Immunological predictors of type 1 diabetes mellitus (literature review)

Background: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency due β-cell destruction and following hyperglycaemia. Specific markers of T1DM are pancreatic islet-targeting autoantibodies that are found months to years before symptom onset, and can be used to identify individuals who are at risk of developing T1DM.Aim: The study is aimed at the review of current knowledge of diabetes-related autoantibodies as biomarkers of T1DM.Materials and methods: Foreign and national clinical studies on this topic were included. PubMed, Medline and ­eLibrary were searched.Results: Modern ideas about known diabetes-specific autoantibodies as markers of autoimmune inflammation of β-cells of the pancreas were discussed. The analysis of their independent diagnostic value in predicting the occurrence of T1DM were carried out.Conclusion: There is no unified concept in the literature on this issue. Current data on autoantibodies in T1DM show a ­significant individual variability in the timing, dynamic changes and autoantibody composition in T1DM progression

Potential risk factors for diabetes mellitus type 1

Diabetes mellitus type 1 (T1D) develops as a result of the interaction of genetic and environmental factors. Genetic predisposition to T1D turns into clinical reality only in half of hereditary cases, which indirectly indicates the importance of external factors, the significance of which is periodically reviewed. Retrospective and prospective clinical foreign and national studies were included. PubMed, Medline and eLibrary were searched. Modern ideas about the possible impact of the main prenatal and postnatal environmental factors on the development of autoimmune response against insulin-producing islet cells and T1D were discussed. The risk of developing type 1 diabetes is determined by the complex interaction of environmental factors and genetic predisposition. The mechanisms of their influence remain rather unknown. Further research is needed to determine strategies of primary and secondary prevention of T1D

Magnetically assembled carbon nanotube tipped pipettes

Applied Physics Letters, 90: pp. 103108-1 - 103108-3.The authors have developed a biological probe at the nanoscale with a magnetic carbon nanotube mCNT tip that has the ability to transfer fluids. Fabrication is performed by injection of mCNTs into micropipettes, which are then positioned as probe tips via magnetophoresis, and affixed with polymeric adhesive. In this letter the authors discuss the magnetic fabrication process and demonstrate the versatility of this probe

Features of COVID-19 course in patients with obesity and dysglycemia

Aim. To study the features of coronavirus disease 2019 (COVID-19) in patients with different severity of carbohydrate metabolism disorders (CMDs), taking into account the possible role of obesity in the acceleration of clinical and laboratory disorders.Material and methods. There were 137 consecutive patients admitted to the infectious disease hospital for COVID-19patients. Three 3 groups were formed: group 1 — 42 patients with concomitant type 2 diabetes (T2D); group 2 — 13 patients with concomitant prediabetes; group 3 — 82 patients without concomitant CMDs.Results. Patients with T2D tended to have a more severe disease course according to the SMRT-CO algorithm (p=0,089), which was associated with the longest hospital stay (p=0,038), the most pronounced (p=0,011) and prolonged (p=0,0001) decrease in oxygen saturation, the maximum percentage of lung injury at the beginning (p=0,094) and at the end (p=0,007) of hospitalization, the greater need for intensive care unit (p=0,050), as well as the highest increase in C-reactive protein and fibrinogen (hypercoagulability and systemic inflammation were noted in all groups). Patients with prediabetes in terms of COVID-19 severity occupied an intermediate position between those with T2D and without CMDs; at the same time, they most often needed the prescription of biological preparations (p=0,001). In the first and second groups, there were larger, compared with the control, proportions of obese people (61,9%, 53,8% and 30,5%, respectively, p=0,003). Prediabetes group had a strong correlation between the severity of viral pneumonitis according to SMRT-CO and the presence of obesity (R=0,69, p=0,009).Conclusion. In patients with impaired carbohydrate metabolism of any severity, COVID-19 is more severe. At the same time, persons with overt T2D are prone to the most severe COVID-19 course, while patients with prediabetes in terms of disease severity occupy an intermediate position between them and those without CMDs. Obesity is a strong risk factor for severe COVID-19 among patients with initial CMDs (prediabetes), which is partly mediated by prior liver dysfunction associated with the metabolic syndrome. The increase in proinflammatory changes and hypercoagulability is associated with COVID-19 severity in patients with and without CMDs. These disorders had the greatest severity and persistence in patients with T2D

Neural Substrate of Cold-Seeking Behavior in Endotoxin Shock

Systemic inflammation is a leading cause of hospital death. Mild systemic inflammation is accompanied by warmth-seeking behavior (and fever), whereas severe inflammation is associated with cold-seeking behavior (and hypothermia). Both behaviors are adaptive. Which brain structures mediate which behavior is unknown. The involvement of hypothalamic structures, namely, the preoptic area (POA), paraventricular nucleus (PVH), or dorsomedial nucleus (DMH), in thermoregulatory behaviors associated with endotoxin (lipopolysaccharide [LPS])-induced systemic inflammation was studied in rats. The rats were allowed to select their thermal environment by freely moving in a thermogradient apparatus. A low intravenous dose of Escherichia coli LPS (10 µg/kg) caused warmth-seeking behavior, whereas a high, shock-inducing dose (5,000 µg/kg) caused cold-seeking behavior. Bilateral electrocoagulation of the PVH or DMH, but not of the POA, prevented this cold-seeking response. Lesioning the DMH with ibotenic acid, an excitotoxin that destroys neuronal bodies but spares fibers of passage, also prevented LPS-induced cold-seeking behavior; lesioning the PVH with ibotenate did not affect it. Lesion of no structure affected cold-seeking behavior induced by heat exposure or by pharmacological stimulation of the transient receptor potential (TRP) vanilloid-1 channel (“warmth receptor”). Nor did any lesion affect warmth-seeking behavior induced by a low dose of LPS, cold exposure, or pharmacological stimulation of the TRP melastatin-8 (“cold receptor”). We conclude that LPS-induced cold-seeking response is mediated by neuronal bodies located in the DMH and neural fibers passing through the PVH. These are the first two landmarks on the map of the circuitry of cold-seeking behavior associated with endotoxin shock

Эффективность и безопасность применения бовгиалуронидазы азоксимера (Лонгидаза) у пациентов с постковидным синдромом: результаты открытого проспективного контролируемого сравнительного многоцентрового клинического исследования DISSOLVE

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase®) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome.The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome.Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded.Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Постковидный синдром (ПКС) после перенесенного COVID-19 (COronaVIrus Disease 2019) – это состояние, которое развивается у пациентов, переболевших COVID-19 и приводит к кумулятивным эффектам в виде одышки и нарушения функции легких. Примечательно, что у пациентов с воспалением дыхательных путей и COVID-19 обнаружены более высокие концентрации гиалуроновой кислоты (ГК). Поскольку бовгиалуронидаза азоксимер (Лонгидаза®) катализирует гидролиз ГК, при назначении данного препарата потенциально можно ожидать снижение концентрации ГК и улучшения функции легких у пациентов с ПКС.Целью исследования DISSOLVE, которое проводилось на начальной стадии пандемии, явилось изучение эффективности и безопасности применения бовгиалуронидазы азоксимера у пациентов с симптомами, связанными с ПКС.Материалы и методы. В открытом проспективном контролируемом сравнительном многоцентровом клиническом исследовании (NCT04645368) принимали участие взрослые пациенты (n = 160), у которых выявлен ПКС. Пациенты, составившие группу лечения (n = 81), получали бовгиалуронидазу азоксимер, лица, составившие группы контроля (n = 79), наблюдались динамически. В рамках исследования выполнялось физикальное обследование, проводилась оценка показателей форсированной жизненной емкости легких (ФЖЕЛ), одышки по шкале модифицированного вопросника Британского медицинского исследовательского совета (Modified Medical Research Council Dyspnea Scale – mMRC), дистанции, пройденной при выполнении 6-минутного шагового теста, и пульсоксиметрии. Эти показатели измерялись в рамках 3 визитов: в 1-й (исходный уровень), 75-й и 180-й дни. Кроме того, регистрировалось число пациентов, у которых наблюдались нежелательные явления (НЯ) и серьезные НЯ.Результаты. Исходные характеристики у пациентов группы лечения и контрольной группы были сходными. В группе лечения отмечено статистически значимое снижение остаточных легочных изменений после визита 2 (75-й день) и визита 3 (180-й день); кроме того, показатели ФЖЕЛ, пульсоксиметрии и переносимости функциональных физических нагрузок статистически значимо увеличились на 75-й и 180-й дни относительно исходного уровня. Показатели одышки по шкале mMRC в группе лечения статистически значимо снизились в течение 75 дней. Профиль безопасности препарата отмечался как благоприятный на протяжении всего исследования.Заключение. При терапии бовгиалуронидазой азоксимером у пациентов с ПКС отмечено улучшение показателей ФЖЕЛ, пульсоксиметрии, переносимости функциональных физических нагрузок и оценки одышки по mMRC

Severe plastic deformation for producing superfunctional ultrafine-grained and heterostructured materials: An interdisciplinary review

Ultrafine-grained and heterostructured materials are currently of high interest due to their superior mechanical and functional properties. Severe plastic deformation (SPD) is one of the most effective methods to produce such materials with unique microstructure-property relationships. In this review paper, after summarizing the recent progress in developing various SPD methods for processing bulk, surface and powder of materials, the main structural and microstructural features of SPD-processed materials are explained including lattice defects, grain boundaries and phase transformations. The properties and potential applications of SPD-processed materials are then reviewed in detail including tensile properties, creep, superplasticity, hydrogen embrittlement resistance, electrical conductivity, magnetic properties, optical properties, solar energy harvesting, photocatalysis, electrocatalysis, hydrolysis, hydrogen storage, hydrogen production, CO2 conversion, corrosion resistance and biocompatibility. It is shown that achieving such properties is not limited to pure metals and conventional metallic alloys, and a wide range of materials are currently processed by SPD, including high-entropy alloys, glasses, semiconductors, ceramics and polymers. It is particularly emphasized that SPD has moved from a simple metal processing tool to a powerful means for the discovery and synthesis of new superfunctional metallic and nonmetallic materials. The article ends by declaring that the borders of SPD have been extended from materials science and it has become an interdisciplinary tool to address scientific questions such as the mechanisms of geological and astronomical phenomena and the origin of life

Wpływ temperatury odkształcenia na mikrostrukturę magnetycznie twardego stopu FeCr22Co15 poddanego rozciąganiu wraz ze skręcaniem

The paper presents the results of microstructure evolution studies of hard magnetic FeCr22Co15 alloy deformed until destruction by tension and torsion in the temperature range 725-850ºC. The temperatures and deformation rates resulted from the condition of superplasticity occurrence in the Fe-Cr-Co alloys. Observations of the longitudinal sections of the deformed samples in the scanning electron microscope showed the formation of a weak gradient microstructure with the highest grain refinement in the surface layer of the material. Increasing the deformation temperature from 725 to 850 ºC increased the homogeneity of the deformation along the tensile axis of the sample. It also brought about the increase of grain size and slight increase of the thickness of fine grains in the surface layer. The precipitation of the intermetallic σ-phase was also observed with its maximum amount in the zones of the highest deformation.Praca przedstawia wyniki badań ewolucji mikrostruktury magnetycznie twardego stopu FeCr22Co15 poddanego odkształceniu poprzez rozciąganie i skręcanie próbek do ich zerwania w przedziale temperatur 725-850ºC. Temperatury i prędkości odkształcenia odpowiadały warunkom nadplastycznosci badanego stopu. Obserwacja mikrostruktury na przekroju podłużnym próbek w skaningowym mikroskopie elektronowym wykazała tworzenie się mikrostruktury o słabym charakterze gradientowym z minimalnym rozmiarem ziaren w warstwie wierzchniej materiału. Zwiększenie temperatury odkształcenia od 725 do 850ºC spowodowało polepszenie jednorodności odkształconej mikrostruktury wzdłuż osi rozciągania próbek oraz zwiększenie rozmiaru ziaren fazy α. Stwierdzono również, że grubość warstwy wierzchniej o drobnym ziarnie w niewielkim stopniu zależy od temperatury odkształcenia. Ponadto stwierdzono obecność fazy międzymetalicznej σ (Fe-Cr), której największa ilość zaobserwowano w warstwie wierzchniej materiału

Metabolicheskie predposylki razvitiya narusheniy ritma serdtsa u bol'nykh sakharnym diabetom 2 tipa

Цель. Изучение влияния декомпенсации углеводного обмена на характер нарушений ритма сердца. Материалы и методы. Под наблюдением находились 142 больных кардиологического профиля. Основную группу составил 101 (71,1%) больной сахарным диабетом 2 типа (СД2). В группу сравнения включен 41 (28,9%) больной без сопутствующего диабета. Клиническое обследование включало суточное мониторирование ЭКГ по методу Холтера, регистрацию сигнал-усредненной ЭКГ с анализом поздних потенциалов желудочков (ППЖ). Определяли уровень гликированного гемоглобина (HbA1c). Проводили количественное исследование продуктов перекисного окисления липидов (ПОЛ). Общая антиоксидантная активность оценивалась по показателю максимальной хемилюминесценции и светосуммы (I max/S, имп/с). Результаты. При анализе полученных результатов выяснилось, что у большинства больных с уровнем HbAlc 8,5% характеризовались наличием ЖЭВГ. Более благоприятные в прогностическом и гемодинамическом отношении аритмии (единичная редкая СВЭ и ЖЭ) наблюдались у больных с уровнем HbAlc в пределах от 7 до 8,5%. В группе со значениями гликированного гемоглобина менее 7% низкие значения первичных продуктов ПОЛ соответствовали низкой активности антиоксидантной системы. В группе с уровнем гликированного гемоглобина в пределах от 7 до 8,5% с увеличением содержания первичных продуктов ПОЛ наблюдалось увеличение антиоксидантной активности, что может рассматриваться как напряжение адаптационных возможностей организма. Изучение уровней продуктов перекисного окисления липидов у больных СД с ППЖ показало, что у данных пациентов отмечались интенсификация процессов ПОЛ с достоверным увеличением трие-новых конъюгатов и ослабление антиоксидантной защиты. У пациентов без СД2 таких зависимостей не найдено. Заключение. Результаты проведенного исследования показывают влияние декомпенсации углеводного обмена с уровнем гликированного гемоглобина более 8,5% на увеличение частоты как ППЖ, так и непосредственно желудочковых экстрасистол высоких градаций. Для таких больных характерны активация процессов перекисного окисления липидов и снижение антиоксидантной активности. Полученные данные могут свидетельствовать о наличии дополнительных метаболических факторов, влияющих на возникновение нарушений ритма сердца. Метод регистрации сигнал-усредненной ЭКГ со значениями QRSt >110 мс, LAS 40 >37 мс и RMS 4