Background: The aim of this study was to compare the level of inammatory parameters in 3 different groups of COVID-19 patients depending on severity of clinical manifestations and to dene which inammatory parameter can be used as predictor of clinical severity and outcome. A total of 51 subjects was included in this study by retrospective review of theMethods: documentation at the Clinic for Infectious Diseases of University Clinical Hospital Mostar. The following data were collected: demographic, clinical symptoms, complications, therapy, and the level of inammatory parameters (C-reactive protein at the admission, procalcitonin, leukocytes, relative neutrophils count, relative lymphocyte count). Depending on the value of paO2/O2 patients were separated into 3 groups: mild, moderate and severe group. Data entry into the tables was followed by statistical data processing using IBM SPSS Statistics v.26 and Microsoft Excel 2013. Most frequent symptoms were fever (82% of all subjects), cough (61%), trouble breathing (55%), shortness ofResults: breath (43%), chest pain (27%), muscle pain (25%), diarrhea (20%), vomiting (6%) and headache (6%). The overall mortality of this study was 35%, with a statistically much higher mortality in severe patients. Also C-reactive protein levels were higher in severe patients. Conclusions: Levels of C-reactive protein on admission were signicantly higher in patients who developed a severe clinical manifestations. Also, mortality in severe patients was statistically higher than the remaining 2 groups of patients. CRP is reported as a prognostic factor in the severity of clinical manifestations and mortality of hospitalized COVID-19 patients.

Purpose Phosphonates, like 3-AminoPropylphosphonic Acid (ApA), possess a great potential for the therapy of bone tumours, and their delivery via cellulose nanocrystals (CNCs) seems a promising approach for their increased efficacy in target tissues. However, the immunological effects of CNC-phosphonates have not been investigated thoroughly. The main aim was to examine how the modification of CNCs with phosphonate affects their immunomodulatory properties in human cells. Methods Wood-based native (n) CNCs were modified via oxidation (ox-CNCs) and subsequent conjugation with ApA (ApA-CNCs). CNCs were characterised by atomic force microscopy (AFM) and nanoindentation. Cytotoxicity and immunomodulatory potential of CNCs were investigated in cultures of human peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MoDCs)/T cells co-cultures by monitoring phenotype, cytokines production, allostimulatory and Th/Treg polarisation capacity. Results AFM showed an increase in CNCs' thickens, elasticity modulus and hardness during the modification with ApA. When applied at non-toxic doses, nCNCs showed a tolerogenic potential upon internalisation by MoDCs, as judged by their increased capacity to up-regulate tolerogenic markers and induce regulatory T cells (Treg), especially when present during the differentiation of MoDCs. In contrast, ox- and ApA-CNCs induced oxidative stress and autophagy in MoDCs, which correlated with their stimulatory effect on the maturation of MoDCs, but also inhibition of MoDCs differentiation. ApA-CNC-treated MoDCs displayed the highest allostimulatory and Th1/CTL polarising activity in co-cultures with T cells. These effects of ApA-CNCs were mediated via GABA-B receptor-induced lowering of cAMP levels in MoDCs, and they could be blocked by GABA-B receptor inhibitor. Moreover, the Th1 polarising and allostimulatory capacity of MoDCs differentiated with ApA-CNC were largely preserved upon the maturation of MoDCs, whereas nCNC- and ox-CNC-differentiated MoDCs displayed an increased tolerogenic potential. Conclusion The delivery of ApA via CNCs induces potent DC-mediated Th1 polarisation, which could be beneficial in their potential application in tumour therapy.

Abstract Introduction: To curb the COVID-19 pandemic, countries across the globe have adopted either a mitigation or anelimination policy, such as the zero-COVID-19 strategy. However, further research is needed to systematically investigate the advantages of the zero-COVID-19 strategy in the literature. To bridge the research gap, this study examines the zero-COVID-19 strategy in terms of its advantages as a global anti-pandemic framework. Methods: A literature review was conducted in PubMed, PsycINFO, and Scopus to locate academic articles that discussed the advantages of the zero-COVID-19 strategy. Braun and Clarke’s thematic analysis approach was adopted to guide the data analysis process. Results: The findings of our study show that the advantages of the zero-COVID-19 strategy range from short-term (e.g., limited virus infections, hospitalizations, and deaths), to medium-term (e.g., reduced presence of other infectious diseases), and long-term (e.g., low incidence of long COVID-19). While local residents mainly leverage these advantages, they also impact the global community (e.g., stable global supply of essentials, such as COVID-19 vaccines). Conclusions: COVID-19 is catastrophic, yet controllable. Our study examined the advantages of the zero-COVID-19 strategy from a nuanced perspective and discussed how these advantages benefit both the local and the global community in pandemic control and management. Future studies could investigate the shortcomings of the zero-COVID-19 strategy, especially its unintended consequences, such as adverse impacts on vulnerable populations’ mental health, so that society could more efficiently, economically, and empathetically capitalize on the potential of the zero-COVID-19 strategy for the betterment of personal and public health.

Background: Antimicrobial photodynamic therapy (PDT) has been introduced as a potential option for peri-implantitis treatment. The aim of this study is to evaluate the antimicrobial effect of a novel technique involving a combination of 445 nm diode laser light with 0.1% riboflavin solution (used as a photosensitizing dye) as applied on a bacterial–fungal biofilm formed on implants and to compare the performance of this technique with that of the commonly used combination of 660 nm diode laser with 0.1% methylene blue dye. Methods: An in vitro study was conducted on 80 titanium dental implants contaminated with Staphylococcus aureus (SA) and Candida albicans (CA) species. The implants were randomly divided into four groups: negative control (NC), without surface treatment; positive control (PC), treated with a 0.2% chlorhexidine (CHX)-based solution; PDT1, 660 nm (EasyTip 320 µm, 200 mW, Q power = 100 mW, 124.34 W/cm2, 1240 J/cm2) with a 0.1% methylene blue dye; and PDT2, 445 nm (EasyTip 320 µm, 200 mW, Q power = 100 mW, 100 Hz, 124.34 W/cm2, 1.24 J/cm2) with a 0.1% riboflavin dye. Results: The PDT1 and PDT2 groups showed greater reduction of SA and CA in comparison to the NC group and no significant differences in comparison to the PC group. No statistically significant differences between the PDT1 and PDT2 groups were observed. Conclusions: A novel antimicrobial treatment involving a combination of 445 nm diode laser light with riboflavin solution showed efficiency in reducing SA and CA biofilm formation on dental implant surfaces comparable to those of the more commonly used PDT treatment consisting of 660 nm diode laser light with methylene blue dye or 0.2% CHX treatment.

Background and Purpose: Improper distribution of health workers is a worldwide problem, especially in developing countries. The shortage of health personnel has been intensified over the past two decades as a result of the emigration of health workers from developing countries to developed ones and disparities between urban and rural regions. Materials and Methods: This cross-sectional, quantitative, and descriptive study was conducted at the University of Sarajevo, Faculty of Health Studies, for two months. The study included 203 3rd-year and 4th-year undergraduate students of all study programs. The chi-square test was used to examine the difference between students’ attitudes about leaving according to gender, grade point, foreign language learning, and high school graduation, as well as different statements of intention to leave or stay. Results: Of 203 respondents, 49(24.1%) were male and 154(75.9%) were female. Thirty-four students (16.75%) stated their attitude towards the definitive departure. Also, 129 students (63.55%) were thinking about leaving after graduation, while 40 students (19.7%) wanted to continue their life in Bosnia and Herzegovina after their studies. Almost half of the female students (49.26%) and slightly more than half of the male students (14.28%) think about leaving after their studies, with a statistically significant difference between men and women who think about leaving and those who stay. The positive attitudes, which the students who are leaving, for the most part, agreed upon were the acquisition of life experience that their occupation profile was sought in other countries, and career development and professional development. The reasons why most students consider leaving the country after their studies are due to the attitude that their education and degree are more valued in other countries, higher living standards in other fields, and career development and professional development. Conclusion: To prevent the migration of health students, retention policies are needed that target immigrant staff. These policies can be extremely important in preventing the problem of a lack of quality health staff in the near future.

The aim of the research was to determine whether the age of the patient affects the duration of the procedure and the amount of ionizied radiation delivered when performing diagnostic coronary angiography. The research was conducted at the Clinic for Invasive Cardiology of the Public Health Institution "University Clinical Center" Tuzla in the period from December 2018. to January 2020. The research included a total sample of 240 respondents, average chronological age of 62.60 ± 9.22 years, ranging from 24 to 85 years. Out of a total of 240 respondents, in 121 respondents coronarny angiography was performed using transradial arterial approach and 119 by performing a transfemoral arterial approach. The total sample was divided into two subsamples of respondents. The first sub-sample consists of respondents up to 65 years of age, and the second sub-sample consists of respondents over 65 years of age. During each performance of coronary angiography, the duration of the procedure (in minutes and seconds) and the amount of radiation delivered during the procedure (in mGy) were measured. The research data were processed using the method of parametric and non- parametric statistics. The Mann-Whitney U test was used to verify the research objective. Based on the obtained research results, it can be concluded that in patients over 65 years of age, the duration of the coronary angiography procedure is longer, and is at the limit of statistical significance (p= 0.057). The amount of delivered radiation is higher in respondents over 65 years of age, but it is not statistically significant (p= 0.396). Keywords: Coronary angiography, coronary disease, procedure duration, age, amount of delivered radiation.

The aim of the study is to present and tune a fully automatic deep learning algorithm to segment colorectal cancers (CRC) on MR images, based on a U-Net structure. It is a multicenter study, including 3 different Italian institutions, that used 4 different MRI scanners. Two of them were used for training and tuning the systems, while the other two for the validation. The implemented algorithm consists of a pre-processing step to normalize and to highlight the tumoral area, followed by the CRC segmentation using different U-net structures. Automatic masks were compared with manual segmentations performed by three experienced radiologists, one at each center. The two best performing systems (called mdl2 and mdl3), obtained a median Dice Similarity Coefficient of 0.68(mdl2) - 0.69(mdl3), precision of 0.75(md/2) - 0.71(md/3), and recall of 0.69(mdl2) - 0.73(mdl3) on the validation set. Both systems reached high detection rates, 0.98 and 0.95, respectively, on the validation set. These encouraging results, if confirmed on larger dataset, might improve the management of patients with CRC, since it can be used as a fast and precise tool for further radiomics analyses. Clinical Relevance - To provide a reliable tool able to automatically segment CRC tumors that can be used as first step in future radiomics studies aimed at predicting response to chemotherapy and personalizing treatment.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.

Background: Familial hypercholesterolemia (FH) is an inherited disorder characterized by significantly elevated levels of low-density lipoprotein (LDL) cholesterol and is usually diagnosed after the occurrence of major adverse cardiovascular event. Aim: The aim of this study was to evaluate FH existence, increase awareness of this disorder, and highlight the importance of early treatment which leads to a reduction of premature cardiovascular events and death. Methods: The research had a cross-sectional, descriptive, and analytical character, and included 6881 (n = 6881) patients who were hospitalized in the Clinic for Heart, Blood Vessel and Rheumatic Diseases, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina, in the period from January 2019 to January 2021. LDL values were analyzed, and all patients with LDL ≥4 mmol/L were included in the study. The Dutch Lipid Score was calculated for all patients, and the findings of invasive coronary angiography were taken into account in those patients for whom it was performed. Results: From 6881 patients, 74 patients had LDL ≥4 mmol/L. Possible FH (score: 3–5) was found in 25 patients, probable FH (score: 6–8) in 2 patients, while the diagnosis of definite FH was not made in any patient. A ST-elevation myocardial infarction was an indication for hospitalization in 44.60% (n = 33), hypertension in 14.87% (n = 11), and angina pectoris in 14.87% (n = 11) of patients. Patients under the age of 65 had higher Dutch Lipid Score compared to the patients above the age of 65, regardless of male or female. Correlational analysis indicated a significant positive relationship between Dutch Lipid Score and level of cholesterol (r =0.385; P < 0.01) and LDL (r = 0.401; P < 0.001). Statistically significant predictors in the explanation of FH were age (β = −0.45; P < 0.001) and LDL (β = 0.52; P < 0.001). Conclusion: LDL values and age are the main determinants of the FH existence, and the effect on LDL values should be imperative in clinical practice.