bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteria-free minicircle DNA system to generate integration-free CAR-T cells
Authors: Cheng Chen , Tang Na , Li Jiaxin , Cao Shiwei , Zhang Tongtong , Wei Xiaofei , Wang Haoyi
Published: July 2018

Background

Chimeric antigen receptor T (CAR-T) cells engineered with lentiviral and retroviral vectors have been successfully applied to treat patients with B cell malignancy. However, viral integration in T cells has the potential risk of mutagenesis, and viral vector production demands effort and is costly. Using non-integrative episomal vector such as minicircle vector to generate integration-free CAR-T cells is an attractive option.

Methods and results

We established a novel method to generate minicircle vector within a few hours using simple molecular biology techniques. Since no bacteria is involved, we named these vectors bacteria-free (BF) minicircle. In comparison with plasmids, BF minicircle vector enabled higher transgene expression and improved cell viability in human cell line, stem cells and primary T cells. Using BF minicircle vector, we generated integration-free CAR-T cells, which eliminated cancer cells efficiently both in vitro and in vivo.

Conclusion

BF minicircle vector will be useful in basic research as well as in clinical applications such as CAR-T and gene therapy. Although the transgene expression of minicircle vector lasts apparently shorter than that of insertional lentivirus, multiple rounds of BF minicircle CAR-T cell infusion could eliminate cancer cells efficiently. On the other hand, a relatively shorter CAR-T cell persistence provides an opportunity to avoid serious side effects such as cytokine storm or on-target off-tumour toxicity.
Understanding the Role of Team Member Personal Style in Project Performance: Does the Type of Innovation Matter?
Authors: Aronson Zvi H. , Reilly Richard R. , Lynn Gary S.
Published: July 2018

Teams are progressively becoming primary in the way employees in organizations conduct work. We investigated the role of staff personal style in project performance for teams working on incremental and radical innovations. Regression results based on 149 teams suggest that, for employees, conscientiousness and agreeableness, predominantly, seem to be beneficial for new product development (NPD) performance. Slope tests promote our proposition that for speed, radical NPD might gain from extra open and stable staff. Further, exceedingly agreeable employees do not seem to provide support when new ideas are fostered, since it could be a precursor to group think and less successful innovation. We provide implications for selection and training of employees assigned to work in innovation teams.
Decentralized Production: The Need for Social Norms-Based Intellectual Property?
Authors: Poesche Jurgen , Pihlajarinne Taina , Alén-Savikko Anette , Nyberg Timo , Kauranen Ilkka
Published: July 2018

The objective of this paper is to explore the need for and possible benefits of social norms-based intellectual property systems in the context of the renaissance of decentralized production. Innovative engineering in addition to powerful information and communications technology enables a renaissance of decentralized production. A central form of such is co-engaging production. This renaissance can already be observed in small-scale 3D printing, microbreweries, small-scale food production in rooftop greenhouses, and small-scale electricity generation with solar panels installed by users of electricity. Individuals engaging in decentralized production typically have limited resources, which may hinder them from applying registration for industrial property rights. Therefore, social norms-based intellectual property can, in some cases, be more cost efficient in the case of decentralized production. In the case of cross-border groups, social norms-based intellectual property can evolve regardless of territorially restricted national legal-based intellectual property rights. The advantages of social norms may override their disadvantages when no great economic interests are involved and the production and the need of protection are short-term by nature. The decentralized characteristic of social norms-based intellectual property brings in new people as creators of creations for which intellectual property protections exist. This can enhance creativity by broadening the cognitive and cultural diversity of the creations. Social norms-based and legal norms-based intellectual property systems are not mutually exclusive and can exist side-by-side.
On the number of incongruent solutions to a quadratic congruence over algebraic integers
Authors: Taki Eldin Ramy F.
Published: July 2018

Over the ring of algebraic integers [Formula: see text] of a number field [Formula: see text], the quadratic congruence [Formula: see text] modulo a nonzero ideal [Formula: see text] is considered. We prove explicit formulas for [Formula: see text] and [Formula: see text], the number of incongruent solutions [Formula: see text] and the number of incongruent solutions [Formula: see text] with [Formula: see text] coprime to [Formula: see text], respectively. If [Formula: see text] is contained in a prime ideal [Formula: see text] containing the rational prime [Formula: see text], it is assumed that [Formula: see text] is unramified over [Formula: see text]. Moreover, some interesting identities for exponential sums are proved.
Contracting thin disks
Authors: Papasoglu Panos
Published: July 2018

We answer a question of Liokumovich–Nabutovsky–Rotman showing that if [Formula: see text] is a Riemannian 2-disk with boundary length [Formula: see text], diameter [Formula: see text] and area [Formula: see text] then [Formula: see text] can be filled by a homotopy [Formula: see text] with [Formula: see text] bounded by [Formula: see text].
The Interstellar Dust Properties of Nearby Galaxies
Authors: Galliano Frédéric , Galametz Maud , Jones Anthony P.
Published: July 2018

This article gives an overview of the constitution, physical conditions, and observables of dust in the interstellar medium of nearby galaxies. We first review the macroscopic, spatial distribution of dust in these objects and its consequences for our ability to study grain physics. We also discuss the possibility of using dust tracers as diagnostic tools. We then survey the current understanding of the microscopic, intrinsic properties of dust in different environments, derived from different observables: emission, extinction, polarization, and depletions, over the whole electromagnetic spectrum. Finally, we summarize the clues about grain evolution, evidenced either on local scales or over cosmic time. We put in perspective the different evolution scenarios. We attempt a comprehensive presentation of the main observational constraints, analysis methods, and modeling frameworks of the distinct processes. We discuss neither the dust properties of the Milky Way and distant galaxies, nor circumstellar or active galactic nucleus torus dust.
Normal patterns of thoracic aortic wall shear stress measured using four-dimensional flow MRI in a large population
Authors: Callaghan Fraser M. , Grieve Stuart M.
Published: July 2018

Wall shear stress (WSS) plays a governing role in vascular remodeling and a pathogenic role in vessel wall diseases. However, little is known of the normal WSS patterns in the aorta as there is currently no practical means to routinely measure WSS and no normal ranges derived from population data exist. WSS measurements were made on the aorta of 224 subjects with normal anatomy using four-dimensional flow MRI with multiple encoding velocities and an optimized postprocessing routine. The spatial and temporal variation in WSS and oscillatory shear index was analyzed using a flat map representation of the unfolded aorta. The influence of aortic shape and velocity on WSS was evaluated using regression analysis. WSS in the thoracic aorta is dominated by axial flow. Average peak systolic WSS was 1.79 ± 0.71 Pa in the aortic arch and was significantly higher at 2.23 ± 1.04 Pa in the descending aorta, with a strong negative correlation with advancing age. The spatial distribution of WSS is highly heterogeneous, with a localized region of elevated WSS along the length of the anterior wall seen across all individuals. Our data demonstrate that accurate four-dimensional flow-derived WSS measurement is feasible, and we further provide a standardized parametric approach for presentation and analysis. We present a normal range for WSS across the lifespan, demonstrating a decrease in WSS with advancing age as well as illustrating the high degree of spatial and temporal variation.

NEW & NOTEWORTHY With the use of four-dimensional flow MRI and postprocessing, accurate direct measurement of wall shear stress (WSS) was performed in a population of normal thoracic aortas ( n = 224). WSS was higher in the descending aorta compared with the aortic arch and decreased with age. A heterogeneous pattern of elevated WSS along the length of the aorta anterior wall was consistent across the population. This work provides normal data across the adult age range, permitting comparison with pathology.
Astrocyte-produced carbon monoxide and the carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by prolonged neonatal asphyxia
Authors: Parfenova Helena , Pourcyrous Massroor , Fedinec Alex L. , Liu Jianxiong , Basuroy Shyamali , Leffler Charles W.
Published: July 2018

Neonatal asphyxia leads to cerebrovascular disease and neurological complications via a mechanism that may involve oxidative stress. Carbon monoxide (CO) is an antioxidant messenger produced via a heme oxygenase (HO)-catalyzed reaction. Cortical astrocytes are the major cells in the brain that express constitutive HO-2 isoform. We tested the hypothesis that CO, produced by astrocytes, has cerebroprotective properties during neonatal asphyxia. We developed a survival model of prolonged asphyxia in newborn pigs that combines insults of severe hypoxia, hypercapnia, and acidosis while avoiding extreme hypotension and cerebral blood flow reduction. During the 60-min asphyxia, CO production by brain and astrocytes was continuously elevated. Excessive formation of reactive oxygen species during asphyxia/reventilation was potentiated by the HO inhibitor tin protoporphyrin, suggesting that endogenous CO has antioxidant effects. Cerebral vascular outcomes tested 24 and 48 h after asphyxia demonstrated the sustained impairment of cerebral vascular responses to astrocyte- and endothelium-specific vasodilators. Postasphyxia cerebral vascular dysfunction was aggravated in newborn pigs pretreated with tin protoporphyrin to inhibit brain HO/CO. The CO donor CO-releasing molecule-A1 (CORM-A1) reduced brain oxidative stress during asphyxia/reventilation and prevented postasphyxia cerebrovascular dysfunction. The antioxidant and antiapoptotic effects of HO/CO and CORM-A1 were confirmed in primary cultures of astrocytes from the neonatal pig brain exposed to glutamate excitotoxicity. Overall, prolonged neonatal asphyxia leads to neurovascular injury via an oxidative stress-mediated mechanism that is counteracted by an astrocyte-based constitutive antioxidant HO/CO system. We propose that gaseous CO or CO donors can be used as novel approaches for prevention of neonatal brain injury caused by prolonged asphyxia.

NEW & NOTEWORTHY Asphyxia in newborn infants may lead to lifelong neurological disabilities. Using the model of prolonged asphyxia in newborn piglets, we propose novel antioxidant therapy based on systemic administration of low doses of a carbon monoxide donor that prevent loss of cerebral blood flow regulation and may improve the neurological outcome of asphyxia.
FGF23 impairs peripheral microvascular function in renal failure
Authors: Verkaik Melissa , Juni Rio P. , van Loon Ellen P. M. , van Poelgeest Erik M. , Kwekkeboom Rick F. J. , Gam Zeineb , Richards William G. , ter Wee Pieter M. , Hoenderop Joost G. , Eringa Etto C. , Vervloet Marc G. ,   the NIGRAM Consortium
Published: July 2018

Cardiovascular diseases account for ~50% of mortality in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) is independently associated with endothelial dysfunction and cardiovascular mortality. We hypothesized that CKD impairs microvascular endothelial function and that this can be attributed to FGF23. Mice were subjected to partial nephrectomy (5/6Nx) or sham surgery. To evaluate the functional role of FGF23, non-CKD mice received FGF23 injections and CKD mice received FGF23-blocking antibodies after 5/6Nx surgery. To examine microvascular function, myocardial perfusion in vivo and vascular function of gracilis resistance arteries ex vivo were assessed in mice. 5/6Nx surgery blunted ex vivo vasodilator responses to acetylcholine, whereas responses to sodium nitroprusside or endothelin were normal. In vivo FGF23 injections in non-CKD mice mimicked this endothelial defect, and FGF23 antibodies in 5/6Nx mice prevented endothelial dysfunction. Stimulation of microvascular endothelial cells with FGF23 in vitro did not induce ERK phosphorylation. Increased plasma asymmetric dimethylarginine concentrations were increased by FGF23 and strongly correlated with endothelial dysfunction. Increased FGF23 concentration did not mimic impaired endothelial function in the myocardium of 5/6Nx mice. In conclusion, impaired peripheral endothelium-dependent vasodilatation in 5/6Nx mice is mediated by FGF23 and can be prevented by blocking FGF23. These data corroborate FGF23 as an important target to combat cardiovascular disease in CKD.

NEW & NOTEWORTHY In the present study, we provide the first evidence that fibroblast growth factor 23 (FGF23) is a cause of peripheral endothelial dysfunction in a model of early chronic kidney disease (CKD) and that endothelial dysfunction in CKD can be prevented by blockade of FGF23. This pathological effect on endothelial cells was induced by long-term exposure of physiological levels of FGF23. Mechanistically, increased plasma asymmetric dimethylarginine concentrations were strongly associated with this endothelial dysfunction in CKD and were increased by FGF23.
Optic Neuritis Possibly Induced by Anti-PD-L1 Antibody Treatment in a Patient with Non-Small Cell Lung Carcinoma
Authors: Mori Sotaro , Kurimoto Takuji , Ueda Kaori , Enomoto Hiroko , Sakamoto Mari , Keshi Yukako , Yamada Yuko , Nakamura Makoto
Published: July 2018

Background: Recent immune therapy with checkpoint inhibitors (CPIs) has demonstrated remarkable antitumor effects on specific tumors, such as malignant lymphoma and non-small cell lung carcinoma. By contrast, CPIs cause an imbalance in the immune system, triggering a wide range of immunological side effects termed immune-related adverse effects (irAEs). Here, we report a rare case of optic neuritis and hypopituitarism during anti-programmed death-ligand 1 (PD-L1) antibody treatment. Case Presentation: A patient with non-small cell lung carcinoma received anti-PD-L1 antibody treatment every 3 weeks; however, the patient started experiencing headaches, general fatigue, anorexia, and diarrhea approximately 1 year after the initiation of the treatment. Moreover, sudden visual loss of the right eye occurred 1 week after the interruption of the anti-PD-L1 antibody treatment. MRI findings showed gadolinium enhancement in the left optic nerve, but no enlargement of the pituitary gland and stalk. Laboratory data showed decreased serum adrenocorticotropic hormone (ACTH), cortisol, and free T4 levels, and a hormone tolerance test indicated hypopituitarism, hypothyroidism, and hypoadrenocorticism. The central scotoma caused by optic neuritis completely disappeared immediately after a course of steroid pulse therapy, and no recurrence occurred up to 2 years after initiation of the steroid pulse therapy while replacement therapy for hypothyroidism and hypoadrenocorticism was continued. Conclusions: The patient presented with optic neuritis and hypopituitarism, possibly due to irAEs of the anti-PD-L1 antibody treatment. Steroid pulse therapy was effective for optic neuritis, suggesting underlying immunological mechanisms. Neurological complications including optic neuritis should be considered when examining patients with cancer undergoing CPI treatment.
Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells
Authors: Jiang Zhi-Jun , Shen Qing-Hua , Chen Hai-Yong , Yang Zhe , Shuai Ming-Qi , Zheng Shusen
Published: July 2018

Background/Aims: Immune tolerance is considered the only way to manage liver transplantation (LT). The current study hypothesized that galectin-1 via the activation of hepatic stellate cells (HSCs) is capable of inducing immune tolerance in LT. Methods: Lentiviral-mediated gene knockdown and overexpression of galectin-1 were conducted in HSC-T6 cells. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to determine galectin-1 expression. LT was performed in 20 C57BL/J6 mice and 20 C3H mice. T-cells were assigned into control, Galectin-1 shRNA, Galectin-1 OE, Galectin-1 OE SB431542, Galectin-1 OE Sulforaphane, Galectin-1 OE Y27632, and Galectin-1 OE UO126 groups. CFSE, flow cytometry, and ELISA were respectively employed to detect T-cell proliferation, CD4+/ CD8+ ratio and IL-2, IL-10 and TGF-β levels. After establishing mouse models of immune tolerance and acute rejection, immunohistochemistry, TUNEL, and immunofluorescence assay were performed to determine CD3+ expression, apoptosis, α-SMA, and desmin. Mouse models of CCl4-induced liver fibrosis were established, followed by assigning the control1 and CCl4 groups. ELISA was used to determine ALT, AST, TBIL and Hyp levels. A total of 3 C57BL/J6 mice (donor) and 6 C3H mice (recipient) were grouped into the control2 and UO126 groups, followed by ELISA detection for IL-2, IL-10 and TGF-β. Results: In T-cells, galectin-1 shRNA increased cell proliferation and IL-2 levels with reduced IL-10 and TGF-β levels, while the Galectin-1 OE and Galectin-1 OE UO126 groups revealed the opposite results. Galectin-1 overexpression elevated the ratio of the CD4+ to CD8+ T-cells. The acute rejection group exhibited enhanced desmin expression and reduced α-SMA expression. Compared with the immune tolerance group, the acute rejection group displayed higher galectin-1 expression, a positive expression rate of CD3+ T-cells, and an increased apoptosis rate. Compared with the control1 group, the CCl4 group exhibited higher galectin-1 expression, ALT, AST, TBIL, and Hyp levels, α-SMA expression and CD4+/CD8+ T-cell ratio, in addition to decreased expression of desmin. Compared with the control2 group, UO126 increased galectin-1 expressions, IL-10 and TGF-β levels and reduced IL-2 levels with inactivated HSCs. Conclusions: The findings of the current study indicated that the overexpression of galectin-1 promoted the activation of HSCs, which reduced the inflammatory response by exerting immunosuppressive effects and accordingly contributed to immune tolerance in LT.
Зміни показників ротової рідини дітей дошкільного віку з гінгівітом під впливом лікувально-профілактичних заходів
Authors: Avdeev A. V. , Zmarko Y. K.
Published: July 2018

Summary. The significant prevalence of inflammatory processes in periodontal tissues of children of different ages indicates insufficient effectiveness of preventive and therapeutic measures. Children of preschool age need special attention in the choice of therapeutic and prophylactic means.The aim of the study – a comparative evaluation of traditional treatment of children aged from 3–5 years with chronic catarrhal gingivitis with therapy with the use of anti-inflammatory gel with neovitin.Materials and Methods. 47 children with chronic catarrhal gingivitis were taken for dispensary observation and divided into groups: the main (23 children) and the comparative (24 children). All children underwent conventional therapy according to the protocols of medical care – basic therapy. In the main group, for a month, pathogenetic agents were used – an anti-inflammatory gel with neovitin, hygiene products were recommended. In the comparative group for local therapy, a 3 % hydrogen peroxide solution was used to rinse the oral cavity (during the first week of treatment) – Rotokan, a therapeutic and prophylactic toothpaste. Control examinations and examination with the definition of the hygienic state of the oral cavity using the hygienic index of Yu. A. Fedorov and V. V. Volodkina, the prevalence and intensity of the inflammatory process in the gums were assessed using the Schiller-Pisarev test and the PMA index, the oral fluid index (formation of oxyradical, urease activity, pH, viscosity, lysozyme content, degree of dysbiosis).Results and Discussion. After the treatment, elimination of gum inflammation in patients of the main group was accompanied by a 2.8-fold decrease in the PMA index; GI – 1.6 times. The reduction in the period of treatment of children was revealed in the application of the proposed treatment regimen. The effectiveness of the treatment was confirmed by a decrease in the formation of oxyradicals immediately after treatment by 15.67 % and 10.98 % (p<0.05), a decrease in urease activity was observed in 8.43 % and 5.47 %; the viscosity of the oral fluid decreased by 54.51 % and 50.51 % (p<0.05), the incidence of dysbiosis decreased by 22.49 % (p<0.05) and 10.36 % in children of the primary and comparative groups, respectively. After 0.5 years, the lysozyme content in the oral fluid of children increased by 21.12 % and 7.09 % (p<0.05), the pH increased by 1.39 % and 0.25 % (p>0.05) in children of the primary and comparative groups, respectively.Conclusions. The use of the proposed therapy with gel with neovitin contributed to the best results of treatment: a decrease in the degree of gingival inflammation by the PMA index by 2.8 times, a decrease in the number of visits to a doctor by 1.1, improvement of the oral fluid of children, and, to a greater extent, six months after the performed treatment.
Методика проведення практичних занять із розділу «Реконструктивно-відновна хірургія щелепно-лицевої ділянки» в умовах кредитно-модульної системи навчання
Authors: Halahdyna A. A. , Herasym L. M.
Published: July 2018

Summary. The article describes the methodology of conducting practical classes on module 5 “Reconstructive-Restorative Surgery of the Maxillofacial Area” for students of the 5th year of the Faculty of Dentistry at the Higher State Educational Institution of Ukraine “Bukovyna State Medical University”.The aim of the study – to increase the level of mastering the educational material on the discipline “Surgical Dentistry” in the 9 th semester at the 5th year.Materials and Methods. We have developed a teaching complex, which includes lectures, practical and individual classes, and aims to improve the efficiency of the discipline “Surgery”.Results and Discussion. In the Higher State Educational Institution of Ukraine “Bukovyna State Medical University” teaching “Surgery” at the 9 th semester of the 5 th year carried out by “cycle” in accordance with the curriculum according to the credit-transfer system. According to the standard curriculum for the study module “Reconstructive surgery, maxillofacial area” 165 hours, including 24 – lecture hours, 86 – practical hours and 55 – individual work of students, the number of creadits – 5.5 are given. For quality study subjects teacher and every student has access to distance learning serve “Moodle” that allows students to expand their knowledge.To facilitate the orientation of students in the curriculum course “Surgical dentistry” in “Moodle” placement schedule of lectures and practical training, thematic plan of practical classes and individual work appropriate methodical instructions, video material, tests.At the end of the cycle, each student must complete the final module control, which takes place after the completion of the study of all the topics of the module at the last lesson.Conclusions. Using this technique within the credit-transfer system is effective for teaching students of the 5-th year dental faculty students, promotes careful study of theoretical issues Module 5 “reconstructive surgery, maxillofacial area” makes it possible to curation dental patients with surgical pathology of maxillofacial area, writing medical documentation, carefully prepares students for writing an integrated licensing exam “Krok-2. Dentistry “and a state final exam, and also contributes to the ultimate goal of education – the training of skilled competitive professionals
Результати аналізу роботи хірургічного кабінету Закарпатської обласної клінічної стоматологічної поліклініки за 2012–2016 роки
Authors: Heley V. M.
Published: July 2018

Summary. This article presents an analysis of the work of a doctor-surgeon-dentist in Preventive Department of Uzhhorod Regional Dental Clinic in 2012–2016. Statistical processing of medical practice data is an important factor in assessing its professional activity, the completeness of duties, and the quality of providing surgical dental services.The aim of the study – to analyze the work of dental surgeon for the period of 5 years.Materials and Methods. According to the authors of most practitioners and dental surgeons, basic problems of organization of dental care are uneven labour load and distribution of surgical-dental care. This analysis of the work of a surgeon in the future will be able to improve the development of mechanisms for qualified medical assistance and improve the efficiency of the functioning of the dental service as a part of the health care system.Results and Discussion. Analyzing the work of a dental surgeon for five years in the study was given monthly performance reporting. The load during the year on the doctor dental surgeon was uneven. Fluctuations in cabinet loading can be explained by fluctuations in the distribution of holiday days and periods of temporary disability of the clinic staff. Accordingly, monthly in the office was worked out from 19.17 to 19.50 working changes. The data shown in the work clearly confirm the theory of cyclicity and seasonality of patient referrals for surgical-dental care, which in turn corresponds to caries morbidity and its complications according to statistical data.Conclusions. As can be seen from the analysis of the obtained data, the surgeon-surgeon dentist over 5 years completed a large amount of medical work, which required a profound knowledge of the methods of examination of patients, differential diagnosis, manual skills and abilities. Must constantly improve their skills while on pre-courses prove proficiency to apply effective methods of pharmacotherapy.
Оцінка впливу остеотропних препаратів на активність процесів пероксидного окиснення ліпідів та антиоксидантної системи при регенерації кісткової тканини в експерименті
Authors: Zubachyk V. M. , Han I. V. , Pasko O. O.
Published: July 2018

Summary. The comparative estimation of the dynamics of the reparative process in bone tissue under the infl uence of MTA and Nano Gen preparations and the proposed compositions based on hydroxyapatite and β-tricalcium phosphate for endodontic treatment is given.The aim of the study – to determine the dynamics of reparative processes in bone tissue under the infl uence of drugs and compositions for endodontic treatment, which is based on the analysis of the results of biochemical studies of lipid peroxidation and antioxidant system.Materials and Methods. The experiment was conducted on 120 white rats, on which the defect of bone tissue was created and fi lled with the studied biomaterials. From the experiment the animals were excised at 14 and 30 days by decapitation under anesthesia and blood samples were taken for biochemical studies. In the blood of rats, the activity of peroxide oxidation processes of lipids – malonic dialdehyde and antioxidant system enzymes – catalase and superoxide dismutase were studied.Results and Discussion. In animal groups where hydroxyapatite and β-tricalcium phosphate based compositions were used, less activity was observed in lipoperoxidation than in animals using MTA and Nano Gen. The proposed compositions possess antioxidant properties that contribute to the reduction of the activity of the infl ammatory process. Compositions based on hydroxyapatite and β-tricalcium phosphate at earlier times restore the balance in the lipid peroxidation system and the antioxidant system, which creates more favorable conditions for biorevitalization and regeneration of non-apical tissues.Conclusions. The compositions based on hydroxyapatite and β-tricalcium phosphate possess antioxidant properties, suppress excessive lipoproxidation processes, contribute to the reduction of the activity of the infl ammatory process, which stimulates the regeneration of bone tissue.
Выбор метода лечения рецидивных паховых грыж
Authors: Grubnik V. V. , Bugridze Z. D. , Vorotyntseva K. O.
Published: July 2018

Цель работы: определить оптимальный метод оперативного вмешательства при рецидивных паховых грыжах.Материалы и методы. В период с сентября 2007 года по май 2011 года на базе Одесской областной клинической больницы было проведено сравнительное рандомизированное исследование, которое включило 82 пациента с рецидивными паховыми грыжами. Причинами рецидивов после первой операции у 14 пациентов стало заживление послеоперационной раны, у 30 пациентов – использование сеток недостаточно больших размеров и в других 38 пациентов – рецидив наступил в связи с нарушением выполнения техники операции Лихтенштейна. Все 82 пациента были разделены на две группы, первая группа пациентов была прооперирована с помощью лапароскопических методов, вторая группа – с помощью операции методом Лихтенштейна.Результаты исследований и их обсуждение. Трансабдоминальная преперитонеальная лапароскопическая пластика ТАРР была выполнена 40 пациентам, при этом ни в одном случае не было конверсии. В группе I продолжительность операции была (87 ± 12) минут. В группе II 42 пациентам была выполнена открытая герниопластика, продолжительность этой операции была немного больше, чем лапароскопическая, что объясняется техническими сложностями выделения из рубцов рецидивной грыжи, краев апоневроза, сетчатого трансплантата и паховой связки. Средняя продолжительность операции в группе II была (112 ± 15) минут. При наблюдении за пациентами группы II в срок от 12 до 24 месяцев у 4 пациентов (9,5 %) был выявлен рецидив грыжи.
Інноваційна діяльність та педагогічна комунікація виклaдача загальної хірургії
Authors: Dronov O. I. , Protsiuk A. , Skomarovskii A. , Gorlach A. , Lubenets T.
Published: July 2018

У роботі зосереджено увагу на аспектах покращення інтелектуальних здібностей студентів на кафедрі загальної хірургії ви­щого медичного навчального закладу. Особливістю є вплив самоменеджменту викладача на ефективність робочого процесу майбутніх спеціалістів. Передбачено збільшення продуктивності застосування знань у процесі навчання, що здійснюється шляхом виконання ряду сучасних методів оптимізації навчального процесу студентів. Знання основ менеджменту і само­менеджменту, практика самоменеджменту вдосконалює навички викладача та прискорює темпи формування національної інтелектуальної медичної еліти.
Ventricular Arrhythmias Underlie Sudden Death in Rats With Heart Failure and Preserved Ejection Fraction
Authors: Cho Jae Hyung , Zhang Rui , Aynaszyan Stephan , Holm Kevin , Goldhaber Joshua I. , Marbán Eduardo , Cingolani Eugenio
Published: July 2018

Background:

Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly common clinically, now rivaling or exceeding HF with reduced ejection fraction. Sudden death is the leading mode of exodus in patients with HFpEF, but the underlying causes are largely unknown. Using ambulatory recordings in a rat model, we test the hypothesis that ventricular arrhythmias (VA) underlie sudden death in HFpEF.

Methods:

Dahl salt-sensitive rats (7 weeks of age) were fed a high-salt diet to induce HFpEF (n=13) or a normal-salt diet (controls, n=9). Transthoracic echocardiography was performed to check systolic and diastolic function at 14 to 18 weeks of age. Telemetric electrocardiographic recordings were analyzed for QT interval duration, burden of premature ventricular contractions, spontaneous VA, and heart rate variability. Survival was monitored twice daily.

Results:

High-salt–fed rats with clear diastolic dysfunction, preserved ejection fraction, and HF signs were diagnosed with HFpEF at 14 to 15 weeks of age. QT and QTc intervals were prolonged in HFpEF rats compared with controls. Heart rate variability was reduced in HFpEF rats compared with controls. Spontaneous VA were more prevalent in HFpEF rats (6/13=46.1% versus 0/9=0% in controls;
P
<0.05), and sudden death was observed in 4 of 13 HFpEF rats. Three of the 4 sudden deaths were associated with VA as the terminal rhythm.

Conclusions:

In this rat model with phenotypically verified HFpEF, sudden death was common and generally associated with VA. Further clinical studies are warranted to determine whether these insights translate to sudden death in HFpEF patients.
Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition
Authors: Hashimoto Toru , Kim Grace E. , Tunin Richard S. , Adesiyun Tolulope , Hsu Steven , Nakagawa Ryo , Zhu Guangshuo , O’Brien Jennifer J. , Hendrick Joseph P. , Davis Robert E. , Yao Wei , Beard David , Hoxie Helen R. , Wennogle Lawrence P. , Lee Dong I. , Kass David A.
Published: July 2018

Background:

Phosphodiesterase type-1 (PDE1) hydrolyzes cAMP and cGMP and is constitutively expressed in the heart, although cardiac effects from its acute inhibition in vivo are largely unknown. Existing data are limited to rodents expressing mostly the cGMP-favoring PDE1A isoform. Human heart predominantly expresses PDE1C with balanced selectivity for cAMP and cGMP. Here, we determined the acute effects of PDE1 inhibition in PDE1C-expressing mammals, dogs, and rabbits, in normal and failing hearts, and explored its regulatory pathways.

Methods:

Conscious dogs chronically instrumented for pressure-volume relations were studied before and after tachypacing-induced heart failure (HF). A selective PDE1 inhibitor (ITI-214) was administered orally or intravenously±dobutamine. Pressure-volume analysis in anesthetized rabbits tested the role of β-adrenergic and adenosine receptor signaling on ITI-214 effects. Sarcomere and calcium dynamics were studied in rabbit left ventricular myocytes.

Results:

In normal and HF dogs, ITI-214 increased load-independent contractility, improved relaxation, and reduced systemic arterial resistance, raising cardiac output without altering systolic blood pressure. Heart rate increased, but less so in HF dogs. ITI-214 effects were additive to β-adrenergic receptor agonism (dobutamine). Dobutamine but not ITI-214 increased plasma cAMP. ITI-214 induced similar cardiovascular effects in rabbits, whereas mice displayed only mild vasodilation and no contractility effects. In rabbits, β-adrenergic receptor blockade (esmolol) prevented ITI-214–mediated chronotropy, but inotropy and vasodilation remained unchanged. By contrast, adenosine A
2B
-receptor blockade (MRS-1754) suppressed ITI-214 cardiovascular effects. Adding fixed-rate atrial pacing did not alter the findings. ITI-214 alone did not affect sarcomere or whole-cell calcium dynamics, whereas β-adrenergic receptor agonism (isoproterenol) or PDE3 inhibition (cilostamide) increased both. Unlike cilostamide, which further enhanced shortening and peak calcium when combined with isoproterenol, ITI-214 had no impact on these responses. Both PDE1 and PDE3 inhibitors increased shortening and accelerated calcium decay when combined with forskolin, yet only cilostamide increased calcium transients.

Conclusions:

PDE1 inhibition by ITI-214 in vivo confers acute inotropic, lusitropic, and arterial vasodilatory effects in PDE1C-expressing mammals with and without HF. The effects appear related to cAMP signaling that is different from that provided via β-adrenergic receptors or PDE3 modulation. ITI-214, which has completed phase I trials, may provide a novel therapy for HF.
Early Regenerative Capacity in the Porcine Heart
Authors: Ye Lei , D’Agostino Giuseppe , Loo Sze Jie , Wang Chen Xu , Su Li Ping , Tan Shi Hua , Tee Gui Zhen , Pua Chee Jian , Pena Edgar Macabe , Cheng Redmond Belen , Chen Way Cherng , Abdurrachim Desiree , Lalic Janise , Tan Ru San , Lee Teck Hock , Zhang JianYi , Cook Stuart Alexander
Published: July 2018

Background:

The adult mammalian heart has limited ability to repair itself after injury. Zebrafish, newts, and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown whether hearts of young large mammals can regenerate.

Methods:

We examined the regenerative capacity of the pig heart in neonatal animals (ages 2, 3, or 14 days postnatal) after myocardial infarction or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance imaging and echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry, and Western blotting were performed to study cell proliferation, sarcomere dynamics, and cytokinesis and to quantify myocardial fibrosis. RNA-sequencing was also performed.

Results:

After myocardial infarction, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day-old pigs. In contrast, older animals developed full-thickness myocardial scarring, thinned walls, and did not recover function. Genome-wide analyses of the infarct zone revealed a strong transcriptional signature of fibrosis in 14-day-old animals that was absent in 2-day-old pigs, which instead had enrichment for cytokinesis genes. In regenerating hearts of the younger animals, up to 10% of CMs in the border zone of the myocardial infarction showed evidence of DNA replication that was associated with markers of myocyte division and sarcomere disassembly.

Conclusions:

Hearts of large mammals have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth.
The holomorph of Fusarium celtidicola sp. nov. from Celtis australis
Authors: SHANG QIU-JU , PHOOKAMSAK RUNGTIWA , CAMPORESI ERIO , KHAN SEHROON , LUMYONG SAISAMORN , HYDE KEVIN D.
Published: July 2018

A novel holomorphic Fusarium species, F. celtidicola is introduced in this study, with evidence from morphological characterisation and phylogenetic analyses. The new species is described and discussed in relation to similar taxa. Analysis of RPB1 and RPB2 sequence data support the placement in Fusarium and its distinctiveness as a new species.
On taxonomic status of Macromitrium leptocarpum and M. subleptocarpum, with comments on M. sulcatum (Bryophytea, Orthotrichaceae)
Authors: YU JING , LI DANDAN , LI YAN , GUO SHUILIANG
Published: July 2018

Macromitrium sulcatum (Hook.) Brid., M. leptocarpum Broth. and M. subleptocarpum Dixon & P. de la Varde are similar in their gametophytes. Having studied their type and ordinary specimens, we treat M. subleptocarpum as a synonym of M. leptocarpum, and the latter as M. sulcatum var. leptocarpum (Broth.) J. Ying, D. D. Li, Y Li & S. L. Guo comb. nov. The variation of M. sulcatum and its infraspecific taxa are also discussed.
Examining the Impact of Group Size on the Treatment Intensity of a Tier 2 Mathematics Intervention Within a Systematic Framework of Replication
Authors: Doabler Christian T. , Clarke Ben , Kosty Derek , Kurtz-Nelson Evangeline , Fien Hank , Smolkowski Keith , Baker Scott K.
Published: July 2018

Group size and treatment intensity are understudied topics in mathematics intervention research. This study examined whether the treatment intensity and overall intervention effects of an empirically validated Tier 2 mathematics intervention varied between intervention groups with 2:1 and 5:1 student-teacher ratios. Student practice opportunities and the quality of explicit instruction served as treatment intensity metrics. A total of 465 kindergarten students with mathematics difficulties from 136 intervention groups participated. Results suggested comparable performances between the 2:1 and 5:1 intervention groups on six outcome measures. Observation data indicated that student practice differed by group size. Students in the 5:1 groups received more opportunities to practice with their peers, while students in the 2:1 groups participated in more frequent and higher quality individualized practice opportunities. Implications in terms of delivering Tier 2 interventions in small-group formats and engaging at-risk learners in meaningful practice opportunities are discussed.
Exploring the Boundary-Heightening Experiences of Black Male Teachers: Lessons for Teacher Education Programs
Authors: Bristol Travis J. , Goings Ramon B.
Published: July 2018

This article uses a phenomenological approach to explore the organizational dynamic of boundary heightening for 27 Black male teachers, across 14 schools, in one urban school district. Black male teachers described being perceived by their colleagues as either incompetent or overqualified to teach their subject matter. These experiences created workplace environments in which participants felt alienated from their colleagues. In response, these Black male teachers strategically erected social boundaries to manage interactions with their colleagues. Black male teacher diversity campaigns in education preparation programs should be informed by Black male teachers’ school-based experiences. The article shows how teacher education programs can redesign facets of their preparation to attend to the boundary-heightening and workplace experiences that Black male teachers may face in becoming teachers of record.
The Madisonian Republic and Modern Nationalist Populism: Democracy and the Rule of Law
Authors: Brunello Anthony R.
Published: July 2018

The U.S. Federal Constitution was built to be a machine for displacing conflict. Madison and the other Framers erected a Federal Republic organized to control populist movements and preserve the interests of the greatest stakeholders, while offering the “most liberty imaginable” in 1788. In 2016, a populist movement ascended to the commanding heights of power. How did it happen and what are the consequences when a faction comes to power? Is it a defect of the modern structure of American government? Has the U.S. Constitution reached a place where it is no longer functional? Or can Madison's Republic continue to work against popular factions rising in a common passion fired by fear and hatred? In tackling these questions, this article suggests that the U.S. Constitutional Framers did not know in 1788 what exiting the aristocratic and feudal world would mean and what kind of state and society the Republic would become. I argue Madison's contributions to The Federalist are exemplars of the engineer showing how each part of the machine fits together to achieve a comprehensive and effective whole. The national populism of the kind circulating around the Western world in 2016 has posed real challenges to that machinery.
The prevalence of Amblyopia in a young Population
Authors: Hashemi Hassan , Saatchi Mohammad , Ali Babak , Yekta Abbasali , Asharlous Amir , Ostadimoghaddam Hadi , Heravian Javad , Khabazkhoob Mehdi
Published: July 2018

Purpose:

The aim of this study was to determine the prevalence of amblyopia and its determinants in Iranian students above 18 years.

Methods:

In this university-based cross-sectional study, multi-stage cluster sampling was used to select participants. After selecting the students, visual acuity, objective, and subjective refraction were measured and the best-corrected visual acuity was determined.

Results:

We evaluated 1462 individuals with a mean age of 22.8 ± 3.1 years in this study, of whom 73% were female. The prevalence of amblyopia was 2.19% (95% confidence interval [CI]: [1.43, 2.93]), of which 6.2% was strabismic, 71.8% was refractive (isometropic and anisometropic), and 22.0% was mix (strabismic and anisometropic). No difference was observed in the prevalence of amblyopia between boys and girls ( p value = 0.315). The prevalence of amblyopia was 3.93%, 1.71%, 3.79%, and 0% in the age group 18–20, 21–25, 26–30, and above 30 years, respectively ( p value = 0.071).

Conclusion:

The results of this study, as the first study investigating the prevalence of amblyopia in Iranian adults, showed a rather higher prevalence of amblyopia in Iranian university students compared to other studies on adults in other countries. Moreover, similar to some other studies, refractive amblyopia had a higher prevalence than other types.
Percutaneous cholecystostomy for biliary decompression in patients with cholangitis and pancreatitis
Authors: Park Jin Myung , Kang Chang Don , Lee Minjong , Park Sung Chul , Lee Sung Joon , Jeon Yong Hwan , Cho Seong Whi
Published: July 2018

Objective

This study was performed to assess the effectiveness and safety of percutaneous cholecystostomy (PC) for biliary decompression.

Methods

We retrospectively analyzed our institution’s PC database from March 2015 to August 2017 and selected patients with biliary obstruction. The primary outcomes were the technical and clinical success rates. As secondary outcomes, adverse events and pain after PC were compared with those of patients who underwent PC for acute cholecystitis during the same period.

Results

Twenty patients underwent PC for biliary obstruction (cholangitis, 19; pancreatitis, 1). The technical and clinical success rates were 100%. The median serum total bilirubin level decreased considerably from 4.5 to 1.4 mg/dL after PC. An adverse event (catheter migration) occurred in 1 patient, and 17 patients developed pain after PC. During the same period, 104 patients underwent PC for cholecystitis. Adverse events occurred in 7 patients, and 62 developed pain. There was no significant difference in the adverse event rate between the cholangitis/pancreatitis and cholecystitis groups (5.0% vs. 6.7%, respectively), but pain occurred considerably more frequently in the cholangitis/pancreatitis group (94.4% vs. 63.9%, respectively).

Conclusions

PC is an effective and safe method for biliary decompression in selected patients. However, attention should be paid to postoperative pain.
Clinical characteristics of lupus enteritis in Japanese patients: the large intestine-dominant type has features of intestinal pseudo-obstruction
Authors: Maruyama A , Nagashima T , Iwamoto M , Minota S
Published: July 2018

This study was performed to investigate the clinical characteristics of lupus enteritis in Japanese patients with systemic lupus erythematosus (SLE). A total of 481 patients with SLE admitted to our hospital between 2001 and 2015 were retrospectively reviewed. Diagnosis of lupus enteritis was based on the following three criteria: (1) abdominal symptoms, (2) diffuse long-segment bowel thickening and (3) a requirement for glucocorticoid therapy. Lupus enteritis was identified in 17 patients (3.5%) and there were two distinct types: small intestine-dominant and large intestine-dominant. Significant differences between the two types were noted with respect to the age, frequency of biopsy-proven lupus nephritis, frequency of rectal involvement, maximum bowel wall thickness, and requirement for steroid pulse therapy. Among patients with large intestine-dominant lupus enteritis, 60% had extra-intestinal symptoms (hydroureter, bladder wall thickening, and bile duct dilatation) that are known complications of intestinal pseudo-obstruction. Two patients with large intestine-dominant lupus enteritis developed intestinal pseudo-obstruction either before or after diagnosis of lupus enteritis. Five patients (29%) developed recurrence during a median observation period of 7.2 years (1.4–14.4 years). In conclusion, large intestine-dominant lupus enteritis resembles intestinal pseudo-obstruction and these two diseases may have a common pathogenesis.