[A rare variant in the TTR gene (p.E112K) is associated with systemic amyloidosis and a new symptom - skin hyperemia in response to ethanol intake: family segregation analysis, literature review, and a clinical case. Case report].

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.

[Difficulties in differential diagnosis of the AL- and ATTR-cardiac amyloidosis. Case report].

The article presents a clinical case describing a complex differential diagnosis of cardiac amyloidosis types and verification of the diagnosis of AL-amyloidosis.

Particles-Matrix Bond in ZnCoO:H and ZnCoAlO:H Films: Issues of Magnetism and Spin Injection.

ZnCoO:H and ZnCoAlO:H films were synthesized by radio frequency magnetron sputtering in a (1 - x)Ar + xH2 mixed atmosphere with x = 0.2-0.5. The films contain different amounts of metallic Co particles (from 7.6% and higher) ~4-7 nm in size. The magnetic and magneto-optical (MO) behavior of the films was analyzed in combination with their structural data. The samples exhibit high values of magnetization (up to 377 emu/cm3) and MO response at room temperature. Two situations are considered: (1) the film magnetism is associated only with isolated metal particles and (2) magnetism is present both in the oxide matrix and in metal inclusions. It has been established that the formation mechanism of the magnetic structure of ZnO:Co2+ is due to the spin-polarized conduction electrons of metal particles and zinc vacancies. It was also found that in the presence of two magnetic components in the films, these components are exchange-coupled. In this case, the exchange coupling generates a high spin polarization of the films. The spin-dependent transport properties of the samples have been studied. A high value of the negative magnetoresistance of the films at room temperature (~4%) was found. This behavior was explained in terms of the giant magnetoresistance model. Thus, the ZnCoO:H and ZnCoAlO:H films with high spin polarization can be considered as sources of spin injection.

[Congenital cholesteatoma of the mastoid process: cases of diagnosis and surgical treatment]. / Vrozhdennaya kholesteatoma sostsevidnogo otrostka visochnoi kosti: sluchai diagnostiki i khirurgicheskogo lecheniya.

A brief review of the epidemiology and pathogenesis of congenital cholesteatoma (CC) of the temporal bone pyramid is presented, classifications reflecting the degree of spread or localization of the process are considered. Variants of local CCs of the mastoid process don't fit into these classifications, as well as there is no statistics on the frequency of their detection and treatment due to the rarity of this pathology. Clinical cases of diagnosis, surgical treatment of CC of the mastoid process and its results are described. Clinical examples indicate a long-term asymptomatic course of CC of the mastoid process, accompanied by a pronounced destructive process in the mastoid process. Early surgical treatment makes it possible to remove the neoplasm as radically as possible and preserve hearing function.

[The effectiveness of transtympanic use of dexamethasone 4 mg in Meniere's disease, severe and moderate course of the disease]. / Effektivnost' transtimpanal'nogo primeneniya deksametazona 4 mg pri bolezni Men'era, tyazhelom i srednetyazhelom techenii zabolevaniya.

The results of transtympanic administration of 4 mg dexamethasone in 37 patients with moderate and severe Meniere's disease are presented. The endolymphatic hydrops was detected in all inner ear structures with predominant accumulation in vestibule and semicircular canals by MRI-visualization before therapy. After 1 month of 4 mg dexamethasone transtympanic therapy the hydrops degree decreased. Daily transtympanic administration of 4 mg dexamethasone for a month leads to reduction of vertigo attacks duration and expression in 92% of cases (follow-up period 24 months) and can be considered when conservative therapy is ineffective before destructive surgical interventions.

[Possibilities of morphological diagnosis of amyloid in the subcutaneous adipose tissue biopsy specimens]. / Vozmozhnosti morfologicheskoi diagnostiki amiloida v bioptatakh podkozhnoi zhirovoi kletchatki.

OBJECTIVE: To retrospectively analyze the results of histological examination of subcutaneous adipose tissue (SAT) biopsy specimens versus the diagnostic value of drugs manufactured by different procedures. MATERIAL AND METHODS: The investigators selected and analyzed the results of biopsy studies with the simultaneous production of two different types of tissue specimens (squashed native specimens, sections from the paraffin blocks) from the abdominal SAT biopsy specimens obtained from 118 patients. In each case, the tissue specimens were stained with Congo red and examined in polarized light, concurrently using the positive control. The criterion for amyloid was the ability of congophilic deposits to birefringence with a characteristic luminescence spectrum when examined in polarized light. RESULTS: Compared to the sections from the paraffin blocks, the native specimens were shown to be of high diagnostic value. The advantages of different types of tissue samples made from SAT biopsy specimens were formulated. CONCLUSION: The SAT biopsy specimens are characterized by the minimal risk to a patient and by the easy way of sampling and are a frequent subject for screening biopsies. In addition to the type of amyloid, the volume, quality, and method of processing the biopsy specimen are responsible for the diagnostic value of SAT examination. The study of squashed native specimens stained with Congo red is most informative when using polarized light.

[Neuroimaging of the endolymphatic hydrops of the labyrinth in severe and moderately severe Meniere's disease]. / Neirovizualizatsiya endolimfaticheskogo gidropsa labirinta pri tyazhelom i srednetyazhelom techenii bolezni Men'era.

The results of magnetic resonance imaging (MRI) of the inner ear 24 hours after intratympanic administration of 1 ml of diluted (1:7) contrast substance for gadolinium-based MRI in 43 patients with moderate and severe Meniere's disease course are presented. It has been revealed that in case of severe and moderate course of Meniere's disease endolymphatic hydrops is presented in all departments of labyrinth: cochlea, vestibule, semicircular canals, but is most pronounced in vestibular department of labyrinth: horizontal semicircular canal and vestibule. The neuroimaging method according to the presented protocol is safe and can be applied in a wide practice both to assess the presence and localization, and the degree of expression of the endolymphatic hydrops.

[Clinical significance of radiological methods for diagnosing endolymphatic hydrops in Ménière's disease]. / Klinicheskaya znachimost' luchevykh metodov diagnostiki endolimfaticheskogo gidropsa pri bolezni Men'era.

Ménière's disease is a chronic disorder of the inner ear, a permanent sing of which is endolymphatic hydrops. For the diagnosis of Ménière's disease in clinical practice, criteria that are primarily based on the clinical picture. However, instrumental methods for diagnosing Ménière's disease, aimed at identifying endolymphatic hydrops, continue to be developed and improved. Radiation diagnostics contribute significant contribution and aimed at identifying the characteristic signs of Ménière's disease. Recently, it has become possible to visualize endolymphatic hydrops using MRI of the temporal bones. This publication presents an analysis of the current state of this topical aspect of the problem of diagnosing Ménière's disease. The purpose of this review is to conduct a comparative analysis of radiation methods for diagnosing Ménière's disease. MATERIAL AND METHODS: The study included publications in English and Russian found in the PubMed, eLibrary database related to the diagnosis of Meniere's disease. RESULTS: A comparative analysis of computed tomography of the temporal bones, magnetic resonance imaging of the temporal bones and diagnostic possibilities for detecting signs characteristic of Ménière's disease are presented. The most diagnostically significant method of studying Ménière's disease is identified. CONCLUSION: MRI of the temporal bones with contrast enhancement is a promising method that can be used to develop an effective treatment algorithm.

[Combination of CT and MRT in the diagnostic of middle ear cholesteatoma. Fusion technology is precise localization tool]. / Sovmeshchenie rentgenovskoi komp'yuternoi i magnitno-rezonansnoi tomografii v diagnostike kholesteatomy srednego ukha. Tekhnologiya Fusion ­ instrument tochnoi lokalizatsii.

Computed tomography (CT) and magnetic resonance imaging (MRI) methods of the middle ear cholesteatoma diagnostic have its advantages and disadvantages. Fusion technology is a post-processing process of CT and MRI images. Its main advantage is the localization of MR-hyperintensive cholesteatoma within the bony anatomical structures obtained on CT, which provides the surgeon with important information both before planning the primary surgical intervention and during a second revision for recurrent cholesteatoma.

[A case of diagnostics and surgical treatment of a patient with a neuroma of the facial nerve]. / Sluchai diagnostiki i khirurgicheskogo lecheniya patsienta s nevrinomoi litsevogo nerva.

The article provides a brief overview of the epidemiology of facial nerve neuromas (FNN, schwannomas), its clinical signs, methods of diagnostic and treatment and indications for their use. A rare clinical case of diagnostics, surgical treatment of FNN with intracranial spread and its results are described in detail. The presented case demonstrates a possible low-symptom course of FNN with intracranial spread. The use of a combined surgical approach (translabyrinthine and extradural subtemporal) in conjunction with neurosurgeons makes it possible to remove FNN with intracranial spread with simultaneous intratemporal neuroplasty of the nerve trunk from the tympanic part of the canal to the bottom of the internal auditory canal with a fragment of the sural nerve with an improvement in the function of the affected nerve.

Genetic Basis of Attenuation of Cold-Adapted Influenza Strain B/Leningrad/14/17/55 - Backup Master Donor Virus for Influenza Type B Live Attenuated Vaccines.

The reassortant vaccine strain of live attenuated influenza vaccine inherits temperature sensitivity and areactogenicity from cold-adapted attenuated master donor virus. In Russia, B/ USSR/60/69 master donor virus (B60) is currently in use for the preparation of live attenuated type B influenza vaccine candidates. Trivalent live attenuated influenza vaccine based on A/ Leningrad/134/17/57 and B60 are licensed for the use in Russia for single dose vaccination of adults and children over 3 years. B/Leningrad/14/17/55 (B14) cold-adapted virus is a backup master donor virus for live attenuated type B influenza vaccine. According to our preliminary estimates, it is more attenuated than B60, which can allow expanding applicability of this vaccine for children under 3 years of age. In this paper, the role of B14 genes in its attenuation was assessed. Representative collection of reassortants of B14 with epidemic influenza B viruses was obtained, a phenotypic analysis of reassortants was performed, and their pathogenicity for animals was assessed. The leading role of PB2 and PA genes in attenuation of B14 master donor virus was proven.

[Clinical and diagnostic observations of a complicated course of chronic otitis media, cholesteatoma in children]. / Kliniko-diagnosticheskie nabliudeniia oslozhnennogo techeniia khronicheskogo gnoinogo kholesteatomnogo srednego otita u detei.

Formation of labyrinth fistulas and destruction of the facial nerve canal in children with middle ear cholesteatoma is rare. Data of children with cholesteatoma of the middle ear, operated in the ENT department of MONIKI, is analyzed. Several clinical observations of multiple-aged patients with the presence of cholesteatoma intra-temporal complications are presented. The preoperative computer tomography made it possible to diagnose the presence of the labyrinth fistula and the destruction of the facial nerve channel, which was confirmed intraoperatively.

Experimental Study of Genetic Constellation of Cold-Adapted Master Donor Viruses for Live Attenuated Influenza Vaccine Type B.

We studied the constellation of genes encoding polymerase complex proteins of master donor viruses for Russian live attenuated influenza vaccine type B. Reassortants of the reserve attenuation donor B/Leningrad/14/17/55 with B/USSR/60/69 master donor virus currently used for manufacturing seasonal influenza vaccine were prepared and examined. Most reassortants obtained by the classical reassortment method inherited all genes from the B/Leningrad/14/17/55 virus except the gene encoding PB1 subunit of the polymerase complex. One reassortant was selected for further evaluation of the role of PB1 gene. Greater attenuation of the strain for experimental animals (mice) in comparison with the original strains was demonstrated. This indicates high degree of constellation of genes of cold-adapted master donor viruses and the important compensating role of amino acid substitutions in the PB1 protein of B/Leningrad/14/17/55 donor virus in preventing viral hyperattenuation.

Amino Acid Substitutions N123D and N149D in Hemagglutinin Molecule Enhance Immunigenicity of Live Attenuated Influenza H7N9 Vaccine Strain in Experiment.

We compared three cold-adapted live attenuated influenza vaccine strains prepared by reverse genetics methods on the basis of master donor virus A/Leningrad/134/17/57 and influenza H7N9 strains A/Anhui/1/2013 and A/Shanghai/1/2013. Two strains based on A/Anhui/1/2013 differed by amino acid positions 123 and 149 in HA1 (123N/149N; 123D/149D). All strains efficiently replicated in developing chicken embryos; A/Shanghai/1/2013-based strain and A/Anhui/1/2013-123N/149N variant were characterized by reduced replication in MDCK cells. Strains based on A/Anhui/1/2013 virus agglutinated erythrocytes with α2,3- and α2,6-linked sialic acid residues, whereas strain A/Shanghai/1/2013 only α2,3. In experiments with BALB/c mice, Anhui-123D/149D strain was most immunogenic and induced high crossreactive humoral immune response, therefore it can be recommended as the model virus for the construction of recombinant vector vaccines based on live attenuated influenza vaccine.

[Intestinal manifestations of Behçet's disease].

Behçet's disease (BD) is a systemic vasculitis of unknown origin, characterized by recurrences of the ulcerative process in the oral cavity and on the genitals, inflammatory damage of the eyes, joints, vessels and other organs. The severity and prognosis of BD determines organ pathology. Intestinal manifestations of BD (intestinal BD) are the least studied. Its verification in BD is complicated by the variety of clinical manifestations, their similarity with inflammatory bowel diseases, the lack of informative laboratory tests, pathognomonic endoscopic and histological signs. Intestinal BD can lead to serious complications (massive bleeding, intestinal perforation and fistula formation), which can not only significantly reduce the quality of the patient's life, but also cause death. Treatment of intestinal BD is not standardized; it is mainly empirical and conducted courses. The purpose of therapy is to achieve clinical remission, healing of intestinal ulcers and prevention of surgery. The article presents a case of severe refractory intestinal BD, requiring twice emergency surgical care - removal of half and then the whole of the colon because of multiple perforations. A brief review of the literature is given and diagnostic difficulties of intestinal BD are discussed.

[Multiple pneumocele associated with temporal bone hyperpneumatization]. / Mnozhestvennoe pnevmotsele pri giperpnevmatizatsii visochnoi kosti.

The authors consider in brief epidemiology, diagnostics, and variants of the surgical treatment of the rare clinical condition pneumocele and pneumoencephalocele of the temporal bone. Diagnostic and surgical modalities for the management of multiple pneumocele associated with temporal bone hyperpneumatization are discussed.

[The role of heat shock proteins 27 and 70 in redox-dependent regulation of apoptosis in Jurkat tumor cells]. / Uchastie belkov teplovogo shoka 27 i 70 v redoks-zavisimoi reguliatsii apoptoza opukholevykh kletok linii Jurkat.

Heat shock proteins Hsp) act as molecular chaperones, protecting enzymes and other proteins against reactive oxygen species. The objective of the study was to investigate the role of Hsp27 in maintaining the balance of the glutathione system and Hsp70 concentrations as well as in implementing Jurkat tumor cell apoptosis. Addition of the Hsp27 inhibitor KRIBB3 (5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)-isoxazol) to Jurkat cells resulted in glutathione redox imbalance (increased GSSG and increased glutathione reductase activity), a decrease in Hsp70 concentrations, and also increased cell apoptosis as compared with to the intact cell culture. The proposed selective regulation of chaperone activity is a promising direction in regulating apoptosis at the cellular level.

[The role of oxidative protein modification and the gluthatione system in modulation of the redox status of breast epithelial cells].

The effects of the SH-group blocker N-ethylmaleimide (NEM) and thiol group protector 1,4-dithioerythritol (DTE) on the redox status of cells HBL-100 cells, oxidative modification of their proteins and the state of glutathione and thioredoxin systems have been investigated. Breast epithelial cells cultivated in the presence of NEM were characterized by decreased redox status, increased glutathione reductase activity, and increased concentrations of products of irreversible oxidative modification of protein and amino acids. Cultivation of HBL-100 cells in the presence of DTE resulted in a shift of the redox status towards reduction processes and increased reversible protein modification by glutathionylation. The proposed model of intracellular redox modulation may be used in the development of new therapeutic approaches to treat diseases accompanied by impaired redox homeostasis (e.g. oncologic, inflammatory, cardiovascular and neurodegenerative disease).

[INFECTIOUS ENDOCARDITIS IN PREGNANT WOMEN].

A case of primary infectious endocarditis with the lesion of mitral valve in a pregnant woman is reported The diseases was caused by meticillin-resistant Staphylococcus aureus. Special attention is given to inefficiency of beta-lactame antibiotics against this infection and beneficial effect of daptomycin therapy. This observation confirms literature data about high frequency of thromboembolic complications of S aureus-induced infectious endocarditis due to the production of various coagulases and von Willebrand factor-binding protein by these microorganisms. An increase of coagulation caused by S. aureus is mediated through activation of prothrombin, factor XIII, and fibrin-binding fibronectin. It requires prescription of direct thrombin inhibitor pradax that proved to yield good results in the treatment of our patient. It is concluded that infectious endocarditis in pregnant women is characterized by an atypical clinical picture due to impaired immunity associated with rapid progression of the process after delivery, high frequency of thromboembolic and DIC syndromes.

Pancreas-preserving approach to "paraduodenal pancreatitis" treatment: why, when, and how? Experience of treatment of 62 patients with duodenal dystrophy.

BACKGROUND: The term "paraduodenal pancreatitis" (PP) was proposed as a synonym for duodenal dystrophy (DD) and groove pancreatitis, but it is still unclear what organ PP originates from and how to treat it properly. OBJECTIVE: To assess the results of different types of treatment for PP. METHOD: Prospective analysis of 62 cases of PP (2004-2013) with histopathology of 40 specimens was performed; clinical presentation was assessed and the results of treatment were recorded. RESULTS: Preoperative diagnosis was correct in all the cases except one (1.9%). Patients presented with abdominal pain (100%), weight loss (76%), vomiting (30%), and jaundice (18%). CT, MRI, and endoUS were the most useful diagnostic modalities. Ten patients were treated conservatively, 24 underwent pancreaticoduodenectomies (PD), pancreatico- and cystoenterostomies (8), Nakao procedures (5), duodenum-preserving pancreatic head resections (5), and 10 pancreas-preserving duodenal resections (PPDR) without mortality. Full pain control was achieved after PPRDs in 83%, after PDs in 85%, and after PPPH resections and draining procedures in 18% of cases. Diabetes mellitus developed thrice after PD. CONCLUSIONS: PD is the main surgical option for PP treatment at present; early diagnosis makes PPDR the treatment of choice for PP; efficacy of PPDR for DD treatment provides proof that so-called PP is an entity of duodenal, but not "paraduodenal," origin.