Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by Leishmania parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. ABSTRACT Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by Leishmania parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. A better understanding of the immunomodulatory effects of miltefosine is central to providing a rationale regarding synergistic mechanisms of activity to combine miltefosine optimally with other conventional and future antileishmanials that are currently under development. Therefore, a systematic literature search was performed to evaluate to what extent and how miltefosine influences the host Th1 response. Miltefosine’s effects observed in both a preclinical and a clinical context associated with immunomodulation in the treatment of leishmaniasis are evaluated in this review. A total of 27 studies were included in the analysis. Based on the current evidence, miltefosine is not only capable of inducing direct parasite killing but also of modulating the host immunity. Our findings suggest that miltefosine-induced activation of Th1 cytokines, particularly represented by increased gamma interferon (IFN-γ) and interleukin 12 (IL-12), is essential to prevail over the Leishmania-driven Th2 response. Differences in miltefosine-induced host-mediated effects between in vitro, ex vivo, animal model, and human studies are further discussed. All things considered, an effective treatment with miltefosine is acquired by enhanced functional Th1 cytokine responses and may further be enhanced in combination with immunostimulatory agents.

Sexting has recently attracted the attention of researchers. The aim of this study was twofold: (a) to investigate the prevalence of sexting among boys and girls, and b) to examine the relationship between different types of sexting and emotional difficulties in high school pupils. The research was conducted on a sample of 711 adolescents aged 14-19 years. The Sexting Behavior Questionnaire was used to assess sexting, while the Depression Anxiety and Stress Scales and the item of suicidality were used to assess emotional difficulties. The results of the study show that the most frequently reported type of sexting is sending sexually explicit content and the rarest is posting sexually explicit content. Boys are more frequently engaged in sexting compared to girls. Furthermore, pupils involved in sexting think about suicidal thoughts and suicide more often. The obtained results suggest that youth do participate in sexting and those who do have some negative thoughts, which emphasize the necessary for both a prevention and intervention approach for this population.

The idea of chatbots firstly appeared in the 1960s. But only after more than half a century passed the world became ready for their implementation into the real life, this being a result of the rapid progress in natural language processing, artificial intelligence, and the global presence of text messaging applications. Today, specialized chatbots exist in different domains, thus helping organizations handle large amount of inquiries. Idea of this project was to develop one friendly chatbot with whom you can talk about politics, movies, weather, sport, emotions and similar everyday things. Friendly chatbot named Zeka, is a web-based chatbot developed with the help of Chatterbot library. Chatbot relies on different natural processing and machine learning algorithms altered by its developers to increase its performance.

Numerous neuroimaging studies have revealed structural brain abnormalities in schizophrenia patients. There is emerging evidence that dysfunctional nerve growth factor (NGF) signaling may contribute to structural brain alterations found in these patients. In this pilot study, we investigated whether there was a correlation between NGF serum levels and gray matter volume (GMV) in schizophrenia patients. Further, we investigated whether there was an overlap between the correlative findings and cross-sectional GMV differences between schizophrenia patients (n = 18) and healthy controls (n = 19). Serum NGF was significantly correlated to GMV in the left prefrontal lobe, the left midcingulate cortex, and the brainstem in schizophrenia patients. However, we did not find any correlations of NGF serum levels with GMV in healthy controls. Schizophrenia patients showed smaller GMV than healthy controls in brain regions located in the bilateral limbic system, bilateral parietal lobe, bilateral insula, bilateral primary auditory cortex, left frontal lobe, and bilateral occipital regions. In a conjunction analysis, GMV in the left midcingulate cortex (MCC) appears negatively correlated to NGF serum levels in the group of schizophrenia patients and also to be reduced compared to healthy controls. These results suggest an increased vulnerability of schizophrenia patients to changes in NGF levels compared to healthy controls and support a role for NGF signaling in the pathophysiology of schizophrenia. As our pilot study is exploratory in nature, further studies enrolling larger sample sizes will be needed to further corroborate our findings and to investigate the influence of additional covariates.

To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood‐onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant improvement (CRIcSLE).

Introduction:Total hip endoprosthesis is one of the most frequent and effective methods that are used in the treatment of progressive degenerative hip changes. After the implantation of total hip endoprosthesis, patients perception on their postoperative improvement and health has big role in their contentment and thus in the success of the surgical procedure. The aim of this survey is to examine whether there are differences in the quality of life of people in third age before and after the implantation of total hip endoprosthesis.Material and methods:The survey included 100 examinees in the third age, above 65 years, of both genders, with the disease of hip joint that had been treated at the Clinics for orthopaedics and traumatology of UKCS by implanting the total endoprosthesis. The examinees were questioned before the surgery and after implanting the total hip endoprosthesis. The survey has covered the period from 1st January 2014 till 31st December 2016. As an instrument tool in the survey well validated SF-36 questionnaire for the estimation of life quality and total health status was used. Results: Evaluating all the elements in SF-36 questionnaire it was determined that statistically significant improvement of all the life quality elements that this questionnaire measured was detected, after the conducted surgery compared to the state before the surgery, p=0.001. Statistically biggest improvement has been detected in limitations that happened because of physical and emotional issues, and then in those that were related to physical and social functioning (p=0.001). Body pains and vitality are also statistically significantly better after the conducted surgery (p=0.001). Conclusion:Out of the results of the survey it derives that the quality of life of the people in third age is significantly better after the surgery of implanting the total hip endoprosthesis.

Abstract Service Startups and Creative Communities can be seen as two sides of the same coin. They are both organizations that adopt service dominant logic to create innovative services. These service models are a double-edged sword as they can facilitate the transition towards sustainability or they can support an unjust, neoliberal ‘gig economy’ that commodifies work and further elongates social inequalities. Understanding the similarities and differences of these organizations reveals a wider issue: the conflict of values between eco-modernist and radical approaches to sustainability. Reviewing the two antithetical positions of this spectrum would allow designers to make informed design choices. Finally, such a review provides a philosophical springboard for further debates in the field of design.

ABSTRACT Background: Risk of cardiovascular disease (CVD) has been associated with stress from serving in a war, but it has not been established whether children who experience war-related stress are at increased CVD risk. Objective: This study aimed to compare CVD risk factors in young adults according to whether they experienced traumatic events as children during the 1990–1995 war in Bosnia and Herzegovina, and whether those exposed to trauma have evidence of subclinical atherosclerosis. Method: We examined 372 first-year medical students who were preschool children during the war (1990–1995) (average age 19.5 ± 1.7 years, 67% female) in 2007–2010. They completed the Semi-Structured Interview for Survivors of War. CVD risk factors and carotid intima–media thickness (CIMT) measurements were obtained and compared in individuals with and without trauma. We also examined whether increased CIMT was independently associated with trauma after adjustment for other risk factors. Results: From multiple logistic regression, only elevated triglycerides (> 1.7 mmol/l) were associated with a 5.2 greater odds of having experienced trauma. The mean CIMT of subjects with trauma was greater than that of non-trauma-exposed subjects (0.53 mm vs 0.50 mm, p = 0.07). Moreover, trauma was independently associated with higher CIMT (difference = 0.036 mm, p = 0.024) after adjustment for CVD risk factors. Conclusions: We show that most CVD risk factors are associated with post-war trauma in young adults, and, if present, such trauma is associated with higher triglycerides and higher levels of CIMT in multivariable analysis. HIGHLIGHTS • Our investigation was to examine whether there are differences in cardiovascular risk factors and subclinical atherosclerosis in persons previously exposed compared to not exposed to trauma during the war in Bosnia and Herzegovina.• We demonstrated that while traditional risk factors are not strongly related to the presence of post-war trauma in young adults, those with greater CIMT appear to have been more likely to have had been prevoiusly exposed to trauma.

BACKGROUND Prefabricated myofunctional appliances (PMAs) are widely advocated for correcting Class II division I malocclusion. However, their effectiveness is associated with a high amount of uncertainty within contemporary literature. OBJECTIVES The aim of this review was to systematically examine the available literature regarding the effectiveness of PMAs in treating Class II division 1 malocclusion in children and adolescents. SEARCH METHODS Comprehensive unrestricted electronic searches in multiple databases as well as manual searches were conducted up to August 2018. SELECTION CRITERIA Randomized controlled trials (RCTs) and non-randomized studies (NRS) matching the eligibility criteria. DATA COLLECTION AND ANALYSIS Two independent review authors were directly involved in study selection, data extraction, and bias assessment. The Cochrane risk of bias tool and the ROBINS-I tool were used for assessing the risk of bias. Quantitative pooling of the data was undertaken with a random-effects model with its 95% confidence interval (CI). RESULTS Three RCTs comparing PMAs to activators and three NRS comparing PMAs to untreated controls met the inclusion criteria. On a short-term basis, exploratory quantitative synthesis indicated that the activators were more effective than the PMAs in correcting overjet with a mean difference of (1.1 mm; 95% CI: 0.44 to 1.77). On a long-term basis, there were no significant differences between the two appliances. Qualitative synthesis indicated less favorable soft tissue changes as well as patient experiences and compliance with the PMAs when compared to the activators. However, PMAs were associated with reduced costs compared to customized activators and modest changes when compared to untreated controls. CONCLUSIONS On a short-term basis, low quality of evidence suggests that PMAs were generally less effective than the activators in treating Class II division 1 malocclusion. The main advantage of PMAs seems to be their reduced costs. These results should be viewed with caution, as a definitive need for high-quality long-term research into this area is required. REGISTRATION PROSPERO (CRD42018108564).

The main circulatory medium of echinoderms is the coelomic fluid. Biochemistry of coelomic fluid is very complex and slightly different from seawater. The main aim of this research was to analyse concentration of electrolytes (potassium, calcium, magnesium, chlorine and sodium), heavy metals (lead, chromium, cadmium and cobalt) and iron in coelomic fluid of sea urchin, Arbacia lixula as an indirect indicator of seawater contamination. After precise statistical evaluation it was observed that electrolyte concentrations were; Na 189.20±11.41 mmol/l, Cl 134.06±37.08 mmol/l, Mg 4.24±1.08 mmol/l, Ca 3.04±0.84 mmol/l. Biochemical content of heavy metals in coelomic fluid was; Co 1.292±0.879 ppm, Pb 0.644±0.131 ppm, Cr 0.116±0.055 ppm, Cd 0.031±0.017 ppm and iron 0.259±0.058 ppm, and it depends on the potential accumulation level in the organism. The composition of electrolyte and heavy metal content varies depending on the composition of seawater. Obtained values are within the range of values most commonly found in low polluted areas of the Adriatic sea. Similar models may be applied for monitoring of heavy metal contamination in marine environment.

The paper focuses on the analysis of multi‐agent systems interacting over directed and time‐varying networks in presence of parametric uncertainty on the interaction weights. We assume that agents reach a consensus, and the main goal of this work is to characterize the contribution that each agent has to the consensus value. This information is important for network intervention applications such as targeted advertising over social networks. Indeed, for an advertising campaign to be efficient, it has to take into account the influence power of each agent in the graph (ie, the contribution of each agent to the final consensus value). In our first results, we analytically describe the trajectory of the overall network, and we provide lower and upper bounds on the corresponding consensus value. We show that under appropriate assumptions, the contribution of each agent to the consensus value is smooth both in time and in the variation of the uncertainty parameter. This allows approximating the contribution of each agent when small perturbations affect the influence of each agent on its neighbors. Finally, we provide a numerical example to illustrate how our theoretical results apply in the context of network intervention.