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Background: APOE ε4 allele is most common genetic risk factor for Alzheimer's disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE ε4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals., Results: We performed APOE gene haplotype analysis for a short block of five SNPs across the gene using the ADNI whole genome sequencing dataset. The compilation of ADNI data with 1000 Genomes identified the APOE ε4 linked haplotypes, which appeared to be distant for the Asian, African and European populations. The common European ε4-bearing haplotype is associated with AD but not with MCI, and the Africans lack this haplotype. Haplotypic inference revealed alleles that may confer protection against AD. By assessing the DNA methylation profile of the APOE haplotypes, we found that the AD-associated haplotype features elevated APOE CpG content, implying that this locus can also be regulated by genetic-epigenetic interactions., Conclusions: We showed that SNP frequency profiles within APOE locus are highly skewed to population-specific haplotypes, suggesting that the ancestral background within different sites at APOE gene may shape the disease phenotype. We propose that our results can be utilized for more specific risk assessment based on population descent of the individuals and on higher specificity of five site haplotypes associated with AD.

The authors analyzed complications in peroral endoscopic myotomy in case of esophageal achalasia in 27 patients. There were noted hypercapnia, carboxyperitoneum, hemorrhage, perforation of mucous coat of esophagus. These complications were suppressed during endoscopic manipulations.

Although the functional role is still unknown for most types of nuclear noncoding repetitive sequences, some of them proved to provide adequate phylogenetic and taxonomic markers for studying the genetic relationships of organisms at the species and within-species levels. Several markers were used in this work. First, microsatellite markers were used to examine populations varying in the extent of genetic subdivision in marine and anadromous fish, including the Chilean jack mackerel Trachurus murphyi, anadromous brown trout Salmo trutta, and isolated and anadromous char populations. Locus polymorphism was proportional to the gene flow between populations in all cases. Second, satellite DNA was used to study the phylogenetic relationships within the genera Salmo, Oncorhynchus, Salvelinus, and Coregonus. Genetic distances agreed well with the taxonomic relationships based on morphological traits and various biochemical markers and correlated with the evolutionary ages estimated for the groups by other markers. Third, RAPD PCR with a set of 20-mer primers was performed to study the genus Coregonus and anadromous and isolated populations and species of the genus Salvelinus. The resulting phylogenetic trees may help to resolve some disputable taxonomic issues for the groups. A comparison showed that several RAPD-detected sequences contain conserved fragments of coding sequences and polymorphic repeats (minisatellites) from intergenic regions or introns. The finding point to a nonrandom nature of repetitive DNA divergence and may reflect the evolution of the fish groups examined. Heterochromatic satellite repeats were assumed to contribute to generating a reproductive barrier.

The objective of the present study was to elucidate the structural and functional mechanisms underlying disturbances of the protective nasolaryngeal barrier with special reference to the following histological and immunohistochemical characteristics of the pharyngeal tonsils (CD4, CD20, CD68, IgA, P53, BCL2, Ki67, TGF-beta) in the children aged 3-6 years and presenting with complicated (n=20) or uncomplicated (n=20) chronic adenoiditis (CA). It was shown that adenoids of the patients with complicated chronic adenoiditis less frequently exhibit markers of active inflammation, such as hyperemia, intraepithelial infiltration, and hemosiderophages. Also, they have the smaller mean area of lymphoid follicles and the number of functional intrafollicular macrophages suggesting impaired immunological reactivity. Lymphoid follicles of the pharyngeal tonsils in the children with uncomplicated chronic adenoiditis show up enhanced density of B-lymphocytes (CD20) and CD69-positive cells which may suggest functional tension. However, density of IgA-producing lymphocytes responsible for the protection of nasolaryngeal mucosa is identical in the patients with complicated and uncomplicated chronic adenoiditis. Taken together with the decreased number of T-helpers (CG4), this finding indicates the compromised immunological response in the children with this pathology. It is concluded that the structural characteristics of pharyngeal tonsils revealed in the present study may provide a basis for the disturbances of congenital and adaptive immunity; moreover, they can serve as the predictors of complications of chronic adenoiditis.

The medical records of 60 patients who underwent surgery to remove the lung metastases of T1-4N0-2 kidney cancer were retrospectively analyzed. The age of patients ranged from 31 to 70 years. Synchronous lung metastases were diagnosed in 20 (33.3%) cases, metachronous - in 40 (66.7%). 53 (88.3%) patients had lesions in one lung, and 7 (11.7%) patients--in both lungs. Solitary metastases were present in 41 (68.3%) patients, multiple--in 19 (31.7%). In 69.4% of cases, the size of lung metastases was more than 2 cm. Metastasis at other sites at the time of surgery on the lungs were present in 1 patient (supraclavicular lymph nodes). The primary tumor was removed in 56 (93.3%) of 60 patients. All 60 patients underwent removal of lung metastases (radical--53 [88.3%]). One patient underwent a radical supraclavicular lymph node dissection. All tumor lesions were removed in 50 (83.3%) patients. Median followup period was 20 (3-155) months. Perioperative complication rate was 6.6%; no deaths caused by complications of treatment were registered. Histologically, metastases of renal cell carcinoma were verified in all removed lesions from the lungs; 3 (5%) patients had mediastinal lymph node metastases. Five- and 10-year overall, specific and recurrence free survival rates were 36.3 and 19.1%, 38.9% and 27.2, 20.4 and 11.7%, respectively. Univariate analysis demonstrated an adverse effect of pN + category, bilateral pulmonary lesions, the presence of mediastinal lymph nodes metastases and non-radical removal of malignant lesions of the lung on the specific survival. Multivariate analysis confirmed a significant effect of radical surgery on the survival.

The authors present results of examination and treatment of 272 patients with Zenker diverticulums of different localization. Features and problems in fibroesophagoscopy in patients with Zenker diverticulum are discussed. Surgical interventions with endoscopic assistance were fulfilled in 37 patients with diverticulum. A new way of endoscopic management of Zenker diverticulum using preparation "Disport" and the method of endoscopic incision of cricofaringeal muscle are proposed. Good clinical results of the treatment were obtained.

On the basis on literature studies and the results of personal studies, the authors describe ultra- and micro-structural changes in the osseous tissue associated with the process of aging. Functional disturbances in tissue processes causing osseous tissue loss and osteoporosis development are characterized. It is suggested that the described changes are induced by age-dependent hypermineralization of the osseous tissue with the consequent disturbances of mechano-transduction. A hypothesis is discussed concerning a novel approach to pharmacological treatment of osteoporosis. Development of a new group of drugs controlling the calcium exchange between the osseous compartment and the blood is considered. Presumed pathogenetic and clinical effects of these drugs are described.

In ornamental carps from the collection of the Experimental Station, All-Russia Research Institute of Fresh-Water Fisheries, fish with a dirty dark tint of body color among orange and white fish were found. This coloration was shown to be due to the presence of black pigment cells in the lower skin layer. In the outer skin layers these cells were almost entirely absent. This color type was found to be determined by the presence of at least one of alleles B1' or B2' of digenic system B1, B2, which is responsible for the development of melanophores in fish skin. Each of the genes of this digenic system is represented by three alleles with the following order of dominance: B > B' > b.

The authors have generalized their experiences with using "Wobenzym" in 140 patients. Schemes of the effective systemic enzyme therapy are proposed for patients of the orthopedic-traumatological profile.

Clinical pharmacokinetics of ethacizine and its effect on parameters of the central and peripheral hemodynamics in the acute period of myocardial infarction were studied. The appearance of an additional maximum or "concentration plateau" on the concentration-time curve following a single intravenous injection of the drug was noted in most cases. To describe experimental data, a three-compartment model with lag time was proposed. The pharmacokinetic parameters obtained indicate that ethacizine is characterized by a less value of clearance and greater period of half-elimination as compared to ethmozine. Ethacizine was shown to exert no considerable effect on hemodynamics that makes it possible to recommend its use in acute myocardial infarction when cardiac rhythm disorders occur.

Based on pharmacodynamic and pharmacokinetic studies in 42 patients with paroxysmal and extrasystolic abnormalities of the rhythm it was established that disopyramide phosphate (ritmilen) is an effective antiarrhythmic agent for atrial fibrillation paroxysms. The drug exerts negative, chronotropic, dromotropic and inotropic effects, especially upon intravenous injections for removal of atrial fibrillatin paroxysms. Ritmilen moderately reduces the blood pressure. When used for removal of atrial fibrillation paroxysms ritmilen is effective in doses of 1.2-1.7 mg/kg intravenously and in doses of 2.5-3.8 mg/kg per os. In patients with chronic ventricular premature heart beat the single effective drug doses amount to 0.61-1.7 mg/kg. After oral use the ritmilen concentration in blood plasma is lower than after intravenous use in adequate doses. No relationship has been found between the drug antiarrhythmic effect and blood plasma concentration.

1. The major metabolites of ethacizin (ethyl 10-[3-diethylaminopropionyl]phenothiazine-2-carbamate) have been isolated from human urine by h.p.l.c. and identified by determination of u.v., i.r., n.m.r. and mass spectra and comparison with spectra of synthetic standard compounds. 2. The pathways of metabolism of ethacizin include N-de-ethylation, sulphoxidation, N-10 amide hydrolysis, aromatic hydroxylation and conjugation.