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Rupture of intracranial aneurysms (IAs) is the most common cause of subarachnoid hemorrhage (SAH). Currently, there is sufficient evidence to indicate that inflammatory responses contribute to aneurysm rupture. Moreover, the familial occurrence of SAH suggests that genetic factors may be involved in disease susceptibility. In the present study, a clinically proven case of IA in a patient who is a heterozygous mutation carrier of the activated leukocyte cell adhesion molecule ( ALCAM )/cluster of differentiation 166 (CD166) gene, is reported. Genomic DNA was extracted from two siblings diagnosed with SAH and other available family members. A variant prioritization strategy that focused on functional prediction, frequency, predicted pathogenicity, and segregation within the family was employed. Sanger sequencing was also performed on the unaffected relatives to assess the segregation of variants within the phenotype. The verified mutations were sequenced in 145 ethnicity-matched healthy individuals. Based on whole exome sequencing data obtained from three individuals, two of whom were diagnosed with IAs, the single-nucleotide variant rs10933819 was prioritized in the family. Only one variant, rs10933819 (G>A), in ALCAM co-segregated with the phenotype, and this mutation was absent in ethnicity-matched healthy individuals. Collectively, ALCAM c1382 G>A p.Gly229Val was identified, for the first time, as a pathogenic mutation in this IA pedigree., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Aitkulova et al.)

Background: The practice of neurosurgery has been profoundly affected by the coronavirus disease 2019 (COVID-19) pandemic in Kazakhstan. Many elective surgeries were postponed or canceled, which resulted in difficulties in hospitalization. In the present study, we aimed to describe the effects of COVID-19 on neurosurgical practice and to determine whether a discrepancy was present in the effects between metropolises and regional cities in Kazakhstan., Methods: We performed an electronic internet-based survey among Kazakhstan's neurosurgeons using the virtual snowball sampling method. The invitation link to complete the questionnaire was sent to neurosurgeons through personal and corporate electronic mail and social networks. The data were analyzed using Excel and Stata., Results: A total of 43 neurosurgeons completed the survey. The distribution of regional and urban respondents was almost equal. The male neurosurgeons outnumbered the female neurosurgeons (93.02% vs. 6.98%). A decrease in consultations (65.34% ± 28.24%) and surgeries (56.55% ± 26.34%) had been observed by all neurosurgeons, regardless of city type. However, the proportion of neurosurgeons who had attended online educational courses during the pandemic was significantly higher (P = 0.001) for the surgeons from major cities (68.18%) compared with the surgeons from smaller cities (19.05%). The regional neurosurgeons tended to perform urgent surgeries on COVID-19-positive patients 3 times more often than had the metropolitan neurosurgeons (P < 0.001)., Conclusions: The true effect of the pandemic remains unknown for Kazakhstan. A discrepancy between the metropolitan and regional cities was found in the present study. Efforts are required and relevant guidelines must be developed to ensure that the neurosurgical treatment of various conditions continues to be available during health emergencies and that the disparities are addressed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Percutaneous spinal endoscopy is used for the treatment of disorders of the lumbar spine, as it has several advantages over traditional surgical methods. The performance of percutaneous spinal endoscopy is not possible without applying anesthesia methods. Two types (local and general) of anesthesia are used for percutaneous spinal endoscopy. Both, local and general anesthesia approaches contribute to safety in surgical procedures. Although it is believed that the method of local anesthesia has more benefits over general anesthesia, such as lowering the risk of postoperative neurological complications in a patient, the literature on the topic is inconclusive. The study aims to perform a comparative analysis of the two anesthesia methods using a prospective case-control design. Patients were divided into two groups: those who received local anesthesia (LA) (20 patients), and those who underwent general anesthesia (GA) (20 patients). As a result of the study, 40% of the patients experienced moderate pain and 5% of the patients experienced excruciating pain intraoperatively in the LA group. Although Visual Analog Scale and Oswestry Disability Index scores improved more rapidly in LA group, at the 12-month check-up point there was no significant difference between cases and controls. Nevertheless, there were postoperative complications such as nerve root injury in 10% of the patients; nausea, vomiting, dizziness, drowsiness in 15% of the patients in the GA group, and an insignificant or no such complications in patients of the LA group. The present study demonstrates that LA contributes to more positive short-term outcomes for patients as it facilitates nerve root damage prevention, and has no postoperative side effects on patients' well being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kerimbayev, Kenzhegulov, Tuigynov, Aleinikov, Urunbayev, Makhambetov, Pan, Abishev, Oshayev, Baiskhanova, Solodovnikov and Akshulakov.)

Sleep spindles have been implicated in sleep protection, depression and anxiety. However, spindle-related brain imaging mechanism underpinning the deficient sleep protection and emotional regulation in insomnia disorder (ID) remains elusive. The aim of the current study is to investigate the relationship between spindle-related brain activations and sleep quality, symptoms of depression and anxiety in patients with ID. Participants (n = 46, 28 females, 18-60 years) were recruited through advertisements including 16 with ID, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 30 matched controls. Group differences in spindle-related brain activations were analyzed using multimodality data acquired with simultaneous electroencephalography and functional magnetic resonance imaging during sleep. Compared with controls, patients with ID showed significantly decreased bilateral spindle-related brain activations in the cingulate gyrus (familywise error corrected p ˂ 0.05, cluster size 4401 mm 3 ). Activations in the cingulate gyrus were negatively correlated with Pittsburgh Sleep Quality Index scores (r = -0.404, p = 0.005) and Self-Rating Anxiety Scale scores (r = -0.364, p = 0.013), in the pooled sample. These findings underscore the key role of spindle-related brain activations in the cingulate gyrus in subjective sleep quality and emotional regulation in ID., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to improve the direct results of reconstructive surgery in patients operated on for complicated forms of colorectal cancer, by using 5-fluorouracil in the postoperative period., Methods: The study involved 126 patients (they were divided into 2 groups) with colorectal cancer, who underwent reconstructive surgery. They underwent a standard clinical examination and a mandatory examination program., Results: The use of 5-fluorouracil in adjuvant treatment in patients with colorectal cancer significantly reduces the number of subjective clinical manifestations (positional tests) in the main group - 17%, and in the control group - 54.3%, as well as objective clinical manifestations (instrumental research methods) in Group I - 13%, and Group II - 89.5%, respectively. The study shows that in re-operated patients with colorectal cancer who received 5-fluorouracil, abdominal adhesions are characterized by a low content of collagen and fibroblasts, low vascularization and a high content of polymerized fibrin strands. It was also found that re-operated patients with colorectal cancer who did not receive 5-fluorouracil, abdominal adhesions are characterized by a high collagen content, a large number of fibroblasts, and severe angiogenesis., Conclusion: It was found that the prolonged administration of 5-fluorouracil statistically significantly reduces the risk of adhesions, thereby showing the effectiveness of preventing adhesive disease of the abdominal organs. It was shown that the prolonged administration of 5-fluorouracil significantly reduces the number of subjective and objective signs of adhesive disease of the abdominal organs, as well as significantly decreases intraoperative and postoperative complications, the duration of the operation, and the amount of blood loss. In the postoperative period, it reduces the length of hospital stay and improves the quality of life of patients.

Background: Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline and/or delamanid as part of their multidrug regimen., Methods: Patients with a positive baseline culture were included. 6-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods., Results: Culture conversion was observed in 83.8% (526 out of 628) of patients receiving an all-oral regimen and 85.5% (425 out of 497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95% CI 0.88-1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients., Conclusions: Among individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study., Competing Interests: Conflict of interest: P.Y. Khan reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: M.F. Franke reports grants from Unitaid, during the conduct of the study. Conflict of interest: C. Hewison reports grants from Unitaid, during the conduct of the study. Conflict of interest: K.J. Seung reports grants from Unitaid, during the conduct of the study. Conflict of interest: H. Huerga reports grants from Unitaid, during the conduct of the study. Conflict of interest: S. Atwood has nothing to disclose. Conflict of interest: S. Ahmed reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen Pharmaceutical, outside the submitted work. Conflict of interest: M. Khan has nothing to disclose. Conflict of interest: T. Sultana has nothing to disclose. Conflict of interest: M. Manzur-ul-Alam has nothing to disclose. Conflict of interest: L.N.Q. Vo reports grants and non-financial support (drugs/equipment) from Unitaid via IRD Global during the conduct of the study. Conflict of interest: L. Lecca has nothing to disclose. Conflict of interest: K. Yae has nothing to disclose. Conflict of interest: S. Kozhabekov has nothing to disclose. Conflict of interest: M. Tamirat has nothing to disclose. Conflict of interest: A. Gelin has nothing to disclose. Conflict of interest: S.C. Vilbrun has nothing to disclose. Conflict of interest: M. Kikvidze has nothing to disclose. Conflict of interest: J. Faqirzai has nothing to disclose. Conflict of interest: A. Kadyrov has nothing to disclose. Conflict of interest: A. Skrahina has nothing to disclose. Conflict of interest: A. Mesic has nothing to disclose. Conflict of interest: N. Avagyan has nothing to disclose. Conflict of interest: M. Bastard reports grants from Unitaid, during the conduct of the study. Conflict of interest: M.L. Rich reports grants from Unitaid, during the conduct of the study; personal fees for consultancy from World Health Organization, other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: U. Khan reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: C.D. Mitnick reports a grant from Unitaid to fund the study and that the endTB Consortium coordinated donations of delamanid (Otsuka Pharmaceutical) and bedaquiline (Janssen) to be used for treatment by some of the patients included in the endTB Observational Study., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Metal-free C-Se cross-couplings via the formation of electron-donor-acceptor (EDA) complexes have been developed. The visible-light induced reactions can be applied for the synthesis of a series of unsymmetrical diaryl selenides employing aryl bromides, aryl iodides as well as aryl chlorides under mild reaction conditions. The scale-up was readily achieved. UV-Vis spectroscopy measurements provide insight into the reaction mechanism.

Carbon Fibre Reinforced Polymers (CFRPs) are commonly used materials in manufacturing components and products in the automotive, aerospace, and wind energy industries generating thousands of tons of waste, thus creating a threat to the environment if not recycled. Therefore, it is important for both academia and industry to investigate various ways of recycling this material. However, there is an urgent need for a reliable cost predication system to assist in making informed decisions, planning sustainable treatment, and developing pricing strategies for different waste treatment scenarios. This research paper presents the development of a fuzzy logic-based system to perform cost estimation of recycling processes of the CFRP. The developed system has taken into consideration uncertainties such as the characteristics of End of Life (EoL) material including its size and weight, its origin and diversity of existing recycling methods, and quantity of recycling waste. Cost drivers were divided into categories such as dismantling, transportation, operation, and capital cost. The system was developed by creating 243 fuzzy rules and three levels of fuzzy sets. Moreover, an interactive user-friendly interface was developed to enable the user to use the system easily and efficiently. Finally, case study results were examined to compare the whole life recycling cost of four different recycling technologies in various scenarios of waste treatment. The developed fuzzy logic-based system has the capability in evaluating the cost structure of CFRP recycling techniques and take into consideration uncertainty factors. Hence, a major contribution of the developed system is its provision of the heuristic rules that aid the decision-making process for selecting a cost-effective recycling method. The visualisation facility of the developed system is also a useful tool in enabling potential users to forecast the cost of the CFRP recycling techniques upfront.

Cost-effective and environmentally responsible ways of carbon fiber-reinforced composite (CFRP) recycling are increasingly important, owing to the rapidly increasing use of these materials in many industries such as the aerospace, automotive and energy sectors. Product designers need to consider the costs associated with manufacturing and the end-of-life stage of such materials to make informed decisions. They also need to understand the current methods of composite recycling and disposal and their impact on the end-of-life costs. A comprehensive literature review indicated that there is no such tool to estimate CFRP recycling costs without any prior knowledge and expertise. Therefore, this research paper proposed a novel knowledge-based system for the cost modelling of recycling CFRP that does not require in-depth knowledge from a user. A prototype of a cost estimation system has been developed based on existing CFRP recycling techniques such as mechanical recycling, pyrolysis, fluidized bed, and supercritical water. The proposed system has the ability to select the appropriate recycling techniques based on a user's needs with the help of an optimization module based on the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). Estimating recycling costs has taken into consideration various factors such as different material types in different industries, transportation, and dismantling costs. The developed system can be employed to support early-stage designers and decision-making stakeholders in terms of understanding and predicting recycling costs easily and quickly.

Background: Major depressive disorder (MDD) is the most common mental disorder associated with suicide attempts. When a patient first visits the clinic, clinicians are often expected to make concrete diagnose about acute suicidal risk. However, the timeliness of suicide attempts correlates with patients with MDD has not been tested., Methods: We divided 1718 first-episode and untreated MDD outpatients into those who did not have suicide attempts (non-attempts), recent suicide attempters (≤14 days before assessment) and long - dated suicide attempters (> 30 days before assessment). Positive Symptom Scale of Positive and Negative Syndrome Scale (PANSS), the 17-item Hamilton Depression Scale, 14 - item Hamilton Anxiety Scale, and clinical global impression of severity scale (CGI-S) was assessed. Body mass index, some glycolipid metabolism and thyroid hormone parameters were measured. A gradient-boosted decision trees statistical model was used to generate equally weighted classification for distinguishing recent and long - dated suicide attempters from non-attempts., Results: The classifier identified higher excitement, hostility, anxiety, depression symptoms and higher free thyroxine (FT4) as risk factors for recent suicide attempters with an estimated accuracy of 87% (sensitivity, 59.1%; specificity, 61.2 %). For long - dated suicide attempters' risk factors, single status, higher anxiety and hostility symptoms, higher LDLC and lower BMI, the estimated accuracy was 88% (sensitivity, 52.8%; specificity, 49.6%)., Conclusions: Risk factors for suicide attempt among patients with MDD can be identified by integrating demographic, clinical, and biological variables as early as possible during the first time see a doctor., (Copyright © 2021. Published by Elsevier B.V.)

Common bunt is known to cause grain yield and quality losses in wheat due to bunt ball formation and infestation of the grain. The aim of this study is to identify for sources of resistance to common bunt in wheat genotypes using phytopathological and molecular methods. In general, studied 60 Kazakh and foreign wheat genotypes were found 15 samples with the Bt9 , Bt8 and Bt11 genes. Carriers of the Bt10 gene include the five varieties. The four resistance genes, Bt8, Bt10, Bt11, Bt9 , and Bt10 were identified in the Karasai variety. Phytopathological and molecular screening of Kazakh and foreign wheat genotypes selected 18 with genes for resistance to the disease. According to evaluation on an artificial infection 19 varieties showed an immune type of reaction. These varieties will be used in breeding programs as donors to create resistant varieties against the common bunt. Thus, approaches can reduce the level of fungicides use and the most effective method to control the common bunt., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background and objectives : The aims of this study were to investigate changes in the hemodynamics associated with different types of aortic prostheses and to evaluate patient-prosthesis mismatch (PPM) at rest and after exercise. Materials and Methods : We retrospectively analyzed 150 patients who presented with indications for aortic valve replacement (AVR) with/without concomitant surgery from March 2019 to January 2020. The study population included 90 (60%) men and 60 (40%) women (mean age, 67.33 ± 10.22 years; range, 37-88 years). Echocardiography data such as peak and mean transprosthetic pressure gradients (Gmax, Gmean), velocity (V), effective orifice area (EOA), and indexed EOA (iEOA) were derived at rest and after exercise at baseline and before discharge. The study patients performed the six-minute walk test (6MWT) on the 5th-7th postoperative day. Results : Stented tissue valves showed excellent performance at rest and after exercise in comparison with mechanical valves, which showed favorable hemodynamics at rest only. At the time of discharge, moderate PPM was observed in 7/74 patients (9.5%) at rest and 5/98 (3.3%) patients after exercise. None of the patients showed severe PPM. EOA and iEOA were not significantly different between the groups. However, the stented group showed more pronounced changes in EOA and iEOA after exercise, whereas the changes in the mechanical valve group did not reach significance. Conclusions: In the early postoperative period, mechanical valves and stented valves showed favorable resting hemodynamics. The PPM rate measured after exercise was lower than that at rest.

To investigate effects of agomelatine and mirtazapine on sleep disturbances in patients with major depressive disorder. A total of 30 depressed patients with sleep disturbances, 27 of which completed the study, took agomelatine or mirtazapine for 8 weeks. Subjective scales were administered, and polysomnography was performed at baseline and at the end of week 1 and 8. Functional magnetic resonance imaging was performed at baseline and at the end of week 8. Compared with baseline, scores on the Hamilton Depression Scale, Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Sleep Dysfunction Rating Scale, and Insomnia Severity Index after 8 weeks of treatment significantly decreased in both groups, with no significant differences between groups, accompanied by significant increases in total sleep time, sleep efficiency, and rapid eye movement (REM) sleep and significant decrease in wake after sleep onset. Mirtazapine treatment increased N3 sleep at week 1 compared with agomelatine treatment, but this difference disappeared at week 8. The increases in the percentage and duration of N3 sleep were positively correlated with increases in connectivity between right dorsal lateral prefrontal cortex (dlPFC) and right precuneus and between left posterior cingulate cortex and right precuneus in both groups, respectively. Functional connectivity (FC) between right dlPFC and left precuneus in mirtazapine group was higher compared with agomelatine group after 8 weeks of treatment. These findings indicated that both agomelatine and mirtazapine improved sleep in depressed patients, and the effect of mirtazapine was greater than agomelatine with regard to rapidly increasing N3 sleep and gradually improving FC in the brain., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Organ Care System (OCS) minimizes the cold ischemic time and allows for optimization of logistics and meticulous recipient preparation. Impact of normothermic ex-vivo preservation using OCS compared with cold storage (CS) for prolonged heart preservation especially beneficial for high-risk recipients bridged to transplantation with Mechanical Circulatory Support (MCS)., Methods: Between 2012 and 2018, we performed a retrospective single-center review of prospectively collected data. All patients who underwent heart transplantation with MCS using the OCS Heart (n = 25) versus standard cold storage (n = 10) were included in this study., Results: During this period, 353 patients were implanted with left ventricular assisted device (LVAD) and 35 (10%) were bridged to heart transplantation. There was no significant difference in donor and recipient characteristics and risk factors. The Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was a trend towards higher estimated risk of death at 1y in the OCS group (14.2 vs. 10.8% p = 0.083). Mean total ischemic time during preservation was statistically significantly longer in CS vs OCS group (210 (23) Vs 74.6 (13) min p = 0.001). Median ex vivo normothermic heart perfusion time in OCS was 348.4(132; 955) min. There was significant difference in total out of body time between OCS group 423(67) Vs CS group 210(23) min p = 0.002). All patients were alive on the 30th days post implant in CS groups and 96% in OCS group (p = 0.5)., Conclusion: Normothermic ex-vivo preservation of the allograft during transportation with the organ care system might be beneficial for long-time out of body organ preservation in comparison of cold storage especially for recipients on mechanical circulatory support.

Background: Preventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ 2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients., Methods: A total of 1,487 schizophrenia patients were included who were 18-65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ 2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors., Results: The χ 2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ 2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ 2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ 2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs. <3000 RMB: 28.6 vs. 42.4%, χ 2 = 6.30, p = 0.036). The overall positive predictive value (PPV) of the logistic regression was 0.740, and the decision-tree model was 0.726. Both models were reliable., Conclusions: For schizophrenic patients discharged from hospital, who had good medication adherence, more higher household income, be employed and normal ability of daily living, would be less likely to relapse. Decision tree provides a new path for doctors to find the schizophrenic inpatient's relapse risk and give them reasonable treatment suggestions after discharge., (Copyright © 2020 Mi, Chen, Fan, Tabarak, Xiao, Cao, Li, Bao, Han, Li, Shi, Guo, Wang, Liu, Wang, Chen, Wu, Ma, Li, Xiao, Liu, Xie, Zhang and Lu.)

Background . The research results of fat-soluble vitamin D 3 (cholecalciferol) encapsulation with β -cyclodextrin have been presented in this work. The vitamin D 3 inclusion complex with β -cyclodextrin was obtained under microwave radiation. The surface morphology of obtained clathrate inclusion complexes was described with the help of a scanning electron microscope. The thermographic measurement results on a differential scanning calorimeter have been presented. The activation energy of the β -cyclodextrin : vitamin D 3 clathrate complex thermal oxidative destruction reaction was calculated. The clathrate thermal destruction kinetic parameters were determined. The inclusion complex spectral properties were characterized by IR-Fourier and 1 H and 13 C NMR spectroscopy. The existence of β -cyclodextrin inclusion complex with vitamin D 3 in a 2 : 1 ratio was confirmed by the experimental results. The activation energy of thermal destruction of the inclusion complex of β -cyclodextrin with vitamin D 3 was calculated using four different methods., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Ryszhan Bakirova et al.)

Background: Expandable titanium implants have proven their suitability as vertebral body replacement device in several clinical and biomechanical studies. Potential stabilizing features of personalized 3D printed titanium devices, however, have never been explored. This in vitro study aimed to prove their equivalence regarding primary stability and three-dimensional motion behavior in the mid-thoracic spine including the entire rib cage., Methods: Six fresh frozen human thoracic spine specimens with intact rib cages were loaded with pure moments of 5 Nm while performing optical motion tracking of all vertebrae. Following testing in intact condition (1), the specimens were tested after inserting personalized 3D printed titanium vertebral body replacement implants (2) and the two standard expandable titanium implants Obelisc™ (3) and Synex™ (4), each at T6 level combined with posterior pedicle screw-rod fixation from T4 to T8., Findings: No significant differences (P < .05) in primary and secondary T1-T12 ranges of motion were found between the three implant types. Compared to the intact condition, slight decreases of the range of motion were found, which were significant for Synex™ in primary flexion/extension (-17%), specifically at T3-T4 level (-46%), primary lateral bending (-18%), and secondary lateral bending during primary axial rotation (-53%). Range of motion solely increased at T8-T9 level, while being significant only for Obelisc™ (+35%)., Interpretation: Personalized 3D printed vertebral body replacement implants provide a promising alternative to standard expandable devices regarding primary stability and three-dimensional motion behavior in the mid-thoracic spine due to the stabilizing effect of the rib cage., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier Ltd.)

Satellite observations of the Ozone Monitoring Instrument (OMI) for tropospheric sulfur dioxide (SO 2 ) and formaldehyde (HCHO) column mass densities (CMD) are analyzed for the period 2005-2016 over the atmosphere of Kazakhstan. Regarding SO 2 the major hot spots relate to regions with high population and large industrial facilities. Such an example is the city of Ekibastuz that hosts the biggest thermal power plants in the country and exhibits the higher SO 2 CMD at national level. The annual average CMD in Ekibastuz reaches 2.5 × 10 -5  kg/m 2 , whereas for the rest of the country respective values are 6 times lower. Other hotspots, mostly urban conglomerates such as Almaty and Nur-Sultan, experience high CMDs of SO 2 in particular years, such as 2008. One of the main reasons for this behavior is the financial crisis of 2008, forcing the application of alternate heating sources based on cheap low-quality coal. Regarding HCHO, an oxygenated Volatile Organic Compound (VOC), the main hot spot is noticed over the city Atyrau, the oil capital of the country where two massive oil fields are located. The highest HCHO CMD (9 × 10 15  molecules/cm 2 ) appears in the summertime due to secondary production as a result of the photo-oxidation of VOCs emitted by industrial sectors, oil refinery plants and vehicles. Strongly elevated HCHO amounts are also observed in Nur-Sultan in 2012 that could be due to the residential coal combustion and vehicle exhaust under poor winter dispersion conditions. Significant reductions in HCHO observed between 2012 and 2015 can be attributed to two significant measures implemented in the country in 2013 that aimed at the improvement of air quality: the introduction of the emission trading system (ETS) for greenhouse gases and Euro-4 standards for new vehicles entering the national vehicle fleet.

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug-associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval-extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval-extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1 hour before the extinction sessions decreased the heroin-priming-induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28 days of withdrawal (ie, remote heroin-associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval-extinction procedure on heroin-priming-induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval-extinction procedure resembled the inhibitory effect of UCS retrieval-extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval-extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin-associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug-associated memories., (© 2019 Society for the Study of Addiction.)

Spinal tumors and unstable vertebral body fractures usually require surgical treatment including vertebral body replacement. Regarding primary stability, however, the best possible treatment depends on the spinal region. The purpose of this in vitro study was to evaluate the effects of instrumentation length and approach size on thoracic spinal stability including the entire rib cage. Six fresh frozen human thoracic spine specimens with intact rib cages (C7-L1) were loaded with pure moments of 5 Nm in flexion/extension, lateral bending, and axial rotation, while monitoring the relative motions of all spinal segments using optical motion tracking. The specimens were tested (1) in the intact condition, followed by testing after vertebral body replacement at T6 level using a unilateral approach combined with (2) long instrumentation (T4-T8) and (3) short instrumentation (T5-T7) as well as a bilateral approach combined with (4) long and (5) short instrumentation. Significant increases of the range of motion ( p < 0.05) were found in the entire thoracic spine (T1-T12) using the bilateral approach and short instrumentation in primary flexion/extension and in secondary axial rotation during primary lateral bending compared to both conditions with long instrumentation, as well as in secondary lateral bending during primary axial rotation compared to unilateral approach and long instrumentation. Compared to the intact condition, the range of motion was significantly decreased using unilateral approach and long instrumentation in flexion extension and secondary lateral bending during primary axial rotation, as well as using bilateral approach and long instrumentation in lateral bending. On the segmental level, the range of motion was significantly increased at T4-T5 level in lateral bending using unilateral approach and short instrumentation and significantly decreased using bilateral approach and long instrumentation compared to their respective previous conditions. Regardless of the approach type, which did not affect thoracic spinal stability in the present study, short instrumentation overall shows sufficient primary stability in the mid-thoracic spine with intact rib cage, while creating considerably more instability compared to long instrumentation, potentially being of importance regarding long-term implant failure. Moreover, short instrumentation could affect adjacent segment disease due to increased motion at the upper segmental level., (Copyright © 2020 Liebsch, Kocak, Aleinikov, Kerimbayev, Akshulakov, Jansen, Vogt and Wilke.)

Immune dysregulation, specifically of inflammatory processes, has been linked to behavioral symptoms of depression in both human and rodent studies. Here, we evaluated the antidepressant effects of immunization with altered peptide ligands of myelin basic protein (MBP)-MBP 87-99 [A 91 , A 96 ], MBP 87-99 [A 91 ], and MBP 87-99 [R 91 , A 96 ]-in different models of depression and examined the mechanism by which these peptides protect against stress-induced depression. We found that a single dose of subcutaneously administered MBP 87-99 [A 91 , A 96 ] produced antidepressant-like effects by decreasing immobility in the forced swim test and by reducing the escape latency and escape failures in the learned helplessness paradigm. Moreover, immunization with MBP 87-99 [A 91 , A 96 ] prevented and reversed depressive-like and anxiety-like behaviors that were induced by chronic unpredictable stress (CUS). However, MBP 87-99 [R 91 , A 96 ] tended to aggravate CUS-induced anxiety-like behavior. Chronic stress increased the production of peripheral and central proinflammatory cytokines and induced the activation of microglia in the prelimbic cortex (PrL), which was blocked by MBP 87-99 [A 91 , A 96 ]. Immunization with MBP-derived altered peptide ligands also rescued chronic stress-induced deficits in p11, phosphorylated cyclic adenosine monophosphate response element binding protein, and brain-derived neurotrophic factor expression. Moreover, microinjections of recombinant proinflammatory cytokines and the knockdown of p11 in the PrL blunted the antidepressant-like behavioral response to MBP 87-99 [A 91 , A 96 ]. Altogether, these findings indicate that immunization with altered MBP peptide produces prolonged antidepressant-like effects in rats, and the behavioral response is mediated by inflammatory factors (particularly interleukin-6), and p11 signaling in the PrL. Immune-neural interactions may impact central nervous system function and alter an individual's response to stress.

Left ventricular assist device (LVAD) outflow graft injury is a very rare complication after LVAD implantation and is usually treated surgically. This is a case report of successful stenting of the damaged outflow graft 2.5 years after LVAD implantation, followed by successful heart transplantation.

Neurosurgery education in Kazakhstan has 55 years of history. The first neurosurgery department was established in 1964 in the city of Almaty, South Kazakhstan (the former capital of Kazakhstan). The department was headed by the pioneer of Kazakhstani neurosurgeons, Prof. Yevgeniya Azarova. A new neurosurgery education system was adopted after a while. To date, 4 medical universities and 1 neurosurgical center in Kazakhstan have a neurosurgery department that prepares around 10 neurosurgeons annually. The country's populations are currently served by more than 300 neurosurgeons. However, isolated regions lack neurosurgical services and a specialized medical workforce. Urbanization results in inequality of receiving medical care among rural and regional inhabitants.To develop and strengthen the neurosurgery services, the National Center for Neurosurgery was opened in the heart of the country. The center has placed great importance on the development of neurosurgery and neurosurgical education in Kazakhstan. The World Federation of Neurosurgical Societies, European Association of Neurosurgical Societies, Asian Congress of Neurosurgeons, and International Society for Pediatric Neurosurgery have held many international meaningful events on neurosurgery at the center. Opened in 2008, the neurosurgery center has prepared 41 neurosurgeons in the residency program. This article seeks to provide readers with an understanding of the state of neurosurgery education in Kazakhstan and its development history.

Background: LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson's disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK., Objective: Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort., Methods: 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis., Results: None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, p =0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, p =0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5., Conclusions: We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts., Competing Interests: The authors have no conflicts of interest., (Copyright © 2020 Rauan Kaiyrzhanov et al.)

Crimean-Congo hemorrhagic fever (CCHF), Q fever, and Lyme disease are endemic to southern Kazakhstan, but population-based serosurveys are lacking. We assessed risk factors and seroprevalence of these zoonoses and conducted surveys for CCHF-related knowledge, attitudes, and practices in the Zhambyl region of Kazakhstan. Weighted seroprevalence for CCHF among all participants was 1.2%, increasing to 3.4% in villages with a known history of CCHF circulation. Weighted seroprevalence was 2.4% for Lyme disease and 1.3% for Q fever. We found evidence of CCHF virus circulation in areas not known to harbor the virus. We noted that activities that put persons at high risk for zoonotic or tickborne disease also were risk factors for seropositivity. However, recognition of the role of livestock in disease transmission and use of personal protective equipment when performing high-risk activities were low among participants.

Pericytes possess high multipotent features and cell plasticity, and produce angiogenic and neurotrophic factors that indicate their high regenerative potential. The aim of this study was to investigate whether transplantation of adipose-derived pericytes can improve functional recovery and neurovascular plasticity after ischemic stroke in rats. Rat adipose-derived pericytes were isolated from subcutaneous adipose tissue by fluorescence-activated cell sorting. Adult male Wistar rats were subjected to 90 min of middle cerebral artery occlusion followed by intravenous injection of rat adipose-derived pericytes 24 h later. Functional recovery evaluations were performed at 1, 7, 14, and 28 days after injection of rat adipose-derived pericytes. Angiogenesis and neurogenesis were examined in rat brains using immunohistochemistry. It was observed that intravenous injection of adipose-derived pericytes significantly improved recovery of neurological function in rats with stroke compared to phosphate-buffered saline-treated controls. Immunohistochemical analysis revealed that the number of blood capillaries was significantly increased along the ischemic boundary zone of the cortex and striatum in stroke rats treated with adipose-derived pericytes. In addition, treatment with adipose-derived pericytes increased the number of doublecortin positive neuroblasts. Our data suggest that transplantation of adipose-derived pericytes can significantly improve the neurologic status and contribute to neurovascular remodeling in rats after ischemic stroke. These data provide a new insight for future cell therapies that aim to treat ischemic stroke patients.

Objectives: Cold crystalloid cardioplegia for donor heart harvesting and cold ischemic storage conditions during the transportation is the standard of care during heart transplantation procedure. Organ care system (OCS) was introduced for more prolonged and reliable ex vivo organ management. This study evaluated the two different techniques used for myocardial preservation during the procurement and transportation of the heart using the OCS., Methods: We performed prospective analysis of 43 patients with heart failure undergoing heart transplantation and using the OCS for donor organ transport. Donor hearts were arrested using blood cardioplegia and conditioning (n = 30) or standard Custodiol (SC) solution ( n = 13). Perfusion and cardiac function parameters were continuously monitored while the donor hearts were perfused in the OCS. Impact of preservation techniques on biochemical parameters and clinical outcomes were evaluated., Results: All donor hearts had stable perfusion and lactate characteristics in the OCS, with similar measures between the two groups at the beginning of the ex vivo perfusion. Ex vivo heart perfusion mean ending concentration of Interleukin (IL)-6 and IL-8 was significantly lower in the blood cardioplegia group compared to the standard care group. Clinical outcomes were comparable between the two groups of patients., Conclusions: The use of blood cardioplegia and conditioning could be a safe method for myocardial protection in distant procurement and preservation of donor hearts in the OCS., (© 2019 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals, Inc.)

Background: Flow diverter devices (FDD) carry risks of postoperative complications when treating aneurysms with wide necks, stenosis, and severe tortuosity of the parent vessel. In this study, we evaluated early and midterm results for the treatment of giant paraclinoid aneurysms managed by trapping and endovascular deployment of FDD., Methods: Medical records were analyzed for patients with giant paraclinoid aneurysms treated between July 2008 and December 2017 at National Centre for Neurosurgery with either a flow diverter or by trapping the aneurysm with or without extracranial-intracranial (EC-IC) bypass surgery. We recorded age, sex, clinical presentation, treatment modality, morbidity, and mortality. Clinical outcomes were assessed using a modified Rankin scale (mRS)., Results: Among 29 consecutive patients, 13 were treated with FDD, and 16 patients were managed by trapping the aneurysm, where 7/16 cases had preliminary EC-IC bypass. Of 16 trapping patients, six were trapped endovascularly and ten were trapped surgically. During the follow-up period (mean 33 months, range 6-96), total exclusion of the aneurysm from the circulation was observed 100% of aneurysms in the trapping group and 84.6% in the FDD group (P = 0.192). Early postoperative morbidity was observed in three (23%) cases in the FDD group, and four (25%) in trapping group (P = 0.525). The FDD group had one (7.7%) fatal complication due to stent occlusion and severe ischemic stroke after three months postoperatively, despite appropriate antiplatelet therapy. There were no mortalities in the trapping group (P = 0.149). The rate of mRS 0-2 did not differ significantly across groups at discharge (81.3% vs. 69.2%; P = 0.667), and all patients had mRS 0-2 at follow-up (P = 1.000)., Conclusions: FDD deployment for giant paraclinoid aneurysms results in comparable angiographic and clinical outcomes to aneurysm trapping. Despite implementation of modern endovascular treatment methods, aneurysm trapping remains a valuable treatment option in carefully selected patients with giant paraclinoid aneurysms.

Lactobacillus casei and Lactobacillus rhamnosus proteins P40 and P75 belong to a large family of secreted cell wall proteins that contain a carboxy(C)-terminal CHAP or NlpC/P60 superfamily domains. In addition to their peptidoglycan hydrolases activity, proteins in this family are specific antigens of pathogens, frequently responsible of interactions with the host. L. rhamnosus GG and L. casei BL23 purified P40 and P75 proteins have antiapoptotic activity by inducing the EGF/Akt pathway. The aim of this work was to study the genetics, phylogeny and dissemination of this family of proteins in the genus Lactobacillus as well as their characteristics and likely function. The scrutiny of their DNA encoding sequences revealed the presence of minisatellite DNA in the P75 encoding gene of L. casei/paracasei strains ( cmu B) with intraspecific indels that gave raise to four different alleles ( cmu B1-4), which are exclusive of this species. Phylogenic analyses suggest that both proteins are present mainly in the L. casei and Lactobacillus sakei phylogenomic groups. A P40 ancestral gene was possibly present in the common ancestor of Enterococcaceae , Lactobacillaceae and Streptococcaceae . P75 is also present in L. casei and L. sakei groups, but its evolution is difficult to explain only by vertical transmission. Antibodies raised against the N-terminal regions of P40 and P75 improved their immunological detection in culture supernatants as they recognized almost exclusively proteins of L. casei/paracasei/rhamnosus strains, highlighting their structural similarity, that allowed to detect them in different fermented dairy products that contained probiotic L. casei strains. Purified P40 and P75 proteins showed no evident lytic activity but they complemented L. casei BL23 cmu A and cmu B defective mutants, respectively, thus proving that they actively participate in cell division.

Background: Glioma patients with mutant isocitrate dehydrogenase have improved survival; this could be in part due to the suppressive effect of mutant IDH on the level of chronic inflammation. This study aimed to prospectively analyze the association of IDH1 mutation status with preoperative levels of blood inflammatory markers: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP), and red cell distribution width (RDW) in gliomas. Patients and methods: Receiver operating characteristic curves for cutoff value determination, various bivariate tests, and survival analyses (Kaplan-Meier curves and Cox regression) were performed. Results: Patients with mutant IDH1 had reduced levels of NLR ( P <0.032) and CRP ( P <0.008). Moreover, these patients showed better median overall survival compared to those without IDH1 mutation ( P <0.000). In univariate analysis, IDH1 mutation status ( P <0.000), NLR ( P <0.000), PLR ( P <0.008), and CRP ( P <0.001) were among the factors associated with survival. By multivariate analysis, IDH1 mutation ( P <0.044) and NLR<2.65 ( P <0.022) remained independent factors associated with better survival; other independent variables were tumor grade ( P <0.000) and location in noneloquent area ( P <0.015). Conclusion: The obtained results show that IDH1 mutation is associated with lower levels of chronic inflammation that could account for an improved prognosis in this group of patients., Competing Interests: The authors report no conflicts of interest in this work.

Tension pneumocephalus is an exceedingly rare complication of cerebrospinal fluid diversion occurring after surgery, trauma or spontaneous fistula formation. We report a case in a patient with a ventriculoperitoneal shunt who developed symptomatic tension pneumocephalus via a skin defect within 24 hours of undergoing bone cement cranioplasty.

To feed the growing human population, global wheat yields should increase to approximately 5 tonnes per ha from the current 3.3 tonnes by 2050. To reach this goal, existing breeding practices must be complemented with new techniques built upon recent gains from wheat genome sequencing, and the accumulated knowledge of genetic determinants underlying the agricultural traits responsible for crop yield and quality. In this review we primarily focus on the tools and techniques available for accessing gene functions which lead to clear phenotypes in wheat. We provide a view of the development of wheat transformation techniques from a historical perspective, and summarize how techniques have been adapted to obtain gain-of-function phenotypes by gene overexpression, loss-of-function phenotypes by expressing antisense RNAs (RNA interference or RNAi), and most recently the manipulation of gene structure and expression using site-specific nucleases, such as CRISPR/Cas9, for genome editing. The review summarizes recent successes in the application of wheat genetic manipulation to increase yield, improve nutritional and health-promoting qualities in wheat, and enhance the crop's resistance to various biotic and abiotic stresses.

Study Objectives: Objective sleep duration has been linked to insomnia severity. However, cognitive functions of people with insomnia with different sleep durations have been seldom addressed. Brain-derived neurotrophic factor (BDNF) has an important role in cognitive function and has been linked to clinical insomnia recently. The present study aimed to evaluate the comprehensive cognitive functions in people with primary insomnia with different objective sleep durations, and further examine the involvement of peripheral BDNF., Methods: Fifty-seven people with insomnia were subdivided into short sleep duration (SSD, sleep time < 6 hr) group and normal sleep duration (NSD, sleep time ≥ 6 hr) group based on polysomnography data. Twenty-nine healthy controls (HC) were matched on age, gender, and education. Cognitive function was assessed using a comprehensive and sensitive neuropsychological test battery. Both objective and subjective insomnia statuses were estimated. Serum BDNF level was measured using enzyme-linked immune sorbent assay., Results: Compared with HC, the SSD group showed impaired neuropsychological performances in spatial span, brief visuospatial memory test, fluency, managing emotions, and continuous performance tests. In contrast, NSD had bad performance only in brief visuospatial memory test and continuous performance tests, and relatively better than SSD group in the latter test. People with SSD insomnia but not NSD had decreased BDNF levels compared with HC, and neuropsychological performance was positively correlated with BDNF levels only in SSD group., Conclusions: Primary insomnia was associated with impaired neuropsychological performance, and the impairment might be related to decreased objective sleep duration. In addition, decreased peripheral BDNF might mediate the impaired cognitive functions of people with insomnia with SSD.

Background: The triple therapy including peginterferon, ribavirin and protease inhibitors was more effective compared to the combination of only peginterferon and ribavirin. This study aimed to assess the cost-effectiveness of triple treatment in either treatment-naïve and treatment-experienced patients in Kazakhstan., Methods: A Markov model was created to assess long-term clinical advantages and the cost-effectiveness of the triple therapy from Kazakhstan payer perspective. Health state transition probabilities, pharmaceutical and other costs (according to the price in 2015), and utility rate were acquired from the published studies and publicly available sources. All used costs and benefits were discounted at 5% per year., Results: Despite treatment background, the patients, receiving boceprevir and telaprevir, were estimated to experience less serious liver-disease complications, more life-years, and more QALYs compared to the patients having standard of care. For treatment-experienced group, boceprevir and telaprevir were dominant, with more QALYs. For all the groups of patients, incremental costs per QALY gained were between USD14995 and USD18075. The total average cost of boceprevir is slightly more costly than a standard duration of treatment with telaprevir, and so is the average cost per SVR. Extensive sensitivity analyses verified robust model results., Conclusion: The inclusion of protease inhibitors to standard management for the therapy of patients with genotype 1 chronic HCV infection in Kazakhstan is predicted to be cost-effective using a typically applied willingness to pay threshold of USD37805 (3 times GDP per capita)., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Background: The relatively low efficiency of biolistic transformation and subsequent integration of multiple copies of the introduced gene/s significantly complicate the genetic modification of wheat (Triticum aestivum) and other plant species. One of the key factors contributing to the reproducibility of this method is the uniformity of the DNA/gold suspension, which is dependent on the coating procedure employed. It was also shown recently that the relative frequency of single copy transgene inserts could be increased through the use of nanogram quantities of the DNA during coating., Results: A simplified DNA/gold coating method was developed to produce fertile transgenic plants, via microprojectile bombardment of callus cultures induced from immature embryos. In this method, polyethyleneglycol (PEG) and magnesium salt solutions were utilized in place of the spermidine and calcium chloride of the standard coating method, to precipitate the DNA onto gold microparticles. The prepared microparticles were used to generate transgenics from callus cultures of commercial bread wheat cv. Gladius resulting in an average transformation frequency of 9.9%. To increase the occurrence of low transgene copy number events, nanogram amounts of the minimal expression cassettes containing the gene of interest and the hpt gene were used for co-transformation. A total of 1538 transgenic wheat events were generated from 15,496 embryos across 19 independent experiments. The variation of single copy insert frequencies ranged from 16.1 to 73.5% in the transgenic wheat plants, which compares favourably to published results., Conclusions: The DNA/gold coating procedure presented here allows efficient, large scale transformation of wheat. The use of nanogram amounts of vector DNA improves the frequency of single copy transgene inserts in transgenic wheat plants.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Previous studies show that neural activities in the medial prefrontal cortex (mPFC) are correlated with moral processing during picture viewing tasks. In this study, we applied transcranial direct current stimulation (tDCS) to determine whether this non-invasive brain stimulation technique could modulate the evaluation of moral violations. Sixty-four subjects were randomly recruited, separated into different groups and tested with 42 pairs of pictures depicting moral violations. Each subject was required to rate the pictures two separate times, i.e., before and after tDCS intervention. We found that anodal tDCS (atDCS) increases cortical excitability over the mPFC (between the Fpz and Fp1 positions) as well as the sense of morality and emotional arousal of the subjects. In conclusion, this study indicated that the mPFC plays an important role in moral judgments while modulating ratings of moral violations under tDCS intervention conditions.

In patients with ischemic heart disease and type 2 diabetes mellitus in 4-6 weeks after acute coronary syndrome (ACS) on stable dual antiplatelet therapy (DAPT) with aspirin and clopidogrel co-adminstrated with rosuvastatin residual platelet reactivity on adenosine diphosphate was higher than in patients receiving atorvastatin. However, the rate of high residual on-clopidogrel treatment platelet reactivity (RCPR) in rosuvastatin-treated patients exceeded the rate of high RCPR in atorvastatin-treated patients insignificantly. In 6 months after ACS residual platelet reactivity did not differ between the groups. After 12 months of DAPT platelet reactivity increased as compared to baseline values both in patients receiving rosuvastatin and in patients receiving atorvastatin without switching. In patients, randomly switching from one statin type to another at 6 month of treatment, platelet reactivity did not change significantly in comparison to baseline and the prevalence of high RCPR was lower than in patients receiving statins without switching. Thus, in patients with diabetes with ACS on DAPT with acetylsalicylic acid and clopidogrel statin treatment should be started with atorvastatin and in 6 months after ACS atorvastatin should be switched to rosuvastatin. This approach will provide lower RCPR within at least first 4-6 weeks after ACS and prevent RCPR increase during 12 months of DATT use in this patients group.

Acromegaly is one of the most common syndromes in pituitary adenomas. Naturally, women with this condition have trouble with their reproductive function. The difficulty in diagnosing acromegaly progression in pregnancy is that there is also production of placental growth hormone observed, making it impossible to differentiate from neoplastic growth hormone production using conventional methods of investigation. This article is about a clinical case of acromegaly in a 22 years old woman who was operated on using transnasal transsphenoidal approach and received postoperative treatment with somatostatin analog - lanreotide acetate autogel - for six months. The woman became pregnant in the course of the treatment. During pregnancy, the GH and IGF-I levels in serum remained within normal limits. Lanreotide acetate therapy was discontinued. The woman successfully gave birth to a healthy baby. There was a remission of the disease after pregnancy.

Background: The prevalence of hypertension in Kazakhstan is high, and the majority of patients are not adequately controlled. Treatment with renal artery denervation (RAD) could represent a useful therapeutic option for a subset of patients in Kazakhstan with resistant hypertension., Aim: To assess the impact of RAD in a cohort of patients from Kazakhstan with resistant hypertension., Methods: Between March 2012 and December 2013, 63 patients underwent RAD at our tertiary care centre. Eligibility criteria were office blood pressure more than 160 mm Hg systolic (SBP) or more than 90 mm Hg diastolic (DBP) despite being treated with three or more antihypertensive medications, including a diuretic. Ambulatory blood pressure was measured at baseline and at month 12, and monitoring also included impact on insulin resistance and renal function., Results: There were significant decreases of 25 ± 24 mm Hg for ambulatory SBP during the daytime and of 26 ± 23 mm Hg for ambulatory SBP during the nighttime (p < 0.0001). We observed significant decreases of 12 ± 14 mm Hg for ambula-tory daytime DBP and of 11 ± 14 mm Hg in ambulatory nighttime DBP (p < 0.0001). A decrease in creatinine clearance was observed from 100.2 ± 33.6 mL/min at baseline to 90.2 ± 22.8 mL/min at month 12 (p < 0.001). Homeostasis model assessment-insulin resistance (HOMA-IR) decreased from 3.0 ± 4.6 at baseline to 2.5 ± 3.7 at 12 months (p = 0.007)., Conclusions: In this population RAD resulted in statistically and clinically significant blood pressure reduction at 12 months with minimal adverse events.

Background: Red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), and platelet count (PLT) routinely tested as part of the complete blood count are indicative of systemic inflammation. The prognostic significance of NLR and PLT in cancer was demonstrated in many studies while the role of RDW has been hardly investigated. The present study aimed to assess the association of RDW, NLR, and PLT with survival and tumor grade in glioma patients., Methods: Clinical data from 178 patients with primary gliomas treated in a single institution were retrospectively analyzed. Receiver operating characteristic curves for cutoff value determination, Kaplan-Meier survival analysis, various bivariate tests, and univariate and multivariate Cox regression analyses were performed., Results: Patients with high RDW (≥13.95) and NLR (≥4) levels had worse overall survival (OS) (Wilcoxon test, P <0.026 and P <0.003, respectively) while the effect of thrombocytosis (≥400×10 9 /L) on prognosis was not significant. Besides, a strong association between RDW and NLR was found (Spearman's rho =0.230, P <0.02; χ 2 =8.887, P <0.03; Mann-Whitney U -test, P <0.017). Moreover, RDW and NLR were significantly associated with tumor grade. In univariate Cox analysis, elevated NLR (hazard ratio, HR 1.385; confidence interval, CI 1.020-1.881, P <0.037), older age (HR 0.452, CI 0.329-0.621, P <0), and higher tumor grade (HR 1.624, CI 1.187-2.223, P <0.002) were associated with poor outcomes. In the multivariate analysis, tumor grade, age, and Karnofsky performance score were identified as being independently prognostic for OS., Conclusion: Preoperative NLR and RDW values can help to evaluate disease progression and outcomes in patients with gliomas, thereby contributing to patient follow-up optimization., Competing Interests: The authors report no conflicts of interest in this work.

Healthcare reforms are often not coupled with a relevant and appropriate monitoring framework, leaving policymakers and the public without evidence about the implications of such reforms. Kazakhstan has embarked on a large-scale reform of its healthcare system in order to achieve Universal Health Coverage. The health-related 2020 Strategic Development Goals reflect this political ambition. In a case-study approach and on the basis of published and unpublished evidence as well as personal involvement and experience (A) the indicators in the 2020 Strategic Development Goals were assessed and (B) a 'data-mapping' exercise was conducted, where the WHO health system framework was used to describe the data available at present in Kazakhstan and comment on the different indicators regarding their usefulness for monitoring the current health-related 2020 Strategic Development Goals in Kazakhstan. It was concluded that the country's current monitoring framework needs further development to track the progress and outcomes of policy implementation. The application of a modified WHO/World Bank/Global Fund health system monitoring framework was suggested to examine the implications of recent health sector reforms. Lessons drawn from the Kazakhstan experience on tailoring the suggested framework, collecting the data, and using the generated intelligence in policy development and decision-making can serve as a useful example for other middle-income countries, potentially enabling them to fast-track developments in the health sector., Competing Interests: Competing interests: None declared.

Aims: The need for the left ventricular assist devices (LVAD) in patients with end-stage heart failure is well established, but prior to 2011, this was not available to patients in Kazakhstan. We describe the development of the sole LVAD programme in the context of a nascent heart transplantation programme and clinical outcomes for the first three years., Methods and Results: From November 2011 to November 2014, 146 patients underwent implantation of 152 VADs (approximately 50 devices implanted per year). We retrospectively analyzed data from 135 LVAD patients who received HeartMate II ( n  = 95) or HeartWare ( n  = 40) devices. In 75 patients LVAD was used as a bridge-to-transplantation and in 60 patients as destination therapy, but only 3 of 135 LVAD patients received heart transplant. Forty-three patients of the LVAD cohort had died by the end of the follow-up period. The mean time on LVAD was 466 ± 330 days (range 5-1200 days). Kaplan-Meier survival estimates for patients who continued on LVAD support were 93% after 1 month, 86% after 6 months and 77% after 12 months. The most common complications within the first 30 days after implant included right ventricular failure ( n  = 20, 1.85 events/patient-year), renal failure ( n  = 19, 1.76 events/patient-year) and bleeding ( n  = 33, 3.0 events/patient-year). Beyond 30 days adverse events included driveline infections ( n  = 46, 0.56 events/patient-year) and stroke ( n  = 33, 0.21 events/patient-year)., Conclusions: LVADs are an important therapeutic alternative to heart transplantation in the context of a developing heart transplant programme with outcomes that are comparable to those reported by other centres.

Plants respond to abiotic stresses by changes in gene regulation, including stress-inducible expression of transcriptional activators and repressors. One of the best characterized families of drought-related transcription factors are dehydration-responsive element binding (DREB) proteins, known as C-repeat binding factors (CBF). The wheat DREB/CBF gene TaRAP2.1L was isolated from drought-affected tissues using a dehydration-responsive element (DRE) as bait in a yeast one-hybrid screen. TaRAP2.1L is induced by elevated abscisic acid, drought and cold. A C-terminal ethylene responsive factor-associated amphiphilic repression (EAR) motif, known to be responsible for active repression of target genes, was identified in the TaRAP2.1L protein. It was found that TaRAP2.1L has a unique selectivity of DNA-binding, which differs from that of DREB activators. This binding selectivity remains unchanged in a TaRAP2.1L variant with an inactivated EAR motif (TaRAP2.1Lmut). To study the role of the TaRAP2.1L repressor activity associated with the EAR motif in planta, transgenic wheat overexpressing native or mutated TaRAP2.1L was generated. Overexpression of TaRAP2.1L under constitutive and stress-inducible promoters in transgenic wheat and barley led to dwarfism and decreased frost tolerance. By contrast, constitutive overexpression of the TaRAP2.1Lmut gene had little or no negative influence on wheat development or grain yield. Transgenic lines with the TaRAP2.1Lmut transgene had an enhanced ability to survive frost and drought. The improved stress tolerance is attributed to up-regulation of several stress-related genes known to be downstream genes of DREB/CBF activators., (© 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Studies of quality of life (QoL) of oncological patients is carried out using questionnaires approved in many international clinical studies. The European Organization for Research and Treatment of Cancer EORTC QLQ-C30 (Quality of Life Questionnary-Core 30) and its special brain cancer module EORTC QLQ-BN20 are widely used in the world neurooncologic practice. They are available in more than 80 official versions of 30 languages of the world. Previously we used the official versions in Russian, which often causes difficulty in understanding for native Kazakh language speakers, who comprise more than 60% of our respondents. This was the reason for creating a version of Kazakh language. Therefore, in 2014 for the first time the process of adaptation of questionnaires to the Kazakh language was initiated., Materials and Methods: The translation process of questionnaires to Kazakh language was held in accordance with the requirements of the European Organization for Research and Treatment of Cancer EORTC on QoL and consisted of the following stages: preparation - translation - pilot testing - approval. The official permission of authors and "Guideline on translation" was obtained which was developed by the working group of the EORTC on QoL. The pilot testing of EORTC QLQ-C30 and QLQ-BN20 questionnaires was conducted on the basis of the Department of Central Nervous System Pathology of the "National Centre for Neurosurgery" in patients with malignant tumors of the central nervous system., Results: The official versions of the EORTC QLQ-C30 and QLQ-BN20 questionnaires in Kazakh language were introduced and adapted in practical neurosurgical operations in Kazakhstan., Conclusions: The approved versions of the questionnaires in Kazakh language are now available for mainstream use on the official website EORTC.com. The versions of these questionnaires can be used in domestic cohort studies and clinical practice in the Republic of Kazakhstan. The use of these tools for assessing QoL will help professionals in the planning of individual treatment strategies and selection of the necessary therapy.