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Introduction. Tetanus, also known as lockjaw, is a very dangerous infectious, acute, usually afebrile disease characterized by muscle spasms. The causative agent of the disease is bacteria Clostridium tetani. This bacteria produces a specific neurotoxin or tetanus toxin with two components: tetanospasmin and tetanolysin. Light chains of tetanospamine cleavage synaptobrevin, which in turn prevent release of the inhibitory neurotransmitter GABA into the synaptic cleft. The α - motor neurons are, therefore, under no inhibitory control, as a result of which they undergo sustained excitatory discharge causing the characteristic motor spasms of tetanus. Materials and Methods. In this research, we attempted to normalize disorders caused by tetanus toxin by using haloperidol (at doses of 4, 5, 6, 7 and 8 mg/kg b.w.), alone and in combination with (-)-nuciferine (at dose of 5 mg/kg b.w.) and aminooxyacetic acid (at dose of 20 mg/kg b.w.). Experiments were conducted on albino mice. Experimental tetanus was induced by application of tetanus toxin. Results and Conclusions. Application of haloperidol (alone and in combination with (-)-nuciferine and aminooxyacetic acid) was carried out 24 hours following the application of tetanus toxin. It was found that haloperidol, given alone in a dose of 4 mg/kg, prolonged the survival time of mice with experimental tetanus, about 24.35 hour compared to the control group. Thus, application of haloperidol in this dose showed to be the only effective method. Additionally, combination of haloperidol with (-)-nuciferine slightly extend survival time, while combination with aminooxyacetic acid produced the best effect on the extension of this period (about 27.74 hour compared to the control group).

Russell King, N. Oruc

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.

L. Montesinos, R. Castaldo, F. Cappuccio, L. Pecchia

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.

F. Van Rhee, P. Voorhees, A. Dispenzieri, A. Fosså, G. Srkalović, M. Ide, N. Munshi, S. Schey et al.

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.

S. Bedri, A. Sultan, M. Alkhalaf, A. Al Moustafa, S. Vranić

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.

T. Hurford, W. Henning, R. Maguire, V. Lekić, N. Schmerr, M. Panning, V. Bray, M. Manga et al.

Tidal interactions between planets or stars and the bodies that orbit them dissipate energy in their interiors. The dissipated energy heats the interior and a fraction of that energy will be released as seismic energy. Here we formalize a model to describe the tidally-driven seismic activity on planetary bodies based on tidal dissipation. To constrain the parameters of our model we use the seismic activity of the Moon, driven by tidal dissipation from the Earth-Moon interactions. We then apply this model to predict the amount of seismic energy release and largest seismic events on other moons in our Solar System and exoplanetary bodies. We find that many moons in the Solar System should be more seismically active than the Earth’s Moon and many exoplanets should exhibit more seismic activity than the Earth. Finally, we examine how temporal-spatial variations in tidal dissipation manifest as variations in the locations and timing of seismic events on these bodies.

Damir Suljevic, Erna Islamagić, Arnela Karahodzic, Zejneb Babic, E. Zukic, E. Sehic, Subha Džafić, A. Alijagić

In this study we analyzed the effects of NaOCl solution on the blood and biochemical parameters of the rainbow trout Oncorhynchus mykiss (Walbaum, 1792). The treatment lasted for three days with prior dechlorination of the water. Significant differences in the concentration of K+, Ca2+, Cl-, proteins, glucose were detected and the largest variations were found for creatinine concentration (P<0.05). Significant differences were found Hct, Hb concentration, RBC, WBC, MCH and MCHC values, percentage ratio of lymphocytes, segmented granulocytes and the total number of neutrophil granulocytes (P<0.05). Small doses of NaOCl alter the acid-base balance, suggesting a very low-level adaption in the rainbow trout.

M. Vraneš, J. Panić, Aleksandar Tot, S. Papović, S. Ostojić, S. Gadžurić

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.

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