The clinical case of limb-girdle muscle dystrophy 2Q associated with myasthenic syndrome and lung damage

Limb-girdle muscle dystrophy 2Q is one of the rarest forms of plectinopathies and is represented by an isolated muscular dystrophic syndrome, according to two previously described literature reports. There are five forms of plectinopathies, including limb-girdle muscle dystrophy 2Q, are caused by mutations in the PLEC gene, the alternative splicing of which determines the synthesis of 9 isoforms of the plectin protein (1, 1a, 1b, 1c, 1d, 1e, 1f, 1g, 3) performing cytolinker function in the neuronal, epithelial and muscle tissue.The article describes the family observation of three sick siblings with the limb-girdle muscle dystrophy 2Q phenotype due to the presence of a new homozygous mutation (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) in the isoform 1f PLEC revealed by whole-exome sequencing. Clinical, electromyography, visualization and histopathological features of limb-girdle muscle dystrophy 2Q were analyzed in detail. The onset of clinical manifestations in all the described siblings was observed in early childhood with moderate weakness mainly in the pelvic girdle muscles and proximal lower limbs with minimal involvement of the muscles of the shoulder girdle. A distinctive aspect is the stagnation of the myodystrophic process until 20—21 years, followed by the progression and development of episodes of respiratory failure, as well as the formation of rigidity of the cervical, thoracic spine and moderate contracture of the Achilles tendons. Typical features are marked atrophy of paravertebral muscles with the formation of pterygoid scapula and the presence of hypertrophy m. gastrocnemius, m. quadriceps femoris, m. deltoideus and m. triceps brachii. Histopathological examination m. vastus lateralis revealed myodystrophic process without inflammatory infiltration, muscle fiber cytoskeleton disorganization resulted from the plectin loss.Electrocardiography signs of the early repolarization syndrome, focal cardiosclerosis and sinus tachycardia are described. For the first time, involvement in the pathological process of pulmonary tissue in the form of noninfectious bronchiolitis, atelectasis, and the development of the myasthenic syndrome causing episodes of respiratory failure resulted in the death of two described siblings aged 29 and 31 years. Discussed pathogenetic role of PLEC 1f isoform in the development of described syndromes, expands understanding of rare nosology limb-girdle muscle dystrophy 2Q

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

A multidisciplinary approach identifies novel biochemical activities involved in the synthesisof C. elegans bile acid-like steroids, which act as hormones that regulate sterol metabolism and longevity

Характеристика лямблиоза и энтеробиоза у детей Астраханской области

Purpose: assessment of the clinical and epidemiological situation of current invasions in children of the Astrakhan region. 315 outpatient cards of children were analyzed in 2016.The diagnosis of Giardiasis was made to 151 children, the diagnosis of Enterobiasis — 164. The age of all observed children ranged from 9 months to 17 years. The largest part was made up of children aged 3 to 14 years of age — 80.3%, among them enterobiasis was identified — in 46.7%, giardiasis — in 33.6% of cases. Most of the children  — 90.5% were from organized groups (they attended preschool institutions or school). The reasons for the examination of all children were varied. Some children — 63.5% went to the doctor with complaints  or clinical symptoms. Another part of the children — 33% of the diagnosis was made as a result of preventive examinations.In most cases — 78.7% various bad habits were identified. Thus, geophagy (the habit of eating the earth) was noted in 33.3% of children, and onigophagy (the habit of biting the nails) in 24.8%. In 21.3% of cases, bad habits were absent. Contact with pets was established in 22.9% of children. According to the ultrasound, most children with giardiasis (83.8%) had pathology (reactive changes of the pancreas, liver, gallbladder dyskinesia, etc.)In case of giardiasis niferator, albendazole was administered. In case of enterobiasis albendazole, pyrantel, and mebendazole were administered in age dosages. After antiparasitic treatment, in 91.4% of cases, the clinical symptoms of the disease completely disappeared, with giardiasis — in 85.4%, with enterobiasis — in 97% of cases.In 1.3% of children with giardiasis, after several courses of antiparasitic drugs, Giardia was found in feces in the absence of complaints and clinical symptoms, indicating a possible Giardia carrier parasite in children.С целью оценки клинико-эпидемиологической ситуации по актуальным инвазиям у детей Астраханской области было проанализировано 315 амбулаторных карт детей, обратившихся в 2016  г. Диагноз Лямблиоз был поставлен 151 ребенку, диагноз Энтеробиоз — 164.Возраст всех наблюдаемых детей составлял от 9 месяцев до 17 лет. Наибольшую часть составили дети в возрасте от 3 до 14 лет жизни — 80,3%, среди них энтеробиоз был выявлен в 46,7%, лямблиоз — в 33,6% случаев. Большинство детей — 90,5% были из организованных коллективов (посещали  детские дошкольные учреждения или школу). Причины обследования всех детей были разнообразными.  Часть  детей  — 63,5% обратились к специалисту в связи с наличием у них тех или иных клинических симптомов и жалоб. Другой части  детей  — 33% диагноз был выставлен в результате профилактических осмотров.В большинстве  случаев — 78,7% были выявлены различные вредные привычки. Так, геофагия (привычка есть землю) отмечалась у 33,3% детей, а онигофагия (привычка грызть ногти) — у 24,8%. В 21,3% случаев вредные привычки отсутствовали. Котакт с домашними животными был установлен  у 22,9% детей. По данным УЗИ, у большинства детей с лямблиозом (83,8%) отмечалась патология (реактивные изменения поджелудочной железы, печени, дискинезия желчного пузыря и др.).В качестве антипаразитарной  терапии при лямблиозе назначался нифуратель, альбендазол, при энтеробиозе — альбендазол, пирантел и мебендазол в возрастных дозировках. После лечения в 91,4% случаев клинические симптомы заболевания полностью исчезли, при лямблиозе — в 85,4%, при энтеробиозе — в 97% случаев.У 1,3% детей с лямблиозом после нескольких курсов антипаразитарными препаратами обнаруживались лямблии в фекалиях при отсутствии жалоб и клинических симптомов, что свидетельствует о возможном паразитоносительстве лямблий у детей

Клинический случай поясно-конечностной мышечной дистрофии 2Q, ассоциированной с миастеническим синдромом и поражением легких

Limb-girdle muscle dystrophy 2Q is one of the rarest forms of plectinopathies and is represented by an isolated muscular dystrophic syndrome, according to two previously described literature reports. There are five forms of plectinopathies, including limb-girdle muscle dystrophy 2Q, are caused by mutations in the PLEC gene, the alternative splicing of which determines the synthesis of 9 isoforms of the plectin protein (1, 1a, 1b, 1c, 1d, 1e, 1f, 1g, 3) performing cytolinker function in the neuronal, epithelial and muscle tissue.The article describes the family observation of three sick siblings with the limb-girdle muscle dystrophy 2Q phenotype due to the presence of a new homozygous mutation (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) in the isoform 1f PLEC revealed by whole-exome sequencing. Clinical, electromyography, visualization and histopathological features of limb-girdle muscle dystrophy 2Q were analyzed in detail. The onset of clinical manifestations in all the described siblings was observed in early childhood with moderate weakness mainly in the pelvic girdle muscles and proximal lower limbs with minimal involvement of the muscles of the shoulder girdle. A distinctive aspect is the stagnation of the myodystrophic process until 20—21 years, followed by the progression and development of episodes of respiratory failure, as well as the formation of rigidity of the cervical, thoracic spine and moderate contracture of the Achilles tendons. Typical features are marked atrophy of paravertebral muscles with the formation of pterygoid scapula and the presence of hypertrophy m. gastrocnemius, m. quadriceps femoris, m. deltoideus and m. triceps brachii. Histopathological examination m. vastus lateralis revealed myodystrophic process without inflammatory infiltration, muscle fiber cytoskeleton disorganization resulted from the plectin loss.Electrocardiography signs of the early repolarization syndrome, focal cardiosclerosis and sinus tachycardia are described. For the first time, involvement in the pathological process of pulmonary tissue in the form of noninfectious bronchiolitis, atelectasis, and the development of the myasthenic syndrome causing episodes of respiratory failure resulted in the death of two described siblings aged 29 and 31 years. Discussed pathogenetic role of PLEC 1f isoform in the development of described syndromes, expands understanding of rare nosology limb-girdle muscle dystrophy 2Q.Поясно-конечностная мышечная дистрофия 2Q является одной из наиболее редких форм плектинопатий и проявляется изолированным мышечным дистрофическим синдромом согласно двум ранее представленным в литературе описаниям. Пять существующих форм плектинопатий, в том числе поясно-конечностная мышечная дистрофия 2Q, обусловлены мутациями в гене PLEC, альтернативный сплайсинг которого определяет синтез 9 изоформ белка плектина (1, 1а, 1b, 1c, 1d, 1е, 1f,1g, 3), выполняющих цитолинкерную функцию в нейрональной, эпителиальной и мышечной тканях.В статье представлено описание семейного наблюдения 3 больных сибсов с поясно-конечностной мышечной дистрофией 2Q, обусловленного наличием новой гомозиготной мутации (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) в изоформе 1f гена PLEC, выявленной с помощью полноэкзомного секвенирования. Детально проанализированы клинические, электронейромиографические, визуализационные и патогистологические особенности поясно-конечностной мышечной дистрофии 2Q. Дебют клинических проявлений у всех описанных членов семьи наблюдался в раннем детском возрасте в виде умеренной слабости преимущественно мышц тазового пояса и проксимальных отделов ног с минимальным вовлечением мышц плечевого пояса. Отличительным аспектом является стагнация миодистрофического процесса до 20—21 года с последующим прогрессированием и развитием эпизодов дыхательной недостаточности, а также формированием ригидности шейного, грудного отдела позвоночника и умеренной контрактуры ахилловых сухожилий. Характерными являются выраженная атрофия mm. paravertebralis с формированием крыловидных лопаток и наличие гипертрофии m. gastrocnemius, m. quadriceps femoris, m. deltoideus и m. triceps brachii. Патогистологическое исследование m. vastus lateralis отражает наличие миодистрофического процесса без воспалительной инфильтрации, дезорганизацию цитоскелета мышечных волокон и утрату плектина. Описаны электрокардиографические признаки синдрома ранней реполяризации, очагового кардиосклероза и синусовой тахикардии. Впервые в литературе представлено сочетание пояс-но-конечностной мышечной дистрофии 2Q с поражением легких в виде неинфекционного бронхиолита, ателектазов и развитием миастенического синдрома, обусловливающими эпизоды дыхательной недостаточности и повлекшие смерть 2 описываемых сибсов в возрасте 29 и 31 года. Обсуждаемое патогенетическое значение 1f-изоформы плектина в развитии описанных синдромов позволяет расширить представление о редкой нозологии — поясно-конечностной мышечной дистрофии 2Q

Магнитно-резонансный паттерн изменений мышц тазового пояса и нижних конечностей у пациентов с дисферлинопатиями

Introduction. Dysferlinopathy is a phenotypically heterogeneous group of hereditary muscular dystrophies caused by mutations in the dysferlin gene (DYSF). Debut in adolescence, predominantly in physically developed patients, combined with the often subacute development of hypercreatine phosphatemia and edematous muscle changes in MRI often leads to diagnostic errors. Purpose of the study: to determine the most typical MRI pattern of muscle damage of the pelvic girdle and lower limb in patients with dysferlinopathy. Materials and methods. 40 people were examined, among which 20 patients with a clinical picture of dysferlinopathy with an equal ratio of Miyoshi phenotypes and LGMD and an average age of 35 (24; 44) years. Comprehensive clinical and instrumental examination included neurological, electroneuromyographic and molecular genetic studies (NGS). Magnetic resonance imaging of the muscles of the pelvic girdle and lower limb was performed in 20 patients and a control group equivalent in sex and age. Results. The use of semi-quantitative MRI indicators — relative signal intensity — D (D=T1 muscle (STIR) / T1 (STIR) subcutaneous fat layer) made it possible to formulate the characteristics of a common typical MRI pattern of muscle involvement in dysferlinopathy. An increase in the intensity of the relative signal D, T1 in the rear muscle group of the thighs and lower legs, indicating fatty infiltration was observed most frequently, while a decrease in D, STIR values was observed in the anterior and medial muscles of the thighs, reflecting the presence of edema of the previous fatty degeneration of these muscles. Conclusion. In addition to the general idea of muscle involvement in dysferlinopathy, it is advisable to consider the «early», «typical / completed» and «late» MRI patterns of dysferlinopathy that increase the effectiveness of the diagnosis of this disease. In the differential diagnosis of the Miyoshi phenotype from LGMD, one should focus on maintaining normal values of D, T1 from m. gluteus maximus and m. popliteus at all stages of the disease.Введение. Дисферлинопатии — это фенотипически гетерогенная группа наследственных мышечных дистрофий, обусловленных мутациями в гене дисферлина (DYSF). Дебют в подростковом возрасте преимущественно у физически развитых пациентов в сочетании с часто подострым повышением сывороточной креатинфосфокиназы и отечными изменениями мышц при магнитно-резонансной томографии (МРТ) часто приводит к диагностическим ошибкам. Цель исследования: определить наиболее типичный магнитно-резонансный (МР) паттерн поражения мышц тазового пояса и нижних конечностей у пациентов с дисферлинопатиями. Материалы и методы. Обследовано 40 человек, среди которых 20 пациентов с клинической картиной дисферлинопатий с равным соотношением фенотипов Миоши и поясно-конечностной мышечной дистрофией (ПКМД) и средним возрастом — 35 (24; 44) лет. Комплексное клинико-инструментальное обследование включало неврологическое, электронейромиографическое и молекулярно-генетическое исследование (NGS). Магнитно-резонансная томография мышц тазового пояса и нижних конечностей проведена 20 пациентам и эквивалентной по полу и возрасту контрольной группе. Результаты исследований. Использование полуколичественных МР-показателей — относительной интенсивности сигнала — D (D=Т1 мышцы (STIR) /Т1(STIR) подкожно-жирового слоя) позволило сформулировать характеристики общего типичного МР-паттерна вовлечения мышц при дисферлинопатиях. Наиболее часто отмечалось повышение интенсивности относительного сигнала D, Т1-ВИ в задней группе мышц бедер и голеней, свидетельствующее о жировой инфильтрации, тогда как снижение величин D, STIR наблюдалось в передних и медиальных мышцах бедер, что отражало наличие отека, предшествующего замещению жировой тканью данных мышц. Заключение. Кроме общего представления о вовлечении мышц при дисферлинопатиях, целесообразно рассматривать «ранний», «типичный/завершенный» и «поздний» МР-паттерны дисферлинопатий, повышающие эффективность диагностики данного заболевания. В дифференциальной диагностике фенотипа Миоши от ПКМД следует ориентироваться на сохранение нормальных величин D, Т1-ВИ от m. gluteus maximus и m. popliteus на всех стадиях заболевания

The Term “Rules-based International Order” in International Legal Discourses

INTRODUCTION. The term “rules-based order” is increasingly referred to in speeches within many international forums as well as declared from national political tribunes. The initial question is whether this notion is of purely political nature (since it is not used in the UN Charter or in other universal international conventions and this term is not relied upon by the International Court of Justice or by the UN International Law Commission). On the other hand, with the popularization of such a political discourse, the frequent usage of this term by representatives of some states (not only of Western States, but also of China, for example) can affect international law. The very application of this term definitely provokes a splash of other questions. How does the term “rules-based order” correlate with the universally recognized term “international legal order”? Does the idea to use the term “rules-based order” have substantive legal grounds? Which rules in concreto1 are meant by the term? Who and how creates these rules? What is the nature of these rules – are they rules of national law and if so – national rules of what State? If these are rules of international law – why is it not reflected in the term? Due to the attractive wording the concept gets widespread, but lacking a common understanding of its content, everyone might put a different meaning into the concept. Does it result in the fact that some officials, representing states, become politically entitled with the right to abuse the international legal order as it is established by modern international law? This research examines these theoretic aspects of the concept “rules-based order”, taking into account that in the context of international relations it may be referred to also as “rules-based international order”. An additional question to answer is whether the concept might be regarded as one of the numerous attempts to adapt the current international law to new challenges.MATERIALS AND METHODS. The research paper is based on the analysis of numerous statements of representatives of states, in which their attitude to the “rules-based order” concept is manifested, positive and critical remarks relating to the concept made by international lawyers, as well as other research papers of Russian and foreign international scholars. The methodological instruments include general scientific and special methods, among them the historical method, methods of formal logic, analysis, synthesis, as well as systemic, comparative legal methods.RESEARCH RESULTS. Although the above-noted questions about the legal meaning of the term “rulesbased order” have arisen only in recent years mainly in the context of the anti-Russian rhetoric of Western politicians, the term has been used much earlier at different levels in a wide variety of topics. The question of inconsistent perceptions of this term is another reflection of a more general problem of weakening or strengthening the universal legally binding international order. One of the appropriate interpretive versions of this concept might be that “rules-based order” means first and foremost the world order which is based on norms of international law (which are mandatory as well known), and on applicable non-binding international rules containing a normative element, such as international rules provided in the documents of intergovernmental organizations and conferences, interstate political arrangements, and other mutually accepted rules, formed in the contemporary practice of international relations. This interpretation allows to bring the concept in line with modern international law. Nevertheless, even within such interpretation, it is necessary to respect the distinction between the norms of international law, which are binding, and other rules, which do not create State’s obligations under international law. Thus, unilateral or “blocking” imposition of values of one State on other States under the guise of rules on which, according to the first State, the world order is based, will not be allowed.DISCUSSION AND CONCLUSIONS. If another interpretation prevails, the “rules-based order” concept may have a negative impact on the existing international legal order insofar as it “washes out” the established legitimate procedures of international law-making, thus rejecting traditional international values of legal stability and diminishing the role of international law in international relations. Such scenario would not only multiply legal uncertainly and even unreasonable expectations among the participants of the international processes, but also might lead to undermining the very fundamentals of modern international law based on the UN Charter. The latter in its turn will inevitably lead to the global legal instability and will dramatically increase the risks of World War III. At the moment, the frequent abuse of the term “rules-based order” by the representatives of the NATO countries in support of their politically motivated statements, agreed upon only among them, impedes achievement of accepted understanding of the concept at the universal level, that might be consistent with international law

ENERGY EFFICIENT DESALINATOR

Objectives. The aim of the research is to develop a thin-film semiconductor thermoelectric heat pump of cylindrical shape for the desalination of sea water.Methods. To improve the efficiency of the desalination device, a  special thin-film semiconductor thermoelectric heat pump of  cylindrical shape is developed. The construction of the thin-film  semiconductor thermoelectric heat pump allows the flow rates of  incoming sea water and outflowing fresh water and brine to be  equalised by changing the geometric dimensions of the desalinator.  The cross-sectional area of the pipeline for incoming sea water is equal to the total area of outflowing fresh water and brine.Results. The use of thin-film semiconductor p- and n-type branches  in a thermo-module reduces their electrical resistance virtually to  zero and completely eliminates Joule's parasitic heat release. The  Peltier thermoelectric effect on heating and cooling is completely  preserved, bringing the efficiency of the heat pump to almost 100%, improving the energy-saving characteristics of the  desalinator as a whole. To further increase the efficiency of the  proposed desalinator, thermoelectric modules with radiation can be  used as thermoelectric devices.Conclusion. As a consequence of the creation of conditions of high rarefaction under which water will be converted to steam, which, at  20° C, is cold (as is the condensed distilled water), energy costs can  be reduced. In this case, the energy for heating and cooling is not  wasted; moreover, sterilisation is also achieved using the ultraviolet  radiation used in the thermoelectric devices, which, on the one hand, generate electromagnetic ultraviolet radiation, and, on the other, cooling. Such devices operate in optimal mode without heat  release. The desalination device can be used to produce fresh water and concentrated solutions from any aqueous solutions, including wastewater from industrial enterprises. The construction materials of the desalination device are environmentally friendly

Medical-Environmental Assessment and Forecasting of Socially Significant Pathology of the Population of the Republic of Dagestan

Aim. The environmental-epidemiological monitoring of socially significant pathology and its forecasting for the development of effective preventive measures and environmental quality management methods in the Republic of Dagestan.Material and Methods. An epidemiological analysis of public health indicators was carried out in 41 municipalities and 10 urban districts of the Republic of Dagestan. This was carried out through current and retrospective analysis of regional health indicators, medical-geographical and mathematical statistical analysis. The data sources for the main indicators reflect the epidemiological situation in the Republic of Dagestan from 1997 to 2016.Results. An understanding of the status of the main epidemiological indicators of the condition of public health of the region's rural and urban population was obtained and future dynamics predicted. An integrated assessment of the well-being of the territory of the republic revealed areas and cities with adverse trends in public health in the main groups of socially significant and environmentally-related pathologies.Conclusions. An integrated assessment of the state of well-being in the Republic of Dagestan by groups of epidemiological indicators of general morbidity, general morbidity of various age groups of the population, socially significant and environmentally-caused morbidity, as well as a forecast of their dynamics, revealed adverse trends in public health in rural populations of Tsuntinskiy, Akhtynskiy, Gunibskiy, Kulinskiy, Tabasaranskiy, Nogayskiy, Novolakskiy, Suleiman-Stalskiy, Khasavyurtskiy, Tarumovskiy districts and of the cities of Kaspiysk, Dagestanskie Ogni, Makhachkala and Kizilyurt. An analysis of the sources of supplies of drinking water revealed a positive correlation between heavy metals content and adverse trends in socially significant pathology in the regions of Northern Dagestan

Ecological and geographic influence on the outcome of real treatment of rheumatoid arthritis

The use of disease-modifying antirheumatic drugs in outpatient practice is insufficient, which ultimately leads to the rapid progression of rheumatoid arthritis (RA), an increase in the risk of developing cardiovascular complications and a decrease in the life expectancy of patients.Использование болезнь-модифицирующих антиревматических препаратов в амбулаторной практике является недостаточным, что в конечном итоге приводит к быстрому прогрессированию ревматоидного артрита (РА), увеличению риска развития сердечно-сосудистых осложнений и уменьшению продолжительности жизни больных