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A. Jogunčić, P. Djuric, A. Gradascevic, Christina Torka, M. Rosenberg, O. Gajic, S. Büttner

Acute kidney injury (AKI) is associated with an increased risk of progression to a severe form in every disease and, moreover, is associated with an increased mortality, and so it is also with coronavirus disease 2019 (COVID-19). AKI is a frequent complication in COVID-19 patients admitted to ICU for severe respiratory failure. ICU treatment itself indirectly could cause or exacerbate renal damage, through suboptimal fluid management, drug toxicity, or low human resources. The aims of this study were to assess AKI prevalence, fluid balance and glomerular filtration rate as a predictor of outcome in COVID-19 patients treated in the intensive care unit. We retrospectively analysed all adult patients admitted to the ICU at a regional hospital in northern Bavaria, from 1st March to 31st December 2020. Clinical data and laboratory results were retrospectively retrieved from the hospital information system and electronic case files. According to the severity of AKI based on the KDIGO criteria, and laboratory values were followed on the first 7 days on the ICU. In total 320 patients patients were included in the study. Level of significance was set to p<0.05. The mean age was 65 ± 19 years, 135 (42%) patients were females, 185 (58%) were males. Median length of ICU stay was 7 (2-13 days) in females, and 8 days (4- to 21 days) in males. At the ICU, 177 patients needed some form of ventilation, from which 109 (needed Invasive mechanical ventilation). During ICU stay, 81 patients have died, with fatality rate of 25%. Patients with AKI (n=48, 15%) at the admission to the ICU, had 2.1 times higher risk of death at the ICU than patients without AKI. There was a statistically significant difference in ICU survival based on a glomerular filtration rate, fluid balance, CRP and leukocyte values, F=1.957, p=0.026; Wilk's Λ=0.724, partial η2 = 0.276 Acute kidney injury is common in coronavirus disease 2019, and it is associated with poor clinical outcomes. Even first couple of days at the ICU could point to the outcome, with markers of inflammation, glomerular filtration rate, and fluid balance being most valuable variables.

K. Ong, Lauryn K. Stafford, Susan A. Mclaughlin, E. Boyko, S. Vollset, Amanda E Smith, Bronte E Dalton, J. Duprey et al.

Summary Background Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding Bill & Melinda Gates Foundation.

Today, tourism represents a strong and important economic branch, whether it concerns economically developed and underdeveloped countries as well as developing countries. It can increase employment in almost all countries, regardless of their level of development. Today's moment is marked by pronounced global crises, which again have a strong negative impact on the economic and social aspects of society, both globally and locally. Tourism, due to its characteristics and the positive effects it achieves in the process of realizing all activities in its area, can greatly reduce the percentage of unemployment in local communities. This positive effect of reducing unemployment is reflected in the possibility of employment for all categories of the unemployed, and particularly vulnerable groups of the unemployed such as people with disabilities, women, young people, the long-term unemployed, etc. Encouraging tourism in states or certain regions can have a favourable positive effect on employment within the territory. the same. For countries and regions that have developed tourism and that do not have pronounced problems with unemployment, activities through tourism increase the country's balance of payments as additional income through exports. Underdeveloped regions and countries and developing countries, by increasing activities through tourism, in addition to being an important source of income, realize a particularly important positive effect through the reduction of unemployment rates in them. Many developed countries, among which Austria is the leader, as a highly developed tourist destination for a long time, institutionally, have realized and use the potential offered by tourism to increase employment and actively use it to reduce the unemployment rate. Unfortunately, in our country and its tourist regions, where tourism is often one of the most important economic branches, this has not been done and they still record high rates of unemployment. Tourism in Bosnia and Herzegovina and Sarajevo Canton is a sector that can make a significant contribution to faster economic development. In our country and its regions and cantons, there are great potentials for increasing tourism activities, which will generate a greater number of jobs in tourism as well as tourism-related economic branches. To successfully solve the problem of unemployment in Bosnia and Herzegovina, its regions and cantons, positive experiences of tourism development through selective forms of tourism can be used, also using models of successful experiences from the world and the countries of the European Union. Keywords: tourism, unemployment, selective forms of tourism, European Union unemployment, Sarajevo Canton unemployment.

G. Bakalović, D. Bokonjić, D. Mihajlović, M. Čolić, Vanja Mališ, Marija Drakul, S. Tomić, I. Jojic et al.

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.

Jurica Baranašić, Y. Niazi, S. Chattopadhyay, L. Rumora, Lorna Čorak, A. V. Dugac, M. Jakopović, M. Samaržija et al.

Abstract Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a p-value < 3.3 × 10–5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1) to be associated with the COPD risk and two with the LC risk (HLA-C, HLA-B), with statistical significance. We also identified two SNPs located in the IL2RA gene associated with LC (rs2386841; p = 1.86 × 10−4) and COPD (rs11256442; p = 9.79 × 10−3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.

Alma Tahric, Haris Kolic, Aida Lavic, Dado Latinovic, Emina Pramenković

To generate oregano essential oil, the leaves and flowering tops of the Origanum vulgare plant go through the process known as steam distillation. This essential oil is known for its antibacterial activity. Bacterial biofilms are microbial communities attached to inert surfaces or tissues and encapsulated in complex matrices. Planktonic bacteria reversibly attach to surfaces, form microcolonies, and generate polymeric matrices around biofilms. Bacteria in biofilms provide bacteria with a safer way to reproduce and survive. This research tests the antibacterial activity and effect on the biofilm formation of Oregano essential oil. The antibacterial activity and effect on biofilm formation were tested against five bacterial strains, including Escherichia coli ATCC 14169, Escherichia coli ATCC 25922, Staphylococcus aureus NCTC 12393, Staphylococcus aureus ATCC 25923, and Staphylococcus aureus ATCC 6538. The concentrations of oil that were used in this research were 100%(v/v), 75%(v/v), 50%(v/v), and 25%(v/v). The best antibacterial effect was achieved against Staphylococcus aureus NCTC 12393 at 25%(v/v) of oil concentration. While performing the experiment, a variety of oregano oil concentrations had significant results for further tests to be performed.

The purpose of this study was to compare the effects of reviparin, dalteparin and enoxaparin on intraoperative blood loss in patients with trochanteric fracture treated with intramedullary nailing. This retrospective multicenter study included 100 patients with trochanteric fracture who were divided into three groups according to the low-molecular-weight heparin administered. In all cases, a short third generation Gamma nail was used for osteosynthesis. Complete blood count and number of red blood cell transfusions (RBC) were evaluated. The mean value of postoperative haemoglobin level was lower in the enoxaparin group compared to the reviparin group, with significant difference (p = 0.001; 95% CI 4.1–18.87). Patients in the dalteparin group received more RBC transfusions compared to the reviparin and enoxaparin group (p = 0.048). The use of enoxaparin and dalteparin in hip fracture patients can result in lower postoperative haemoglobin levels and more RBC transfusions compared to reviparin.

The goal in the present paper was to examine the combined and relative impact of fine motor ability, auditory working memory, and processing speed on fluid intelligence in a sample of early elementary school students. Our participant sample was 145 children (Mage = 9.1 years, SD = 1.1; 80 boys, 65 girls). We used the Raven’s Colored Progressive Matrices Test as a measure of fluid intelligence and five other measures to represent the three predictor variables: the Grooved Pegboard Test as a measure of fine motor skills, Digit Span Forwards and Digit Span Backwards tests as measures of working memory, and Rapid Automatized Naming and Letter-Digit Substitution tasks as measures of processing speed. Regression analyses indicated that only two of these measures had a statistically significant association with the fluid intelligence test scores, namely, scores on the Grooved Pegboard (fine motor skills) and Digit Span Backwards (working memory) tests, with these two measures explaining 35% of the variance in the fluid intelligence test scores. Thus, fine motor skills and working memory were correlated with fluid intelligence in early elementary-grade students. Until the directions of these relationships are better understood, we might assume that interventions aiming to increase young children’s fluid intelligence, or at least their intelligence scores, might partly target working memory and fine motor skills.

E. Carneiro, Camila Santos Paiva, Fabianne Silveira Cardoso, Silvia Angélica da C. B. Jacques, Ana Luiza Marques Serrano, Mariana dos Santos Ribeiro, C. Costa

Objetivo: Apresentar a implantação e desenvolvimento de um processo sistematizado de prescrição de Projeto Terapêutico Singular (PTS) para pacientes internados em um Centro de Reabilitação do Centro-Oeste brasileiro e seus desdobramentos e potencialidades para aplicação em diversos perfis de pacientes hospitalizados. Relato de experiência: A metodologia de prescrição e gerenciamento de PTS nos serviços da instituição conta com o envolvimento do paciente, sua família e equipe multiprofissional, que desempenham diversos papéis durante o processo: desde a avaliação de diagnóstico e prognóstico, até o gerenciamento de dados e desenvolvimento de planos de ação de melhoria. A implantação do PTS conforme a metodologia proposta se mostrou adaptável e funcional para gerenciar a jornada do paciente e auxiliou a organização e manejo da equipe diante dos prognósticos apresentados. A prescrição do PTS trouxe mais agilidade e funcionalidade na avaliação e manejo dos casos, proporcionando condutas mais assertivas voltadas às necessidades e desejos dos pacientes. Considerações finais: O gerenciamento do PTS contribui para o alcance de diversas metas institucionais e proporciona melhores desfechos clínicos aos pacientes, impactando diretamente na qualidade de vida dos mesmos, além da redução de custos e melhoria da performance da gestão sócio-econômica da saúde pública.

Introduction: The most important biochemical reactions of the human organism take place in the liver, and therefore it represents one of the most important organs for life. Parameters that play an important role in the diagnosis and monitoring of patients are the enzymes ALT, AST, GGT, ALP, and bilirubin. Objective: To evaluate the serum activity of enzymes and bilirubin in patients with liver cirrhosis and liver cancer. Materials and methods: The study included 120 patients aged over 50 years. Among them, 40 patients had liver cirrhosis, 40 had cancer and liver metastases, and 40 patients were apparently healthy (control group). The concentrations of AST, ALT, GGT, and ALP were determined on Abbott Architect i2000sr biochemical analyzer and Dimension analyzer. Results: The study showed that the mean values of the studied parameters were significantly higher in subjects with liver cirrhosis and cancer with liver metastases than in the control group. A statistically significant difference (p <0.05) was found in ALP and bilirubin concentrations between the studied groups. In addition, the study revealed a statistically significant difference (p <0.05) in ALT, AST, and GGT activity between subjects with cancer and the control group and subjects with cirrhosis and the control group. Conclusions: The results confirm that the activities of enzymes ALT, AST, GGT, ALP, and bilirubin were increased in subjects with cirrhosis and cancer compared to the control group.

A. Božič, V. Tomić, Željka Bilinovac, Martina Orlović Vlaho

Introduction: Many epidemiological studies have shown a connection between vitamin D deficiency and increased incidence of type 1 diabetes. Objective: The aim of this study is to determine the impact of vitamin D levels in children with newly diagnosed type 1 diabetes, taking into account the following parameters: gender, place of residence, positive/negative family history, comorbidities. Respondents and methods: The research was conducted through a retrospective analysis of the medical records of the Children's Disease Clinic of the University Clinical Hospital Mostar. The research included a sample of 30 children diagnosed with type 1 diabetes, treated at the Department of Endocrinology and Metabolic Diseases, Clinic for Children's Diseases, University Clinical Hospital Mostar. Results: The research consisted of 30 participants treated at the Department of Endocrinology and Metabolic Diseases, Clinic fo Children's Disease. The sample consists of 40% (n=12) male respondents and 60% (n=18) female respondents. Slightly more than half of the respondnents, 53.3% (n=16) lived in the city, while the remaining 46.7% (n=14) lived in the countryside. Statistical analysis of the patients with newly diagnosed type 1 diabetes, showed that there were significantly more patients (70%) with positive family history of diabetes mellitus than those with negative. In this study, 26.7% (n=8) patients with newly diagnosed type 1 diabetes had comorbidities, compared to 73.3% patients without comorbidities (n=22). Patients living in rural areas had significantly higher values of vitamin D3 concentration compared do those who lived in urban areas. Conclusion: 83.3% of subjects with newly diagnosed type 1 diabetes have a reduced level of vitamin D at the time of diagnosis. Numerous studies have shown a link between vitamin D deficiency and an increased risk of developing diabetes. Due to all of the above, supplementation and control of vitamin D is recommended, especially in children who have a risk in the form of positive family history and comorbidities such as Hashimoto's thyroiditis, and celiac disease from an early age for the purpose of prevention.

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