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.

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.

Sitagliptin Induces Tolerogenic Human Dendritic Cells.

Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-ß, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-ß) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-ß+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.

Efficacy of nebulized hypertonic saline versus normal saline in the treatment of acute bronchiolitis in inpatient infants.

Aim Compare the efficacy of nebulized hypertonic saline and normal saline in the treatment of infants hospitalized for bronchiolitis. Methods This retrospective study was conducted at the Department of Pulmonology, Paediatric Clinic, Clinical Centre University of Sarajevo, covering the period from January 2015 to December 2019 and comprising 380 children aged between 1 and 12 months having bronchiolitis. One group received nebulized hypertonic saline (NHS, 3% NaCl)), and another group received nebulized normal saline (NNS, 0.9% NaCl). The control group did not receive any of these treatment options. Results There was no statistically significant difference between the treatment groups regarding length of hospital stay (LOS) and Clinical Severity Score (CSS) at admission and discharge as well as in oxygen therapy duration and antibiotic use, the duration of symptoms before hospital admission, frequency of nasal discharge, elevated temperature, dyspnoea, cough and dehydration. Conclusion The results of this study are consistent with several recent studies or meta-analyses and support the evidence against the use of NHS in hospitalized infants with mild or moderate bronchiolitis.

Dysfunctions of Neutrophils in the Peripheral Blood of Children with Cystic Fibrosis.

Dysfunction of neutrophils in patients with cystic fibrosis (CF) is best characterized in bronchoalveolar lavage (BAL), whereas peripheral blood neutrophils are less examined, and the results are contradictory, especially in younger populations. Therefore, this work aimed to study functional and phenotypic changes in circulating neutrophils in children with CF. The study included 19 CF children (5-17 years) and 14 corresponding age-matched healthy children. Isolated neutrophils were cultured either alone or with different stimuli. Several functions were studied: apoptosis, NET-osis, phagocytosis, and production of reactive oxygen species (ROS), neutrophil elastase (NE), and 11 cytokines. In addition, the expression of 20 molecules involved in different functions of neutrophils was evaluated by using flow cytometry. CF neutrophils showed reduced apoptosis and lower production of NE and IL-18 compared to the healthy controls, whereas IL-8 was augmented. All of these functions were further potentiated after neutrophil stimulation, which included higher ROS production and the up-regulation of CD11b and IL-10 expression. NET-osis was higher only when neutrophils from moderate-severe CF were treated with Pseudomonas aeruginosa, and the process correlated with forced expiratory volume in the first second (FEV1). Phagocytosis was not significantly changed. In conclusion, circulating neutrophils from children with CF showed fewer impaired changes in phenotype than in function. Functional abnormalities, which were already present at the baseline levels in neutrophils, depended on the type of stimuli that mimicked different activation states of these cells at the site of infection.

The comparison of SARS-CoV-2 antibody levels in medical personnel induced by different types of vaccines compared to the natural infection.

INTRODUCTION: During the last two and a half years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread around the world. Most of the SARS-CoV-2 vaccines are designed to produce anti-SARS-CoV-2 immunoglobulin G (IgG) against the viral S-glycoprotein. The aim of this study was to measure the anti-S antibody titres among the medical personnel who had been fully vaccinated with different types of vaccines, and to compare them with those who were COVID-19 convalescents. MATERIAL AND METHODS: In this study serum was collected from 261 healthcare workers, of whom 227 were vaccinated, while 34 were recovered participants who were not immunised. Serum samples were collected 21 days after the first dose and 60 and 180 days after the second dose of the vaccines and tested with a commercial ELISA kit. RESULTS: The highest antibody level (12 AU/ml) was measured in the Pfizer-BioNTech group, followed by Sinopharm (9.3 AU/ml), Sputnik V (5.9 AU/ml), Sinovac (4.6 AU/ml) and Oxford/Astra- Zeneca vaccine (2.5 AU/ml) 60 days after the second dose of the vaccines (90 days after the first dose). The seropositivity rate for mRNA vaccine was 88.5%, for vector vaccines 86.2% and for inactivated vaccines 71.4%. When comparing these antibody levels with COVID-19 convalescents, higher antibody titres were found in vaccinated participants (5.76 AU/ml vs 7.06 AU/ml), but the difference was not significant (p = 0.08). CONCLUSIONS: Individuals vaccinated with mRNA and vector vaccines had a higher seroconversion rate compared to the group vaccinated with inactivated vaccines, or convalescents.

Periodontal Disease in Young Adults as a Risk Factor for Subclinical Atherosclerosis: A Clinical, Biochemical and Immunological Study.

Although a strong relationship between periodontal disease (PD) and atherosclerosis was shown in adults, little data are published in younger PD patients. Therefore, this study aimed to investigate and correlate clinical parameters of PD, pro- and immunoregulatory cytokines in gingival crevicular fluid (GCF) and serum, biochemical and hematological parameters associated with atherosclerosis risk, and carotid intima-media thickness (IMT) in our younger study participants (n = 78) (mean age 35.92 ± 3.36 years) who were divided into two equal groups: subjects with and without PD. PD patients had higher values of IMT, hs-CRP, triglycerides, total cholesterol, and LDL; most proinflammatory and Th1/Th17-associated cytokines in GCF; and IL-8, IL-12, IL-18, and IL-17A in serum compared to subjects without PD. These cytokines in GCF positively correlated with most clinical periodontal parameters. Clinical periodontal parameters, TNF-α and IL-8 in GCF and IL-17A, hs-CRP, and LDL in serum, had more significant predictive roles in developing subclinical atherosclerosis (IMT ≥ 0.75 mm) in comparison with other cytokines, fibrinogen, and other lipid status parameters. Hs-CRP correlated better with the proinflammatory cytokines than the parameters of lipid status. Except for serum IL-17A, there was no significant association of clinical and immunological PD parameters with lipid status. Overall, these results suggest that dyslipidemia and PD status seem to be independent risk factors for subclinical atherosclerosis in our younger PD population.

Boosting ICU capacity during the COVID-19 pandemic in the western Balkan region, The Republic of Srpska experience.

Background: Response to the outbreak of poliomyelitis in mid-1950 led to recognition and consequent development of critical care. Seventy years later the humankind was struck by COVID-19, another major challenge for critical care medicine which was especially big in Low-Resources-Settings where more than two thirds of the world population live, including the population of the Republic of Srpska (RS). Design and methods: The main aim was to show an overview of all interventions in order to boost hospitals' capacities to the level which is sufficient to manage high amount of critically ill COVID-19 patients in the RS. A before-after cohort study design was conducted to evaluate the effects of interventions for increase in preparedness and capacity of ICUs for admission and treatment of COVID-19 critically ill patients in nine hospitals in the RS. Results: Following interventions, the biggest and university affiliated hospital in the RS has increased ICU capacities: total number of ICU beds increased by 38% and number of ventilators by 114%. Availability of machines for veno-venous extracorporeal membrane oxygenation (vvECMO) increased by 100%. Number of doctors who were involved in treatment of critically ill patients increased by 47% and nurse/patient's ratio reached 1:2.5. Similarly, all other hospitals experienced boosting of ICU beds by 189% and ventilators by 373% while number of doctors increased by 108% and nurse/patient's ratio reached 1:4. Conclusion: All interventions implemented during COVID-19 pandemic outbreak in the RS resulted in increasing capacity for treatment of critically ill patients, but the education of health care professionals was identified as the most important conducted intervention.

Pediatricians' Attitudes Toward Child Sexual Abuse in the Republic of Srpska.

Child sexual abuse (CSA) affects all cultures and sociodemographic sections. As health professionals, pediatricians are often the first line of defense when it comes to CSA identification and reporting. Our previous study examined encounters, competence, beliefs, and reporting regarding CSA among pediatricians in countries of the former Yugoslavia, Serbia, and Montenegro. Following up on this work, we expanded our research to another neighboring country, the Republic of Srpska (RS). Sixty pediatricians were surveyed in 2020, comprising 30% of all practicing pediatricians in the Republic of Srpska. Compared to their colleagues from Serbia and Montenegro, RS pediatricians revealed an increased perception that children are often abused by someone they do know well, were more confident in their abilities to detect CSA, reported a higher number of CSA cases, and were more interested in further trainings on the subject of CSA. Despite this, the level of underreporting remained high (40%). To our knowledge, this is the first study to both assess and compare CSA-related attitudes in this part of the world. Key differences between RS, other two neighboring countries as well as from other countries worldwide are likely to stem from the level of pediatricians' training and education, as well as from the socio-cultural and legislation context. Although encouraging, our data indicate a need for further research in the countries of the former Yugoslavia.

Mesenchymal Stromal Cells from Healthy and Inflamed Human Gingiva Respond Differently to Porphyromonas gingivalis.

Gingiva-Derived Mesenchymal Stromal Cells (GMSCs) have been shown to play an important role in periodontitis. However, how P. gingivalis, one of the key etiological agents of the disease, affects healthy (H)- and periodontitis (P)-GMSCs is unknown. To address this problem, we established 10 H-GMSC and 12 P-GMSC lines. No significant differences in morphology, differentiation into chondroblasts and adipocytes, expression of characteristic MSCS markers, including pericyte antigens NG2 and PDGFR, were observed between H- and P-GMSC lines. However, proliferation, cell size and osteogenic potential were higher in P-GMSCs, in contrast to their lower ability to suppress mononuclear cell proliferation. P. gingivalis up-regulated the mRNA expression of IL-6, IL-8, MCP-1, GRO-α, RANTES, TLR-2, HIF-1α, OPG, MMP-3, SDF-1, HGF and IP-10 in P-GMSCs, whereas only IL-6, MCP-1 and GRO-α were up-regulated in H-GMSCs. The expression of MCP-1, RANTES, IP-10 and HGF was significantly higher in P-GMSCs compared to H-GMSCs, but IDO1 was lower. No significant changes in the expression of TLR-3, TLR-4, TGF-ß, LAP, IGFBP4 and TIMP-1 were observed in both types of GMSCs. In conclusion, our results suggest that P-GMSCs retain their pro-inflammatory properties in culture, exhibit lower immunosuppressive potential than their healthy counterparts, and impaired regeneration-associated gene induction in culture. All these functions are potentiated significantly by P. gingivalis treatment.

Seroprevalence of SARS-CoV-2 antibodies among primary healthcare workers in the Republic of Srpska, Bosnia & Herzegovina: A cross-sectional study.

Healthcare workers (HCW) in primary healthcare centres in the Republic of Srpska, Bosnia and Herzegovina, are on the first combat line with COVID-19. This study aimed to assess the seroprevalence of SARS-CoV-2 among HCW at the primary healthcare centres and to analyse the risk exposure to COVID-19, clinical signs and vaccination status. A cross-sectional study was conducted among HCW at the selected primary healthcare centres between 19 March and 30 April 2021. Antibodies against the SARS-CoV-2 virus were detected by enzyme-linked immunosorbent assay (ELISA). A total of 1,023 HCW (mean age 45 years; 71% female) were included in the study. The anti-SARS-CoV-2 antibodies were detected in 69.5% of all participants. There was a significant difference in seropositivity among primary healthcare centres from different geographical regions. As many as 432 (42%) of all participants had confirmed COVID-19 symptoms before the study and, 84.8% of them were seropositive. This study showed that 702 primary HCW were vaccinated with any of these vaccines: Sputnik V, Sinopharm, Pfizer/Biontech. High titre of SARS-CoV-2 antibodies was found amongst those who received one (92.6%) or both (97.2%) doses of vaccines. In this study, we report high prevalence of SARS-CoV-2 antibody among HCW in primary healthcare in the Republic of Srpska, Bosnia and Herzegovina during the third pandemic wave.

Seroprevalence of SARS-CoV-2 antibodies and knowledge, attitude and practice toward COVID-19 in the Republic of Srpska-Bosnia & Herzegovina: A population-based study.

The aim of the study was to assess the seroprevalence of SARS-CoV-2 in the Republic of Srpska, Bosnia and Herzegovina, and to analyse the knowledge, attitudes and practices of the population toward COVID-19. This population-based study was conducted in a group of 1,855 randomly selected individuals from all municipalities from 1 December 2020 to 15 January 2021. All individuals were asked to sign a consent form and to fill in a questionnaire, following which a blood samples were collected. Total anti-SARS-CoV-2 antibodies were determined in serum specimens using the total Ab ELISA assay. The overall seroprevalence rate was 40.3%. Subjects aged <65 years were 2.06 times more likely to be seropositive than those aged ≥65, and 30% of seropositive individuals presented no COVID-19 symptoms. The household members of seropositive individuals were 2.24 times more likely to develop COVID-19 symptoms than the household members of seronegative individuals. More than 95% of respondents believe that preventive measures are very important to control the infection transmission. Majority of respondents wear the masks properly, maintain the required physical distance whenever possible and wash hands with soap. Nearly 50% of individuals were of the opinion that the vaccine could prevent the infection. This study showed that an overall SARS-CoV-2 seropositivity rate by the middle of January 2021 was very high. Attitudes and practices regarding the COVID-19 indicate that additional efforts should be taken in order to improve the health education with a focus on preventive measures and vaccination.

Competence-Based Curriculum Development in Nursing Education: A Story From the Western Balkans.

This article describes the process of competence-based curriculum development in nursing education at Western Balkan (WB) universities. Nursing education in the WB has been noncompliant with the standard educational approaches of the European Union's directive on regulated professions. The overall aim of the TEMPUS project "Competency-Based Curriculum Reform in Nursing and Caring in Western Balkan Universities" was to bring curricular reform for bachelor's nursing education in the WB region in line with competence-based education and professional standards to demonstrate compliance with all member countries of the European Union.

Pulp Sensitivity: Influence of Sex, Psychosocial Variables, COMT Gene, and Chronic Facial Pain.

INTRODUCTION: The purpose of this study was to evaluate the associations of variability in pulp sensitivity with sex, psychosocial variables, the gene that encodes for the enzyme catechol-O-methyltransferase (COMT), and chronic painful conditions (temporomandibular disorders [TMDs]). METHODS: The study was composed of 97 subjects (68 women and 29 men aged 20-44 years). The electric (electric pulp tester) and cold (refrigerant spray) stimuli were performed on mandibular lateral incisors. The results were expressed as pain threshold values for electric pulp stimulation (0-80 units) and as pain intensity scores (visual numeric scale from 0-10) for cold stimulation. The Research Diagnostic Criteria for TMD were used to assess TMD, depression, and somatization. DNA extracted from peripheral blood was genotyped for 3 COMT polymorphisms (rs4680, rs6269, and rs165774) using the real-time TaqMan method. Multivariate linear regression was used to investigate the joint effect of the predictor variables (clinical and genetic) on pulp sensitivity (dependent variables). RESULTS: Threshold responses to electric stimuli were related to female sex (P < .01) and the homozygous GG genotype for the rs165774 polymorphism (P < .05). Pain intensity to cold stimuli was higher in TMD patients (P < .01) and tended to be higher in women. Multivariate linear regression identified sex and the rs165774 COMT polymorphism as the determinants of electric pain sensitivity, whereas TMD accounts for the variability in the cold response. CONCLUSIONS: Our findings indicate that sex/a COMT gene variant and TMD as a chronic painful condition may contribute to individual variation in electric and cold pulp sensitivity, respectively.

A comprehensive assessment of medical schools in Bosnia and Herzegovina.

OBJECTIVES: To perform internal and external evaluations of all 5 medical schools in Bosnia and Herzegovina against international standards. METHODS: We carried out a 2-stage survey study using the same 5-point Likert scale for internal and external evaluations of 5 medical schools in Bosnia and Herzegovina (Banja Luka, Foca/East Sarajevo, Mostar, Sarajevo and Tuzla). Participants consisted of managerial staff, teaching staff and students of medical schools, and external expert assessors. Main outcome measures included scores on internal and external evaluation forms for 10 items concerning aspects of school curriculum and functioning: 'School mission and objectives'; 'Curriculum'; 'Management'; 'Staff'; 'Students'; 'Facilities and technology'; 'Financial issues'; 'International relationships'; 'Internal quality assurance', and 'Development plans'. RESULTS: During internal assessment, schools consistently either overrated their overall functioning (Foca/East Sarajevo, Mostar and Tuzla) or markedly overrated or underrated their performance on individual items on the survey (Banja Luka and Sarajevo). Scores for internal assessment differed from those for external assessment. These differences were not consistent, except for the sections 'School mission and objectives', 'Curriculum' and 'Development plans', which were consistently overrated in the internal assessments. External assessments was more positive than internal assessments on 'Students' and 'Facilities and technology' in 3 of 5 schools. CONCLUSIONS: This assessment exercise in 5 medical schools showed that constructive and structured evaluation of medical education is possible, even in complex and unfavourable conditions. Medical schools in Bosnia and Herzegovina have successfully formed a national consortium for formal collaboration in curriculum development and reform.

Temptation of academic medicine: second alma mater and "shared employment' concepts as possible way out?

Apparently, in developing and in well-developed societies we are confronted with a crisis of academic medicine in all aspects: health care, teaching, and research. Health care providers in teaching hospitals are under pressure to generate revenues, academic research is pressed to keep pace with institutions devoted solely to research, and teaching is often understood not as privilege and honor but as burden and nuisance. The key problem and the principal cause of the crisis are low interest of the best young graduates to follow an academic career in a world where the benefits and values of the private sector are prevailing. Confronted with these circumstances and the continuous perils of permanent brain-drain, we developed an innovative concept of "shared employment' where two academic institutions (one in a developed and one in a developing country) will collaborate in development and support of fresh talents, building elite academic staff. Most academic exchange programs developed so far have proved to be ineffective and of poor vitality, in spite of loud exclamations, high expectations, and a huge amount of good will involved. In contrast, the suggested cooperation will be based exclusively on mutual interest and clearly defined benefits for all involved parties.