.8 times higher in the group with vascular invasion (p < 0.001). Patients with rectal cancer and high IMP3-protein level will have a shorter overall survival relative to patients without or with low levels of IMP3. The analysis of IMP3 expression by immunohistochemistry pointed IMP3 as an independent prognostic factor of clinical stage II rectal cancer.

Decreased Expression of Cytotoxic Proteins in Decidual CD8+ T Cells in Preeclampsia.

In our study, we aimed to establish expression of cytotoxic CD8+ T cells in the decidua basalis and the maternal peripheral blood (mPBL) of severe and mild preeclampsia (PE) and compare to healthy pregnancies. Decidual tissue and mPBL of 10 women with mild PE, 10 women with severe PE, and 20 age-matched healthy pregnancy controls were analyzed by double immunofluorescence and qPCR, respectively. By double immunofluorescence staining, we found a decreased total number of cells/mm2 in decidua basalis of granulysin (GNLY)+ (p ˂ 0.0001), granzyme B (GzB)+(p ˂ 0.0001), GzB+CD8+(p ˂ 0.0001), perforin (PRF1)+ (p ˂ 0.0001), and PRF1+CD8+ (p ˂ 0.01) in the severe PE compared to control group. Additionally, we noticed the trend of lower mRNA expression for GNLY, granzyme A (GZMA), GzB, and PRF1 in CD8+ T cells of mPBL in mild and severe PE, with the latter marker statistically decreased in severe PE (p ˂ 0.001). Forkhead box P3 (FOXP3) mRNA in CD8+ T cells mPBL was increased in mild PE (p ˂ 0.001) compared to controls. In conclusion, severe PE is characterized by altered expression of cytotoxic CD8+ T cells in decidua and mPBL, suggesting their role in pathophysiology of PE and fetal-maternal immune tolerance.