COVID-19-related stress response among adult females: Relevance of sociodemographics, health-related behaviors and COVID-19 contact.

Women were more affected than men during the COVID-19 pandemic. This study aimed to investigate COVID-19-related stress response in adult women and its association with the relevant socioeconomic, lifestyle and COVID-19-related factors. This research was carried out in eight randomly chosen cities from September 2020 to October 2021. To examine stress, we distributed the COVID Stress Scales (CSS) and the Perceived Stress Scale (PSS). Women also fulfilled a general socio-epidemiologic questionnaire. The study included 1,264 women. Most women were healthy, highly educated, employed, married, nonsmokers who consumed alcohol. The average total CSS score suggested a relatively low COVID-19 related stress), while 1.7% of women had CSS ≥ 100. The mean PSS was around the mid-point value of the scale. Older women, who were not in a relationship, didn't smoke, didn't drink alcohol, but used immune boosters, had chronic illnesses and reported losing money during the pandemic had higher CSS scores. A higher level of stress was also experienced by women exposed to the intense reporting about COVID-19, had contact with COVID-19 positive people or took care of COVID-19 positive family members. In this sample of predominantly highly educated women few women experienced very high stress level, probably due to the study timing (after the initial wave) when the pandemic saw attenuated stress levels. To relieve women from stress, structural organization and planning in terms of health care delivery, offsetting economic losses, controlled information dissemination and psychological support for women are needed.

Halogenated Boroxine K2[B3O3F4OH] Modulates Metabolic Phenotype and Autophagy in Human Bladder Carcinoma 5637 Cell Line.

Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.

Reversion of methacholine induced bronchoconstriction with inhaled diazepam in patients with asthma.

BACKGROUND: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. AIM: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. PATIENTS AND METHODS: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. RESULTS: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. CONCLUSIONS: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.

Trends and patterns of antibiotics use in Serbia from 2006 to 2021: Pre-COVID-19 period versus COVID-19 pandemic.

BACKGROUND: Global rise in antibiotic utilization has been strongly associated with the resistance of bacteria to antibiotics. The COVID-19 saw an increase in the use of antibiotics in some countries. The aim of this study was to evaluate antibiotic utilization from 2006 to 2021 in the Republic of Serbia. METHODS: Data on antibiotic use were retrieved from the national annual reports on the official website of the Medicines and Medical Devices Agency of Serbia during the period 2006 to 2021. To evaluate trends in the use of antibiotics in Serbia, linear, and joint regression analyses were performed. RESULTS: The analysis of the antibiotics use over a sixteen-year period included a total of 50 antibiotics. A significant increase during the COVID-19 pandemic was observed for glycylcyclines that is, new-generation tetracyclines (tigecycline), third-generation cephalosporins (ceftazidime, ceftriaxone, and cefixime), respiratory fluoroquinolones (levofloxacin and moxifloxacin), carbapenems (ertapenem), and oxazolidinones (linezolid) utilization. Moreover, an almost negligible use of new ß-lactam/ß-lactamase inhibitors during the prepandemic period increased significantly during the COVID-19 pandemic period. CONCLUSIONS: A significant increasing trend in the use of specific antibiotics classified as the "Watch" and "Reserve" antibiotics during the pandemic period was observed.

The Impact of Cytokines on Coagulation Profile in COVID-19 Patients: Controlled for Socio-Demographic, Clinical, and Laboratory Parameters.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

The Impact of Cytokines on Health-Related Quality of Life in Adolescents with Allergic Rhinitis.

BACKGROUND: Frequent episodes of nasal symptoms are the usual clinical manifestations (CM) of allergic rhinitis (AR) and have a significant negative impact on health-related quality of life (HRQoL) in adolescents. The purpose of this cross-sectional study was to test the hypothesis that cytokines in nasal mucus may be associated with HRQoL in adolescents with AR. METHODS: European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), "The Adolescent Rhinoconjunctivitis Quality of Life Questionnaire" (AdolRQLQ) and the Total 4 Symptom Score (T4SS) scoring system were administered to 113 adolescents with AR, nonallergic rhinitis (NAR) and to healthy control subjects. Nasal secretions were sampled and tested for 13 cytokines using a multiplex flow cytometric bead assay. RESULTS: The AR group had significantly lower EQ-5D-3L (0.661 ± 0.267 vs. 0.943 ± 0.088; p < 0.001) and higher AdolRQLQ total scores (2.76 ± 1.01 vs. 1.02 ± 0.10; p < 0.001) compared to the control group. The AR group had higher concentrations of IL-1ß (p = 0.002), IL-6 (p = 0.031), IL-8 (p < 0.001), IL17-A (p = 0.013) and IL-18 (p = 0.014) compared to the control group, and IL-1ß, IL-6, IL17-A and IL-18 were significantly (p < 0.050) increased with disease progression. Cytokines IL-1ß, IL-6, as well as severe CM, were identified as significant predictors of lower HRQoL in adolescents with AR. CONCLUSIONS: This study identified IL-1ß, IL-6, as well as severe CM, as predictors of lower HRQoL in adolescents with AR. However, these results should only serve as a starting point for additional confirmation research.

Adrenal Abscesses: A Systematic Review of the Literature.

Objective: To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Design: Systematic literature review. Methods: We performed a search in the PubMed database using search terms: 'abscess and adrenal glands', 'adrenalitis', 'infection and adrenal gland', 'adrenal abscess', 'adrenal infection' and 'infectious adrenalitis'. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Results: Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with Histoplasma capsulatum (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia (p = 0.048). Conclusion: Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, Histoplasma capsulatum is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.

Antibiotic consumption and antimicrobial resistance in the SARS-CoV-2 pandemic: A single-center experience.

Introduction: Antimicrobial resistance and the rapid spread of multiresistant bacteria represent one of the main public health problem in limited resources countries. This issue is significantly worsening since the COVID-19 pandemic due to the unreasonably increased antibiotics prescription to patients with confirmed SARS-CoV-2 infection. The aim of this study was to examine whether COVID-19 pandemic (2020, 2021) was associated with increased antibiotic consumption in inpatient and outpatient settings in the middle size urban region (Republic of Srpska/Bosnia and Herzegovina) in comparison to period before the pandemic (2019). Additionally, we aimed to determine antimicrobial resistance and the presence of multiresistant bacteria in the regional hospital ("Saint Apostol Luka" Hospital Doboj) in 2021. Methodology: The consumption of antibiotics in inpatient was calculated as Defined Daily Dose per one hundred of patient-days. The consumption of antibiotics in outpatient was calculated as Defined Daily Dose per thousand inhabitants per day. Resistance of bacteria to antibiotics is expressed as a rates and density for each observed antibiotic. The rate of resistance was calculated as a percentage in relation to the total number of isolates of individual bacteria. The density of resistance of isolated bacteria against a specific antibiotic was expressed as the number of resistant pathogens/1000 patient days. Results: Antibiotic consumption in hospital setting registered during 2019, 2020 and 2021 was as follows: carbapenems (meropenem: 0.28; 1.91; 2.33 DDD/100 patient-days, respectively), glycopeptides (vancomycin: 0.14; 1.09, 1.54 DDD/100 patient-days, respectively), cephalosporins (ceftriaxone: 6.69; 14.7; 14.0 DDD/100 patient-days, respectively) and polymyxins (colistin: 0.04; 0.25; 0.35 DDD/100 bed-days, respectively). Consumption of azithromycin increased drastically in 2020, and dropped significantly in 2021 (0.48; 5.61; 0.93 DDD/100 patient-days). In outpatient setting, an increase in the consumption of oral forms of azithromycin, levofloxacin and cefixime, as well as parenteral forms of amoxicillin-clavulanic acid, ciprofloxacin and ceftriaxone, was recorded. In 2021, antimicrobial resistance to reserve antibiotics in hospital setting was as follows: Acinetobacter baumanii to meropenem 66.0%, Klebsiella spp to cefotaxime 67.14%, Pseudomonas to meropenem 25.7%. Conclusion: Recent COVID-19 pandemic was associated with increased antibiotic consumption in inpatient and outpatient settings, with characteristic change of pattern of azithromycin consumption. Also, high levels of antimicrobial resistance to reserve antibiotics were registered in hospital setting with low prevalence of identified pathogen-directed antimicrobial prescription. Strategies toward combat antimicrobial resistance in the Doboj region are urgently needed.

Public Knowledge, Attitudes, and Practices towards Antibiotic Use and Antimicrobial Resistance in Eastern Region of Bosnia and Herzegovina in the COVID-19 Pandemic.

The constant worsening of antimicrobial resistance (AMR) imposes the need for an urgent response. Use of antibiotics (AB), both due to irrational prescribing by doctors and irrational use by patients, is recognized as one of the leading causes of this problem. This study aimed to identify knowledge, attitudes, and practices about AB use and AMR within the general population, stratified by age, gender, and urban/rural areas during the COVID-19 pandemic. This questionnaire-based cross-sectional study was conducted in April 2022 among patients who visited three health centers in the eastern region of Bosnia and Herzegovina. A high frequency of AB use was observed during the COVID-19 pandemic (64.2% of respondents were treated with AB). Age and place of residence have not been shown to be factors associated with AB use practices that pose a risk for AMR. However, female gender (ß = 0.063; p = 0.041), better knowledge (ß = 0.226; p < 0.001), and positive attitudes (ß = 0.170; p < 0.001) about use of AB and towards to AMR proved to be factors associated with better practice by respondents. Women, younger respondents, and respondents from urban areas showed better knowledge, attitudes, and behavior about the use of AB and AMR during the COVID-19 pandemic.

Renal Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review of 71 Cases.

Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney.

Consumption of Antibiotics in Primary Care Setting before and during COVID-19 Pandemic in Republic of Srpska, Bosnia and Herzegovina.

The pandemic of COVID-19 has brought many changes in health care systems at all levels of health care. The increase in the number of cases of COVID-19 has led to overuse and misuse of antibiotics.The aim of this study was to compare the consumption of antibiotics for systemic use in outpatients in the Republic of Srpska (RS), before and during the first year of the COVID-19 pandemic, as well as the association between antibiotic consumption and the rate of incidence and mortality of COVID-19. The total consumption of the antibiotics for systemic use (J01) in outpatients in the Republic of Srpska during 2019 was 19.40 DDD/TID, with an increase to 30.80 DDD/TID in 2020.Significantly higher use of penicillin (10.58 ± 11.01 DDD/TID in 2019 vs. 17.10 ± 13.63 DDD/TID in 2020), cephalosporins (2.68 ± 1.90 DDD/TID in 2019 vs. 5.93 ± 2.77 DDD/TID in 2020) and macrolides (2.14 ± 2.22 DDD/TID in 2019 vs. 3.40 ± 3.44 DDD/TID in 2020) was observed during the pandemic period. It is necessary to improve the prescribing practice of antibiotics at the primary health care level, public awareness about rational use of antibiotics, as well as the current antibiotic stewardship programs and control their implementation.

Suppurative Thrombosis of the Portal Vein (Pylephlebits): A Systematic Review of Literature.

Suppurative portal vein thrombosis (pylephlebitis) is an uncommon condition usually associated with an intra-abdominal infection or inflammatory process. In this study, we aimed to synthesize data on previously published cases according to the PRISMA guidelines. A total of 103 patients were included. Patients were more commonly male (71.8%) and had a mean age of 49 years. The most common infection associated with pylephlebitis was diverticulitis (n = 29, 28.2%), and Escherichia coli was the most isolated pathogen (n = 21, 20.4%). Blood cultures were positive in 64 cases (62.1%). The most common site of thrombosis was the main portal vein (PV) in 59 patients (57.3%), followed by the superior mesenteric vein (SMV) in 40 patients (38.8%) and the right branch of the PV in 30 patients (29.1%). Sepsis developed in 60 patients (58.3%). The mortality rate in our review was 8.7%, and independent risk factors for mortality were the presence of pertinent comorbidities (OR 5.5, p = 0.02), positive blood cultures (OR 2.2, p = 0.02), and sepsis (OR 17.2, p = 0.049).

Knowledge, Attitudes and Practices of Parents and Pediatricians Regarding Antibiotic Use among Children: Differences in Relation to the Level of Education of the Parents in the Republic of Srpska Bosnia and Herzegovina.

Antibiotics are often misused, especially for the treatment of upper respiratory tract infections (URTIs) in children, where their use is unnecessary and leads to antimicrobial resistance. This study sought to explore the knowledge, attitudes and practices (KAP) of parents and pediatricians on the use of antibiotics among children and whether the level of education of parents has an impact on their KAP. The research was carried out among 1459 parents of children under 6 years of age and among 18 pediatricians. Sixty percent of pediatricians (61.1%) were prescribed antibiotics daily in their practice. Most of the surveyed parents (98.4%) state that doctors are their main source of information when deciding on the use of antibiotics in the treatment of their children. Parents with a higher level of education use television less often as a source of information when making this decision compared to parents with a lower level of education (p = 0.039, i.e., p = 0.003). The majority of parents (80.7%) knew that Panklav (amoxicillin/clavulanic acid) is an antibiotic, while 52.5% identified Pancef (cefixime) as an antibiotic. Parents with a higher level of education correctly identified antibiotics significantly more often (p < 0.001). This study shows that in the Republic of Srpska, parents have adequate knowledge about antibiotics, especially those with a higher level of education, who show better KAP when it comes to antibiotic use.

Validity and reliability of the Serbian COVID Stress Scales.

This study aimed to generate a linguistic equivalent of the COVID Stress Scales (CSS) in the Serbian language and examine its psychometric characteristics. Data were collected from September to December 2020 among the general population of three cities in Republic of Serbia and Republic of Srpska, countries where the Serbian language is spoken. Participants completed a socio-demographic questionnaire, followed by the CSS and Perceived Stress Scale (PSS). The CSS was validated using the standard methodology (i.e., forward and backward translations, pilot testing). The reliability of the Serbian CSS was assessed using Cronbach's alpha and McDonald's omega coefficients and convergent validity was evaluated by correlating the CSS with PSS. Confirmatory factor analysis was performed to examine the construct validity of the Serbian CSS. This study included 961 persons (52.8% males and 47.2% females). The Cronbach's alpha coefficient of the Serbian CSS was 0.964 and McDonald's omega was 0.964. The Serbian CSS with 36 items and a six-factorial structure showed a measurement model with a satisfactory fit for our population (CMIN/DF = 4.391; GFI = 0.991; RMSEA = 0.025). The CSS total and all domain scores significantly positively correlated with PSS total score. The Serbian version of the CSS is a valid and reliable questionnaire that can be used in assessing COVID-19-related distress experienced by Serbian speaking people during the COVID-19 pandemic as well as future epidemics and pandemics.

Increased systemic sST2 in patients with end stage renal disease contributes to milder liver damage during HCV infection.

INTRODUCTION: Hepatitis C Virus (HCV) is the leading cause of chronic liver disease and is a serious global health problem. Hepatitis C infection is highly prevalent in patients with end stage renal disease (ESRD), due to frequent exposure to blood and blood products, nosocomial transmission of HCV, and prolong hemodialysis duration. The aim of the study was to evaluate the influence of IL-33/ST2 signaling pathway on severity of the liver disease in ESRD HCV+ patients. METHODOLOGY: Blood samples from patients with end stage renal disease (ESRD) and hepatitis C infection (HCV), 20 patients with HCV infection, 20 patients with ESRD and 20 healthy control donor patients were taken for the examination of biochemical parameters, for the determination of the serum cytokine concentration, and for the molecular diagnostics of HCV. RESULTS: Systemic sST2 positively correlated with serum level of urea and creatinine, respectively. Serum sST2 was significantly increased in ESRD HCV+ patients in comparison to HCV+ group. sST2/IL-1, sST2/IL-4 and sST2/IL-23 ratios were significantly increased in serum of ESRD HCV+ patients in comparison to HCV+ patients. Significantly higher systemic level of sST2 and sST2/IL-1 and sST2/IL-4 ratios were measured in ESRD patients compared to non-ESRD patients. CONCLUSION: These results suggested that elevated level sST2, as the consequence of renal failure, causes less destruction of liver in HCV infection.

Compassion fatigue and compassion satisfaction among family physicians in the Republic of Srpska, Bosnia and Herzegovina.

Aims. The aim of this study was to examine self-perceived compassion fatigue and compassion satisfaction among family physicians in Bosnia and Herzegovina and describe potential contributing factors. Methods. The cross-sectional study enrolled 120 family physicians. Professional quality of life compassion satisfaction and fatigue version 5 (ProQOL5) was used to assess compassion satisfaction and two components of compassion fatigue, secondary traumatic stress and burnout. The symptoms of chronic fatigue were evaluated using the Chalder fatigue scale. Results. The majority of family physicians had moderate levels of compassion satisfaction (70%), burnout (75%) and secondary traumatic stress (55.8%). Family physicians with higher levels of secondary traumatic stress reported chronic fatigue (p = 0.001), longer length of service (p = 0.024) and residency training (p = 0.041). Chronic fatigue (p = 0.001), living in a rural environment (p = 0.033), larger size of practice (p = 0.006) and high number of patients with chronic disease (p = 0.001) were associated with a higher risk of burnout. Conclusion. Family physicians with large practices, long years of experience, a high number of chronically ill patients and experiencing chronic fatigue are at risk of developing compassion fatigue. A systematic exploration of compassion fatigue in relation to working conditions might provide an appropriate starting point for the development of preventive interventions.

Prostaglanin-E2 Potentiates the Suppressive Functions of Human Mononuclear Myeloid-Derived Suppressor Cells and Increases Their Capacity to Expand IL-10-Producing Regulatory T Cell Subsets.

Myeloid-derived suppressor cells (MDSC) emerged as major factors driving the tumor progression due to numerous immunosuppressive mechanisms they possess. Prostaglandin (PG)E2 is shown critical for the induction of MDSC and their suppressive functions in vivo, but it is poorly understood how it affects the capacity of MDSC to induce different subsets of regulatory T cells (Treg). By using a novel protocol for the generation of mononuclear (M)-MDSC, we showed that PGE2 potentiates the GM-CSF/IL-6-dependent induction of CD33+CD11b+HLA-DR-CD14+ M-MDSC in vitro. PGE2 diminished the capacity of GM-CSF/IL-6 M-MDSC to produce proinflammatory cytokines upon activation and augmented their capacity to produce IL-27, IL-33, and TGF-ß. These results correlated with an increased potential of GM-CSF/IL-6/PGE2 M-MDSC to suppress T cell proliferation, expand alloreactive Th2 cells, and reduce the development of alloreactive Th17 and cytotoxic T cells. Interestingly, GM-CSF/IL-6/PGE2 M-MDSC displayed a lower capacity to induce TGF-ß-producing FoxP3+ regulatory Treg compared to GM-CSF/IL-6 M-MDSC, as a consequence of reduced IDO-1 expression. In contrast, GM-CSF/IL-6/PGE2 M-MDSC potentiated IL-10 production by CD8+T, Th2, and particularly CD4+FoxP3- type 1 Treg, the latter of which depended on ILT3 and ILT4 expression. Cumulatively, PGE2 potentiated the suppressive phenotype and functions of GM-CSF/IL-6-induced M-MDSC and changed the mechanisms involved in Treg induction, which could be important for investigating new therapeutic strategies focused on MDSC-related effects in tumors and autoimmune diseases.

Self- Perceived Stress in Relation to Anxiety, Depression and Health-related Quality of Life among Health Professions Students: A Cross-sectional Study from Bosnia and Herzegovina.

INTRODUCTION: The purpose of the present study was to examine self-perceived stress of health professions students at the Faculty of Medicine Foca, and to explore its association with anxiety, depression and health-related quality of life. METHODS: The cross-sectional study enrolled 451 students at the Faculty of Medicine (medicine, dentistry, nursing and speech therapy). Survey instruments were distributed at the conclusion of the spring semester during the last required lecture for each year and study programme class. Perceived stress was assessed using the 14-item Perceived Stress Scale. The students were evaluated for symptoms of depression and anxiety, using Zung's self-assessment inventory for depression and the Spielberger State-Trait Anxiety Inventory (STAI). European Quality of Life-5 dimensions were used for describing and evaluating health. Multivariate analyses were carried out using logistic regression to examine the relationship between the outcome variable and selected determinant factors. RESULTS: A high degree of stress was reported by 1.6% of students, while the majority of students had either moderate (70.6%) or low degree (27.5%) of stress. The significant independent factors associated with perceived stress were anxiety score (OR, 0.339; CI 95%, 0.276-0.403) and EQ-5D score (OR, 0.044; CI 95%, 0.033-0.085). A high degree of perceived stress (OR, 0.624; CI 95%, 0.507-0.704), the presence of depression (OR, 0.800; CI 95%, 0.513-1.087), and low quality of life were associated with anxiety (OR, 0.073; CI 95%, 0.018-0.128). CONCLUSION: Higher levels of perceived stress predispose health professions students for anxiety and lower quality of life. The study programme was not a significant determinant of perceived stress sore.

The effects of interprofessional diabetes education on the knowledge of medical, dentistry and nursing students.

OBJECTIVES: Interprofessional teamwork is best attained through education that promotes mutual trust and effective communication. The primary aim of the study was to evaluate the impact of interprofessional learning on knowledge about diabetes. METHODS: The cross-sectional study included students of medicine, dentistry and nursing at the Faculty of Medicine Foca, Bosnia and Herzegovina. The students were randomly allocated into one of two groups. Group 1 attended an interprofessional course on diabetes while group 2 was divided into three subgroups and each of the subgroups attended an uniprofessional diabetes course. The measuring instrument used in the course in order to assess the participants' knowledge about diabetic care was a test containing multiple-choice questions about diabetes. The Interprofessional Questionnaire was used to explore the attitudes, views, values and beliefs of students regarding interprofessional education (IPE). RESULTS: No statistically significant difference in total score on the test was found between the groups at baseline, but at follow-up the difference was highly statistically significant (F=10.87; p=0.002). The students from Group 1 had better results (21.82 points), compared to Group 2 (18.77 points). The statistically significant difference was observed in mean values (t=-3.997; p=0.001), between Groups 1 and 2; the students from Group 1 obtained 20.42 points, which is considered to indicate a respectively positive self-assessment of communication and teamwork skills. However, Group 2 indicated a negative self-assessment of communication and teamwork skills. CONCLUSION: The findings suggest that IPE activities may provide health profession students with valuable collaborative learning opportunities.

Family physicians' perspectives on clinical guidelines, a survey from the Republic of Srpska, Bosnia and Herzegovina.

BACKGROUND: Despite considerable efforts to promote and support clinical practice guidelines (CPGs) use, adherence has often been suboptimal universally. OBJECTIVES: The aim of this study was to assess to which extent family physicians (FPs) in Republic of Srpska (RS), Bosnia and Herzegovina (BiH) accept or reject the concept and practice of CPGs and evidence-based medicine (EBM). METHODS: A cross-sectional survey was conducted among FPs from the RS, BiH in the period between January and March 2014. Recruitment of FPs was performed combining two different strategies, in-person recruitment at family medicine conferences and mailed invitations. The Questionnaire included19 questions from the existing Healthcare Monitor Questionnaire, divided into four thematic blocks and 11 self-designed questions. RESULTS: Seventy-seven per cent of 131 interviewed physicians reported already using guidelines in the treatment of patients, while 22.9% of them are undecided or disagree. As the reason for rejecting guidelines, 13.0% of the physicians stated they did not support their content, 12.2% found that limited knowledge about guidelines prevented their application, and another 12.2% reported that the current guidelines were not practical enough. All groups would rather not use guidelines developed by a governmental institution. CONCLUSION: Most physicians in the RS, BiH accept and declare application of CPG. However, a substantial percentage remains sceptical, using CPGs only as an exception, or rejecting them due to their content or impracticability. [Box: see text].