Combination of active stage of diabetic Charcot neuroosteoarthropathy and diabetic lower limb macroangiopathy

Combination of active stage of diabetic Charcot neuroosteoarthropathy and diabetic lower limb macroangiopathy is the rare condition. In the present paper we describe two cases of development of acute Charcot foot in the non-critically ischemic foot. The first case is the patient with previously diagnosed intermitted claudication and the second case is patient who developed the Charcot foot 5 months later after successful endovascular treatment of arterial occlusions of his left lower limb. In both cases the absence of redness in the early stage, the mild-to-moderate pain and mild temperature gradient between affected and non-affected feet were noticed. The clinical course of the Charcot disease in the first patient was favourable. He used walker for 9 months and his foot shape was preserved and deformity was considered as mild. The second patient had more active and profound destructions due to delay of the treatment. He was casted, however his deformity progressed and the treatment continues up to date. In both patients the MRI revealed more affected bones compared with X-ray. These cases emphasize the importance of keeping in mind the Charcot disease even in patients with diabetic peripheral vascular disease

Short-term outcomes of treatment of active stage of Charcot foot in outpatient setting

Background: Treatment options in patients with an acute Charcot foot is not well standardized and still challenging.Aims: To evaluate the results of the non-operative treatment of patients with active stage of diabetic charcot arthropathy in outpatient foot clinic and to identify factors influenced on treatment results.Materials and methods: Medical files of 141 patients with unilateral ulcer-free active charcot arthropathy were reviewed. 78 patients agreed for treatment (total contact cast or walker), 63 patients refused of treatment (follow-up only). The time of resolution of the acute stage, severity of final deformities and foot-related complications were evaluated. Refusers were asked about the cause of their decision.Results: Mean delay of the diagnosis was 3,2±2,8 months. Main causes of the refuse were: mistrust to doctor - 38%, problems with employment - 33%, home/family problems - 18%, medical reasons - 11%. Median healing times (months) in the treatment group vs controls: 9 (6 - 19) 15 (13 - 25) (p=0,001) and progression of the initial deformity: 14% and 35%, respectively (p=0,01). Foot-related complications: 17,5% in the treatment group and in 55,6% of controls (including 6 amputations) (p=0,001). Frequency of breaking the cast/walker - 32%/16,6%. Foot lesions due to cast/walker: 13,6%/41,7% (p<0,01). Median healing times (months) with walkers - 13 (11 - 19), with casts - 9 (6 - 15) months (р=0,02). The use of crutches shortened healing time.Conclusions: The significant delay of diagnosis was revealed. The refuse rate in our cohort was high and main causes of the refuse were social and psychological. Neglect of treatment leads to high frequency and severity of foot-related complications. We noticed high rate of breaking of walkers and casts and device-related foot lesions. Total contact casts were more effective and safe compared with walkers

Changes in loading distribution in patients with Charcot foot during long-term follow-up

Background. The inactive stage of the diabetic Charcot arthropathy foot (CA) is characterised by fixed foot deformities and an absence of inflammation. However, it remains unclear if the shape of the foot and its biomechanics change during long-term follow-up. Aim. To evaluate changes in loading distribution of the affected foot, in patients with inactive CA, during long-term follow-up. Materials and methods. Twenty seven patients with unilateral inactive CA (19 females, 8 males) were studied. Computer pedography (emed AT, novel gmbh) was performed and baseline and the last studies were analysed. Maximal peak pressures (PP) were obtained for the first and the last studies and the percentage of the PP change was calculated for the total follow-up period and for periods: 24 months, 2448 months, 48 months. Results. PP increased: under the hallux 50%; 1st metatarsal30.7%; 2nd toe20%; 2nd toe6%; midfoot9%. PP decreased under 35 toes up to 67%. Significant changes at the first period were found under 35 toes only (62%). The increase in loading under the other parts of the foot appeared at 24 months; however, these changes became significant between 24 and 48 months and peaked after 48 months of follow-up. The maximal increase of PP was noticed under the hallux, the 2nd toe, metatarsals 13 and the midfoot. Conclusions. We revealed the gradual redistribution of PP, under the different parts of the foot, in patients with inactive CA. This redistribution reflects changes in the shape of the affected foot. The loading increased under the hallux, the 2nd toe and the corresponding metatarsals, 3rd metatarsal and midfoot, and decreased under the 35 toes. These changes increased during the follow-up, becoming more pronounced after 4 or more years. Our data may be useful for constructing custom-made footwear for patients with CA

Pedographic assessment of the impact of off-the-shelf orthopedic shoes on the load distribution under the feet in patients with a high risk of developing diabetic foot syndrome

BACKGROUND: It is known that the so-called “rocker” outsole helps to reduce the load on the forefoot and toes. Such an outsole is available in ready-made orthopedic shoes of some Russian manufacturers, however, an objective assessment of their impact on the load distribution under the foot during walking has not been carried out.AIMS: To study the pressure distribution inside the off-the-shelf orthopedic shoes“Sursil-Ortho” in comparison with the load inside the shoes used by patients on a daily basis.METHODS: We studied 20 patients (40 feet) with a high risk of diabetic foot syndrome. According to clinical data, a risk regions were determined on the plantar surface of the feet. In-shoe pedography (pedar, novel,Germany) was performed in shoes usually worn by the patients, and in orthopedic shoes“Sursil-Orto”(Moscow). The maximum peak pressure (MPP) was calculated. Criterion of efficiency: MPP in the risk region<200 kPa or reducing it by 25% or more.RESULTS: There was a significant decrease of the median MPP in the forefoot and in the risk region. The percentage of feet with MPP >200 kPa in the risk region decreased from 58% to 30% (p=0,014), in any area of the forefoot — from 63% to 30% (p=0,04). The increase in MPP under the midfoot and hindfoot did not exceed +14% (ns). Tested footwear was effective in 71% of cases. Predictors of the insufficient effect were: higher initial MPP in the risk region, risk region on the hallux or in the lateral part of the forefoot.CONCLUSIONS: Shoes with a rigid rocker outsole significantly reduce the pressure under the forefoot and under the toes during walking. The degree of load reduction varies: the lateral part of the forefoot and 2-5 toes are most unloaded, and the hallux and medial forefoot are slightly less

Point-of-Care Blood Glucose Testing: Post-Market Performance Assessment of the Accu-Chek Inform II Hospital-Use Glucose Meter

Background. A point-of-care glucose testing (POCT) is an essential component of care in patients with hyperglycemia and hypoglycemia in inpatient and outpatient settings. In Russian medical facilities (MFs), conventional glucose meters designed for self-monitoring by patients with diabetes are commonly used for POCT. These home-use meters have two serious disadvantages: the first is large measurement bias and the second – they can’t be integrated into laboratory information systems, so measurement data have to be recorded into patient charts manually. Both factors may lead to medical errors. It is reasonable to use in the MFs specialized POCT glucose meters, as they are superior to conventional ones in accuracy and may be easily connected to laboratory information systems. With this in mind, physicians at the Russian Children’s Clinical Hospital decided to substitute conventional meters with the Accu-Chek Inform II POCT meter, however, after preliminary performance assessment of the model. Aim. To test the Accu-Chek Inform II performance characteristics: accuracy, linearity, repeatability, and mean absolute relative difference (MARD). Materials and methods. Performance of the Accu-Chek Inform II was tested by comparing the results of parallel CGL measurements with the meter and reference laboratory analyzer in capillary blood samples. Overall, 99 parallel CGL measurements were made in 45 samples. Accuracy was evaluated according to the ISO 15197-2013 and POCT12-A3 criteria. Results. The Accu-Chek Inform II meter met the requirements of ISO 15197-2013 and POCT12-A3 and demonstrated high linearity (correlation coefficient, r=1,0), good repeatability (mean coefficient of variation, CV=1,38%) and acceptable MARD (4,9%). Conclusion. The Accu-Chek Inform II POCT glucose meter may be efficiently and safely used in inpatient and outpatient MFs and particularly in pediatric clinics

Erratum in "Point-of-Care Blood Glucose Testing: Post-Market Performance Assessment of the Accu-Chek Inform II Hospital-Use Glucose Meter" (DOI: 10.26442/00403660.2023.12.202522)

In the article "Point-of-care blood glucose testing: post-market performance assessment of the Accu-Chek Inform II hospital-use glucose meter," published in the Terapevticheskii Arkhiv journal, Vol. 95, No.12, 2023 (DOI: 10.26442/00403660.2023.12.202522), errors were made: the term "measurements at the place of treatment" was changed, as well as the section "Conflict of interest." At the request of the authors' team, errors in the conflict of interest and the wording of the term have been corrected, and the section "Information about the authors" has been updated. The publisher replaced the original version of the published article with the corrected one; the information on the website was also corrected. Correct text of the section "Conflict of interest": Conflict of interest. All authors are not employees or consultants of Roche Diagnostics and have not received any compensation from Roche Diagnostics. Correct wording of the term in Russian: "измерения по месту лечения". Changes were made to the title of the article in Russian: "Измерения глюкозы по месту лечения: пострегистрационное испытание госпитального глюкометра Акку-Чек Информ II", the text of the abstract, keywords, citation, in the text of the article, and abbreviations. Information of the place of work has been updated: Center for Laboratory Diagnostics of the Russian Children Clinical Hospital, a Branch of the Pirogov Russian National Research Medical University. The publisher apologizes to readers and authors for the errors and is confident that the correction of errors will ensure the correct perception and interpretation of the results of the study described in the text

Characterization of Zoobenthos and Export of Biomass and Polyunsaturated Fatty Acids due to Emergence of Midges (Diptera, Chironomidae) from Three Saline Lakes of South Siberia

В течение двух вегетационных сезонов определяли таксономический состав, численность, биомассу зообентоса трех соленых озер: Шира, Шунет и Учум, расположенных в аридных степях Южной Сибири. Мы также оценили продукцию, потенциальный экспорт биомассы и физиологически ценных омега‑3 полиненасыщенных жирных кислот (ПНЖК) на сушу при вылете комаров-звонцов (Diptera, Chironomidae). Зообентосные сообщества изученных водоемов характеризовались низким таксономическим разнообразием и были представлены в основном личинками насекомых сем. Chironomidae и Ceratopogonidae, а также рачками Gammarus lacustris в озерах Шира и Шунет. В целом таксономический состав, численность и продуктивность изученных сообществ амфибионтных насекомых существенно различались. В оз. Шира доминантами являлись личинки Polypedilum bicrenatum, Сhironomus nigrifrons и Glyptotendipes salinus. В оз. Шунет основную часть численности сообщества обеспечивали личинки рода Procladius и Chironomus salinarius, наряду с P. bicrenatum. Бентос оз. Учум был представлен личинками рода Procladius, подсем. Orthocladiinae и сем. Ceratopogonidae. Продукция хирономид озер Шира, Шунет и Учум за период 30 дней составила в среднем 16,1 ± 4,1, 45,6 ± 13,6 и 9,6 ± 4,6 г сырой массы / м2, соответственно, увеличиваясь с ростом индекса Е. В. Балушкиной, оценивающего степень загрязненности воды. Потенциальный экспорт биомассы имаго хирономид из озер колебался от 0,6 до 3,1 г сырой массы / м2 акватории в год. Величина продуктивности и экспорта биомассы на сушу, вероятно, определялась количеством пищи (органического вещества) в донных отложениях. Имаго Glyptotendipes, вылетающие из озер Шунет и Шира, и имаго Orthocladiinae, роившиеся близ озера Учум, имели близкие величины содержания ПНЖК на единицу сырой массы. Таким образом, продуктивность, а не таксономический состав хирономидного сообщества, может быть более важным фактором при экспорте ПНЖК из соленых озерDuring two growing seasons, we studied the biomass, the number, and the species composition of zoobenthos in three saline lakes, Shira, Shunet, and Uchum, located in arid steppe of South Siberia, Russia. We also estimated productivity and export of biomass and physiologically significant omega‑3 polyunsaturated fatty acids (PUFAs) associated with the emergence of amphibiotic insects from these lakes. All zoobenthic communities had low taxonomic diversity with insect larvae of Chironomidae and Ceratopogonidae families and amphipod Gammarus lacustris constituting their major portion. Overall taxonomic composition and productivity of the lakes differed considerably. Among amphibiotic insects, larvae of Polypedilum bicrenatum, Сhironomus nigrifrons, and Glyptotendipes salinus were the most abundant in Lake Shira. In Lake Shunet, in addition to the dominant P. bicrenatum, zoobenthos was mainly represented by larvae of Chironomus salinarius and two Procladius species. Benthos of Lake Uchum was distinctly dominated by the Procladius genus, Orthocladiinae subfamily, and Ceratopogonidae family larvae. Production of chironomids in Shira, Shunet, and Uchum was 16.1 ± 4.1, 45.6 ± 13.6, and 9.6±4.6 g wet weight / m2 for 30 days, respectively, increasing with an increase in E. V. Balushkina’s index, which estimates water quality. Potential export of chironomid biomass ranged from 0.6 to 3.1 g wet weight / m2 of aquatic area per year. We suggested that productivity and biomass export were related with the quantity of food (organic matter) in the sediments. Glyptotendipes adults, which emerged from Lakes Shunet and Shira, and Orthocladiinae adults, which emerged from Lake Uchum, had similar contents of omega‑3 PUFAs per unit of wet weight. Thus, productivity rather than taxonomic composition of chironomid communities might be a more important factor for export of PUFAs from saline lake

Core Proteome of the Minimal Cell: Comparative Proteomics of Three Mollicute Species

Mollicutes (mycoplasmas) have been recognized as highly evolved prokaryotes with an extremely small genome size and very limited coding capacity. Thus, they may serve as a model of a ‘minimal cell’: a cell with the lowest possible number of genes yet capable of autonomous self-replication. We present the results of a comparative analysis of proteomes of three mycoplasma species: A. laidlawii, M. gallisepticum, and M. mobile. The core proteome components found in the three mycoplasma species are involved in fundamental cellular processes which are necessary for the free living of cells. They include replication, transcription, translation, and minimal metabolism. The members of the proteome core seem to be tightly interconnected with a number of interactions forming core interactome whether or not additional species-specific proteins are located on the periphery. We also obtained a genome core of the respective organisms and compared it with the proteome core. It was found that the genome core encodes 73 more proteins than the proteome core. Apart of proteins which may not be identified due to technical limitations, there are 24 proteins that seem to not be expressed under the optimal conditions

Derivatives of 9-phosphorylated acridine as butyrylcholinesterase inhibitors with antioxidant activity and the ability to inhibit β-amyloid self-aggregation: potential therapeutic agents for Alzheimer’s disease

We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ42) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results. All new compounds weakly inhibited AChE and off-target CES. Dihydroacridines with aryl substituents in the phosphoryl moiety inhibited BChE; the most active were the dibenzyloxy derivative 1d and its diphenethyl bioisostere 1e (IC50 = 2.90 ± 0.23 µM and 3.22 ± 0.25 µM, respectively). Only one acridine, 2d, an analog of dihydroacridine, 1d, was an effective BChE inhibitor (IC50 = 6.90 ± 0.55 μM), consistent with docking results. Dihydroacridines inhibited Aβ42 self-aggregation; 1d and 1e were the most active (58.9% ± 4.7% and 46.9% ± 4.2%, respectively). All dihydroacridines 1 demonstrated high ABTS•+-scavenging and iron-reducing activities comparable to Trolox, but acridines 2 were almost inactive. Observed features were well explained by quantum-chemical calculations. ADMET parameters calculated for all compounds predicted favorable intestinal absorption, good blood–brain barrier permeability, and low cardiac toxicity. Overall, the best results were obtained for two dihydroacridine derivatives 1d and 1e with dibenzyloxy and diphenethyl substituents in the phosphoryl moiety. These compounds displayed high inhibition of BChE activity and Aβ42 self-aggregation, high antioxidant activity, and favorable predicted ADMET profiles. Therefore, we consider 1d and 1e as lead compounds for further in-depth studies as potential anti-AD preparations

Practical recommendations for choosing an immunobiological preparation for the treatment of severe bronchial asthma of T2-endotype

Biological therapy of bronchial asthma (BA) is a modern method of treating severe forms of the disease, that are uncontrolled by traditional pharmacotherapeutic approaches. Currently, 5 monoclonal antibody (AT) preparations are registered in the world for the treatment of severe bronchial asthma (SBA) of the T2 endotype (T2-SBA) – antibodies, binding to immunoglobulin (Ig) E (anti-IgE – omalizumab), interleukin antagonists (IL)-5 (anti-IL-5 – mepolizumab, resizumab) and its receptor (anti-IL-5Rα – benralizumab), as well as antibodies, that selectively bind to the IL-4 and -13 receptor (anti-IL-4 /13Rα – dupilumab). The article presents data on the effectiveness of these drugs in relation to the key characteristics of SBA, formulates clinical and laboratory criteria, the study of which in real practice can potentially predict the likelihood of a clinical response to a particular type of biological therapy. An algorithm is proposed for choosing a targeted therapy strategy for patients with SBA, clinically associated with allergies, for patients with severe non-allergic eosinophilic BA and for patients with eosinophilic BA of a combined phenotype.Биологическая терапия бронхиальной астмы (БА) представляет собой современный метод лечения тяжелых форм заболевания, неконтролируемых при помощи традиционных фармакотерапевтических подходамов. В настоящее время в мире зарегистрированы 5 препаратов моноклональных антител (АТ) для лечения тяжелой бронхиальной астмы (ТБА) Т2-эндотипа (Т2-ТБА) – АТ, связывающие иммуноглобулин (Ig) Е (анти-IgE – омализумаб), антагонисты интерлейкина (IL)-5 (анти-IL-5 – меполизумаб, реслизумаб) и его рецептора (анти-IL-5Rα – бенрализумаб), а также АТ, избирательно связывающиеся с рецептором IL-4 и -13 (анти-IL-4/13Rα – дупилумаб). В статье приведены данные об эффективности указанных препаратов в отношении ключевых характеристик ТБА, сформулированы клинико-лабораторные критерии, при исследовании которых в реальной практике потенциально может быть предсказана вероятность клинического ответа на тот или иной вид биологической терапии. Предложен алгоритм выбора стратегии таргетной терапии для пациентов с ТБА, клинически ассоциированной с аллергией, для больных тяжелой неаллергической эозинофильной БА и для страдающих эозинофильной БА сочетанного фенотип