The World's First Implantation of a Personalized Microporous Titanium Sternum with Motile Costal Clip Connections: A Case Report.

Extensive chest wall defects occur in 28% of all sternal resection cases and are a major challenge in thoracic surgery. These cases are generally considered "critical defects" requiring primary or secondary reconstruction using various types of flaps, mesh repairs, bone autografts, or endoprosthesis. The past decade witnessed rapid advances in the application of personalized endoprostheses in thoracic surgery. Surgeons began to use carbon or titanium grafts for personalized sternum replacement. The main advantages of these implants are superior cosmetic effect, biocompatibility, and low risk of infection. Herein, we present a case of a 55-year-old patient with an indication for extended sternum resection due to metastatic thyroid cancer. The patient underwent extended sternum resection, followed by the implantation of a personalized microporous titanium sternum equipped with graspers for atraumatic rib fixation.

Metformin counters oxidative stress and mitigates adverse effects of radiation exposure: An overview.

Metformin (1,1-dimethylbiguanidine hydrochloride) (MF) is a drug that has long been in use for the treatment of type 2 diabetes mellitus and recently is coming into use in the radiation therapy of cancer and other conditions. Exposure to ionizing radiation disturbs the redox homeostasis of cells and causes damage to proteins, membranes, and mitochondria, destroying a number of biological processes. After irradiation, MF activates cellular antioxidant and repair systems by signaling to eliminate the harmful consequences of disruption of redox homeostasis. The use of MF in the treatment of the negative effects of irradiation has great potential in medical patients after radiotherapy and in victims of nuclear accidents or radiologic terrorism.

Approaches for the complex assessment of polychemical pollution of permafrost-affected soils and the upper layer of permafrost.

The analysis of about 200 samples taken from 42 permafrost-affected soil profiles was carried out on four key sites in different regions of cryolithozone (West Siberia, Central, North, and North-East Yakutia) characterized by different active layer depths and soil lithology. The aim of the study was to determine the influence of different processes of cryogenic mass-exchange on the redistribution and accumulation of major pollutants such as petroleum products, acid-soluble forms of trace elements, polycyclic hydrocarbons, and technogenic radionuclides transferred via atmospheric transport or after the local anthropogenic impact in different soil horizons of Cryosols and in the upper layers of permafrost. Samples were analyzed using modern precise techniques (direct γ-spectrometric measurements with Ge(Li) and NaI(Tl) detectors; fluorometric method; reversed-phase high-performance liquid chromatography; spectrofluorimetric detection; atomic absorption spectrometry with flame atomization). The study has shown that processes (cryoturbations, frost heaving, gelifluction along with fluvial processes) that strongly affect Cryosols' profile structure can also lead to the active migration and accumulation of local and global pollutants in the middle and lowermost suprapermafrost soil horizons. The accumulation of some pollutants in suprapermafrost horizons of cryogenic soils and in the upper layers of permafrost (in particular, petroleum products and mobile forms of trace elements) can be associated with a combination of factors, such as the relatively light particle size distribution, relatively weak manifestation of cryoturbation processes, and low thickness of the active layer (about 40-60 cm). The integral calculation of the geoaccumulation index values has shown that all of the groups of human-affected soil horizons are moderately to extremely polluted by petroleum hydrocarbons (and at a relatively lower level by trace elements) and the maximum pollution stands for the suprapermafrost horizons as well as in cryoturbated or buried fragments of organogenic matter in some cases. The maxima of the heavy PAH content in permafrost-affected soils can be confined to horizons enriched with anthropogenic inclusions and artifacts (for example, construction slag, coal) and to individual horizons of soils buried as a result of both cryogenic and alluvial processes. The specific activity of the technogenic radionuclide cesium in cryogenic soils revealed its association mainly with the surface organogenic and organomineral horizons of the studied profiles and rarely observed in the cryoturbated fragments of these horizons in the middle and suprapermafrost layers of soil profiles. The necessity of the complex analytical assessment of the permafrost-affected soils has been revealed especially in case of studying of the ecological state of the anthropogenically affected Cryosols.

Formation of long-lived reactive species of blood serum proteins induced by low-intensity irradiation of helium-neon laser and their involvement in the generation of reactive oxygen species.

It was demonstrated that low-intensity radiation of helium-neon (He-Ne) laser at 632.8nm, which leads to the transition of oxygen to a singlet state, causes the formation of reactive oxygen species (ROS) - hydrogen peroxide, hydroxyl and superoxide (hydroperoxide) radicals - in aqueous solutions. The oxygen effect - dependence of hydrogen peroxide formation on the concentration of molecular oxygen - was shown, and the participation of singlet oxygen, hydroxyl radicals and superoxide (hydroperoxide) radicals in this process was testified. Laser radiation-induced ROS in solutions of blood serum proteins, bovine serum albumin and bovine gamma-globulin, cause the formation of long-lived reactive protein species (LRPS) with a half-life of about 4h. The generation of LRPS caused by laser irradiation results in prolonged several-hour generation of ROS - hydrogen peroxide, hydroxyl and superoxide radicals. As affected by LRPS, coupled radical reactions lead to conversion of dissolved molecular oxygen to hydrogen peroxide. Irradiation with light sources away from the oxygen absorption band is not attended by formation of ROS and LRPS. A consideration is provided for the possible molecular mechanisms of ROS formation under the influence of He-Ne laser irradiation, the role of proteins in their generation and the biological significance of these processes.

Protection of mice against X-ray injuries by the post-irradiation administration of inosine-5'-monophosphate.

The aim of the present study was to investigate the radiation modulating properties of inosine-5'-monophosphate (IMP). Mice injected introperitoneally (i.p.) with IMP 15 minutes after irradiation with a lethal irradiation dose of 7 Gy have better survival rates comparative to irradiated mice non treated with IMP. The dose reduction factor of the IMP is 1.22. Using a hematologdical test we demonstrated that administration of IMP alleviates the symptoms of radiation-induced leukopenia and thrombocytopenia. The DNA damage in bone marrow and thymus cells of irradiated mice was measured by flow cytofluorometry and micronucleus test (MN-test). The tests show that i.p. administration of IMP to irradiated animals leads to a significant reduction of the DNA damage level. In this paper we show that IMP substantially modulates the damaging effects of ionizing radiation protecting irradiated mice and it is a promising agent for a treatment of leukopenia.

The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex.

The WD repeat-containing protein receptor for activated protein kinase C (RACK)-1 has been linked to a variety of signaling systems including protein kinase C, growth factors, and IFNs. In the IFN system, RACK-1 functions as an adaptor recruiting the transcription factor STAT1 to the receptor complex. However, RACK-1 should play a broader role in type I IFN signaling because mutation of the RACK-1 binding site in the IFN-alpha receptor 2/beta subunit of the type I IFN receptor abrogates not only STAT1, but also STAT2, activation. In this study, we demonstrate that RACK-1 serves as a scaffold protein for a multiprotein complex that includes the IFN-alpha receptor 2/beta-chain of the receptor, STAT1, Janus kinase 1, and tyrosine kinase 2. In vitro data further suggest that within this complex tyrosine kinase 2 is the tyrosine kinase responsible for the phosphorylation of STAT1. Finally, we provide evidence that RACK-1 may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin.

Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation.

Kinases of the Jak family (Jak1/2/3 and Tyk2) interact with the membrane proximal domain of different cytokine receptors and play a critical role in the activation of cytokine and growth factor signaling pathways. In this report we demonstrate that both the Box 1 and Box 2 motif collaborate in the association and activation of Jak1 by type I interferons. Mutational analysis of the beta chain of type I interferon receptor (IFNalphaRbetaL/IFNAR2) revealed that Box 1 plays a more significant role in activation than in the association with Jak1. On the contrary, the Box 2 motif contributes more to the association with Jak1 than to kinase activation. Additionally, the study of the Jak1 binding sites on the IL2 receptor beta (IL2Rbeta), IFNgammaRalpha/IFNGR1, and IL10Ralpha/IL10R1 chains suggests that cytokine receptors have two different kinds of interaction with Jak1. One form of interaction involves the Box 1 and the previously described Box 2 motif, which we now designate as Box 2A, characterized by the VEVI and LEVL sequences present in IFNalphaRbetaL/IFNAR2 and IL2Rbeta subunits, respectively. The second form of interaction requires a motif termed Box 2B, which is present in the IFNgammaRalpha/IFNGR1 (SILLPKS) and IL10Ralpha/IL10R1 (SVLLFKK) chains. Interestingly, Box 2B localizes close to the membrane region (8-10 amino acids from the membrane) similar to Box 1, whereas Box 2A is more distal (38-58 amino acids from the membrane).

Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors.

The interaction between receptors and kinases of the Janus kinase (Jak) family is critical for signaling by growth factors, cytokines, and IFNs. Therefore, the characterization of the domains involved in these interactions is pivotal not only in understanding kinase activation but also in the development of drugs that mimic or inhibit signaling. In this report, we have characterized the domains of Jak1 required to associate with distinct cytokine receptor subunits: IFN-alpha R beta L, IFN-gamma R alpha, IL-10R alpha, IL-2R beta, and IL-4R alpha. We demonstrate that two regions of Jak1 are necessary for the interaction with cytokine receptors. First, a common N-terminal region that includes Jak homology (JH) domain 7 and the first 19 aa of JH6, and, second, a C-terminal region (JH6-3) that was different for distinct receptors. The contribution of the two different regions of Jak1 to cytokine receptor binding was also variable. Deletion of JH7-6 impaired the association of IL-2R beta and IL-4R alpha chains with Jak1 but did not have a major impact on the binding of Jak1 to IFN-alpha R beta L or IL-10R alpha. Interestingly, regardless of the effect on receptor binding, removal of JH7-6 completely abrogated kinase activation, indicating that this domain is required for ligand-driven kinase activation and, thus, for proper signaling through cytokine receptors.