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.

Inappropriate Use of Topical Corticosteroides in the Dermatology Outpatient.

INTRODUCTION: Topical corticosteroids are group of drugs which have anti-in?ammatory, immuno-suppressive, anti-proliferative and vasoconstrictive effects and are among the most commonly prescribed medication, important and efficacious for management of various dermatological disorders. Strict implementation of the existing regulations is the need of the hour to prevent their widespread abuse. Aim of the study was to investigate the usage of topical corticosteroids therapy with the recipe of a doctor and without it. SUBJECTS AND METHODS: The subjects were patients who visited Pharmacies in Mostar from April to July 2020 and were buying topical corticosteroids with or without a recipe or medical report from the doctor. 80 subjects completed a questionnaire themselves included: the way of buying a topical corticosteroids, the information about using topical corticosteroids earlier, the information about subject's visits to the doctor; the length of time using topical corticosteroids, the type of topical corticosteroids used, the part of body the topical corticosteroids was applied on. RESULTS: A total of 80 subjects were treated in the observed period, 58.8% were female. 72.5% subjects had already used local corticosteroids, 62.50% purchased the drug at the recommendation of the pharmacist, 66.30% had no recent diagnosis or no diagnosed disease at all, 21.25% used the drug for more than a month, the most often purchased one was moderate potent local corticosteroid Betamethasone diproprionate 0.05%. Most commonly subjects applied local corticosteroids on arms (50%). CONCLUSION: Strict regulations regarding only prescription-based dispensing of local corticosteroids must be put into practice. This will hopefully bring down both the extremes of ever increasing cases of steroid-induced dermatoses in everyday dermatology practise on one hand and the irrational fears of using TCs in well justified indications on the other.

Impact of COVID-19 Pandemic on Mental Health of Medical Students at the University of Mostar.

BACKGROUND: Previous studies have shown that medical students are more prone to depression, more tired, and more prone to emotional exhaustion, depersonalization and burnout syndrome than other students. In terms of mental health, they are a "more vulnerable" than individuals of the same age in the general population. In December 2019 in Wuhan (China) the outbreak of pneumonia caused by the new coronavirus captured worldwide attention. The implementation of strict quarantine measures kept a large number of people in self-isolation which affected all aspects of life. Objective of the study is to determine the direct impact of the COVID-19 pandemic on mental health and quality of life of medical students and the differences in the impact between genders and years of study. SUBJECT AND METHODS: This is a cross-sectional study conducted from May 25 to June 5 2020. It includes medical students who resided in the country affected by the COVID-19 pandemic. Participants completed a modified anonymous online questionnaire that assessed the Impact of Event Scale, indicators of negative mental health impacts, social and family support, and lifestyle changes due to a pandemic. RESULTS: The mean IES score in the participants showed a moderate stressful impact, with the mean IES score of females being significantly higher than that of males (29 vs. 19) with p<0.001. More than half of the participants had an IES score ≥26. With the onset of the pandemic, 71.5% of all medical students reported feeling increased stress from commitments. CONCLUSIONS: the pandemic had stressful impact on the mental health of medical students and it was significantly more stressful for women and students in the preclinical years of study. The COVID-19 pandemic had no impact on social and family support, however a positive impact on the lifestyle of medical students was found.

Oral Cavity Colonization with Multidrug-Resistant Gram-Negative Bacteria after Preoperative Prophylactic Use of Antibiotics as a Risk Factor for Ventilator-Associated Pneumonia.

BACKGROUND: Although it was previously shown that prolonged prophylactic antibiotic exposure and multiple inadequate antibiotic therapies are independent risk factors for multidrug-resistant ventilator associated pneumonia there were no studies investigating whether pre-operative prophylactic dose of antibiotics changes oral microbiome and increases the risk of ventilator associated pneumonia. The aim of the study was to determine if pre-operative prophylactic dose of antibiotics affects the oral microbiome, increases the colonization with Gram-negative bacteria and subsequent risk of ventilator associated pneumonia. SUBJECTS AND METHODS: Mechanically ventilated adult patients receiving surgical antibiotic prophylaxis were included in the study. The presence of Gram negative microorganisms in the pre-prophylactic and post-prophylactic oral swabs and tracheal aspirates, as well as the occurrence of ventilator associated pneumonia, were analyzed. RESULTS: Number of patients colonized with Gram negative bacteria in post- prophylactic oral swab was significantly higher compared to oral swab taken before prophylactic antibiotic. On the other hand, the number of patients with Gram- negative bacteria in tracheal aspirates remained similar as in post- prophylactic oral swabs. Moreover, we found that presence of Gram- negative bacteria in both pre- and post- prophylactic oral swabs was in the positive correlation with the presence of Gram- negative bacteria in tracheal aspirates. CONCLUSIONS: This study showed increased colonization of oral cavity with Gram- negative bacteria after preoperative prophylactic antibiotics. Furthermore, receiving two prophylactic antibiotics from WHO Watch list increased the incidence of Gram- negative bacteria in oral swabs and tracheal aspirates, and the risk of ventilator associated pneumonia development.

Diagnosis of perioperative anaphylaxis.

Every agent used during the perioperative period may be involved and have the potential to trigger both allergic, IgE and non-IgE reaction as well as non-specific (non-allergic) reactions. In many cases, an allergic mechanism cannot be ruled out and systematic investigations should be tested of all drugs and agents the patient was exposed to prior to the reaction. The complexity of agents used for anaesthesia and surgery present challenges when attempting to identify the culprit drugs and select proper testing to better recognition of trigger. The diagnosis of preoperative anaphylactic or anaphylactoid reaction is clinical and based upon the presence of characteristic symptom and signs that begin suddenly and developed rapidly in most cases. Elevations of mast cell mediators such as tryptase and histamine in the blood can help to distinguish anaphylaxis from other disorders that present with similar clinical picture. The secondary investigations of adverse perioperative drug reactions are highly specialised and include skin testing, in vitro testing and in some cases challenge tests. Any suspected reaction during anaesthesia must be extensively investigated and these diagnostic tests should be done in specialised centres. The cooperation between anaesthesiologists and allergists is necessary to provide the necessary diagnostic tests to identify the responsible drug, to carry out prevention and to provide recommendations for future anesthetic procedures.

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.

Allergic reactions and anesthesia.

The diagnosis of allergic reactions during anesthesia is difficult. For example, cardio-respiratory symptoms may be due to the accompanying pharmacological effects of anesthetics and poor interpretation of the reaction during anesthesia. It is important to distinguish whether a real allergic reaction has occurred. Accidents with anesthetics and muscle relaxants are observed more often than we expect. Proper anaphylaxis rarely occurs during anesthesia (1: 20000). Muscle relaxants are the most common causes, followed by latex, chlorhexidine, antibiotics and opioids. To confirm the diagnosis it is necessary to perform a larger number of blood and skin tests. Targeted diagnostic approach and therapy allow avoiding more difficult events. Anesthesia should be selected for those medications that have been tested. Additionally, patients should be premedicated with antihistaminics and systemic steroids, as the emergence of intolerance is not completely excluded by negative testing. There is no gold standard for testing, even if every method is precisely performed; there are always false positive and false negative results. When anaphylaxis appears, urgent approach is needed to provide the patient with appropriate treatment. It is necessary to act according to the established algorithms and treatment protocols. Many anesthesiologists will not ever see such a reaction, and very few will see more than one during their work life. Awareness of allergy in anesthesia is still insufficient.