Solid-phase enzyme modification via affinity chromatography

In the present study antileukemic enzyme L-asparaginase (ASNase) and catalase (as a model enzyme) were modified in solid-phase with activated polyethylene glycol (PEG ) by using ligand-immobilized affinity column systems L-asparagine- 2 Sepharose CL-4B and Procion red-Sepharose CL-4B, respectively. Studies on change of specific activity with modification time showed negligible differences between batches of modified catalase. Modification of ASNase for 1 h resulted in 50.2% recovery of the specific activity and the attachment of 69 molecules of PEG per molecule of ASNase forming ‘PEGylated 2 ASNase’. Sequential modification of ASNase by activated PEG and heparin resulted in coupling of about nine molecules of heparin per molecule of PEGylated ASNase. Intravenous (i.v.) administration of PEG -modified ASNase showed prolonged 2 presence in the blood circulation and no adverse effects or symptoms of anaphylaxis were observed in presensitized mice.(METU AFP-99-06-02-23

The Smooth Away From Expected (SAFE) non-inferiority frontier: theory and implementation with an application to the D3 trial

Background In a non-inferiority trial, the choice of margin depends on the expected control event risk. If the true risk differs from expected, power and interpretability of results can be affected. A non-inferiority frontier pre-specifies an appropriate non-inferiority margin for each value of control event risk. D3 is a non-inferiority trial comparing two treatment regimens in children living with HIV, designed assuming a control event risk of 12%, a non-inferiority margin of 10%, 80% power and a significance level (α) of 0.025. We consider approaches to choosing and implementing a frontier for this already funded trial, where changing the sample size substantially would be difficult. Methods In D3, we fix the non-inferiority margin at 10%, 8% and 5% for control event risks of ≥9%, 5% and 1%, respectively. We propose four frontiers which fit these fixed points, including a Smooth Away From Expected (SAFE) frontier. Analysis approaches considered are as follows: using the pre-specified significance level (α=0.025); always using a reduced significance level (to achieve α≤0.025 across control event risks); reducing significance levels only when the control event risk differs significantly from expected (control event risk <9%); and using a likelihood ratio test. We compare power and type 1 error for SAFE with other frontiers. Results Changing the significance level only when the control event risk is <9% achieves approximately nominal (<3%) type I error rate and maintains reasonable power for control event risks between 1 and 15%. The likelihood ratio test method performs similarly, but the results are more complex to present. Other analysis methods lead to either inflated type 1 error or badly reduced power. The SAFE frontier gives more interpretable results with low control event risks than other frontiers (i.e. it uses more reasonable non-inferiority margins). Other frontiers do not achieve power close (i.e. within 1%) to SAFE across the range of likely control event risks while controlling type I error. Conclusions The SAFE non-inferiority frontier will be used in D3, and the non-inferiority margin and significance level will be modified if the control event risk is lower than expected. This ensures results will remain interpretable if design assumptions are incorrect, while achieving similar power. A similar approach could be considered for other non-inferiority trials where the control event risk is uncertain

FEM analysis of the biaxial cyclic loading of the elastoplastic plate with concentrators: asymptotic states

Elements of structures which work in real conditions quite often are affected by variable temperatures and loadings. Nowadays due to the growth of interest to the knowledge of asymptotic behavior of the inelastic structure subjected to cyclic loading, direct and incremental methods of stabilized state determining begin to develop. If loadings vary and the body deforms elastically, then its durability is defined by fatigue characteristics of material, failure comes after a large number of cycles. If the body experiences elasto-plastic deformation, at loadings below limit, achievement of a dangerous state at rather small number of cycles is possible. In the present study results of finite-element (FEM) calculations of the asymptotical behavior of an elastoplastic plate with the central circular and elliptic holes under the biaxial cyclic loading for three different materials are presented. Incremental cyclic loading of the sample with stress concentrator (the central hole) is performed in the multifunctional finite-element package SIMULIA Abaqus. The ranges of loads found for shakedown, cyclic plasticity, ratcheting are presented. The results obtained are generalized and analyzed. Convenient normalization is suggested. The chosen normalization allows us to present all computed results, corresponding to separate materials, within one common curve with minimum scattering of the points. Convenience of the generalized diagram consists in a possibility to find an asymptotical behavior of an inelastic structure for materials for which computer calculations were not made should be included

INFLUENCING FACTOFS ON SUCCESSFUL BODILY‒SELF’S BECOMING OF MID-LIFE CRISIS

The Aim of this publication is to study the functioning of bodily‒self during the mid–life crisis.Material and methods: psychodiagnostical complex for research the psychosomatic competence and bodily–self of personality consists of the five methods: «The bodily‒self’s verbalization» uncompleted sentences (by T. B. Khomulenko; the introspective experimental method for diagnostic the imagination ability (by T. B. Khomulenko, K. M. Rodina); the method of intraseption sensitivity diagnostic (by T. B. Khomulenko, K. M. Rodina; the reflective method «My attitude to my own body» (by E. B. Stankovskaia); the color a person body dissatisfaction test (CAPT) by V. G. Sakharova adaptation. The diagnostic indicators of all the methods have been conducted analysis of r-Pearson’s correlation, which has been spread to 42 variables scales. The composition of the experimental sample consisted of men and women in the age range from 39 to 50 years old.Results: Breaking the relationship with bodily‒self is creates favourable conditions for the emergence of psychosomatic’s crisis that causes the destructive phenomena in personality. In turn, the bodily‒self is serving a part of the cognitive component of psychosomatic competence the sufficient level of which one is reduction the crisis’s state. Therefore, the article aims is to study the peculiarities of bodily‒self’s functioning of personality in the mid–life crisis’s period. The results of the study have been showed that midlife crisis has specific features of psychosomatic competence and functioning of the bodily‒self which manifested in a positive attitude to the whole body image, and to sample some of its parts. In the process, it was discovered prospects of creating correction and developing programs of bodily‒self personality reconnect. The differences of perception your own body and bodily‒self by women and men leads us to further development the problems in the context of sexual dimorphism.Conclusions: The mid-life crisis and the psychosomatic crisis are unrelated. It’s means that the crisis of the psychosomatic may occur at any period of a life and with a specific age is not connected. The mid–life crisis has the specific features of psychosomatic competence and the bodily‒self’s functioning.Keywords: bodily‒self, psychosomatic competence, mid-life crisis, psychosomatic phenomena, family factors.У статті розглядаються явище тілесного Я під час кризи середнього віку. Порушення взаємозв'язку з тілесним-Я сприяє виникненню психосоматичної кризи, яка викликає деструктивні явища в особистості. У свою чергу, тілесний-сам служить частиною когнітивної складової психосоматичної компетентності, достатній рівень якої скорочує стан кризи. Тому метою статті є вивчення особливостей функціонування особистості в періоді кризи середнього віку. Результати дослідження показали, що криза середнього віку має специфічні особливості психосоматичної компетентності та функціонування тілесного Я, що проявляється в позитивному ставленні до всього образу тіла, а також деяких його частин. У процесі було виявлено перспективи створення корекційно-розвивальної програм відновлення тілесного Я. Відмінності у сприйнятті власного тіла та тілесного Я жінками та чоловіками становить перспективу вивчення проблеми у контексті статевих відмінностей.Ключові слова: тілесне-Я, психосоматична компетентність, криза середнього віку, психосоматичні явища, сімейні фактори

Tuberculosis and HIV co-infection in children

HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes. Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV. CONCLUSION: Data on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings

Syphilis, hepatitis C and HIV in Eastern Europe

PURPOSE OF REVIEW: Eastern Europe and Central Asia (EECA) has experienced large-scale epidemics of syphilis, hepatitis C virus (HCV) and HIV over the past few decades. Here, we review recent evidence on the epidemiology of and the response to these intersecting epidemics. RECENT FINDINGS: The HIV epidemic in EECA continues to expand, with new infections increasing by more than 50% between 2010 and 2015. HCV is now in the top 10 causes of death in EECA, with Russia accounting for more than half of the global burden of HCV infections, but access to direct-acting antivirals remains a major obstacle for control of the epidemic. Although syphilis incidence is generally declining, high prevalence is reported in key populations, particularly sex workers and people who inject drugs. Recent epidemiological studies have highlighted very high prevalence of HIV, syphilis and HCV in prison populations, alongside poor access to prevention and treatment. SUMMARY: Multiple factors are contributing to the ongoing and overlapping HIV, HCV and syphilis epidemics in EECA, including low coverage with antiretroviral therapy and insufficient scale of prevention services. Further research is required to estimate the burden of infections and identify effective prevention and treatment strategies in hard-to-reach key populations, particularly men who have sex with men