INCREASED BONE TURNOVER IN OBESE POSTMENOPAUSAL FEMALES

ABSTRACT Epstein-Barr virus (EBV) is a well-characterized oncovirus, associated with several malignancies. The complex and heterogeneous nature of colorectal cancer (CRC) has led to many epidemiological causal associations with CRC. However, a direct causal link between microbial infections and CRC has not been established yet. Our review indicates that the current evidence for the presence and role in EBV in CRC is insufficient and contradictory. The design of the analyzed studies, sample size as well as methodology used for EBV detection varied markedly and consequently may not lead to meaningful conclusions. The presence of EBV in other colorectal tumors (lymphomas, smooth muscle tumors) is in line with their status at other anatomic locations and may have therapeutic implications with EBV-specific vaccines. On the other hand, studies exploring EBV in colorectal adenoma-carcinoma sequence and its molecular genetic characteristics are largely missing and may significantly contribute to a better understanding of the role of EBV in CRC.

RELIABILITY OF URINE AS SOURCE FOR BIOLOGICAL INFORMATION FOR RISK ESTIMATION FOR PROSTATE MALIGNANCY

ABSTRACT This introductory paper sets the scene for the special issue on migration in the Western Balkan region. First, we briefly outline the background to the research networking initiative in the Western Balkans—‘WB-MIGNET’—which resulted in producing the set of papers presented here. Then we describe the context in which the analysis of migration, return and development in the Western Balkans takes place, highlighting the role of diasporas and return migration. The region exemplifies a wide range and interrelation of migratory forms, including temporary and permanent labour migration, forced migration of refugees, temporary displacement, high-skilled migration and transit migration. Quite apart from the scale and diversity of migratory phenomena in this region, the special relevance of the Western Balkans rests on mass emigration, predominantly of educated young people, and their possible return, including to post-conflict areas, and role in the development of their home countries. Such processes within the Western Balkans also offer useful lessons for designing future migration policies in Europe and worldwide. The final section of this introductory paper summarizes the papers that follow and highlights their originality and key findings.

Acute sleep deprivation is known to affect human balance and posture control. However, the effects of variations in sleep quality and pattern over consecutive days have received less attention. This study investigated the associations between day-to-day variations in sleep quality and standing balance in healthy subjects. Twenty volunteers (12 females and 8 males; age: 28.8 ± 5.7 years, body mass index: 23.4 ± 3.4 kg/m2, resting heart rate: 63.1 ± 8.7 bpm) with no history of sleep disorders or balance impairments participated in the study. Sleep and balance were assessed over two consecutive days. Sleep quality variations were assessed using sleep diary, actigraphy and heart rate variability (HRV) measures. Sleep was monitored at home, using an unobtrusive wearable device. Balance was assessed in a gait lab using foot centre of pressure (COP) displacement during quiet standing. Subjects with a day-to-day deterioration in sleep quantity and quality (i.e., decreased duration and increased fragmentation, increased nocturnal activity and decreased HRV) exhibited significant changes in balance (i.e., larger COP area, amplitude and standard deviation). Conversely, subjects with no significant alterations in sleep quantity and quality showed no significant changes in COP displacements. These results confirmed our hypothesis that changes in sleep quality and pattern over consecutive days may affect balance.

AN IMPACT OF DIABETES DURATION ON SERUM ASYMMETRIC DIMETHYLARGININE CONCENTRATION

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti-interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.

Increasing evidence is demonstrating that a patient’s unique genetic profile can be used to detect the disease’s onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine (PM) and pharmacogenomics (PG) in clinical practice. Here we investigated the perceptions of students from different universities in Bosnia and Herzegovina (BH) towards PG/PM as well as related ethical, legal, and social implications (ELSI). This descriptive, cross-sectional study is based on the survey of 559 students from the Faculties of Medicine, Pharmacy, Health Studies, Genetics, and Bioengineering and other study programs. Our results showed that 50% of students heard about personal genome testing companies and 69% consider having a genetic test done. A majority of students (57%) agreed that PM represents a promising healthcare model, and 40% of students agreed that their study program is well designed for understanding PG/PM. This latter opinion seems to be particularly influenced by the field of study (7.23, CI 1.99–26.2, p = 0.003). Students with this opinion are also more willing to continue their postgraduate education in the PM (OR = 4.68, CI 2.59–8.47, p < 0.001). Furthermore, 45% of students are aware of different ethical aspects of genetic testing, with most of them (46%) being concerned about the patient’s privacy. Our results indicate a positive attitude of biomedical students in Bosnia and Herzegovina towards genetic testing and personalized medicine. Importantly, our results emphasize the key importance of pharmacogenomic education for more efficient translation of precision medicine into clinical practice.

The densities and viscosities of synephrine hydrochloride and octopamine hydrochloride aqueous solutions were determined. Apparent molar volumes, apparent molar volume at infinite dilution, viscosity B-coefficients and hydration number were calculated, and it was found that synephrine hydrochloride acts as a better structure maker than octopamine hydrochloride in aqueous solutions. The densities of the investigated salts were measured in aqueous d-fructose solutions, and the corresponding apparent molar volumes of transfer at infinite dilution were determined. Its taste behavior was discussed based on the calculated values for apparent specific volume and intrinsic viscosity. Molecular dynamics simulations and radial distribution functions were applied in order to understand the nature of the interactions and water structuring in the studied systems. The change in taste behavior was observed with increasing concentration of the cosolute, and it was found that the addition of sugar increases the bitterness of the solution. From a molecular docking study on the bitter receptor TAS2R38, the strongest interactions for synephrine-HCl were noted causing the most bitter taste.