Multisystem inflammatory syndrome in children (MIS-C) is a rare complication of SARS-CoV-2 infection in the pediatric population, caused by extensive activation of immune system. The understanding of the distorted immune response is still in the early stages.To analyze comprehensively immune profile in MIS-C patients including detailed serologic response to SARS-CoV-2 in comparison with control groups.Blood samples of consecutive MIS-C patients were collected at admission. Flow cytometric analysis of all lymphocyte populations including T and B cell differentiation was performed. Immunophenotyping was performed by six-color panels for the detection of lymphocyte subpopulations. Anti-SARS-CoV-2 specific antibodies were measured in the patients serum. The IgA and IgG antibodies against S protein, the IgG S1 and S2 specific antibodies, antibodies against nucleoprotein and neutralising antibodies were measured. Patients were assessed for a wide range of auto-antibodies, namely ANA, anti-ENA (Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, Pm/Scl 100, Scl-70), myositis specific antibodies (EJ, MDA-5, TIH-Y, Ro52, SAE-1, SAE-2, NXP-2), anti-dsDNA, anti-phopholipid antibodies (aCl IgA, IgG, IgM, antiβ2GPI IgG, IgM) and ANCA. Control groups to compare specific antibody response consisted of 14 healthy children and 19 healthy adults, who had SARS-CoV-2 infection in the last 2 months.Samples of 20 patients were included (14/20 boys, median age 12.4 years). Patients had higher percentage of double negative T cells and low numbers of of cytokine producing T cells Th1, Th2 and Th17. . Numbers of immune competent and CD21+ transitional B cells were also lowered. All patients had positive antibodies against SARS-CoV-2 including neutralising antibodies. Nine (9/19; 47 %) patients had high titer (≥1:160) of neutralising antibodies. Results were compared with 2 control groups; 14 healthy children (7/14 boys; median age 8 years,) and 19 healthy adults, who all experienced SARS-CoV-2 infection in the last two months. Patients with MIS-C had significantly higher levels of anti-S IgA (p<0.0001), patients with MIS-C and healthy children had significantly higher titers of anti-S1 (p=0.001) and significantly lower titers of anti-S2 (p=0.016) in comparison to adults (Figure 1). No differences were found in the titers of neutralising antibodies and anti-N antibodies. All patients were ANA negative, 19/20 patients were anti-ENA negative, whereas 1 patient had anti-Ro antibodies in low titre. Three patients had aCL IgG in medium titre and 2 patients anti-beta2GPI IgG in low titre. Patients were negative for all other autoantibodies.The immune response in MIS-C patients is specific with most prominent differences in elevated percentage of double negative T cells and low numbers of Th1, Th2, Th17 and CD21+ transitional B cells. MIS-C patients have distinct serologic response with high anti-S IgA, high anti-S1 and low anti-S2 titres.Figure 1.Antibody titres in patient group and control groups. Mean value with SEM s shown.None declared.

A growing number of professional societies in clinical and medically related disciplines investigate evidence, make recommendations, and take action to advance gender equity. Evidence on women’s advancement and leadership in the context of the European Alliance of Associations for Rheumatology, EULAR, is limited [1].The objective of the EULAR Task Force on Gender Equity in Academic Rheumatology was to establish the extent of the unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology and develop a framework to address this through EULAR and Emerging EULAR Network (EMEUNET).Potential interventions to accelerate gender-equitable career advancement in academic rheumatology were gathered from a narrative review of the relevant literature, expert opinion of a multi-disciplinary Task Force (comprised of 23 members from 11 countries), data from the surveys of EULAR scientific member society leaders, EULAR and EMEUNET members, and EULAR Executive Committee members. These interventions were rated by Task Force members, who ranked each according to perceived priority on a five-point numeric scale from 1 = very low to 5 = very high.A framework of 29 potential interventions was formulated, which covers six thematic areas, namely, EULAR policies, advocacy and communication, EULAR Congress and associated symposia, training courses, mentoring/peer support, and EULAR funding (Figure 1).Figure 1.A framework of potential interventions with the levels of priority, mean and standard deviation (SD)The framework provides structured interventions for accelerating gender-equitable career advancement in academic rheumatology.[1]Andreoli L, Ovseiko PV, Hassan N, et al. Gender equity in clinical practice, research and training: Where do we stand in rheumatology? Joint Bone Spine 2019;86(6):669-72.The task force is grateful to EULAR for funding this activity under project number EPI 024.None declared

Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of around 3 in 1, 000,000 children. It is known that in pediatric jSSc cohorts, there are a significant number of patients with overlap features, such as arthritis and myositis. However, the disease burden between those with and without overlap features in jSSc has not been defined.Compare the clinical phenotype between children with and without overlap features in the juvenile systemic scleroderma inception cohort (jSScC).A cross-sectional study was performed using baseline visit data. Demographic, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were extracted from jSScC. Comparison between patients with and without overlap features was performed using chi-square test and Mann Whitney U-test.At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s onset was 10 years (±3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Overlap features occurred 17% (n=30) of the cohort, 12.5% in the diffuse cutaneous (dc) jSSc and in 30% in the limited cutaneous (lc) jSSc. Significant differences in clinical characteristics were found between those patients with compared to without overlap characteristics. Patients with overlap features presented more frequently with Gottron papules (p=0.007), swollen joints (p=0.019), muscle weakness (p=0.003), and lung involvement documented by decreased DLCO < 80% (p=0.06) and/or abnormal high resolution computed tomography (p=0.049). Anti-PM/Scl autoantibodies were also more common in this group (p=0.001). Significantly more patients without overlap features had Raynaud´s (p=0.006). Physician Global Assessment of disease activity was significantly higher in patients with overlap features (41 vs 34; p=0.041). (Table 1.)Table 1.Demographic and clinical characteristics of jSSc patients with and without overlap features.Whole CohortN=175Patients without overlapN=145Patients with overlapN=30P valueFemale to Male Ratio 4.3:1(142/33)4:1(116/29)6.5:1(26/4)0.395Cutaneous subtypeDiffuse subtype (N)73% (128)11216Limited subtype (N)27% (47)3317Mean disease duration (years)3.1 (± 2.7)3.2 (± 2.8)3.1 (± 2.2)0.291Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud10.0 (± 3.8)10 non-Raynaud10.0 (± 3.7)7 non-Raynaud0.931Mean age of onset of non-Raynaud´s (years)10.2 (± 3.8)10.2 (± 3.9)9.8 (± 3.7)Disease modifying drugs (N)88% (154) 89% (129)83% (25)0.388Raynaud´s phenomenon90% (158)93% (135)77% (23)0.006Anti-PMScl18% (12/68)9% (5/53)47% (7/15)0.001Gottron Papules (N)27% (46/171)23% (33/144)48% (13/27)0.007DLCO <80% (N)44% (39/88)39% (28/71)65% (11/17)0.06Abnormal findings in HRCT (N)44% (59/133)40% (43/107)62% (16/26)0.049Proportion of patients with swollen joints 18% (32) 14% (21) 37% (11)0.019Muscle Weakness (N) 21% (31/149)16% (20/123) 42% (11/26)0.003Physician global disease activity(0-100) min -max35 (0-90) n=14134 (0-90) n=11441 (0-80) n=270.041Results from this large international cohort of jSSc patients demonstrate significant differences between patients with and without overlap features. Patients with overlap have significantly more interstitial lung disease and more physician rated disease activity and should not be considered to have more “mild disease”.Supported by the “Joachim Herz Stiftung”None declared

Abstract Digital transformation has put tremendous pressure on employees to innovate with the use of information technology (IT). This paper explores the extent to which digital literacy and personal innovativeness contribute to individual’s innovative work behavior (IWB). To test our hypotheses, we apply double bootstrapping chained mediation analyses paired with relative importance analysis on a dataset collected from employees (N = 167) in a pharmaceutical company. The results showed the existence of a double-mediation chain whereby digital practices and attitude toward digitalized innovation mediate the positive relationship between digital literacy and IWB. Surprisingly, said chain was not supported for personally innovative individuals, indicating that digital literacy plays a relatively more important role in stimulating attitudes toward digitalized innovation and IWB. Our findings add further specificity to research on digital natives and may help organizations understand the role of digital literacy and personal innovativeness in organizationally-relevant outcomes, such as IWB.

Background: The use of computer assisted surgery, navigation (NAV) in shoulder arthroplasty is still under discussion, regarding the clinical outcome and prosthesis longevity, especially when combining these factors with cost, time and surgeon’s experience. Beside the NAV, there has been in use patient-specific instrumentation (PSI) as an additional tool for more precise glenoid implant position. Surgical NAV and PSI for glenoid implant positioning in anatomic and reverse total shoulder arthroplasty are in last years under observation and discussion. Objective: To critically review and evaluate the current literature regarding the use of computer navigation and PSI in shoulder arthroplasty. Methods: Critical review of the existing literature. Results: Cost-effectiveness, prosthesis longevity and revision arthroplasty rate have not yet been proven clinically. Moreover, heterogeneity is high in studies that include different positioning systems (NAV, PSI and standard instrumentation). Heterogeneity is due to differences in surgical technique, implants, surgeon’s expertise, radiographic image analysis technique. Conclusion: The use of navigation systems and PSI should be clinically proven in the shoulder arthroplasty. Independent experts’ opinion and independent high level studies lack at the moment. There will be still a lot of talk regarding this topic in future.

Background According to available scientific references and textbooks, there are contradictory views concerning the etiology of signs and symptoms of TMD. Objectives The aim of this study was to determine a correlation between the incidence of signs and symptoms of TMD in children aged 12-18 who do not wear a fixed orthodontic appliance and the incidence of signs and symptoms of TMD in children who wear a fixed orthodontic appliance. Material and Methods The total number of 120 subjects were included in this survey and divided into two groups. There were 60 respondents in the experimental group that consisted of 30 boys and 30 girls with different types of malocclusion, who were treated with a fixed orthodontic straight wire technique. The remaining 60 respondents, which was a group that also consisted of 30 boys and 30 girls, were patients with neutroclusion. Results The results of the study have shown that the TMJ clicking sound symptom, the most common symptom of TMD, occurs with almost equal prevalence in both groups of respondents; specifically, 56.4% in orthodontic patients, and 46.6% in the control group respondents. A statistically significantly higher percentage of female respondents in both groups have experienced headache problems (p <0.03). Conclusion On the basis of the statistics obtained as a result of this research, we can come to the conclusion that there is no correlation between the fixed orthodontic treatment and the development of signs and symptoms of TMD.

Introduction: Dental implantology is the branch of dentistry that is gaining greater significance because a larger number of patients come with requests of implant placements. During dental implant placements, with patients with whom operation is carried out in the mandible, very frequently nervus alveolaris inferior can be injured. The nerve injury may occur during the implant placement, but the nerve may also be injured in case of harvesting of intraoral bone graft. During the bone graft harvesting, but also during any other procedure in the dentistry that entails working on vestibular side of corpus of the mandible, in order not to injure the nervus alveolaris inferior, it is important to familiarize oneself with the distance of the nerve from the outer vestibular cortex of the mandible. The objective of the study was to assess the vestibular bone thickness of the mandible in relation to the mandibular canal with the help of analysis of cone-beam computed tomography (CBCT) images.Methods: It was accessed the database of CBCT images taken at the School of Dental Medicine at the University of Sarajevo, where out of 700 reviewed CBCT images, an analysis of 322 CBCT images was conducted that satisfied inclusion criteria of the study. CBCT images were taken using of ORTHOPHOS SLX imaging unit. The measurement was conducted by Sidexis program on cross-section of CBCT image. The measurement of vestibular bone thickness was performed, by measuring the distance from the lateral wall of the mandibular canal to buccal mandibular compact bone, in the region of the second premolar, of the first and the second molar.Results: There were statistically significant differences in vestibular bone thickness between men and women on both sides in the region of the second premolar (p < 0.001) and first molar (p = 0.016 right, p = 0.018 left). T-test demonstrated no statistically significant difference in the vestibular bone thickens between men and women on either side in the case of vestibular bone thickness of the center of the second molar (p = 0.397 right, p = 0.743 left).Conclusion: Values of vestibular thickness of the mandible are larger with men than with women in all measuring points; however, statistically more significant differences between genders have been detected in the second premolar and center of the first molar.

We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening.

Bosnia and Herzegovina represents a very suitable experimental space for the analysis of integrative policy in the conditions, war and long-lasting crisis, of a devastated society which, due to the challenges of history, is deeply divided. In such a space, applying the analytical model designed and used by Seymour Lipset and Stein Rokan, the paper deals with the detection of social divisions that underlie party preferences in the 1990 elections for the Assembly of the Socialist Republic of Bosnia and Herzegovina. Analyzes of pre-election and post-election activities of political entities show the existence of an important link between ethno-confessional characteristics and attitudes on political issues and party preferences, which in accordance with the used theoretical model creates preconditions for talking about social divisions that have turned into party divisions. It can be determined that they are bh. political parties formed, with all their specifics, on the basic lines of Bosnia and Herzegovina social divisions. In the analysis of the relationship between social and political space and the influence of the structure of society on political relations and divisions, it is possible to determine that party divisions and divisions, their segmentation and polarization are conditioned, above all, by the depth and dynamics of fundamental Bosnia and Herzegovina social divisions. The divisions that emerged in the pre-election period of 1990 (we can conditionally define them as divisions communism vs anti-communism) were pushed into the background in the first post-election year and priority was given to the split that S. Lipset and S. Rokan defined as the center-periphery split. (or the territorial-cultural split as, after adaptation, Professor Nenad Zakošek called it). The second part of the paper presents an overview of the most important political parties in the 1990 elections and continues to examine the applicability of S. Lipset and S. Rokan's theory of turning social divisions into party divisions, this time in the first year of ethno-confessional parties in Bosnia and Herzegovina. Analyzing the basic lines of historical ethnic and confessional divisions in Bosnia and Herzegovina society and in the sphere of political (sub) system through indicators such as: predominant (ethnic, confessional, linguistic, cultural and regional) identifications, the relationship between ethno-confessional and civil, the relationship to the rights and freedoms guaranteed in Bosnia and Herzegovina. According to the Constitution, the attitude towards different solutions to the state question (remaining in the common state of Yugoslavia vs. the independent Republic of Bosnia and Herzegovina) tested the hypothesis that historical lines of ethno-confessional splits represent the basic determinant of political goals. It can be seen that the territorial-cultural divide (primarily in the form of center-periphery conflict) is actually a kind of complete split, given that it is a split that involves conflict between stable social groups (residents of the center and periphery but also members of different ethnic and confessional communities). In the Bosnia and Herzegovina case, these are (ethnic and confessional) communities that have different views on the most important issues of the social organization of the common state, which results in open conflict on the political scene in the form of voting for different political options, which can be transformed by ethnopolitical elites. (very easily) into various forms of violence against others and different in the territory that is under their political (and police) control.

The aim of this research was to examine the impact of aircraft noise on communities near the Belgrade Airport by conducting short-term noise measurements. Apart from the noise abatement procedure published in the Aeronautical Information Publication for Belgrade Airport, there are still neither publicly available reports of the actual efforts made towards the aircraft noise reduction nor the description of the current noise situation. In order to estimate the current noise situation, eighteen aircraft overflight noise measurements were taken in two settlements in specific sound-sensitive community areas around the Belgrade Airport. The results showed that level differences between background noise and aircraft overflights were higher than 10 dB for each measurement and could be considered significant. Furthermore, preliminary compatibility analysis with acoustic zoning was performed. Average daily noise levels were estimated from these short-term measurements and were compared to legal noise limits for different acoustic zones. The results indicate that in some cases noise levels exceed the legal threshold, which should encourage land use planners to include the issue of Belgrade acoustic zoning on the agenda, but also prompt Belgrade Airport to implement continuous noise and flight tracks monitoring.

Abstract Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms – direct or via transcription factors such as NRF2 and NF-κB – and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

Recent research in AI ethics has put forth explainability as an essential principle for AI algorithms. However, it is still unclear how this is to be implemented in practice for specific classes of algorithms—such as motion planners. In this paper we unpack the concept of explanation in the context of motion planning, introducing a new taxonomy of kinds and purposes of explanations in this context. We focus not only on explanations of failure (previously addressed in motion planning literature) but also on contrastive explanations—which explain why a trajectory A was returned by a planner, instead of a different trajectory B expected by the user. We develop two explainable motion planners, one based on optimization, the other on sampling, which are capable of answering failure and constrastive questions. We use simulation experiments and a user study to motivate a technical and social research agenda.

The task of every government, especially during the Covid-19 pandemic, is to provide services and goods for citizens and to maintain economic order. Therefore, the combination of legislation, the judiciary and administration is inevitable. Moreover, public administrations must transform the way they function by using more information and communication technology in order to remain responsive and efficient. This challenge was further revealed during lockdowns in individual countries, which affected their social and economic development. The solution to that challenge is the implementation of e-government in the public sector. It also increases innovation in governance processes as well as efficiency and effectiveness by offering more participative opportunities to citizens. Hence, a mature level of e-government development also arises. Nevertheless, there are significant differences among the levels of e-government development in the EU-28. The aim of this article is to assess the influence of e-government maturity on government effectiveness and efficiency in the EU-28. In order to obtain empirical results, a two-stage least square regression (2SLS) was applied. The empirical results show that e-government maturity positively and significantly contributes to enhancing government effectiveness and efficiency in the EU-28. In addition, the rule of law plays an important role in each stage regression model. Based on the empirical results, we can conclude that e-government is inevitable and should ensure the proper functioning of public administration during the Covid-19 pandemic.  

Cadmium (Cd2+) is toxic metal and environmental pollutant. Accumulation of cadmium in the kidney results initially in proximal tubule dysfunction. Although Cd2+ toxicity is well documented, all mechanisms that are involved in the early stages of nephrotoxicity, especially considering low micromolar concentrations of Cd2+ ions are still unknown. The Aim of this study was to investigate the effects acute exposure to different peritubular micromolar concentrations of cadmium (0.25, 0.50, 1.0, 2.0, 3.0, 5.0 μmol/L) on the peritubular cell membrane potential in proximal tubular cells of frog kidney. The experiments were performed on isolated, doubly perfused kidneys of Rana esculenta of both sexes. Aortic and portal vein were cannulated in order to perfusate luminal and peritubular cell membraine. In controled conditions, Ringer solution was simultaneously used to perfusate both cell membraines. Cadmium chloride (different concentrations: 0.25, 0.50, 1.0, 2.0, 3.0, 5.0 μmol/L) were added to the peritubular perfusate separately, by switching the peritubular perfusate from the control Ringer solution to Ringer solution with addition of cadmium ions. Peritubular cell membrane potentials (PD) were measured with conventional 3 mol/L KCl microelectrodes. The peritubular application of different micromolar Cd2+ concentrations led to a rapid, sustained, reversible hyperpolarization of the peritubular cell membrane: 0.25 µmol/L, by −3.3±0.4 mV (n=8, p<0.001); 0.50 µmol/L, by −3.0±0.5 mV (n=11, p<0.001); 1.0 µmol/L, by −2.9±0.6 mV (n=8, p<0.01); 2.0 µmol/L, by −4.2±0.4 mV (n=13, p<0.01); 3.0 µmol/L, by −3.4±0.3 mV (n=14, p<0.001); 5.0 µmol/L, by −3.0±0.4 mV (n=10, p<0.001). After switching the perfusion from Ringer solution with addition of cadmium ions to control Ringer, the peritubular membraine potential returned to the average values that were maintained before the peritubular Cd2+ application (p>0.05). Comparing the effect of different Cd2+ concentrations, there was no difference in the hyperpolarization of the peritubular cell membrane (p>0.05).Each cell served as its own control. Different low micromolar concentrations of Cd2+ provoked rapid and sustained hyperpolarization of peritubular membrane potential that did not show concentration-dependent response.