Systemic Inflammatory Effects of Traumatic Brain Injury, Femur Fracture, and Shock: An Experimental Murine Polytrauma Model

Objective. Despite broad research in neurotrauma and shock, little is known on systemic inflammatory effects of the clinically most relevant combined polytrauma. Experimental investigation in an animal model may provide relevant insight for therapeutic strategies. We describe the effects of a combined injury with respect to lymphocyte population and cytokine activation. Methods. 45 male C57BL/6J mice (mean weight 27 g) were anesthetized with ketamine/xylazine. Animals were subjected to a weight drop closed traumatic brain injury (WD-TBI), a femoral fracture and hemorrhagic shock (FX-SH). Animals were subdivided into WD-TBI, FX-SH and combined trauma (CO-TX) groups. Subjects were sacrificed at 96 h. Blood was analysed for cytokines and by flow cytometry for lymphocyte populations. Results. Mortality was 8%, 13% and 47% for FX-SH, WD-TBI and CO-TX groups (P < 0.05). TNFα (11/13/139 for FX-SH/WD-TBI/CO-TX; P < 0.05), CCL2 (78/96/227; P < 0.05) and IL-6 (16/48/281; P = 0.05) showed significant increases in the CO-TX group. Lymphocyte populations results for FX-SH, WD-TBI and CO-TX were: CD-4 (31/21/22; P = n.s.), CD-8 (7/28/34, P < 0.05), CD-4-CD-8 (11/12/18; P = n.s.), CD-56 (36/7/8; P < 0.05). Conclusion. This study shows that a combination of closed TBI and femur-fracture/ shock results in an increase of the humoral inflammation. More attention to combined injury models in inflammation research is indicated

Predictive factors for beneficial application of high-frequency electromagnetics for tumour vaporization and coagulation in neurosurgery

<p>Abstract</p> <p>Objective</p> <p>To identify preoperative and intraoperative factors and conditions that predicts the beneficial application of a high-frequency electromagnetic field (EMF) system for tumor vaporization and coagulation.</p> <p>Methods</p> <p>One hundred three subsequent patients with brain tumors were microsurgically treated using the EMF system in addition to the standard neurosurgical instrumentarium. A multivariate analysis was performed regarding the usefulness (ineffective/useful/very helpful/essential) of the new technology for tumor vaporization and coagulation, with respect to tumor histology and location, tissue consistency and texture, patients' age and sex.</p> <p>Results</p> <p>The EMF system could be used effectively during tumor surgery in 83 cases with an essential contribution to the overall success in 14 cases. In the advanced category of effectiveness (very helpful/essential), there was a significant difference between hard and soft tissue consistency (50 of 66 cases vs. 3 of 37 cases). The coagulation function worked well (very helpful/essential) for surface (73 of 103 cases) and spot (46 of 103 cases) coagulation when vessels with a diameter of less than one millimeter were involved. The light-weight bayonet hand piece and long malleable electrodes made the system especially suited for the resection of deep-seated lesions (34 of 52 cases) compared to superficial tumors (19 of 50 cases).</p> <p>The EMF system was less effective than traditional electrosurgical devices in reducing soft glial tumors. Standard methods where also required for coagulation of larger vessels.</p> <p>Conclusion</p> <p>It is possible to identify factors and conditions that predict a beneficial application of high-frequency electromagnetics for tumor vaporization and coagulation. This allows focusing the use of this technology on selective indications.</p

МАТЕМАТИЧЕСКАЯ МОДЕЛЬ СИСТЕМЫ ЗАЩИТЫ ИНФОРМАЦИИ НА ОСНОВЕ ДИОФАНТОВА МНОЖЕСТВА

Development of the asymmetric cryptography started with the appearance of the first knapsack information protection system, when, in 1978, Ralph Merkel and Martin Hellman proposed to use different keys for forward and reverse mapping data for encryption. Now this model, like many based on are considered to be insecure. As a result the authority of knapsack systems was low. However, some of these systems are still considered persistent, for example, the model proposed in 1988 by Ben Shore and Ronald Rivest. In the article stated and solved the problem of argumentation of cryptographic strength of the non-standard knapsack information security systems. Justified diophantine difficulties that arise in the study of vulnerabilities of the investigated information security systems. Revealed the qualitative features of non-standard knapsack systems that increase their resistance to known attacks. In this paper, we propose a mathematical model of polyalphabetic cryptosystem, in which the algorithm of inverse transformation of closed text is algorithmically unsolvable problem for the analyst. It’s permeated with the idea K.Shennon, who believed that cryptosystems, containing Diophantine problems, have the greatest variation in the selection of key. Развитие ассиметричной криптографии началось с появления разработки первой рюкзачной системы защиты информации, когда в 1978 го- ду Ральф Меркель и Мартин Хеллман предложили использовать разные ключи для прямого и обратного преобразования данных при шифровании. Это была одна из первых криптосистем с открытым ключом, но она оказалась криптографически нестойкой. Позже Ади Шамир показал, что система Меркля-Хеллмана является ненадежной, и на данный момент эта модель, как и многие, основанные на ней были скомпрометированы. Как следствие, авторитет рюкзачных систем защиты информации был зани- жен. Тем не менее, некоторые из них, до сих пор считаются стойкими, например, модель, предложенная в 1988 году Беном Шором и Рональ- дом Ривестом. Несмотря на это попытки ее усовершенствования до сих пор не прекращаются, о чем свидетельствуют цикл работ Осипяна В.О. и других авторов. Более полный обзор работ в области анализа системы Меркля-Хеллмана и ее развития дан Б. Шнайером. Отметим особо, что все нестандартные задачи о рюкзаках KG (обобщенная задача), KU (уни- версальная или суперобобщенная задача), KF (функциональная задача), впервые сформулированные и введенные Осипяном В.О., принадлежат классу NP-полных задач. В данной работе обоснованы диофантовы трудности, возникающие при поиске уязвимостей в указанных системах защиты информации. На основе анализа ранее предложенных рюкзачных моделей выявлены качественные особенности нестандартных рюкзачных систем, повышающие их стойкость к известным атакам. Предлагается математическая модель полиалфавитной криптосистемы, в которой алгоритм обратного преобразования закрытого текста сводится к алгоритмически неразрешимой проблеме для аналитика. В статье красной нитью проходит идея К. Шеннона, который считал, что наибольшей неопределённостью при подборе ключей обладают криптосистемы, содержащие диофантовы трудности.

Deletion Mutants of VPg Reveal New Cytopathology Determinants in a Picornavirus

BACKGROUND: Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes 3 copies of VPg. Why FMDV encodes three VPgs is unknown. METHODOLOGY AND PRINCIPAL FINDINGS: we have constructed four mutant FMDVS that encode only one VPG: either VPg(1), VPg(3), or two chimeric versions containing part of VPg(1) and VPg(3). All mutants, except that encoding only VPg(1), were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The effect of R55W in 2C was to mediate an increase in the extracellular viral RNA release without a detectable increase of total viral RNA that correlated with an enhanced capacity to alter and detach BHK-21 cells from the monolayer, the first stage of cell killing. CONCLUSIONS: The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. Implications for picornaviruses pathogenesis are discussed

An Expert Consensus Statement on the Management of Large Chondral and Osteochondral Defects in the Patellofemoral Joint

© The Author(s) 2020. Background: Cartilage lesions of the patellofemoral joint constitute a frequent abnormality. Patellofemoral conditions are challenging to treat because of complex biomechanics and morphology. Purpose: To develop a consensus statement on the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint using a modified Delphi technique. Study Design: Consensus statement. Methods: A working group of 4 persons generated a list of statements related to the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint to form the basis of an initial survey for rating by a group of experts. The Metrics of Osteochondral Allografts (MOCA) expert group (composed of 28 high-volume cartilage experts) was surveyed on 3 occasions to establish a consensus on the statements. In addition to assessing agreement for each included statement, experts were invited to propose additional statements for inclusion or to suggest modifications of existing statements with each round. Predefined criteria were used to refine statement lists after each survey round. Statements reaching a consensus in round 3 were included within the final consensus document. Results: A total of 28 experts (100% response rate) completed 3 rounds of surveys. After 3 rounds, 36 statements achieved a consensus, with over 75% agreement and less than 20% disagreement. A consensus was reached in 100.00% of the statements relating to functional anatomy of the patellofemoral joint, 88.24% relating to surgical indications, 100.00% relating to surgical technical aspects, and 100.00% relating to rehabilitation, with an overall consensus of 95.5%. Conclusion: This study established a strong expert consensus document relating to the functional anatomy, surgical indications, donor graft considerations for osteochondral allografts, surgical technical aspects, and rehabilitation concepts for the management of large chondral and osteochondral defects in the patellofemoral joint. Further research is required to clinically validate the established consensus statements and better understand the precise indications for surgery as well as which techniques and graft processing/preparation methods should be used based on patient- and lesion-specific factors

Direct Interaction between Two Viral Proteins, the Nonstructural Protein 2CATPase and the Capsid Protein VP3, Is Required for Enterovirus Morphogenesis

In spite of decades-long studies, the mechanism of morphogenesis of plus-stranded RNA viruses belonging to the genus Enterovirus of Picornaviridae, including poliovirus (PV), is not understood. Numerous attempts to identify an RNA encapsidation signal have failed. Genetic studies, however, have implicated a role of the non-structural protein 2CATPase in the formation of poliovirus particles. Here we report a novel mechanism in which protein-protein interaction is sufficient to explain the specificity in PV encapsidation. Making use of a novel “reporter virus”, we show that a quasi-infectious chimera consisting of the capsid precursor of C-cluster coxsackie virus 20 (C-CAV20) and the nonstructural proteins of the closely related PV translated and replicated its genome with wild type kinetics, whereas encapsidation was blocked. On blind passages, encapsidation of the chimera was rescued by a single mutation either in capsid protein VP3 of CAV20 or in 2CATPase of PV. Whereas each of the single-mutation variants expressed severe proliferation phenotypes, engineering both mutations into the chimera yielded a virus encapsidating with wild type kinetics. Biochemical analyses provided strong evidence for a direct interaction between 2CATPase and VP3 of PV and CAV20. Chimeras of other C-CAVs (CAV20/CAV21 or CAV18/CAV20) were blocked in encapsidation (no virus after blind passages) but could be rescued if the capsid and 2CATPase coding regions originated from the same virus. Our novel mechanism explains the specificity of encapsidation without apparent involvement of an RNA signal by considering that (i) genome replication is known to be stringently linked to translation, (ii) morphogenesis is known to be stringently linked to genome replication, (iii) newly synthesized 2CATPase is an essential component of the replication complex, and (iv) 2CATPase has specific affinity to capsid protein(s). These conditions lead to morphogenesis at the site where newly synthesized genomes emerge from the replication complex