Current status of molecular diagnostics for lung cancer.

The management of lung cancer (LC) requires the analysis of a diverse spectrum of molecular targets, including kinase activating mutations in , (), and oncogenes, G12C substitutions, and , , and gene fusions. Administration of immune checkpoint inhibitors (ICIs) is based on the immunohistochemical (IHC) analysis of PD-L1 expression and determination of tumor mutation burden (TMB). Clinical characteristics of the patients, particularly age, gender and smoking history, significantly influence the probability of finding the above targets: for example, LC in young patients is characterized by high frequency of kinase gene rearrangements, while heavy smokers often have G12C mutations and/or high TMB.

Ethnicity-specific BRCA1, BRCA2, PALB2, and ATM pathogenic alleles in breast and ovarian cancer patients from the North Caucasus.

Background: Mountain areas of the North Caucasus host several large ethnic communities that have preserved their national identity over the centuries.

Methods: This study involved high-grade serous ovarian cancer (HGSOC) and breast cancer (BC) patients from Dagestan (HGSOC: 37; BC: 198), Kabardino-Balkaria (HGSOC: 68; BC: 155), North Ossetia (HGSOC: 51; BC: 104), Chechnya (HGSOC: 68; BC: 79), Ingushetia (HGSOC: 19; BC: 103), Karachay-Cherkessia (HGSOC: 13; BC: 47), and several Armenian settlements (HGSOC: 16; BC: 101). The group of BC patients was enriched by young-onset and/or family history-positive and/or bilateral and/or receptor triple-negative cases.

Comprehensive evaluation of the test for 5'-/3'-end mRNA unbalanced expression as a screening tool for ALK and ROS1 fusions in lung cancer.

Background: Despite the progress in the development of next-generation sequencing (NGS), diagnostic PCR assays remain to be utilized in clinical routine due to their simplicity and low cost. Tests for 5'-/3'-end mRNA unbalanced expression can be used for variant-independent detection of translocations, however, many technical aspects of this methodology require additional investigations.

Methods: Known ALK/ROS1 fusions and 5'-/3'-end unbalanced expression were analyzed in 2009 EGFR mutation-negative non-small cell lung cancer (NSCLC) samples with RT-PCR tests, which were optimized for the use with FFPE-derived RNA.

[The relationship between visual dysfunction and cognitive deficit in schizophrenia].

Objective: To investigate whether visual processing abnormalities are the result of visual dysfunction involving cognitive impairment or independent abnormalities and to identify the relationship of visual impairments with cognitive functions and severity of psychopathological symptoms.

Material And Methods: We compared results of visual size perception and actions on objects (motor assessment) in patients with schizophrenia (=37), including patients with non-resistant schizophrenia (=19) and healthy individuals (=20). Cognitive impairments were assessed with BACS.

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study.

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use.

Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program.

Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)).

Comparative study of blood pressure and echocardiographic values of male cynomolgus macaques (Macaca fascicularis).

Background: Primates represent a unique object for biomedical research, in particular in the field of physiology and pathology of the cardiovascular system. Echocardiography is the most important non-invasive method for the intravital study of the heart structure and function, intracardiac and systemic haemodynamics. The available data on reference values of echocardiographic parameters in primates are limited.

Treating non-small cell lung cancer with selumetinib: an up-to-date drug evaluation.

Introduction: RAS-RAF-MEK-ERK signaling is implicated in tumor development by promoting cell proliferation and other cancer hallmarks. MEK1/2 kinases are up-regulated in the majority of human cancers due to activation of tyrosine kinase receptors, RAS proteins, BRAF kinase, or some other members of the MAPK pathway. Targeting of MEK1/2 kinases may counterbalance cancer progression.

Multiple Glycation Sites in Blood Plasma Proteins as an Integrated Biomarker of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might be sensitive indicators of alterations in blood glycation levels.

Variability in lung cancer response to ALK inhibitors cannot be explained by the diversity of ALK fusion variants.

Multiple laboratory evidences indicate that distinct variants of ALK translocations differ in their biochemical properties and responsiveness to ALK tyrosine kinase inhibitors (TKIs). These data are supported by some clinical studies, which showed improved responses to crizotinib in non-small cell lung cancer (NSCLC) patients carrying particular variants of ALK translocation. We retrospectively considered 64 Russian patients with ALK-rearranged NSCLC, who were treated by crizotinib (n = 23), ceritinib (n = 39) or alectinib (n = 2).

First experience of hematopoietic stem cell transplantation treatment of Shwachman-Diamond syndrome using unaffected HLA-matched sibling donor produced through preimplantation HLA typing.

The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD).

[Genetic Risk Factors of Macrovascular Complications in Patients With Type 2 Diabetes].

High risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM) is caused by insulin resistance and atherogenic dyslipidemia that may be genetically determined. The aim of this study was to assess the association of polymorphic genetic variants APOA5 (S19W/rs3135506), CETP (Taq1B/rs708272), PON1 (Q192R /rs662) and PPARG (Pro12Ala /rs1801282) with T2DM and macrovascular complications in patients with T2DM resident in Northwestern Russia. We examined 386 patients with T2DM and 199 healthy controls.

[The speech audiometry test with the verbal tasks and motor responses].

The objective of the present study was to estimate the possibility of using the Russian version of the speech audiometry test with the verbal tasks and motor responses (VTMR test) for the examination of the patients of the advanced and senile age suffering from hearing impairment and cognitive disorders. A total of 20 subjects at the age between 60 and 83 years were enrolled in the study. All of them presented with grade II-III bilateral symmetric chronic sensorineural hearing loss associated with mild cognitive disorders.

[The study of the efficacy of Botulinum toxin type A in patients with poststroke upper-limb spasticity ULIS-II: an analysis of Russian patients].

Aim: To assess the efficacy of Botulinum toxin type A (BoNT-A) injections in routine practice.

Material And Methods: An international, post-marketing, multi-center, observational, prospective, longitudinal study included patients ≥18 years with poststroke upper-limb spasticity in whom a decision to inject BoNT-A had already been made, and who had no previous treatment with BoNT-A or BoNT-B within the last 12 weeks. The responder rate was assessed by the patient-centered goal attainment scaling (GAS).

[An analysis of treatment of the Russian group of patients in the international observational study «Factors influencing response to botulinum toxin type A in patients with idiopathic cervical dystonia»].

Aim: The analysis of the results of treatment of the Russian patient population in the frame of international, multicenter, non-interventional study of CD, the primary purpose of which was to determine the response rate to therapy with BTA at the peak of the effect: after one course of injections in settings of routine practice, as well as the results of application of modern definition for "response" to treatment with BTA.

Material And Methods: In Russia 60 patients with idiopathic CD were included. Patients were classified as «responders» according to the following 4 criteria: effect size (improvement by ≥ 25% assessed by TWSTRS); effect duration: ≥ 12 weeks interval between the BTA injection and the day when the patient reported a decrease of clinical effect, indicating the need for repeated treatment; good tolerability of treatment (no treatment-related serious adverse events (AEs) during the study period); patient-reported Clinical Global Improvement (CGI) score is +2 («significant improvement») or +3 («very significant improvement») at the visits 2 or 3.

[The results of the multicenter pharmaco-epidemiological observational project on the use of mydocalm in the treatment of pain syndromes with the muscle spasm].

The prospective multicenter open noncomparative pharmaco-epidemiological observational project on the use of mydocalm in real clinical practice has been completed in 2013. The project has been performed in 2090 clinical/rehabilitation settings in 284 cities of 13 countries using the results of 35,383 patients. The project aimed to assess the safety of treatment (percentage of patients with adverse-effects) and pain relieving efficacy as well as patient's satisfaction with the treatment.

Changes in intracellular potentials of snail neurons induced by β-phenylglutamic acid hydrochloride.

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutamine, or glutarone) in concentrations of 1, 10, 100, and 1000 μM reversibly and dose-dependently modulated the intracellular action potentials in Plantorbarius corneus snail neurons and hyperpolarized the membrane by 9.1±2.5% with maximum shift of resting potential at 100 μM.

Perfusion scintigraphy method for the diagnosis of pulmonary circulation disorders in rats during disease simulation.

We proposed a modified method for radiological studies of the lungs in small laboratory animals applicable for studies of vascular dysfunctions at different stages of experimental disease formation - chronic obstructive disease of the lungs and pulmonary artery thromboembolism.

Characteristics of bacterial biofilms during long-term culturing.

We studied properties of bacterial biofilms during long-term culturing. The biofilms were preserved for more than 90 days under the chosen conditions. At the same time, amounts of matrix and cells underwent periodic changes.

Protective effect of fenspiride on the bronchi in rats with chronic obstructive pulmonary disease.

We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on contractive activity of bronchial smooth muscles on the model of chronic obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen dioxide. The administration of fenspiride during the acute stage of the disease (day 15) abolished the constricting effect of the pollutant on the bronchial smooth muscles. Dilatation effect of fenspiride in a low dose (0.

[Cognitive functions and treatment of their impairment in elderly patients with the vertebrobasilar issufficiensy].

Authors studied impairment of cognitive functions in 180 patients, aged 56-74 years, with chronic blood flow deficiency in the vertebrobasilar territory. Along with neurological examination, we used MRI of the brain and the cervical spine, MRI-angiography, ultrasound Doppler method, EEG, ECG, clinical and biochemical blood testing. Cognitive functions were assessed using standard neuropsychological tests (a word retrieval test, the Mini-Mental State Examination, the Frontal Assessment battery, the Schulte test, the Landolt test, Wechsler tests, the Wisconsin Card Sorting Test and others).

Activity of succinate dehydrogenase in the neocortex and hippocampus of Mongolian gerbils with ischemic and reperfusion brain injury.

We analyzed changes in activity of SDH, one of the most important enzymes of the Krebs cycle, in the cytoplasm of hippocampal and cortical neurons of Mongolian gerbils (Meriones unguiculatus) at the early and delayed reperfusion period after global brain ischemia. The data indicate that SDH activity in pyramidal neurons of various hippocampal areas and in neurons of II, III and V layers of cerebral cortex after 7-min forebrain ischemia depends on both the localization of these neurons and duration of the postischemic reperfusion. SDH activity in neurons significantly increased on days 2 and 7 after reperfusion.

Interaction of blockers of ionotropic NMDA receptors and metabotropic glutamate receptors in a working memory test in rats.

Glutamate, the main excitatory neurotransmitter in the mammalian CNS, acts via ionotropic and metabotropic receptors. Results from in vitro studies demonstrating tight interactions between ionotropic NMDA receptors and subtype 5 metabotropic glutamate receptors (mGlu5) have shown that blockade of mGlu5 receptors increases the behavioral effects of NMDA receptor antagonists. The aim of the present work was to study the actions of the highly selective mGlu5 receptor antagonist MTEP alone and in combination with MK-801, a blocker of the NMDA receptor-associated ion channel, on performance of a delayed selection task (a test of working memory) in rats.