T1w/T2w ratio is associated with the brush sign and perfusion delay in watershed regions in patients with moyamoya angiopathy.

BACKGROUND: It has been shown recently using the T1w/T2w mapping technique that white matter microstructural integrity impairments exist in watershed regions patients with moyamoya angiopathy (MMA). We hypothesized that these changes could be associated with the prominence of other neuroimaging markers of chronic brain ischemia, such as perfusion delay and the brush sign. METHODS: Thirteen adult patients with MMA (24 affected hemispheres) were evaluated using brain MRI and CT perfusion. The T1w/T2w signal intensity ratio, which reflects white matter integrity, was calculated in watershed regions (centrum semiovale and middle frontal gyrus). Brush sign prominence was evaluated with susceptibility-weighted MRI. Additionally, brain perfusion parameters such as cerebral blood flow (CBF), cerebral blood volume (CBF), and mean transit time (MTT) were assessed. Correlations between white matter integrity and perfusion changes in watershed regions, as well as the prominence of the brush sign, were evaluated. RESULTS: Statistically significant negative correlations between the prominence of the brush sign and the T1w/T2w ratio values from the centrum semiovale and middle frontal white matter were found (R = -0.62 to 0.71, adjusted p < 0.05). Furthermore, there was a positive correlation between the T1w/T2w ratio values and the MTT values from the centrum semiovale (R = 0.65, adjusted p < 0.05). CONCLUSIONS: We revealed that T1w/T2w ratio changes are associated with the prominence of the brush sign as well as white matter hypoperfusion in watershed regions in patients with MMA. This could be explained by chronic ischemia due to venous congestion in the deep medullary vein territory.

A novel antivirulent compound fluorothiazinone inhibits Klebsiella pneumoniae biofilm in vitro and suppresses model pneumonia.

The problematic treatment of infections caused by multiple-resistant Klebsiella, especially in ICU, is the leading cause of prolonged hospitalization and high mortality rates. The use of antibiotics for the prevention of infections is considered unreasonable as it may contribute to the selection of resistant bacteria. In this regard, the development of drugs that will be effective in preventing infection during various invasive procedures is extremely necessary. We have shown that the developed innovative antibacterial compound fluorothiazinone (FT) that suppresses the formation of biofilms is effective in the prevention of a model pneumonia caused by a multi-resistant clinical K. pneumoniae isolate. Prophylactic use followed by treatment with FT in mice with acute pneumonia modulates the local innate immune response without suppressing protective properties in the early stages of infection, while contributing to a decrease in the bacterial load in the organs and preventing lethal pathological changes in the lungs at later stages of K. pneumoniae infection. Further development of such antivirulence drugs and their use will reduce morbidity and mortality in nosocomial infections, as well as reduce the number of antibiotics used.

Neuroimaging in Moyamoya angiopathy: Updated review.

Moyamoya angiopathy (MMA) is a rare condition characterized by steno-occlusion of terminal portions of the internal carotid arteries and/or their proximal branches with the formation of collateral vessels network (moyamoya vessels). These changes result in chronic ischemia of the brain parenchyma with subsequent serious cerebrovascular accidents. The prognosis of MMA could be dramatically improved if the diagnosis and assessment are prompt and accurate. It is also crucial to define the indications, optimal timing, volume, and tactics of revascularization surgery, as well as longitudinal observation after treatment. It is therefore necessary to use strict criteria for decision making, including radiological criteria. In today's world, neuroimaging is a valuable diagnostic tool that continually evolves and provides us with more and more information about structural and functional changes in different pathological conditions. However, due to MMA's rarity, its neuroimaging can be challenging. The purpose of this review is to summarize a contemporary knowledge regarding neuroimaging in patients with MMA and to discuss the main difficulties associated with visualizing this condition.

Cases of Q fever detected in residents of the novosibirsk region hospitalized with suspection of infections transmitted by ticks.

Coxiella burnetii is the causative agent of Q fever (coxiellosis), which, in addition to acute manifestations, often occurs in a latent form, is prone to chronic course and, in the absence of antibiotic therapy, has a high risk of disability or death. As a result of the presence of a wide range of clinical manifestations specific to other infectious diseases, the use of laboratory test methods (LTM) is required to make a diagnosis. The presence of Q fever anthropurgic foci in the Novosibirsk region was described in the 90s of the last century, but due attention to its laboratory diagnostics is not paid in this region. The aim of the study was to identify genetic and serological markers of the causative agent, C. burnetii, in patients of the Novosibirsk region who were admitted for treatment with fever with suspected tick-borne infections (TBIs). DNA marker of the causative agent of Q fever was detected in blood samples by real time PCR in 9 out of 325 patients. In three patients, the presence of C. burnetii DNA was confirmed by sequencing of the IS1111 and htpB gene fragments. In ELISA tests, antibodies against the causative agent of coxiellosis were detected in the blood sera of 4 patients with positive results of PCR analysis. Contact with tick was registered in 7 out of 9 patients who had C. burnetii DNA and lacked markers of other TBIs. Six people were infected in the Novosibirsk region, two suffered from tick's bite in Altai, and one case was from the Republic of Kyrgyzstan. Thus, a complex approach using both PCR analysis and ELISA provided the identification of markers of the Q fever causative agent in patients admitted with suspected TBIs, thereby differentiating it from other infections. Contact with ticks in most cases suggests that infection with C. burnetii had a transmissible pathway.

Molecular origin of the heterogeneity in the nematic and smectic liquid crystals: Elastic constants, gradients of order parameters, and visualization of small objects.

The formation of heterogeneous nematic and smectic liquid crystals in the general case of an arbitrary geometry is investigated in the framework of molecular-statistical approach [Emelyanenko and Khokhlov, J. Chem. Phys. 142, 204905 (2015)JCPSA60021-960610.1063/1.4921684]. The molecular aspects of the orientational and translational orderings at the curved surfaces of small solid objects dispersed in liquid crystal are considered, and the differential equations for gradients of the order parameters in vicinities of the small objects are presented in the general form. The five elastic constants are obtained within the same approach, from which we were able to predict that a significant space variations of the order parameters can be observed within the 0.5-0.8µm area around any small object, almost independently of its own dimension. Therefore, the liquid crystals can be a simple tool for the optical visualization of nano-objects. It is also demonstrated that the kind of molecular self-organization (smectic, nematic or conventionally isotropic) at the surfaces of small solid objects can be different from that in the bulk of mesogenic material. Totally we predict eight various combinations of simple states at the surfaces and in the bulk depending on the solid objects' size and temperature. It is also shown that the surfaces of 10µm-size solid objects and larger act almost as flat surfaces, while the surfaces of 1µm-size solid objects and smaller act almost as point defects.

[Development of additive systemic effects when taking ß-blockers in patients with glaucoma and concurrent chronic diseases]. / Razvitie sistemnykh additivnykh effektov pri prieme ß-adrenoblokatorov u patsientov s glaukomoi na fone khronicheskikh zabolevanii.

Examining the somatic state of glaucomatous patients that enroll for treatment, we are increasingly confronted with a serious problem of inconsistency in prescribing beta-blockers (ß-blockers) by ophthalmologists, cardiologists and therapists. PURPOSE: To assess the frequency and extent of adverse reactions at simultaneous local and systemic prescription of ß-blockers to patients with glaucoma and systemic vascular pathology. MATERIAL AND METHODS: The study included 112 patients that have been taking ß-blockers for at least 6 months. The main group consisted of 39 patients with primary open-angle glaucoma (POAG) in combination with cardiovascular disease; the first comparison group - 36 patients with POAG without systemic vascular pathology; the second comparison group - 37 patients with systemic vascular pathology without glaucoma. In the main and first comparison groups, double instillations of 0.5% timolol or 0.5% betaxolol were used as monotherapy. RESULTS: Adverse reactions to the long-term usage of ß-blockers were found in 82% of the main group patients with cardiovascular diseases. They manifested as bradycardia or bronchospasm (38% patients), combination of bradycardia and vascular hypotension or bronchospasm (18%), or combination of 3-4 types of adverse reactions (26%); in the first and second comparison groups - in 36% and 30%, respectively (p<0.05). CONCLUSION: The most severe multifactorial adverse reactions developed due to long-term use of combinations of systemic and local ß-blockers: 100 mg metoprolol or 10 mg bisoprolol with 0.5% timolol.

[Comprehensive treatment of a child with an extensive composite odontoma]. / Kompleksnoe lechenie rebenka s obshirnoi sostavnoi odontomoi.

Odontoma make up about 22% of all odontogenic tumors. Diagnosis and treatment of odontoma in children has a number of features: the variability of the clinical and X-ray picture, the appearance of signs during the period of changing teeth, retention or the difficulty of the eruption of complete teeth in the affected area. In the process of growth odontoma can cause significant deformation of the jaw bones. The delay of the change of deciduous teeth can also be regarded as a risk factor for the formation of deviations from the normal formation of the dental system in children. This article analyzes the symptoms, clinical picture and complex treatment of a 13-year-old patient with this pathology. A clinical case demonstrates the need for regular check-ups at a pediatric dentist, an x-ray examination of the jaws in order to timely detect abnormalities in the development of the dentition of the child, diagnosis and treatment of malformations and tumors in children.

[Clinical and neurophysiological effects of dual-target high-frequency rTMS over the primary motor and prefrontal cortex in Parkinson's disease]. / Klinicheskie i neirofiziologicheskie effekty terapevticheskoi sochetannoi vysokochastotnoi ritmicheskoi transkranial'noi magnitnoi stimulyatsii motornoi i lobnoi kory pri bolezni Parkinsona.

OBJECTIVE: To evaluate therapeutic effects of navigational dual-target high-frequency rTMS over the primary motor (M1, bilateral) and the left dorsolateral prefrontal cortex (DLPFC) on clinical dynamics of Parkinson's disease (PD) symptoms in a parallel placebo-controlled study. MATERIAL AND METHODS: The study included 46 patients randomized into equal therapeutic and placebo rTMS groups. Navigational therapeutic and placebo10 Hz rTMS was applied over the M1 and DLPFC areas (20 daily sessions, for 3 weeks). Assessment of the dynamics of clinical symptoms was performed using the MDS UPDRS scale (Parts I-IV) before the first session, immediately after 20 sessions, and 4-6 weeks after the rTMS course. Non-motor and mental symptoms were assessed using the Hamilton Depression Rating Scale (HDRS-17), Beck depression inventory (BDI-II), Depression, Anxiety and Stress (DASS-21) scales and the Mini Mental State Examination (MMSE). RESULTS: Significant therapeutic effects of rTMS compared to placebo were established: a greater decrease in overall score on the MDS-UPDRS scale (parts I-IV), a decrease in the severity of non-motor (part I) and motor symptoms (part III, with a large therapeutic effect for the symptoms of rigidity, bradykinesia and postural instability), as well as the severity of motor complications of dopamine replacement therapy (part IV). The effects of rTMS on motor symptoms persisted 4 weeks after the end of the stimulation course. It is also important to note significant positive dynamics in both rTMS and placebo groups in the form of comparable reduction in the severity of everyday motor symptoms (MDS-UPDRS part II), improvement of the total scores on MMSE, HDRS, BDI-II, DASS-21. CONCLUSIONS: The dual-target high-frequency rTMS over the primary motor cortex (bilateral) and the left dorsolateral prefrontal cortex has positive therapeutic effects on the motor and affective symptoms of Parkinson's disease, which are significantly stronger than that of the placebo stimulation.

[Influence of chronic alcohol treatment on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes in the mouse brain: Role of the C1473G polymorphism in the gene encoding tryptophan hydroxylase 2].

Tryptophan hydroxylase 2 (Tph-2) is the key enzyme in serotonin biosynthesis. Serotonin is one of the main neurotransmitters involved in the regulation of various physiological functions and behavior patterns. The influence of chronic ethanol consumption on the expression of the Bdnf, Bax, Bcl-xL, and CASP3 genes was studied in the brain structures of B6-1473C (C/C) and B6-1473G (G/G) mice that had been obtained on the base of the C57BL/6 strain. The strains differed in the genotype for the C1473G single nucleotide polymorphism in the Tph-2 gene and in Tph-2 enzyme activity. It was found that chronic alcohol treatment led to a significant increase in the expression of the Bdnf gene in the midbrain of B6-1473G mice, but not in B6-1473С. Chronic alcohol treatment considerably decreased the expression of the ultimate brain apoptosis effector, caspase 3, in the frontal cortex, but increased it in the hippocampus of B6-1473G mice. At the same time, chronic ethanol administration reduced the level of the antiapoptotic Bcl-xL mRNA in the midbrain of B6-1473C mice. Thus, the C1473G polymorphism in the Tph-2 gene considerably influenced the changes in the expression patterns of genes involved in the regulation of neurogenesis and neural apoptosis induced by chronic ethanol treatment.

Fast combustion waves and chemi-ionization processes in a flame initiated by a powerful local plasma source in a closed reactor.

Results are presented from experimental studies of the initiation of combustion in a stoichiometric methane-oxygen mixture by a freely localized laser spark and by a high-current multispark discharge in a closed chamber. It is shown that, preceding the stage of 'explosive' inflammation of a gas mixture, there appear two luminous objects moving away from the initiator along an axis: a relatively fast and uniform wave of 'incomplete combustion' under laser spark ignition and a wave with a brightly glowing plasmoid behind under ignition from high-current slipping surface discharge. The gas mixtures in both the 'preflame' and developed-flame states are characterized by a high degree of ionization as the result of chemical ionization (plasma density n(e)≈10(12) cm(-3)) and a high frequency of electron-neutral collisions (ν(en)≈10(12) s(-1)). The role of chemical ionization in constructing an adequate theory for the ignition of a gas mixture is discussed. The feasibility of the microwave heating of both the preflame and developed-flame plasma, supplementary to a chemical energy source, is also discussed.

[Bright prospects and deplorable state of prolonged home mechanical ventilation in Russia: two cases' description].

The report describes two patients with lateral amyotrophic sclerosis complicated by respiratory insufficiency. Instead of long-term hospitalization to ICU the patients were kept at home, where prolonged mechanical ventilation was applied to them: in the first case - through tracheostomy tube, in the second - through mask. The use of prolonged home mechanical ventilation therapy instead of long-term hospitalization to ICU is discussed.

[Fibronectin level of the blood plasma of patients with congenital heart defects]. / Uroven' fibronektina v plazme krovi bol'nykh vrozhdennymi porokami serdtsa.

Enzyme immunoassays have shown mean fibronectin (FN) level to be 241.0 +/- 15.1 micrograms/ml in normal children between 2 and 15 years of age. Similar assays in 57 patients with congenital heart diseases (CHD) before and after surgery demonstrated preoperative FN decrease in 56% of patients, that was directly related to the extent of hemodynamic disorders, while postoperative FN level depended on the range and type of surgical trauma and the presence of inflammatory or suppurative-septic complications. Within 3 postoperative days, FN drops below normal level in 95% of patients. In spite of therapeutic use of blood and blood components, FN deficiency was not compensated for until day 10 after surgical correction of the valvular defect.

[Quantitative immunoenzyme determination of fibronectin in biological fluids]. / Kolichestvennoe immunofermentnoe opredelenie fibronektina v biologicheskikh zhidkostiakh.

Quantitative immunoenzyme assay of fibronectin in blood plasma is developed. Isolation and purification of fibronectin from human blood plasma, harvesting of specific antibodies to fibronectin, production of the antibodies and peroxidase conjugates and step-by-step procedure of the immunoenzyme assay in a "sandwich" modification are described. The assay was applied for diagnostics of several infectious and somatic diseases.

[Plasma fibronectin level in newborn infants with suppurative inflammatory diseases]. / Soderzhanie plazmennogo fibronektina u novorozhdennykh detei s gnoino-vospalitel'nymi zabolevaniiami.

The level of plasma fibronectin was determined in healthy newborns (45 plasma samples were examined in the control group) and in newborns with pyo-septic diseases (67 plasma samples were examined) by the immunoenzyme method (on the basis of the "sandwich" modification of the immunoenzyme analysis). Noticeable hypofibrinectinemia was observed in the infants with pyo-inflammatory diseases, particularly in cases of generalized forms. Combined modality etiopathogenetic therapy including i.v. plasma transfusion, did not exceed fibronectin deficiency in clinical convalescence of infants. Fibronectin deficiency is regarded as a risk factor of the development and generalization of pyo-inflammatory diseases.