The discussion about whether the internet addiction disorder should be considered a primary addiction disorder or a secondary disorder due to other psychiatric illnesses is a very current topic. Although the term "addiction" has historically been associated with the pathological use of psychoactive substances, research over the past few decades indicates that various behaviors are also part of the spectrum of addiction. Accordingly, addictions to psychoactive substances and behavioral addictions overlap in several segments, but there are also certain differences between them. Taking into account these statements, the subject of this research was the analysis of the personality structure of Internet addicted adolescents, aimed at identifying if there are specific differences in certain personality dimensions between adolescents addicted to the Internet (reference group) and adolescents who abuse psychoactive substances, as well as in adolescents from the non-clinical population. The methodology was applied to a sample consisting of 125 respondents of both genders, aged 13 to 24, of whom 27 were from the clinical group of Internet addicts, 24 from the clinical group of psychoactive substance addicts, and 74 from the non-clinical population. A questionnaire was used for assessing Internet addiction (Internet Addiction Test) and a questionnaire for assessing the personality of adolescents (Belgrade Personality Inventory of Adolescents). The results indicate that we cannot talk about a specific profile that distinguishes respondents who are addicted to the Internet. However, despite the limitations, significant differences in certain dimensions indicate certain deviations between groups of adolescents with Internet addiction, addiction to psychoactive substances and the non-clinical population. Low research curiosity, poorly developed perseverance and goal orientation play a significant role in the aetiopathogenesis of Internet addicts. We conclude that the obtained results can have a significant role in solving the current dilemma whether Internet addiction disorder should be considered a primary addiction disorder or a secondary disorder due to other psychiatric diseases.

Eating disorders affect both the physical health, but also the psychological and social aspects of life of the people who suffer from them. The World Health Organization (WHO) uses the term "quality of life" to define the individuals' perception of their position in life in the context of their culture and values, and in relation to their goals, expectations, standards and concerns, to express a wide range of changes in the life of a person. Some of these changes are either caused or affected by eating habits that often present in a form of eating disorders. In recent decades, there has been growing interest in finding adequate questionnaires to help identify and measure the severity of eating disorders, as well as the quality of life of these patients. Several studies have been conducted on this topic, and scientific evolution and progress will be discussed in detail below to identify the most appropriate questionnaire to assist clinicians in their therapeutic practices. The primary objective is the detailed identification and classification of eating disorders in line with the most recent findings. The secondary objective is identification and classification of the questionnaires for testing eating disorders and quality of life. We conducted a review of the current research into developing the possibility of detecting eating disorders and potential health risks in untreated patients. The following index data bases were digitally searched: PubMed-Medline, Web of Science, Scopus, Cochrane database of systematic reviews, Embase, Epistemonikos, all searched up to August 2022. The combination of keywords revised in the list of medical subject headings (MeSH) was used to select relevant articles: (eating disorders) and (tests and/or questionnaires for eating disorders and quality of life). The analysis included meta-analyses, systematic reviews and original scientific articles. Special attention was paid to the discussion on identifying and providing insight into eating disorders in line with the latest findings, as well as to the examination and description of questionnaires for exploring eating disorders and quality of life. Among the first questionnaires used in practice to assess the quality of life of patients with eating disorders were Short Form-36 (SF-36) and the Eating Disorder Examination Questionnaire (EDE-K). Although generic questionnaires were applied and had produced good results, there is still no specific questionnaire on the quality of life of persons with eating disorders. New discoveries emerge as the search continues for highly specialized and sensitive questionnaires. Several instruments and questionnaires are used to get a final result in several studies investigating the connection between the intensity of symptoms caused by eating disorders and the quality of life, which shall be discussed below. Great progress has been made in evaluating and designing appropriate questionnaires to help clinicians and researchers in diagnostics, developing treatment strategies and providing prognoses for eating disorders, as well as in assessing the quality of life of these patients. Most studies and research come to the conclusion that a combination of multiple questionnaires simultaneously is the best choice for detection and prevention of deterioration in the quality of life of patients with eating disorders, as well as for considering the predictive factors that pertain to the quality of life. It is important to emphasize frequent comorbidity of other mental illnesses, such as depression and anxiety, meaning that it is important to use instruments that help in early detection of these comorbidities during examination.

227 Наше писмо уреднику анализира сазнања о интензитету и учесталости паралелног појављивања вазомоторних, соматских и психолошких симптома у климактеријуму, менопаузи и понеких у постменопаузи. Написан је да подстакне стручну и научну јавност да критички анализира питања и да предложи одређени правац деловања унутар могућности репродуктивне ендокринологије, менталног здравља и методологија расположивих за примену опција лечења. Писмо уреднику такође пружа најновију перспективу сазнања која служи сврси и покреће контроверзну тему у нади да ће се боље разумети концепт (симптома и третмана).

This letter to editor contains an overview of commentary article in which the authors explain how they designed the novel biomarker. The Electrophysiologic Coefficient of Depressiveness - δEPCD detects the presence of a depressive disorder while being able to quantify its severity. This biomarker follows vital function - high frequency heart rate variability in relation with neuroactive metabolic components - concentration ratio between quinolinic acid, and kynurenine acid and it is both sensitive and specific in regard to depressive disorders. Diagnostics of depressive disorders could be improved by checking this novel biomarker and/or re-assessment of individuals who might have depression as well as in rising the awareness about the depressive disorders' prevalence and treatment. So far biomarkers have been classified as dynamic (descriptive) or static (prognostic). With this new complex biomarker, that comprises potentials of both categories, we might be able to introduce a new category - a physiological biomarker. Physiological biomarkers should not have exclusive application within the depressive disorder, but the future research should identify more physiological biomarkers related to other diseases.However, the findings need further evidence procuring new information regarding diagnostics of depressive disorders. Though it presents a novel methodology which would add to a biomarkers research, more specifically type-classification, lack of clear and concise protocol regarding clinical interpretation and a consistent administrative structure and/or logistics to perform the measurements are present. For this reason, further research in different settings and on a larger sample size are necessary.

COVID-19 pandemic has put traditional forms of work and education on hold for many institutions. The impact of the transition to "online" work and education mode on mental and education on mental health is particularly interesting. The primary objective of this paper was to to identify advantages and disadvantages of transition to the online work regime that were additionally exacerbated by the pandemic (managerial aspect). The secondary objective was to consider this impact on the mental health of the individuals (socio-psychological aspects). A review of the literature published so far related to the work and teaching process in the Covid-19 pandemic recommends an online regime whenever possible. The results in the labor market domain indicate that if a person is self-disciplined, does not require supervision, has clear tasks and motivation, the online regime provides a number of benefits to such an employee, and consequently to the employer. On the other hand, for people who find motivation to work primarily in contact with colleagues, require supervision, lack self-discipline, as well as for those who aspire to managerial positions, teleworking does not give favorable results. In the field of teaching, in online education, quantitative analysis shows an improved success of pupils and students, but raises the question of whether this success is backed by real knowledge. The identified health consequences for individuals exposed to long-term online interaction regimes are, primarily: burnout syndrome, isolation from friends, problems in family relationships, experience of reduced happiness at home, general poor health and lack of sleep. It is likely that this regime will continue to some extent in the foreseeable future; work organizations and educational institutions will need to implement formalized policies that take into account support for managing the boundary between work and home activities, role clarity, workload, performance indicators, technical support, facilitating networking and training for managers.

Atherosclerosis is the underlying cause of cardiovascular diseases (CVDs) such as myocardial infarction and ischemic stroke. It is a lipid-triggered chronic inflammatory condition of the arterial vascular wall that is driven by various inflammatory pathways including atherogenic cytokines and chemokines. D-dopachrome tautomerase (D-DT), also known as macrophage migration inhibitory factor-2 (MIF-2), belongs to the MIF protein family, which is best known for its pathogenic role in a variety of inflammatory and immune conditions including CVDs. While MIF is well known as a promoter of atherogenic processes, MIF-2 has not been studied in atherosclerosis. Here, we investigated atherosclerosis in hyperlipidemic Mif-2−/−Apoe−/− mice and studied the role of MIF-2 in various atherogenic assays in vitro. We found that global Mif-2 deficiency as well as its pharmacological blockade by 4-CPPC protected against atherosclerotic lesion formation and vascular inflammation in models of early and advanced atherogenesis. On cellular level, MIF-2 promoted monocyte migration in 2D and 3D and monocyte arrest on aortic endothelial monolayers, promoted B-cell chemotaxis in vitro and B-cell homing in vivo, and increased macrophage foam cell formation. Dose curves and direct comparison in a 3D migration set-up suggest that MIF-2 may be a more potent chemokine than MIF for monocytes and B cells. We identify CXCR4 as a novel receptor for MIF-2. The evidence relies on a CXCR4 inhibitor, CXCR4 internalization experiments, MIF-2/CXCR4 binding studies by yeast-CXCR4 transformants, and fluorescence spectroscopic titrations with a soluble CXCR4 surrogate. Of note, Mif-2−/−Apoe−/− mice exhibited decreased plasma cholesterol and triglyceride levels, lower body weights, smaller livers, and profoundly reduced hepatic lipid accumulation compared to Apoe−/− mice. Mechanistic experiments in Huh-7 hepatocytes suggest that MIF-2 regulates the expression and activation of sterol-regulatory element binding protein-1 and −2 (SREBP-1, SREBP-2) to induce lipogenic downstream genes such as FASN and LDLR, while it attenuated the activation of the SREBP inhibiting AMPK pathway. Studies using receptor Inhibitors showed that SREBP activation and hepatic lipoprotein uptake by MIF-2 is mediated by both CXCR4 and CD74. Lastly and in line with a combined role of MIF-2 in vascular inflammation and hepatic lipid accumulation, MIF-2 was found to be profoundly upregulated in unstable human carotid plaques, underscoring a critical role for MIF-2 in advanced stages of atherosclerosis. Together, these data identify MIF-2 as a novel atherogenic chemokine and CXCR4 ligand that not only promotes lesion formation and vascular inflammation but also strongly affects hepatic lipogenesis in an SREBP-mediated manner, possibly linking atherosclerosis and hepatic steatosis.

Introduction. Higher level of knowledge and frequent contacts with peers with disabilities can influence the emergence of more positive attitudes of students towards peers with disabilities. In regard to that, our aim was to test the importance of knowledge, contact frequency and other possible factors influencing attitudes of students toward disabled peers. Methods. The study included 140 students of 4th and 5th grade of primary schools. The research was conducted in the period from December 2020 to March 2021 in two primary schools. The Chedoke McMaster scale was used to examine students' attitudes toward peers with disabilities, while Contact with Disabled Persons Scale and the Children's Knowledge about Handicapped Persons Scale were used to assess frequency of contact and knowledge about disabilities. Results. Girls showed a significantly higher level (25.21±6.21) of frequency of contacts with students with disabilities compared to boys (19.66±7.30) (p=0.043) and higher level of knowledge (27.88±5.88) about disabilities compared to boys (25.50±4.69) (p=0.009). Respondents who attended school together with children with disabilities (31.07 ± 8.41) showed a significantly higher level of frequency of contacts with students with disabilities compared to respondents who did not attend school with peers with disabilities (13.72±6.32) (p=0.001). Conclusion. Higher level of knowledge and frequent contacts with peers with disabilities does not have influence on the emergence of more positive attitudes of students towards peers with disabilities.

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is an evolutionarily conserved multi-protein complex, consisting of eight subunits termed CSN1-CSN8. The main biochemical function of the CSN is the control of protein degradation via the ubiquitin-proteasome-system through regulation of cullin-RING E3-ligase (CRL) activity by deNEDDylation of cullins, but the CSN also serves as a docking platform for signaling proteins. The catalytic deNEDDylase (isopeptidase) activity of the complex is executed by CSN5, but only efficiently occurs in the three-dimensional architectural context of the complex. Due to its positioning in a central cellular pathway connected to cell responses such as cell-cycle, proliferation, and signaling, the CSN has been implicated in several human diseases, with most evidence available for a role in cancer. However, emerging evidence also suggests that the CSN is involved in inflammation and cardiovascular diseases. This is both due to its role in controlling CRLs, regulating components of key inflammatory pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and complex-independent interactions of subunits such as CSN5 with inflammatory proteins. In this case, we summarize and discuss studies suggesting that the CSN may have a key role in cardiovascular diseases such as atherosclerosis and heart failure. We discuss the implicated molecular mechanisms ranging from inflammatory NF-κB signaling to proteotoxicity and necrosis, covering disease-relevant cell types such as myeloid and endothelial cells or cardiomyocytes. While the CSN is considered to be disease-exacerbating in most cancer entities, the cardiovascular studies suggest potent protective activities in the vasculature and heart. The underlying mechanisms and potential therapeutic avenues will be critically discussed.

ABSTRACT Objective/Background: About 15% of grievers experience complicated grief. We determined cross-sectional and longitudinal relations of grief and complicated grief with sleep duration and quality in the general population of elderly adults. Participants: We included 5,421 men and women from the prospective population-based Rotterdam Study. Methods: The Inventory of Complicated Grief was used to define grief and complicated grief. We assessed sleep with the Pittsburgh Sleep Quality Index. Results: After 6 years, 3,511 (80% of survivors) underwent the follow-up interview. Complicated grief was cross-sectionally associated with shorter sleep duration and lower sleep quality. These associations were explained by the presence of depressive symptoms. The prospective analyses showed that sleep duration and sleep quality did not decline further during follow-up of persons who experienced grief or complicated grief. Conclusion: In community-dwelling, middle-aged and older adults, persons with normal and complicated grief had both a shorter sleep duration and a lower sleep quality, mainly explained by depressive symptoms. However, prospective analyses showed that sleep quality and sleep duration do not decline further in persons with normal grief and complicated grief.