Репозиторий Университета

© 2019 Background and aim: The increase of the carbohydrate-deficient transferrin (CDT) as results of an heavy intake of alcohol for at least two weeks, is a well-known biochemical modification since the middle ‘70s. Notwithstanding the first commercial kit for the diagnosis of chronic alcohol abuse based on this biomarker was commercially accessible already thirty years ago, only expensive analytical methods are currently available for its determination. The present paper shows a new approach intrinsically sensitive and specific, based on a specific derivatization of transferrin, and not requiring sophisticated instrumentation. Methods: The proposed procedure is based on a selective chelation of terbium (III) by transferrin followed by detection using an characteristic Fluorescence Resonance Transfer Energy (FRET) phenomenon (ex 298 nm - em 550 nm). Results: The proposed procedure showed a limit of detection of 2.5 pmol/mL and a reproducibility intra-day and inter-days <15% and 20%, respectively. The results obtained analyzing 40 serum samples using the developed method, were compared with those obtained with HPLC-Vis and an R2 = 0.8854 was found. Conclusions: Considering its main features (low-cost, ease of operation, minimum need of instrumentation) the present method is suitable for application in screening contexts and in non-strictly regulated environments (e.g. clinical diagnosis) as well as in developing countries or remote areas.

© 2019 Elsevier Ltd Objective: Polymorphous adenocarcinoma of salivary gland (PAC) is rare. Despite being described as a low risk histology, some patients develop regional and distant metastasis. More aggressive behavior has been attributed to a PAC subcategory called cribriform adenocarcinoma of minor salivary glands (CAMSG). We examined oncological outcomes of PAC. Patients and methods: Fifty-seven patients with PAC were identified from an institutional database of 884 patients surgically treated for salivary gland malignancies from 1985 to 2015. Detailed histopathological analysis was performed. Survival outcomes were calculated using the Kaplan-Meier method. Factors predictive of recurrence were identified using the Cox proportional hazard method. Results: Fifty-four (95%) had tumors of minor salivary gland origin; the most frequent location was the oral cavity in 41 (76%), specifically the hard palate in 32 (55%). Forty-six patients (81%) were clinical T1-T2; 3 (5%) had a clinically positive neck. Thirty-two patients (56%) were classified as PAC and 14 (25%) as CAMSG. Forty-four patients (77%) had surgery alone; 13 (23%) had surgery and postoperative radiotherapy. The 5- and 10-year overall survival and disease-specific survival were 88% and 79% and 98% and 94%, respectively (median follow up 84 [1–159] months); 5- and 10-year recurrence-free survival were 93% and 88%, respectively. Univariate analysis showed male sex, III/IV stage, and CASMG variant had increased incidence of recurrence but were not statistically significant. Conclusion: PAC of the salivary glands is an indolent disease with good survival outcomes. Recurrence is uncommon and tends to occur late. Long-term follow-up is indicated in patients with this disease.

© 2019 Elsevier Inc. The article is dedicated to the life and work of Dr. Roy Selby (1930–2002), an American neurosurgeon who founded neurosurgery in Malaysia. Dr. Selby stayed in Malaysia from July 1963 to May 1970. He opened the first neurosurgical department at the general hospital in Kuala Lumpur and established a training program under which Malaysian physicians and nurses were sent to neurosurgery centers in the United States and Canada. Some physicians came back and headed local neurosurgical units. On his return to the United States, Dr. Selby practiced neurosurgery until 1986, when he had to give it up due to the impact of progressive congestive heart failure. From 1986 to 1994, Dr. Selby taught graduate courses in the Department of Psychology at East Texas State University, Texarkana, Texas. He was a pioneer of spinal surgery and founded the Lumbar Spine Society. Dr. Selby was a world citizen neurosurgeon and advocated international standards of training in neurosurgery. From 1985 to 1994, he was chairman of the Archives Committee of the American Association of Neurological Surgeons. Dr. Selby serves as a model of a physician as a humanist.

© 2019 Elsevier Inc. Asialo-human transferrin (asialo-hTf) is a glycoform of the human serum protein transferrin characterized by the lack of the sialic acid (SA) terminal unit. It is known that glycosylation micro-heterogeneity and the presence of SA are strongly involved in protein functioning and pathophysiological activities. Some hTf glycoforms are valuable biomarkers for the detection of both genetic defects of glycosylation and/or sialoform distribution changes. The detection of the carbohydrate deficient transferrin (CDT) glycoforms is currently a widely employed method for the diagnosis of chronic alcohol abuse. The physiological significance of asialo-hTf is still unclear, despite its important biological implications. The current knowledge suggests that asialo-hTf may be involved in regulation of iron transport and release at the hepatic level, which, consequently, could strongly be affected by alcohol consumption. For these reasons, a deeper understanding of asialo-hTf structure and its physiological role is required, and an improved method of its analysis would favor the detection of both chronic abuse and other habits of alcohol intake and/or misuse. Thus, suitable analytical methods possessing higher sensitivity and specificity in comparison with the currently available techniques are certainly recommended. The present review summarizes the studies on asialo-hTf structure, roles, and detection techniques mainly in relation to its possible use as a potentially additional useful biomarker of alcohol abuse, and underlines its prospective value as a forensic and diagnostic tool.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. In in vitro experiments on cultures of human multipotent stem cells from the human bone arrow and dental pulp, we studied direct reprogramming towards neuro-glial lineage cells using a cocktail of small molecules. Reprogramming by the previously published protocol (with a cocktail containing β-mercaptoethanol, LIF, VPA, CHIR99021, and RepSox) and by the optimized protocol (VPA, RG108, А83-01, dorsomorphin, thiazovivin, CHIR99021, forskolin, and Isx9) allows obtaining cells with immunophenotypic and genetic signs of neural stem cells. However, neither the former, nor the optimized protocols allowed preparing neural progenitors capable of adequate terminal differentiation from both bone marrow-derived mesenchymal stem cells and nestin-positive neural crest-derived mesenchymal stem cells. Real-time PCR demonstrated the expression of some neurogenesis markers, but neural stem cell-specific expression pattern was not observed. The findings lead us to a conclusion that reprogramming with small molecules without additional factors modifying gene expression does not allow reproducible production of human neural stem cell-like progenitors that can be used as the source of neural tissue for the regenerative therapy.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Olfactory ensheathing cells showed significant effects on the regeneration of the spinal cord in experimental models and in clinical trials. However, the use of these cells in the therapy of posttraumatic cysts of the spinal cord has not been studied. Cultures of human and rat olfactory mucosa were obtained according to the protocols developed by us. Passage 3-4 cultures are most enriched with olfactory ensheathing cells and are preferable for transplantation. We performed transplantation of 750,000 olfactory ensheathing cells into the region of modeled cysts. The therapeutic effect of human cells was more pronounced. The positive dynamics of recovery of motor activity in the hind limbs of rats can reflect regenerative processes in the spinal cord after transplantation of olfactory ensheathing cells into the region of posttraumatic cysts.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Anorexia nervosa (AN) is an eating disorder often occurring in adolescence. AN has one of the highest mortality rates amongst psychiatric illnesses and is associated with medical complications and high risk for psychiatric comorbidities, persisting after treatment. Remission rates range from 23% to 33%. Moreover, weight recovery does not necessarily reflect cognitive recovery. This issue is of particular interest in adolescence, characterized by progressive changes in brain structure and functional circuitries, and fast cognitive development. We reviewed existing literature on fMRI studies in adolescents diagnosed with AN, following PRISMA guidelines. Eligible studies had to: (1) be written in English; (2) include only adolescent participants; and (3) use block-design fMRI. We propose a pathogenic model based on normal and AN-related neural and cognitive maturation during adolescence. We propose that underweight and delayed puberty—caused by genetic, environmental, and neurobehavioral factors—can affect brain and cognitive development and lead to impaired cognitive flexibility, which in turn sustains the perpetuation of aberrant behaviors in a vicious cycle. Moreover, greater punishment sensitivity causes a shift toward punishment-based learning, leading to greater anxiety and ultimately to excessive reappraisal over emotions. Treatments combining physiological and neurobehavioral rationales must be adopted to improve outcomes and prevent relapses.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Human serum albumin nanoparticles (HSA-NPs) have been widely used as drug delivery systems. In most cases, HSA-NPs are formed by the method of desolvation in the presence of glutaraldehyde as a crosslinking agent. In the present study, we showed the possibility of crosslinking human serum albumin (HSA) molecules with natural agents, urea, and cysteine at the nanoparticle level under mild conditions (at room temperature of 20–25 °C). Optimal concentrations of the interacting components (HSA, urea, and cysteine) were found to produce nanoparticles with optimal physico-chemical parameters (particle size, polydispersity, zeta potential, yield, etc.) for application as drug carriers. We used hydroxyurea (HU), a simple organic compound currently used as a cancer chemotherapeutic agent. The results indicated sizes of 196 ± 5 nm and 288 ± 10 nm with a surface charge of −22 ± 3.4 mV and −17.4 ± 0.5 mV for HSA-NPs (20 mg/mL of HSA, 0.01 mg/mL of cysteine, and 10 mg/mL of urea) and HSA–HU-NPs (2 mg/mL of HU), respectively. The yield of the HSA–HU-NPs was ~93% with an encapsulation efficiency of ~77%. Thus, the particles created (immobilized with HU) were stable over time and able to prolong the effect of the drug.

© 2019 Arthroscopy Association of North America The Latarjet procedure is very popular and is the method of choice in cases of glenoid bone loss and anterior-inferior instability or revision procedures. However, recurrence is common after this procedure. One of the methods of revision after the Latarjet procedure is the Eden-Hybinette technique. However, recurrence occurs after this bone grafting procedure as well. The primary reasons for recurrence are graft resorption and capsular deficiency. To improve these outcomes, transfer of the long head of the biceps for capsular reinforcement has been recommended by several authors. We describe an all-arthroscopic procedure, performed after the Latarjet technique, that combines bone block transfer, trans-subscapular transposition of the long head of the biceps, and anterior labroplasty. This technique can significantly reinforce the deficient capsule through the sling effect and cover the graft for prophylaxis against bone resorption.

© 2019 American Pharmacists Association® Various drug delivery systems (DDSs) are often used in modern medicine to achieve controlled and targeted drug release. Diffusional release of drugs from DDSs is often the main mechanism, especially at early times. Generally, average dimensions of DDS are used to model the drug release, but our recent work on drug release from fibers demonstrated that taking into account diameter distribution is essential. This work systematically investigated the effect of size distribution on diffusional drug release from DDSs of various geometric forms such as membranes, fibers, and spherical particles. The investigation clearly demonstrated that the size distribution has the largest effect on the drug release profiles from spherical particles compared to other geometric forms. Published experimental data for drug release from polymer microparticles and nanoparticles were fitted, and the diffusion coefficients were determined assuming reported radius distributions. Assuming the average radius when fitting the data leads to up to 5 times underestimation of the diffusion coefficient of drug in the polymer.

© 2019 Elsevier Ltd Bovine pericardium (BP) is an extensively used biomaterial utilised in a wide range of biomedical devices such as bioprosthetic heart valves. However, the mechanical testing techniques that assess soft biomaterial tissue like BP are varied with no common method utilised across the literature, producing variations and contradictions in reported values. Uniaxial testing is a common technique used to measure traditional mechanical characteristics of ultimate tensile strength (UTS), modulus and the percentage strain at failure. The aim of this study was to take two standard uniaxial test parameters, strain rate and the number of preconditioning cycles and to elucidate recommendations for the standardisation of a uniaxial method, while also measuring not so common parameters of low modulus and hysteresis. Samples post uniaxial testing were treated and analysed with scanning electron microscopy (SEM) and an imaging software (ImageJ) to measure the effect of the parameters on the crimping structure and orientation of the collagen fibres. The study recommends an extension rate of 10 mm/min and 5 preconditioning load-unload cycles as a starting point for the standardisation of a uniaxial testing method. The image analysis of the collagen structure carried out provides a quantitative assessment of the BP post mechanical testing and allows for a better understanding of the behaviour of BP under stress.

Тhe rapid increase in the frequency of сesarian section (CS) observed in recent years (up to 60% in some countries) is alarming and reduces the reproductive potential of the population. The operated uterus remains the main indication for CS (up to 40%). This is the factor which may allow reducing the frequency of the CS by subsequent delivering through the birth canal. A comparative analysis of maternal and neonatal outcomes enabled the authors to develop a two-stage delivery technology for patients with a caesarean scar, including the usage of the programmed delivery method. The presented algorithm confirmed the validity of vaginal delivery in such patients, and reduced the number of complications up to 4 times. Neonatal morbidity in children born through the birth canal in such patients was comparable to physiological birth.

© 2019 by the authors. Cutaneous leishmaniasis (CL) is one of the most important infectious diseases in the world and is increasing day by day. No effective vaccine has been made against this disease, so far. An important issue with this disease is the development of drug resistance or no response to drug, which is going to spreading that its mechanism has not yet been completely identified. The main aim of this study was to assessment the expression of RNAPII gene in no response to drug and susceptible isolates of Leishmania major. The patients with CL from the central and North of Iran were considered for this study. The samples were transferred in RNAlater solution and stored in -20 °C. RNA extraction and cDNA synthesis were performed. The gene expression analysis was done with SYBR Green Real Time PCR Written informed consent was filled up by patients and then information forms were written based on Helsinki declaration. Statistical analysis was done with SPSS (16.0; SPSS Inc, Chicago) using independent t-test. P ≤ 0.05 was considered significant. It was observed that the gene expression of RNAPII in the no response to drug isolates was lower than that the one in drug sensitive isolates. A change in the expression of RNAP II in no response to drug isolates of L. major can indicate the potential role of this gene in the related mechanism.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Near-IR spectroscopy is a promising analytical method in pharmacy. It was shown that it can be used as a rapid method for confirming the identity and analyzing the purity of kemantane (5-hydroxyadamantan-2-one) drug substance.

© 2019, Pleiades Publishing, Inc. Abstract: Genetic engineering is considered as background for crop protection against pest damage by adding new genes inside the grains. Rice, like other cereals is included in gene engineering experiments. The questions about possible gene transfer related to food safety appear. It is important to find any additional genes or fragments in animal tissues after consumption of genetically modified (GM) food. Therefore, in this study, the remaining of CryIA(b) gene and P35 were assessed in the liver of rats fed with GM rice. This work presents an experimental study with the intervention of GM rice feeding by Sprague Dawley rats. Overall, 20 male and 20 female SD rats were fed by pellets made by GM rice in 50% of needed carbohydrate for 90 days. Then, sampling was done from rats liver. DNA extraction was done based on the protocol. The quality and quantity of the extracted DNA was done by agarose gel electrophoresis and spectrophotometry, respectively. Detection of GM genes residues, including CryIA(b), P35, and T35 was done by Polymerase Chain Reaction using specific primer pairs. The results were analyzed by agarose gel electrophoresis alongside with 50 bp DNA ladder. The results were compared with the ones in control groups with feeding by standard pellet of non-modified rice. All amplification tests were done in triplicates. Analysis of the amplification of P35, CryIA(b) and T35 showed no residues inside the liver tissue. The results showed no significant difference in the presence of transgenic gene of cryIA(b), T35, and P35 in the liver tissue between the control and experiment groups. Therefore, this study rejects the possibility of gene settle of GM rice gene residues in liver tissue of the animal model studied.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Acid-sensing ion channels (ASICs) are proton-gated sodium-selective channels that are expressed in the peripheral and central nervous systems. ASIC1a is one of the most intensively studied isoforms due to its importance and wide representation in organisms, but it is still largely unexplored as a target for therapy. In this study, we demonstrated response of the ASIC1a to acidification in the presence of the daurisoline (DAU) ligand. DAU alone did not activate the channel, but in combination with protons, it produced the second peak component of the ASIC1a current. This second peak differs from the sustained component (which is induced by RF-amide peptides), as the second (DAU-induced) peak is completely desensitized, with the same kinetics as the main peak. The co-application of DAU and mambalgin-2 indicated that their binding sites do not overlap. Additionally, we found an asymmetry in the pH activation curve of the channel, which was well-described by a mathematical model based on the multiplied probabilities of protons binding with a pool of high-cooperative sites and a single proton binding with a non-cooperative site. In this model, DAU targeted the pool of high-cooperative sites and, when applied with protons, acted as an inhibitor of ASIC1a activation. Moreover, DAU’s occupation of the same binding site most probably reverses the channel from steady-state desensitization in the pH 6.9–7.3 range. DAU features disclose new opportunities in studies of ASIC structure and function.

© 2019, Mary Ann Liebert, Inc., publishers 2019. The purpose of our work was to study late cardiac complications after treatment for Hodgkin's lymphoma (HL) in children and adolescents. Methods: Sixty-seven patients were examined in the long term (>5 years) after chemoradiotherapy for HL according to two different programs of treatment (groups I and II). Mean total doses of radiotherapy (RT) to the mediastinum were 37.2 and 28.9 Gy, respectively. The status of the heart was assessed at the mean age of 22.7 years with electrocardiography (ECG) and echocardiography (EchoCG). Mean terms of follow-up were 16.4 and 9.5 years for group I and group II, respectively. Results: Incidence of ECG changes was equal between the groups (88% and 90%). The prevalence of signs of valvular calcifications and fibrosis was 70.9% after mediastinal doses ≥30 Gy, and 16.6% after lower doses (p = 0.002). Those changes led to considerable valvular dysfunction in four patients. EchoCG signs of pulmonary hypertension were seen in 33.3% patients of group I versus 4.8% in group II (p = 0.047). Pericardial effusion was observed in 7.4% and 5.1%, respectively (p = 1.0). Left ventricular ejection fraction decreased slightly only in two patients (one in each group). Conclusions: The RT mediastinal dose level is the important risk factor of late heart complications. Nevertheless, the differences in the rate and severity of those complications between the groups should be viewed with caution because of differences in the age at baseline and in follow-up terms. The survivors of HL should undergo life-long regular examinations of the heart status.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose of review More than 30 years ago, the first molecular structures of allergens were elucidated and defined recombinant allergens became available. We review the state of the art regarding molecular AIT with the goal to understand why progress in this field has been slow, although there is huge potential for treatment and allergen-specific prevention. Recent findings On the basis of allergen structures, several AIT strategies have been developed and were advanced into clinical evaluation. In clinical AIT trials, promising results were obtained with recombinant and synthetic allergen derivatives inducing allergen-specific IgG antibodies, which interfered with allergen recognition by IgE whereas clinical efficacy could not yet be demonstrated for approaches targeting only allergen-specific T-cell responses. Available data suggest that molecular AIT strategies have many advantages over allergen extract-based AIT. Summary Clinical studies indicate that recombinant allergen-based AIT vaccines, which are superior to existing allergen extract-based AIT can be developed for respiratory, food and venom allergy. Allergen-specific preventive strategies based on recombinant allergen-based vaccine approaches and induction of T-cell tolerance are on the horizon and hold promise that allergy can be prevented. However, progress is limited by lack of resources needed for clinical studies, which are necessary for the development of these innovative strategies.

© 2019 Journal of Pediatric Urology Company Introduction: Urinary incontinence is one of the most commonly treated disorders in children at school age. Recently, a new, wearable bladder sensor became available, the SENS-U Bladder Sensor. The SENS-U is a small, wireless ultrasonic sensor, which continuously monitors the bladder filling and provides a personalized notification when it is time to go to the toilet. In this study, the aim was to examine the performance of the SENS-U as a full-bladder–based notification system in children during daily life activities. Patients and methods: In this pilot study, children (6–16 years) who were admitted for an inpatient bladder training were included. Parallel to one training day, the child would wear the SENS-U to estimate the bladder filling and it informed the child when the bladder was almost full. When the child received a full-bladder notification, the child was taught to inform the urotherapist/researcher, in order to determine the level of response. Results: Fifteen patients (boys/girls: 7/8; mean age: 11.5 ± 1.7 years) were included. Based on a personalized volume-based threshold, the SENS-U notified these children of a full bladder with a median notification rate of 92.9%. In the remaining cases, children voided before the threshold was reached (e.g. defecation). Children responded positively to the notification of the SENS-U, resulting in a median level of response equal to 100%. Conclusion: The SENS-U was able to monitor the natural bladder filling accurately during activities of daily living and provided a personalized notification to the children when it was almost time to go to the toilet. Future research will focus on investigating the efficacy of the SENS-U compared to daily clinical practices.[Figure presented]

© 2019 Elsevier Ltd The anionic ring-opening polymerization of carbazole-containing monomers, (9-carbazolylmethyl)thiirane (M1)and (3,6-di-tert-butyl-9-carbazolylmethyl)thiirane (M2), with hexanethiol or pentaerythritol tetrakis(3-mercaptopropionate)(PETMP)as initiators and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD)as catalyst at 20 °C in tetrahydrofuran or N,N-dimethylformamide as solvents has been studied. The polymerization of these monomers proceeds in a living fashion affording linear and star-shaped polymers with controlled molecular weight (Mn = 4000–15,000 g mol−1)and relatively low polydispersity (Đ < 1.3). It was demonstrated that end-capping of polymers by trifluoroacetic anhydride allowed to protect thiol end groups from oxidative coupling, which typically leads to the broadening of molecular weight distribution of the synthesized polymers. The thermal, photophysical and electrochemical properties of the synthesized linear and star-shaped polymers were estimated.