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Introduction: Adolescence is characterised as a period of further development and maturation of higher executive functions (EF). It is well established that EF play an important role in social skills and academic competence of typically developing adolescents. Purpose: The goal of this study was to examine the relationship between executive functions (EF) and academic competency and social skills in adolescents with a mild intellectual disability. In particular, we were interested to examine which EF have the greatest impact on social skills and academic competency. Methods: EF were measured with the Behaviour Rating Inventory of Executive Functions (BRIEF), and social and academic competences were measured with the Social Skills Rating System (SSRS). The sample for this study consisted of 44 adolescents with mild intellectual disability aged 15-18 years old (mean age 16.7 years, SD1.4). Results: The results of this study clearly pointed to the strong relationship between these constructs. Of all EF, planning had the strongest impact on academic success, and monitoring had the strongest impact on social skills. Conclusion: EF are susceptible to training effects, we thus propose early interventions in these domains in order to increase the social and academic competence of persons with an intellectual disability.

A. Malki, Rasha Abu ElRuz, I. Gupta, A. Allouch, S. Vranić, A. Al Moustafa

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

BACKGROUND Cerebrospinal levels of isoprostanes (IsoPs) have been established as biomarkers of oxidative stress in Alzheimer's disease (AD) and vascular dementia (VD). The value of peripheral levels in the diagnostics of these diseases is less conclusive. The aim of this study was to determine serum 8-iso-prostaglandin-F2alpha (8-iso-PGF2α) levels in Bosnian AD and VD patients and to establish whether there is an association between 8-iso-PGF2α serum concentration and cognitive impairment (CI) in patients with dementia. SUBJECTS AND METHODS Serum levels of 8-iso-PGF2α were measured by enzyme immunoassay method in AD (n=30) and VD patients (n=30) and control subjects (CG, n=30). The AD and VD group were further stratified according to the level of CI. RESULTS The serum 8-iso-PGF2α levels were significantly higher in the AD (74.00 pg/mL) and VD groups (38.00 pg/mL) compared to the CG (17.50 pg/mL). A significant difference in serum 8-iso-PGF2α levels between patients with moderate and severe CI was not established in either AD or VD. CONCLUSION Serum 8-iso-PGF2α proved to be a good biomarker in AD and VD, however it cannot be recommended for the differentiation of moderate and severe CI.

A. Kramer, Rianne Boenink, V. Stel, C. Santiuste de Pablos, F. Tomović, E. Golan, Julia Kerschbaum, N. Seyahi et al.

Abstract Background The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry collects data on kidney replacement therapy (KRT) via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article summarizes the 2018 ERA-EDTA Registry Annual Report, and describes the epidemiology of KRT for kidney failure in 34 countries. Methods Individual patient data on patients undergoing KRT in 2018 were provided by 34 national or regional renal registries and aggregated data by 17 registries. The incidence and prevalence of KRT, the kidney transplantation activity and the survival probabilities of these patients were calculated. Results In 2018, the ERA-EDTA Registry covered a general population of 636 million people. Overall, the incidence of KRT for kidney failure was 129 per million population (p.m.p.), 62% of patients were men, 51% were ≥65 years of age and 20% had diabetes mellitus as cause of kidney failure. Treatment modality at the onset of KRT was haemodialysis (HD) for 84%, peritoneal dialysis (PD) for 11% and pre-emptive kidney transplantation for 5% of patients. On 31 December 2018, the prevalence of KRT was 897 p.m.p., with 57% of patients on HD, 5% on PD and 38% living with a kidney transplant. The transplant rate in 2018 was 35 p.m.p.: 68% received a kidney from a deceased donor, 30% from a living donor and for 2% the donor source was unknown. For patients commencing dialysis during 2009–13, the unadjusted 5-year survival probability was 42.6%. For patients receiving a kidney transplant within this period, the unadjusted 5-year survival probability was 86.6% for recipients of deceased donor grafts and 93.9% for recipients of living donor grafts.

D. Marjanović, D. Primorac, V. Matišić, Vitorio Perić, Vilim Molnar, R. Zadro

In a relatively short period of time new coronavirus disease (COVID-19) has become a global threat, both to human health and to the functioning of human society in general. This pandemic is certainly neither the first nor is it likely to be the last disease episode in human history. At the moment, it is still too early to make a reliable assessment of its total effect on human civilization, but it can already be stated that this disease, and its causative agent SARS-CoV-2 virus, have caused a strong scientific response all around the World. For the first time in this magnitude, it has united the resources of large scientific institutions and companies with the aim of finding solutions for fast and accurate virus detection procedures, effective and safe vaccine, reliable medical treatments, etc. It is astonishing that only a month has passed from the first officially detected case to the complete sequencing of the SARS-CoV-2 virus genome and the creation of the first detection systems based on RT-PCR method. After that, numerous scientific teams and companies worked together, or independently, to improve the detection methods. Their work included further optimization of PCR and other genetic approaches, as well as the development of detection methods based on the analysis of specific antibodies and viral antigens. The aim of this paper is to review the results that were achieved in this area so far, analyze the strategies currently used in the world and the region, and to predict future steps in the process of optimizing and improving methods for SARS CoV-2 detection in individual patients and the global human population.

Soumaya Allouch, I. Gupta, Shaza Malik, Halema F Al Farsi, S. Vranić, A. Al Moustafa

Breast and cervical cancers comprise 50% of all cancers during pregnancy. In particular, gestational breast cancer is considered one of the most aggressive types of cancers, which is a rare but fatal disease. However, the incidence of this type of cancer is increasing over the years and its prevalence is expected to rise further as more women delay childbearing. Breast cancer occurring after pregnancy is generally triple negative with specific characterizations of a poorer prognosis and outcome. On the other hand, it has been pointed out that this cancer is associated with a specific group of genes which can be used as precise targets to manage this deadly disease. Indeed, combination therapies consisting of gene-based agents with other cancer therapeutics is presently under consideration. We herein review recent progress in understanding the development of breast cancer during pregnancy and their unique subtype of triple negative which is the hallmark of this type of breast cancer.

Mirza Hebib

Book Review: Law in the Roman Provinces, (ed.) K. Czajkowski and B. Eckhardt: Oxford University Press, 2020, xii + 526 str.

The aim of this article is to present a review of the research surrounding the short-term and long-term psychological and health consequences of child abuse and neglect. Research papers related to the consequences of child abuse and neglect and published in leading academic journals were identified and reviewed. We found that most of the available research suggests that there is a variety of negative outcomes among those exposed to physical, sexual and emotional abuse, neglect, witnessing domestic violence and multi-type childhood abuse. Specifically, there was evidence of significant short-term and long-term consequences encompassing physical and mental health difficulties, subsequent perpetrations, social and cognitive difficulties, and attachment. Conclusion  – The results of this review confirm that there is a wide range of short-term and long-term difficulties that are associated with child abuse and neglect. This variety of difficulties should be taken into account in approaching complex and multidisciplinary assessment and treatment.

U radu su prikazani rezultati istraživanja učinkovitosti skidera Ecotrac 55V. Istraživanje je provedeno u šumskom odjelu 89, gospodarska jedinica »Igman«, uz primjenu studija rada i vremena. Trajanje radnoga vremena ustanovljeno je »povratnom« metodom snimanja. Ovisnost vremena trajanja radnih operacija o utjecajnim čimbenicima utvrđena je uz primjenu višestruke regresijske analize. Primijenjena je sortimentna metoda izrade drva. Snimljeni su ovi utjecajni čimbenici: stanje traktorskoga puta (podloge), udaljenost privlačenja drva skiderom, udaljenost privitlavanja drva, broj komada u tovaru, obujam tovara i uzdužni nagib traktorskoga puta. Udio operativnoga vremena u ukupnom radnom vremenu iznosi 38,75 %, a udio vremena prekida rada 37,56 %. Norme vremena i učinka izražene su u ovisnosti o udaljenosti privlačenja, dok su za ostale utjecajne čimbenike korištene prosječne vrijednosti. Utvrđena je norma vremena u iznosu od 8,34 min/m3 za udaljenost privlačenja od 100 m, odnosno 17,65 min/m3 za 900 m. Učinak se traktora kreće u intervalu od 57,58 m3/radnom danu za udaljenost privlačenja od 100 m do 27,20 m3/radnom danu za 900 m. Analiza je pokazala da postoji mogućnost povećanja učinkovitosti primjenom bolje organizacije rada i smanjenjem udjela prekida rada u ukupnom radnom vremenu, osobito prekida iz organizacijskih i osobnih razloga (prekida zbog jela i prekida zbog odmora i osobnih potreba radnika).

L. Greenberg, L. Ryom, B. Neesgaard, G. Wandeler, T. Staub, M. Gisinger, Michael Skoll, H. Günthard et al.

BACKGROUND Limited data exist comparing clinical outcomes of two-drug regimens (2DRs) and three-drug regimens (3DRs) in people living with HIV. METHODS Antiretroviral treatment-experienced individuals in RESPOND switching to a new 2DR or 3DR from 1/1/12-1/10/18 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression. RESULTS Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median 52.6 years [interquartile range 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%).There were 619 events during 27,159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU [95% CI 20.7-24.5]) on 3DRs, 79 (30.9/1000 PYFU [24.8-38.5]) on 2DRs. The most common events were death (7.5/1000 PYFU [95% CI 6.5-8.6]) and non-AIDS cancer (5.8/1000 PYFU [4.9-6.8]). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio: 0.92 [0.72-1.19]; p=0.53). CONCLUSIONS This is the first large, international cohort assessing clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes; further research on resistance barriers and long-term durability of 2DRs is needed.

S. B. van der Meer, Inesa Hadrović, Annika Meiners, K. Loza, M. Heggen, S. Knauer, P. Bayer, T. Schrader et al.

A strategy toward epitope-selective functionalized nanoparticles is introduced in the following: ultrasmall gold nanoparticles (diameter of the metallic core about 2 nm) were functionalized with molecular tweezers that selectively attach lysine and arginine residues on protein surfaces. Between 11 and 30 tweezer molecules were covalently attached to the surface of each nanoparticle by copper-catalyzed azide alkyne cycloaddition (CuAAC), giving multiavid agents to target proteins. The nanoparticles were characterized by high-resolution transmission electron microscopy, differential centrifugal sedimentation, and 1H NMR spectroscopy (diffusion-ordered spectroscopy, DOSY, and surface composition). The interaction of these nanoparticles with the model proteins hPin1 (WW domain; hPin1-WW) and Survivin was probed by NMR titration and by isothermal titration calorimetry (ITC). The binding to the WW domain of hPin1 occurred with a KD of 41 ± 2 μM, as shown by ITC. The nanoparticle-conjugated tweezers targeted cationic amino acids on the surface of hPin1-WW in the following order: N-terminus (G) ≈ R17 > R14 ≈ R21 > K13 > R36 > K6, as shown by NMR spectroscopy. Nanoparticle recognition of the larger protein Survivin was even more efficient and occurred with a KD of 8 ± 1 μM, as shown by ITC. We conclude that ultrasmall nanoparticles can act as versatile carriers for artificial protein ligands and strengthen their interaction with the complementary patches on the protein surface.

Roeland W. H. Smits, Cornelia G. F. van Lanschot, Y. Aaboubout, M. D. de Ridder, V. N. Hegt, E. Barroso, C. Meeuwis, A. Sewnaik et al.

Background Inadequate resection margins in oral cavity squamous cell carcinoma have an adverse effect on patient outcome. Intraoperative assessment provides immediate feedback enabling the surgeon to achieve adequate resection margins. The goal of this study was to evaluate the value of specimen-driven intraoperative assessment by comparing the margin status in the period before and the period after the introduction of specimen-driven assessment as a standard of care (period 2010–2012 vs period 2013–2017). Methods A cohort of patients surgically treated for oral squamous cell carcinoma at the Erasmus MC Cancer Institute, Rotterdam, between 2010–2012 was studied retrospectively and compared to results of a prospectively collected cohort between 2013–2017. The frequency, type and results of intraoperative assessment of resection margins were analyzed. Results One hundred seventy-four patients were included from 2010–2012, 241 patients were included from 2013–2017. An increase in the frequency of specimen-driven assessment was seen between the two periods, from 5% in 2010–2012 to 34% in 2013–2017. When performing specimen-driven assessment, 16% tumor-positive resection margins were found in 2013–2017, compared to 43% tumor-positive resection margins overall in 2010–2012. We found a significant reduction of inadequate resection margins for specimen-driven intraoperative assessment (p < 0.001). Also, tumor recurrence significantly decreased, and disease-specific survival improved when performing specimen-driven intraoperative assessment. Conclusions Specimen-driven intraoperative assessment improves resection margins and consequently, the outcome of oral cancer patients. We advocate this method as standard of care.

Jun Ru Anderson, F. Memić, Ismar Volic

Multiple Indicator Cluster Surveys (MICS), supported by UNICEF, are one of the most important global household survey programs that provide data on health and education of women and children. We analyze the Serbia 2014–2015 MICS dataset using topological data analysis which treats the data cloud as a topological space and extracts information about its intrinsic geometric properties. In particular, our analysis uses the Mapper algorithm, a dimension-reduction and clustering method which produces a graph from the data cloud. The resulting Mapper graph provides insight into various relationships between household wealth—as expressed by the wealth index, an important indicator extracted from the MICS data—and other parameters such as urban/rural setting, ownership of items, and prioritization of possessions. Among other uses, these findings can serve to inform policy by providing a hierarchy of essential amenities. They can also potentially be used to refine the wealth index or deepen our understanding of what it captures.

Abstract Objectives The aim of this prospective study was to correlate the Doppler ultrasonography of the uterine arteries with the Kurjak Antenatal Neurodevelopmental Test (KANET), to investigate the effect of uterine artery flow assessed by the Doppler on fetal behavior. Methods A population of 80 pregnant women in the second trimester of pregnancy was included for uterine artery Doppler (UAD) assessment. The investigation group consisted of 40 women with abnormal UAD, while the control group consisted of 40 women with normal UAD. The inclusion criteria for the investigated group were: gestation above 20 weeks, and an abnormal finding of Doppler ultrasonography of the uterine arteries. All patients underwent a KANET test and were followed up to the end of their pregnancy. Results There was a statistically significant difference in the average score of KANET tests between the two groups (9.20±3.32 vs. 13.55±2.21; p=0.001). In the first group, an abnormal flow on the side of the placenta affected the score of the KANET test (B=11.948; p=0.005), while abnormal flow on the opposite side did not affect the score of the KANET test (p>0.05). Physiological flow had no effect on the KANET test in the control group (p>0.05). Conclusions Abnormal flow affects the value of the KANET score, and can be used as one of the parameters in evaluation of probable fetal neurodevelopmental disorders.

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