Morphofunctional Characteristics of the Vessels of the Subareolar Lymphatic Plexus in Breast Cancer with Metastasis to the Lymph Nodes of the Axillary Lymphatic Collector.

The subareolar Sappey's plexus was studied using color lymphography and immunohistochemical methods with a panel of antibodies to podoplanin, smooth muscle actin, low molecular weight cytokeratin AE1/AE3, and GATA3 on archival material obtained during radical mastectomies and sectoral resections with lymph node dissection from 86 patients diagnosed with non-special type breast cancer. At the macro- and microscopic levels, the connection between the subareolar lymphatic plexus and the lymphatic system of the breast parenchyma has been demonstrated. In triple negative breast cancer with metastases to the axillary lymph nodes, the involvement of subareolar lymphatic plexus into lymphogenous metastasis to the lymph nodes of the axillary lymphatic collector was shown.

Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer.

Unlabelled: DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 cancer genomes followed by the interrogation of CRISPR-Cas9 loss-of-function screens across >700 cancer cell lines, we determined that passenger coamplifications are accompanied by distinct dependency profiles.

CRISPR/Cas9 Screen in Gastric Cancer Patient-Derived Organoids Reveals KDM1A-NDRG1 Axis as a Targetable Vulnerability.

Viability CRISPR screens have proven indispensable in parsing genome function. However, their application in new, more physiologically relevant culturing systems like patient-derived organoids (PDOs) has been much slower. To probe epigenetic contribution to gastric cancer (GC), the third leading cause of cancer-related deaths worldwide, the first negative selection CRISPR screen in GC PDOs that faithfully preserve primary tumor characteristics is performed.

Efficient Correction of Oncogenic KRAS and TP53 Mutations through CRISPR Base Editing.

Unlabelled: KRAS is the most frequently mutated oncogene in human cancer, and its activating mutations represent long-sought therapeutic targets. Programmable nucleases, particularly the CRISPR-Cas9 system, provide an attractive tool for genetically targeting KRAS mutations in cancer cells. Here, we show that cleavage of a panel of KRAS driver mutations suppresses growth in various human cancer cell lines, revealing their dependence on mutant KRAS.

[A pilot study of idebenone in the treatment of patients with hereditary myopathies].

Objective: To evaluate the efficacy of the energotropic drug idebenon in hereditary neuromuscular pathology.

Material And Methods: A total of 9 patients with hereditary myopathies were examined during treatment with idebenone. Determination of muscle strength was carried out on the British medical research Council scale (0 points - no active movements, 5 points - no muscle weakness).

Using CRISPR-Cas9 to Dissect Cancer Mutations in Cell Lines.

The CRISPR-Cas9 technology has revolutionized the scope and pace of biomedical research, enabling the targeting of specific genomic sequences for a wide spectrum of applications. Here we describe assays to functionally interrogate mutations identified in cancer cells utilizing both CRISPR-Cas9 nuclease and base editors. We provide guidelines to interrogate known cancer driver mutations or functionally screen for novel vulnerability mutations with these systems in characterized human cancer cell lines.

RNAi-Mediated Screen of Primary AML Cells Nominates MDM4 as a Therapeutic Target in NK-AML with Mutations.

() mutations belong to the most frequent genetic aberrations found in adult acute myeloid leukemia (AML). Recent evidence suggests that these mutations arise early in leukemogenesis, marking leukemic progenitors and stem cells, and persist through consolidation chemotherapy, providing a pool for AML relapse. Currently, there are no therapeutic approaches directed specifically against this cell population.

Can we really teach cognitive behavioral therapy with a massive open online course?

A better training in psychotherapy is needed for psychiatry trainees. Online Cognitive Behavioural Therapies (CBT) could be a good solution. Free and wide audience course like Massive Open Online course (MOOCs) increase dissemination and accessibility of the training.

[Histological study of urethral plate: a search of the best material for surgical treatment of hypospadias in children].

Aim: to study the microstructure of the urethral plate in patients with a proximal form of hypospadias to justify the use of tissues from the ventral penile surface when creating an artificial urethra.

Materials And Methods: A histological study of surgical specimens from 10 patients with proximal hypospadias was carried out. The urethral plate, a strip of tissue from the ectopic external urethral orifice located in the penoscrotal angle, to the coronary sulcus, was completely excised and processed by various techniques.

[The cellular composition of explanted bioprosthetic heart valves in infective endocarditis].

Objective: To perform immunohistochemical typing of cells as a component of bioprosthetic (BP) heart valves explanted during reoperations for prosthetic valve endocarditis.

Material And Methods: The authors investigated 8 models of KemCor and PeriCor artificial heart valves produced by NeoCor Company (Kemerovo, Russia), which were explanted from the mitral position due to infection of xenogeneic implanted material. The following markers: CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD34 and VEGFR2 (endotheliocytes), CD68 (monocytes/macrophages), vimentin (fibroblasts), and α-smooth muscle actin (smooth muscle cells), were used for immunohistochemical typing of cells as a component of the analyzed samples.

[Hereditary spastic paraplegia type 4 (SPG4) in Russian patients].

Aim: To investigate molecular, clinical and genealogical characteristics of SPG4 in a first representative Russian group, to estimate SPG4 proportion among all DNA-diagnosed spastic paraplegias.

Material And Methods: Fifty unrelated Russian families with SPG4 detected in the course of clinical and molecular studies of spastic paraplegias were studied. Clinical, genealogical and several molecular methods were used, i.

[Mitochondrial disorders in multiple sclerosis].

Aim: To determine the mitochondrial dysfunction in multiple sclerosis (MS).

Material And Methods: Fourteen adult patients with MS and 23 healthy people were examined. Cytochemical analysis of lymphocytes in peripheral blood was carried out.

[Outcomes and treatment of myasthenic crisis].

Aim: The analysis of fatal outcomes of myasthenic crisis in patients with myasthenia.

Material And Methods: The data on 19 patients with myastheniccrisis admitted at the Moscow Regional Research and Clinical Institute («MONIKI») over 12 years (1997-2009) have been summarized.

Results And Conclusion: There are more than 600 patients with myasthenia in the Moscow region, including 13% patients with onset after 60 years.

Spectrum and Frequency of the GJB2 Gene Pathogenic Variants in a Large Cohort of Patients with Hearing Impairment Living in a Subarctic Region of Russia (the Sakha Republic).

Pathogenic variants in the GJB2 gene, encoding connexin 26, are known to be a major cause of hearing impairment (HI). More than 300 allelic variants have been identified in the GJB2 gene. Spectrum and allelic frequencies of the GJB2 gene vary significantly among different ethnic groups worldwide.

Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is the major and likely the only type of autosomal dominant cerebellar ataxia in the Sakha (Yakut) people of Eastern Siberia. The prevalence rate of SCA1 has doubled over the past 21 years peaking at 46 cases per 100,000 rural population. The age at death correlates closely with the number of CAG triplet repeats in the mutant ATXN1 gene (r = -0.

Grinding and polishing instead of sectioning for the tissue samples with a graft: Implications for light and electron microscopy.

A broad use of the graft replacement requires a detailed investigation of the host-graft interaction, including both histological examination and electron microscopy. A high quality sectioning of the host tissue with a graft seems to be complicated; in addition, it is difficult to examine the same tissue area by both of the mentioned microscopy techniques. To solve these problems, we developed a new technique of epoxy resin embedding with the further grinding, polishing, and staining.

[The vaccines based on the replicon of the venezuelan equine encephalomyelitis virus against viral hemorrhagic fevers].

The status of the various recombinant DNA and RNA-derived candidate vaccines, as well as the Venezuelan equine encephalomyelitis virus (VEEV) replicon vaccine system against extremely hazardous viral hemorrhagic fevers, were reviewed. The VEEV-based replication-incompetent vectors offer attractive features in terms of safety, high expression levels of the heterologous viral antigen, tropism to dendritic cells, robust immune responses, protection efficacy, low potential for pre-existing anti-vector immunity and possibility of engineering multivalent vaccines were tested. These features of the VEEV replicon system hold much promise for the development of new generation vaccine candidates against viral hemorrhagic fevers.

[Cellular Composition of Calcified Bioprosthetic Heart Valves].

With the aim to assess the mechanisms of the structural dysfunctions associated with xenograft tissue calcification, we investigated the cellular composition of the explanted xenoaortic epoxy-treated bioprosthetic heart valves. In the leaflets, we revealed multiple cells with retained internal structure. Most of them located on the leaflet surface, at the areas of collagen destruction, and near calcium deposits.

Bioethical issues of preventing hereditary diseases with late onset in the Sakha Republic (Yakutia).

Background: Prenatal diagnosis of congenital and hereditary diseases is a priority for the development of medical technologies in Russia. However, there are not many published research results on bioethical issues of prenatal DNA testing.

Objective: The main goal of the article is to describe some of the bioethical aspects of prenatal DNA diagnosis of hereditary diseases with late onset in genetic counselling practice in the Sakha Republic (Yakutia) - a far north-eastern region of Russia.

Mutant OmpF porins of Yersinia pseudotuberculosis with deletions of external loops: structure-functional and immunochemical properties.

Recombinant mutant OmpF porins from Yersinia pseudotuberculosis outer membrane were obtained using site-directed mutagenesis. Here we used four OmpF mutants where single extracellular loops L1, L4, L6, and L8 were deleted one at a time. The proteins were expressed in Escherichia coli at levels comparable to full-sized recombinant OmpF porin and isolated from the inclusion bodies.