Association of rs12722 COL5A1gene variation with risk of anterior cruciate ligament rupture

Objective: to determine the influence of rs12722 (C/T)COL5A1 gene variation on ACL rupture in Europeans of Ural region of Russia. Materials and methods: the case group included 173 patients with diagnosed anterior cruciate ligament (ACL) ruptures; control group included 370 asymptomatic persons. Both groups were similar on a sex, age, growth, weight and BMI. Results: the following genotypic frequencies were observed (in %): case group - a T/T of 34,1, C/T of 46,8, C/C of 19,1; control group - a T/T of 25,4, C/T of 50,8, C/C 23,8. Genotypic frequencies in both groups met Hardy-Weinberg equilibrium. Significant difference of allelic frequencies was revealed between two groups (p = 0,039). Persons with a T/T genotype had a significantly increased risk of ACL ruptures in comparison with persons with C/T + C/C genotypes (x2 = 4,408, p = 0,036, OR = 1,52, 95% confidence interval: 1,027 - 2,249). Conclusions: this is the first study that shown the association of rs12722 COL5A1 gene variation with risk of an ACL rupture in Russian population

Elite athletes' genetic predisposition for altered risk of complex metabolic traits

BACKGROUND: Genetic variants may predispose humans to elevated risk of common metabolic morbidities such as obesity and Type 2 Diabetes (T2D). Some of these variants have also been shown to influence elite athletic performance and the response to exercise training. We compared the genotype distribution of five genetic Single Nucleotide Polymorphisms (SNPs) known to be associated with obesity and obesity co-morbidities (IGF2BP2 rs4402960, LPL rs320, LPL rs328, KCJN rs5219, and MTHFR rs1801133) between athletes (all male, n = 461; endurance athletes n = 254, sprint/power athletes n = 207), and controls (all male, n = 544) in Polish and Russian samples. We also examined the association between these SNPs and the athletes’ competition level (‘elite’ and ‘national’ level). Genotypes were analysed by Single-Base Extension and Real-Time PCR. Multinomial logistic regression analyses were conducted to assess the association between genotypes and athletic status/competition level. RESULTS: IGF2BP2 rs4402960 and LPL rs320 were significantly associated with athletic status; sprint/power athletes were twice more likely to have the IGF2BP2 rs4402960 risk (T) allele compared to endurance athletes (OR = 2.11, 95% CI = 1.03-4.30, P <0.041), and non-athletic controls were significantly less likely to have the T allele compared to sprint/power athletes (OR = 0.62, 95% CI =0.43-0.89, P <0.0009). The control group was significantly more likely to have the LPL rs320 risk (G) allele compared to endurance athletes (OR = 1.26, 95% CI = 1.05-1.52, P <0.013). Hence, endurance athletes were the “protected” group being significantly (p < 0.05) less likely to have the risk allele compared to sprint/power athletes (IGF2BP2 rs4402960) and significantly (p < 0.05) less likely to have the risk allele compared to controls (LPL rs320). The other 3 SNPs did not show significant differences between the study groups. CONCLUSIONS: Male endurance athletes are less likely to have the metabolic risk alleles of IGF2BP2 rs4402960 and LPL rs320, compared to sprint/power athletes and controls, respectively. These results suggest that some SNPs across the human genome have a dual effect and may predispose endurance athletes to reduced risk of developing metabolic morbidities, whereas sprint/power athletes might be predisposed to elevated risk

Тромботическая окклюзия у пациентов с острым ишемическим инсультом

Currently, reperfusion therapy is the main method of treating patients with ischemic stroke (IS). The safety and efficacy of systemic thrombolytic therapy with a recombinant tissue plasminogen activator in patients with IS within 3 hours, and then 4.5 hours after the onset of symptoms of the disease was demonstrated in the NINDS (1995) and ECASS III (2008) studies. In 2018, based on the results of five studies, clear indications were formulated for performing thrombectomy (TE) in patients with IS, which involve the detection of thrombosis of a large stroke-associated artery. Given the continuous growth in the number of the adult population, which constitutes the bulk of patients with IS, information on the prevalence of patients with thrombotic occlusion of cerebral arteries, who are potential candidates for TE, may be important for regional vascular centers.Aim of study. To describe IS patients admitted within the 6-hour “therapeutic window”.Materials and methods. The study included 145 patients with cerebral IS who were admitted within the first 6 hours after the onset of symptoms of the disease. All patients underwent computed tomographic (CT) angiography in order to verify the occlusion of the cerebral artery.Results. In our study, a correlation was established between the NIHSS severity of IS and the likelihood of verification of stroke-related artery thrombosis by CT angiography, but in 32.6% of patients with severe stroke (NIHSS at least score 14), no thrombotic occlusion was detected, and in 13% of patients with a clinic of mild acute cerebrovascular accident (NIHSS no more than 6), on the contrary, thrombotic occlusion was detected. Mortality in patients with verified thrombotic occlusion of the cerebral artery was higher than in patients without it (38% versus 10.5%, p&lt;0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p&gt;&lt;0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p &gt;&lt;0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively). CONCLUSION 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. Keywords: ischemic stroke, reperfusion therapy, cerebral artery thrombosis, cryptogenic stroke&gt;˂0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p˂0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p˂0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively).Conclusion. 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. В настоящее время реперфузионная терапия является основным методом лечения пациентов с ишемическим инсультом (ИИ). Безопасность и эффективность системной тромболитической терапии при помощи рекомбинантного тканевого активатора плазминогена у пациентов с ИИ в пределах 3 часов, а в последующем 4,5 часа от начала симптомов заболевания была продемонстрирована в исследованиях NINDS (1995) и ECASS III (2008). В 2018 году, основываясь на результатах пяти исследований, были сформулированы четкие показания для выполнения тромбэктомии (ТЭ) у пациентов с ИИ, которые подразумевают выявление тромбоза крупной инсульт-связанной артерии. В условиях непрерывного роста числа взрослого населения, составляющего основную массу пациентов с ИИ, информация о распространенности больных с тромботической окклюзией церебральных артерий, являющихся потенциальными претендентами для выполнения ТЭ, может быть важной для региональных сосудистых центров.Цель исследования. Охарактеризовать пациентов с ИИ, поступающих в 6-часовом «терапевтическом окне».Материал и методы. В исследование включены 145 пациентов с церебральным ИИ, поступивших в первые 6 часов от начала развития симптомов заболевания. Всем пациентам с целью верификации окклюзии церебральной артерии выполняли компьютерную томографическую (КТ) ангиографию.Результаты. В нашем исследовании была установлена корреляция между тяжестью ИИ по шкале NIHSS и вероятностью верификации при помощи КТ-ангиографии тромбоза инсульт-связанной артерии, но у 32,6% пациентов с клиникой тяжелого инсульта (NIHSS не менее 14 баллов) не было выявлено тромботической окклюзии, а у 13% пациентов с клиникой легко протекающего острого нарушения мозгового кровообращения (NIHSS не более 6 баллов), напротив, тромботическая окклюзия была выявлена. Летальность у пациентов с верифицированной тромботической окклюзией церебральной артерии была статистически значимо выше, чем у пациентов без таковой (38% против 10,5%, р&lt;0,001). Столь значительная разница между показателями летальности была обусловлена исходно более тяжелым инсультом (оценка по NIHSS при поступлении 17 [10; 23] против 5 [2; 10], p&gt;&lt;0,001, статистически значимо) у больных с тромботической окклюзией инсульт-связанной артерии, а также большей частотой статистически значимых грубых расстройств глотания (30% против 9,5%, p&gt;&lt;0,002, статистически значимо), являющихся фактором риска развития пневмонии и такого коморбидного фона, как хроническая болезнь почек и фибрилляция предсердий (30% против 13,7%, р=0,018 и 58% против 29,5%, р=0,001 соответственно). Выводы 1. Тромбоз церебральной инсульт-связанной артерии выявлен у 34,5% пациентов с ишемическим инсультом, поступающих в первые 6 часов от начала заболевания. 2. Основной причиной невыполнения тромбэктомии у пациентов с ишемическим инсультом, поступивших в 6-часовом «терапевтическом окне», является отсутствие верификации тромбоза инсульт-связанной артерии при помощи компьютерной томографической ангиографии. По причине тромбоза другой локализации (отличной от тромбоза внутренней сонной артерии и/или М1 сегмента средней мозговой артерии) 10% пациентов с верифицированным тромбозом не соответствовали существующим в настоящее время критериям отбора для выполнения тромбэктомии. Ключевые слова: ишемический инсульт, реперфузионная терапия, тромбоз мозговой артерии, криптогенный инсульт&gt;˂ 0,001). Столь значительная разница между показателями летальности была обусловлена исходно более тяжелым инсультом (оценка по NIHSS при поступлении 17 [10; 23] против 5 [2; 10], p˂ 0,001, статистически значимо) у больных с тромботической окклюзией инсульт-связанной артерии, а также большей частотой статистически значимых грубых расстройств глотания (30% против 9,5%, p˂ 0,002, статистически значимо), являющихся фактором риска развития пневмонии и такого коморбидного фона, как хроническая болезнь почек и фибрилляция предсердий (30% против 13,7%, р=0,018 и 58% против 29,5%, р=0,001 соответственно).Выводы. 1. Тромбоз церебральной инсульт-связанной артерии выявлен у 34,5% пациентов с ишемическим инсультом, поступающих в первые 6 часов от начала заболевания. 2. Основной причиной невыполнения тромбэктомии у пациентов с ишемическим инсультом, поступивших в 6-часовом «терапевтическом окне», является отсутствие верификации тромбоза инсульт-связанной артерии при помощи компьютерной томографической ангиографии. По причине тромбоза другой локализации (отличной от тромбоза внутренней сонной артерии и/или М1 сегмента средней мозговой артерии) 10% пациентов с верифицированным тромбозом не соответствовали существующим в настоящее время критериям отбора для выполнения тромбэктомии.

Diagnosis of microaspiration syndrome in children with bronchial asthma using non-invasive methods

For the purpose of identification of a microaspiration syndrome among children as a possible reason of development of bronchial asthma we suggested a number of noninvasive methods: questioning, lactose identification, average capacity of lipophages in the induced sputum of a bronchial tree within 21 patients from 10 to 17 years. The conducted research resulted in 38% of children with bronchial asthma had a high probability of having of a microaspiration syndrome. The recommended research methods have been proved efficient.С целью выявления микроаспирационного синдрома у детей, как возможной причины развития бронхиальной астмы нами были предложены ряд неинвазивных методов: анкетирование, выявление лактозы, средняя нагруженность липофагов в индуцированной мокроте бронхиального дерева у 21 пациента от 10 до 17 лет. В результате проведенного исследования 38% детей с бронхиальной астмой имели высокую вероятность наличия синдрома микроаспирации. Была доказана эффективность предложенных методов исследования

ПЕРВИЧНЫЕ РЕЗУЛЬТАТЫ АОРТО-БЕДРЕННОГО ШУНТИРОВАНИЯ С ПРИМЕНЕНИЕМ РОБОТ-АССИСТИРОВАННОЙ ХИРУРГИЧЕСКОЙ СИСТЕМЫ DA VINCI

Introduction. Robot surgery is one of the most high-demand and dynamic developing realms of medicine. It is widely used in urology, proctology, thoracic, cardiovascular surgery and gynecology. In February 2018 a robot surgery centre opened in Volga Federal District of the Russian Federation based on the clinic of the Bashkir State Medical University (city of Ufa).Materials and methods. The present paper demonstrates the first successful robot-assisted vascular operations within a master-class called "Aorto-Femoral Shunting with the use of robot-assisted surgical system Da Vinci".Results. Exemplified with three operations: two linear aorto-femoral shunting and lumbar sympathectomy demonstrate technical peculiarities and advantages of robot-assisted vascular surgery. The findings show positive short-term results of the performed surgical interference that combine minimal injury and blood loss which help to reduce hospital stay in an intensive therapy department and intestinal distention duration. These clinical effects enabled to provide early activization of patients and possibility to adequately correct nutritional status with enteral feeding. The above-mentioned advantages eventually resulted in reduction of post-operation stay of patients in in-patient department and of cost of treatment.Conclusion. Robot-assisted surgical system Da Vinci being the most cutting-edge in the realm of endoscopic surgery, enables to carry out operational interference with minimal blood loss and injury of tissues which helps to reduce postoperation and recovery periods. Введение. Роботическая хирургия — одна из самых востребованных и динамически развивающихся областей медицины, широко используемая в урологии, онкологии, проктологии, торакальной, сердечно-сосудистой хирургии и гинекологии. В феврале 2018 года состоялось открытие первого роботического центра хирургии в Приволжском федеральном округе Российской Федерации на базе Клиники Башкирского государственного медицинского университета (г. Уфа).Материалы и методы: в настоящей работе представлен первый опыт успешных робот-ассистированных сосудистых операций в рамках мастер-класса «Проведение аорто-бедренного шунтирования с применением роботассистированной хирургической системы Da Vinci».Результаты. На примере трех операций: двух линейных аорто-бедренных шунтирований и поясничной симпатэктомии показаны технические особенности и преимущества робот-ассистированной сосудистой хирургии. Продемонстрированы положительные ближайшие результаты проведенных хирургических вмешательств, сочетающих в себе минимальную травматичность и кровопотерю, способствующих сокращению пребывания пациентов в отделении интенсивной терапии и продолжительности пареза кишечника. Данные клинические эффекты позволили обеспечить раннюю активизацию пациентов и возможность адекватной коррекции нутритивного статуса энтеральным питанием. Указанные преимущества в итоге привели к сокращению послеоперационного пребывания пациентов в стационаре и стоимости лечения.Заключение: робот-ассистированная хирургическая система Da Vinci, являясь самой совершенной в области эндоскопической хирургии, позволяет проводить оперативное вмешательство с минимальной кровопотерей и травматизацией тканей, что способствует сокращению послеоперационного и восстановительного периодов.

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance.

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium

The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes

Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2). Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F-actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell