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Introduction: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological syndrome caused by pathogenic variants in the C19orf12 and is characterized by iron deposition in the basal ganglia and substantia nigra. Only a limited number of cohort studies were published to date and the prevalence of MPAN remains uncertain., Methods: Recruited subjects with MPAN in Russia were diagnosed by whole-exome sequencing or Sanger sequencing of the C19orf12 gene. Data of over 14000 whole exome sequencing analyses was used to calculate the estimated disease frequency. RNA analysis was performed by RT-PCR. QSVanalyzer software was used to quantify the allelic disbalance., Results: We describe the clinical and molecular characterizations of 17 patients with MPAN. DNA analysis detected three previously undescribed pathogenic/likely pathogenic variants in the C19orf12 gene. The estimated disease frequency was calculated to be 1:619150. We describe unusual clinical observations in several cases. One patient showed severe neurogenic muscle weakness along with a lack of marked spasticity or optic nerve atrophy. In another mild clinical case with the NM_001031726.3:c.204_214del (p.(Gly69Argfs*10)) variant in a heterozygous state, a marked allelic disbalance was observed on the RNA level with reduced expression level of the wild-type allele. Thus, this case became the first one of a possible regulatory variant causing MPAN., Conclusion: We reported a detailed clinical and molecular characterization of the third-largest MPAN cohort. We expanded the mutational and clinical spectrum of MPAN. Moreover, we calculated the estimated MPAN frequency in the Russian population for the first time., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The aim of the present randomized controlled clinical trial was to evaluate the outcomes of the use of free gingival graft (FGG), of a collagen matrix and of vestibuloplasty to increase the amount of keratinized attached mucosa (KM) before healing abutment placement., Method and Materials: The study was a randomized, parallel-group controlled investigation. All patients were treated to increase the KM width before placement of implant-supported prostheses. The implants were placed 3 to 6 months before the interventions. Three techniques were tested: an apically positioned flap (control group), FGG (test group 1), and use of a collagen matrix (test group 2). Biopsy was performed during healing abutment placement by means of a mucotome., Results: A total of 63 patients were recruited and treated, and 58 were available for follow-up visits. After 4 weeks, the KM width gain was 1.93 ± 0.85 mm, 4.85 ± 1.11 mm, and 3.03 ± 0.58 mm, respectively, for control group, test group 1, and test group 2. Postoperative pain was significantly higher in the FGG group than in the others. Edema and hyperemia decreased gradually during the first week without significant differences among groups., Conclusion: Despite the limitations of the study, it was found that FGG was the most effective technique to augment the amount of KM in sites of implant placement. The use of a collagen matrix could be a viable alternative to diminish the intervention's impact on patients' postoperative quality of life.

Aqueous-saline human placenta extract (HPE) is known to possess antioxidant activity due to the high concentration of bioactive substances. This fact allows its application in clinical practice in order to treat oxidation-induced diseases. Extract antioxidant activity is mainly conditioned by proteins. Freezing of extracts has been shown to lead to their antioxidant activity increasing due to protein conformation changes.Different biological models are widely used in order to evaluate efficacy of novel antioxidants and mechanisms of their action. One such model appears to be erythrocytes under nitrite-induced oxidative stress. Nitrite is known to be able to penetrate erythrocyte membrane and to oxidize hemoglobin. In order to investigate whether HPE is able to decrease nitrite-induced oxidative injuries and to evaluate the protein contribution to this process, spectrophotometric and electron spin resonance (ESR) assays were used.Experimental data have revealed that antioxidant activity of extracts and of some of their fractions correlates with methemoglobin concentration lowering. Preliminary erythrocyte incubation with an extract fraction of 12 kDa allows preservation of the structural-dynamic cytosol state the closest to the control.

At present, the question of how the structural state of the erythrocyte cytosol is arranged to maintain essential permeabilities successfully both at normal temperature and during periods with a significant body temperature reduction during hypobiosis remains unanswered. In the present work, we performed comparative investigations of temperature-dependent changes in the cytosol state of erythrocytes from animals subjected to natural (winter hibernating ground squirrels) or artificial hypobiosis. The cytosol state was evaluated by the ESR method of spin probes (TEMPON) within the temperature range of 0-50 degrees C. Erythrocyte resistance to acid hemolysis, which is limited by the permeability of membranes for protons and the state of the anion channel, were determined using the method described by Terskov and Getelson [Biofizika 2 (1957) 259]. A change in cytosol microviscosity of erythrocytes was found as well as a temperature-dependent increase in acid resistance of erythrocytes. Our investigations allow us to conclude that physiological changes occurring in a mammalian organism during natural and artificial hypobiosis are accompanied by structural modifications of the erythrocyte cytosol. The temperature range where these modifications are observed (8, 15, 40 degrees C) suggests that the most probable modifying link is spectrin and/or the sites of its interaction with membrane. The interaction of cytoskeletal components with the cell membrane plays a key role in regulation of membrane permeability, suggesting an important role of this interaction in the adaptive reactions of erythrocytes.

The effect of rapid freeze-thawing on the structural rearrangement of integral and peripheral membrane proteins was studied using fluorescent spectroscopy. It was discovered that a long wave shift occurred in the fluorescence spectra of cytochrome P450, both in solution and within phospholipid vesicles. The efficiency of quenching of membrane-bound cytochrome P450 with acrylamide also increased after freezing. Similarly, a long wave shift in the fluorescence, spectra occurred after freezing spectrin solution and erythrocyte ghosts. These data are interpreted in terms of physical and chemical factors in the medium affecting the spectral properties of protein chromophores, and suggest that an increase occurs in the polarity of the microenvironment of the protein molecules, resulting in conformational modification. Study of the temperature dependence of spectrin fluorescence in solution, and within erythrocyte ghosts, suggests that modification of protein dynamics occurs both during freezing and during thawing. Despite various differences in the structure of the protein molecules, and in the phospholipid environment and solvent composition, freeze-thawing results in unilateral, irreversible conformation changes, more prominent in peripheral than integral proteins. The possibility that these changes contribute to cryoinjury to cell membranes is discussed.

Erythrocyte membranes of ground squirrels taken from hibernating, awakening and active animals with the body temperatures of 4, 30 and 36 degrees C, respectively, have been shown by freeze-fracture technique to differ in morphology of the PF surface, density and distribution patterns of intramembrane particles. The ultrastructural changes in membrane caused by temperature were confirmed by the data on alterations of dynamics parameters of the lipid bilayer and spectral characteristics of membrane proteins.

Quantitative methods for evaluation of impairments in the functional state of liver tissue by means of a generalized biochemical index enabled to evaluate efficiency of hemosorption as compared with other methods of preoperative treatment of patients with mechanical jaundice of calculous genesis. Hemosorption was found to contribute most effectively to restoration of the liver tissue functional state decreasing the risk of acute liver tissue insufficiency during the postoperational period.