Drug Repurposing by Simulating Flow Through Protein-Protein Interaction Networks.

As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and used support vector machine to identify potentially effective drugs in our model disease, psoriasis. Using this method, we screened about 1,500 marketed and investigational substances, identified 51 drugs that were potentially effective, and selected three of them for experimental confirmation. All drugs inhibited tumor necrosis factor alpha-induced nuclear factor kappa B activity in vitro, suggesting they might be effective for treating psoriasis in humans. Additionally, these drugs significantly inhibited imiquimod-induced ear thickening and inflammation in the mouse model of the disease. All results suggest high prediction performance for the algorithm.

Electric-field-induced nematic-cholesteric transition and three-dimensional director structures in homeotropic cells.

We study the phase diagram of director structures in cholesteric liquid crystals of negative dielectric anisotropy in homeotropic cells of thickness d which is smaller than the cholesteric pitch p. The basic control parameters are the frustration ratio d/p and the applied voltage U. Upon increasing U, the direct transition from completely unwound homeotropic structure to the translationally invariant configuration (TIC) with uniform in-plane twist is observed at small d/p < or = 0.5. Cholesteric fingers that can be either isolated or arranged periodically occur at 0.5 < or = d/p<1 and at the intermediate U between the homeotropic unwound and TIC structures. The phase boundaries are also shifted by (1) rubbing of homeotropic substrates that produces small deviations from the vertical alignment; (2) particles that become nucleation centers for cholesteric fingers; (3) voltage driving schemes. A novel reentrant behavior of TIC is observed in the rubbed cells with frustration ratios 0.6 < or = d/p < or = 0.75, which disappears with adding nucleation sites or using modulated voltages. In addition, fluorescence confocal polarizing microscopy (FCPM) allows us to directly and unambiguously determine the three-dimensional director structures. For the cells with strictly vertical alignment, FCPM confirms the director models of the vertical cross sections of four types of fingers previously either obtained by computer simulations or proposed using symmetry considerations. For rubbed homeotropic substrates, only two types of fingers are observed, which tend to align along the rubbing direction. Finally, the new means of control are of importance for potential applications of the cholesteric structures, such as switchable gratings based on periodically arranged fingers and eyewear with tunable transparency based on TIC.

[Systemic necrotizing vasculitis]. / Do pytannia systemnykh nekrotyzuiuchykh vaskulitiv.

Systemic necrotic angiites as well as Vegenera granulomatosis were shown according to literature data and the experience of the authors to be polysymptomatic. The fact makes diagnostics difficult. Multi-biopsies is recommended to conduct a histological verification of the disease.

[The radiodiagnosis of the indicators of pancreatic cancer]. / Luchevaia diagnostika pokazatelei raka podzheludochnoi zhelezy.

For suspicion of pancreatic cancer 84 patients were subjected to ultrasonic examination, computerized tomography, x-ray of the stomach and duodenum and as indicated endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography combined with external cholangiostomy. The semeiotics of cancer of the pancreas was evaluated on the basis of radiation methods. Practical recommendations on the diagnosis and scope of surgical treatment as assessed preoperatively are given.

[Comprehensive evaluation of long-term results of surgical treatment and principles of postoperative rehabilitation of children with anorectal atresia]. / Kompleksnaia otsenka otdalënnykh rezul'tatov khirurgicheskogo lecheniia i printsipy posleoperatsionnoi reabilitatsii detei s anorektal'noi atreziei.

The examination and treatment of 22 children at the age of from 2 to 14 years after surgical correction of fistulous forms of atresia of the anus and rectum was carried out. In all the patients, besides of general clinical investigations, the special studies of the large intestine with the use of roentgenologic and functional methods were performed. A scale-table for assessment of a degree of anal incompetence have been developed, criteria for choice of rational tactics for rehabilitation of the patients established.

[Computerized tomography of the organs of the small pelvis in children with anorectal atresia]. / Komp'iuternaia tomografiia organov malogo taza u detei s anorektal'noi atreziei.

In 12 children with the different forms of anorectal atresia, for studying the state of a sphincter apparatus of the rectum and assessment of quality of its bringing down into the perineum after proctoplasty, computerized tomography of the organs of a small pelvis was used. Underdeveloped and undifferentiated musculus levator ani in children with high anorectal atresia and fistula to the urinary bladder was revealed. The method permits to establish exact location of the intestine brought down relative to musculus levator ani and external anal sphincter.

[Pathologic abrasion]. / Abraziunea patologicá.

By "pathologic abrasion" is defined the excessive loss of the hard dental substance, which may lead to a total removal of the anatomic crown. This is one of most severe affections of ADM but also one of the best tolerated for a certain length of time. Four aspects of abrasion are frequently noted:--helicoidal abrasion--ad palatum abrasion;--horizontal abrasion;--keylock type abrasion. Excessive abrasion is due to bruxisme in most of the cases, and also to diet, but to a lesser extent. In most of the patients DVO is not modified because, as abrasion persists the continuous process of dental eruption, as well as of the alveolar processes develops. This is the reason for which it has been concluded that DVO should not be removed by prosthetic therapy in patients with extreme abrasion. The most simple solutions should be selected, avoiding complicated therapies because "the ideal treatment" is not always successful for a long time.

[Correlation between occluding trauma and dental erosion]. / Corelatia dintre traumatismul ocluzal si eroziunile dentare.

The study presents data obtained by examination of a lot of patients with erosions of the teeth. At the same time histologic sections were prepared from teeth with cuneiform lesions that had to be removed as a result of parodonthopathic processes. Histological studies that have been carried out have demonstrated hyperemia of the dental pulp, and blood suffusion, sometimes accompanied by oedema. Slight rarefaction of dentine was also noted in other microscopic fields, with characteristic enlargement of the interdentinal spaces. The fact that the histological picture does not provide too much data on the etiopathogenic mechanism of the cuneiform lesions it may be considered that the occluding trauma is one of the major causes of these coronal lesions. Occluding balancing as performed by the authors in these patients have always demonstrated the presence of erosions in teeth that had suffered from occluding trauma. By this attitude and with these means of therapy one can prevent the development of new lesions of the cuneiform type, and thus contribute to the decrease in the morbidity, and to the prevention of the various disturbances in the dentomaxillary apparatus.