Effects of diabetes family history and exercise training on the expression of adiponectin and leptin and their receptors

The daughters of patients with diabetes have reduced insulin sensitivity index (ISI) scores compared with women with no family history of diabetes, but their ISI increase more in response to exercise training(1). The present study aimed to determine whether differences between these groups in exercise-induced changes in circulating adiponectin and leptin concentrations and expression of their genes and receptors in subcutaneous adipose tissue (SAT), could explain differences in the exercise-induced changes in ISI between women with and without a family history of diabetes

Methyltrimethoxysilane-based elastic aerogels: effects of the supercritical medium on structure-sensitive properties

Effects caused by the type of solvent used for supercritical drying on the properties of methyltrimethoxysilane-based aerogels were studied. All of the aerogel samples studied were found to be hydrophobic and to efficiently adsorb nonpolar organic compounds

A Multi-Model Paradigm in Application to the Analysis of the Factors Defining the Epizootic Situation in the Communities of Non-Synanthropic Small Mammals in Ekaterinburg

The aim of the work was to rank statistical models for assessing the contribution of a number of factors that determine the epizootic situation on natural-focal infectious diseases in the communities of non-synanthropic small mammals (SM) in the forests of Ekaterinburg.Materials and methods. The SM survey was carried out for three years in the summer-autumn period. The animals were caught with snap tpaps on a standard bread bait, 9705 trap-nights were worked out. To identify infections (hemorrhagic fever with renal syndrome, tularemia, leptospirosis, yersiniosis, pseudotuberculosis), 333 SM specimens (rodents and shrews of six species) were used, randomly taken from the general sample. To determine the pathogens, the methods of enzyme immunoassay and polymerase chain reaction were used. The cumulative infection rate of small mammals with all studied natural-focal infections was evaluated. Statistical data processing was carried out from the standpoint of a multi-model approach. The selection of models was performed using the Akaike information criterion with the calculation of the sum of the weights of the models based on their full spectrum (SW).Results and discussion. Carriers of all of the mentioned above infections, except for pseudotuberculosis, have been identified in the forest parks of Ekaterinburg. According to the ranking, the model with three predictors received the highest weight: species, year, and the abundance of SM of the previous year in a particular habitat. The most significant predictors for the full spectrum of models are the year (SW=1), species (SW=0.6), abundance of animals in the current and previous year (SW=0.48). The distribution of positive samples by species of small mammals corresponded to their ranking by abundance in the community. The influence of the factors “season” (summer or autumn) and “area” (place of capture of animals) turned out to be insignificant on the scale of the studies (SW = 0.3 and 0.16, respectively). The percentage of infected samples in total for all infections varied significantly by location and year (0–60%). The possible significance of unaccounted factors is discussed: landscape features and the mode of using forest parks, dispersal of small mammals. The conclusion is made about the usefulness of the multi-model approach in the analysis of the data from epizootiological studies

Ilizarov bone transport combined with the Masquelet technique for bone defects of various etiologies (preliminary results)

BACKGROUND: The Ilizarov bone transport (IBT) and the Masquelet induced membrane technique (IMT) have specific merits and shortcomings, but numerous studies have shown their efficacy in the management of extensive long-bone defects of various etiologies, including congenital deficiencies. Combining their strong benefits seems a promising strategy to enhance bone regeneration and reduce the risk of refractures in the management of post-traumatic and congenital defects and nonunion that failed to respond to other treatments. AIM: To combine IBT and IMT for the management of severe tibial defects and pseudarthrosis, and present preliminary results of this technological solution. METHODS: Seven adults with post-traumatic tibial defects (subgroup A) and nine children (subgroup B) with congenital pseudarthrosis of the tibia (CPT) were treated with the combination of IMT and IBT after the failure of previous treatments. The mean number of previous surgeries was 2.0 ± 0.2 in subgroup A and 3.3 ± 0.7 in subgroup B. Step 1 included Ilizarov frame placement and spacer introduction into the defect to generate the induced membrane which remained in the interfragmental gap after spacer removal. Step 2 was an osteotomy and bone transport of the fragment through the tunnel in the induced membrane, its compression and docking for consolidation without grafting. The outcomes were retrospectively studied after a mean follow-up of 20.8 ± 2.7 mo in subgroup A and 25.3 ± 2.3 mo in subgroup B. RESULTS: The “true defect” after resection was 13.3 ± 1.7% in subgroup A and 31.0 ± 3.0% in subgroup B relative to the contralateral limb. Upon completion of treatment, defects were filled by 75.4 ± 10.6% and 34.6 ± 4.2%, respectively. Total duration of external fixation was 397 ± 9.2 and 270.1 ± 16.3 d, including spacer retention time of 42.4 ± 4.5 and 55.8 ± 6.6 d, in subgroups A and B, respectively. Bone infection was not observed. Postoperative complications were several cases of pin-tract infection and regenerate deformity in both subgroups. Ischemic regeneration was observed in two cases of subgroup B. Complications were corrected during the course of treatment. Bone union was achieved in all patients of subgroup A and in seven patients of subgroup B. One non-united CPT case was further treated with the Ilizarov compression method only and achieved union. After a follow-up period of two to three years, refractures occurred in four cases of united CPT. CONCLUSION: The combination of IMT and IBT provides good outcomes in post-traumatic tibial defects after previous treatment failure but external fixation is longer due to spacer retention. Refractures may occur in severe CPT

Key differences between anti-PD-1/PD-L1 inhibitors

Indications  to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors  showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors  (CPI) in the future may allow  to solve the problem of rechallenge  and reintroduction after management of severe IRAEs

Common Patterns of Prediction of Literacy Development in Different Alphabetic Orthographies

We are grateful to Brett Kessler for computing the consistency estimates in each of the four languages of this studyPrevious studies have shown that phoneme awareness, letter-sound knowledge, rapid automatized naming (RAN), and verbal memory span are reliable correlates of learning to read in English. However, the extent to which these different predictors have the same relative importance in different languages remains uncertain. In this article, we present the results from a 10-month longitudinal study that began just before or soon after the start of formal literacy instruction in four languages (English, Spanish, Slovak, and Czech). Longitudinal path analyses showed that phoneme awareness, letter-sound knowledge, and RAN (but not verbal memory span) measured at the onset of literacy instruction were reliable predictors, with similar relative importance, of later reading and spelling skills across the four languages. These data support the suggestion that in all alphabetic orthographies, phoneme awareness, letter-sound knowledge, and RAN may tap cognitive processes that are important for learning to read.Grant PITN-215961 – ELDEL from the Marie Curie, Seventh Framework Programm

Osmotic and buffer properties of adapted infant formulas "Baby" and "Similaс"

Infant formulas were reconstituted by dilution with several types of water, taking into account the recommendations on the package. The acid buffer capacity of infant formula is higher than that the breast milk. According to the set criteria (ph, buffer capacity for acid, osmolality, electrical conductivity) for children aged from 0 to 6 months, infant formula "Malyutka 1" is most suitable. In practice, according to the survey, it is used much less often compared to the "Similac 1".Молочные смеси восстанавливали путем разведения соответствующими типами вод, учитывая рекомендации на упаковке. Буферная ёмкость по кислоте у молочных смесей выше, чем у грудного молока. По совокупности критериев (рн, буферная емкость по кислоте, осмоляльность, электропроводность) для детей в возрасте от 0 до 6 месяцев наиболее подходит МС «Малютка 1». На практике, по данным проведенного анкетирования, ее используют значительно реже по сравнению со смесью Similac 1

Comparative analysis of IL-1β blood serum concentration, neutrophil-to-lymphocytes ratio in peripheral blood, and the levels of PD-L1 expression in malignant tissues of the patients with various solid tumors

The action of checkpoint inhibitors is based on activation of T cell antitumor immunity, and, therefore, the search for markers of lymphocyte functional activity before starting the therapy is highly relevant. Determination of the PD-L1 expression in tumor tissues reflects immunosuppressive activity of malignant cells, and it is used as a predictive marker in clinical practice. The ratio of neutrophils to lymphocytes in tumor tissue and in peripheral blood can also indicate the activity of adaptive immunity and correlates with the efficacy of therapy. It has been shown that a high level of interleukin 1 beta in the tumor microenvironment is associated with immunosuppression of lymphocytes and, possibly, reflects the activity of the tumor microenvironment. The aim of this work is to study the relationship between tumor expression of PD-L1, the concentration of serum interleukin-1 beta and the ratio of neutrophils and lymphocytes in peripheral blood.Before starting therapy with checkpoint inhibitors in patients with various solid tumors (n = 50), the serum level of interleukin-1 beta was determined by ELISA (ELISA-Best, Novosibirsk, Russia), expression of PD-L1 in the tumor by immunohistochemical method, complete blood count was performed using cytometry. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using the statistical methods of Fisher, Mann-Whitney, and Spearman.The average value of the index of the ratio of neutrophils and lymphocytes (NLR) in peripheral blood was 2.65± 0.21 (95% CI 2.22-3.07). The index value of more than 3.5 was found in 18% (9/50) of patients. The mean value of the PD-L1 expression level was 23.02±4.52% (95% CI 13.86-32.18). Expression of PD-L1 in tumor tissue was detected in 60.1% (25/40) of patients, among whom an increased expression of more than 50% was detected in 20.0% (5/25) of cases. A positive weak correlation was found between the concentration of interleukin 1 beta and the number of leukocytes (r = 0.34; p = 0.019) and index (r = 0.32; p = 0.029). The level of PD-L1 expression in tumor tissue also had a weak positive correlation with the serum interleukin 1 beta concentration (r = 0.33; p = 0.037) and the neutrophil-lymphocyte ratio (r = 0.33; p = 0.034). In the group of patients with PD-L1 expression > 5%, the mean value of the concentration of interleukin 1 beta was 1.65±0.62 pg/ml, and the mean value of the index was 4.26±0.94 х 10 9/l, which exceeds the values groups with undetectable PD-L1, but the differences were not statistically significant.The obtained result may indicate the influence of the immunosuppressive properties of the tumor on the state of the patient's immunity. Comprehensive determination of tumor PD-L1 expression, serum interleukin 1 beta concentration and the ratio of neutrophils and lymphocytes in peripheral blood can be used as an assessment of the patient's immune status before starting treatment with checkpoint inhibitors