Resource function of conceptual and metacognitive abilities in adolescents with different forms of dysontogenesis.

This study investigated the level of conceptual and metacognitive abilities and their interaction in adolescents with different forms of dysontogenesis. The total sample (N= 173) included four groups of young adolescents (11-12 years old): with normal development, with infantile cerebral palsy (CP), with attention deficit hyperactivity disorder (ADHD), and with delayed intellectual development (DID). We measured the adolescents’ performance on tests of conceptual abilities (the use of categories at different grades of generalization, the discovery of abstract meaning and implicit connections between concepts) and metacognitive abilities (attention selectivity, as measured by Mtinsterberg’s test and the understanding of hidden pictures, and attention organization, as measured by indices of cognitive styles). The results showed, first, that in comparison with normal adolescents, the adolescents with CP and ADHD had a deficit of metacognitive abilities, but they did not differ in rates of conceptual abilities. As for adolescents with DID, even though they had lower rates of conceptual abilities and attention selectivity, they did not differ from the “norm” group on some indices of attention organization. Second, a tendency for the disintegration of conceptual and metacognitive abilities (as measured by correlation and factor analysis) was most clearly seen in the adolescents with ADHD and DID. The adolescents with CP and ADHD had conceptual (categorial and generative) abilities as a mental resource, and the adolescents with DID had metacognitive abilities as a mental resource. The resource function of conceptual and metacognitive abilities was determined not only by their level but also by the extent of their interaction (integration)

Value of determining the cerebrospinal fluid protein markers of amyloidosis and neurodegeneration in the diagnosis of vascular and neurodegenerative cognitive impairments

The article presents data on different forms of moderate cognitive impairments (MCI) and the specific features of their transformation to dementia. Cerebrospinal fluid (CSF) was investigated in 60 patients with the amnestic and neurodynamic types of MCI, in 15 patients with vascular dementia (VD), 50 patients with Alzheimer’s disease (AD), and 23 patients with mixed vascular and neurodegenerative dementia (MVND). The specific features of β-amyloid and τ-protein concentrations were established in the preclinical stages of dementia, which reflects the main components of the pathogenesis of neurodegeneration. In the amnestic form of MCI and AD, there was drastically decreased Aβ-42 and increased τ-protein levels in SCF. As cognitive impairments progressed, there was a rise in the concentration of τ-protein; its level correlated with the severity of dementia. In MND, the level of Aβ-42 was significantly reduced while the concentration of τ-protein was much increased; moreover, to a greater extent than in AD and VD. Cerebrovascular damage and neurodegeneration were related to each other and mutually worsened clinical and pathogenic effects

Bentho-pelagic relations in the deep-water part of the Okhotsk Sea by the data of stable isotopes С and N analysis

Composition, abundance, diet and trophic status are analyzed for dominant benthic and pelagic species in the deep-water Okhotsk Sea on the data collected in demersal and pelagic trawl surveys conducted by Pacific Fisheries Research Center (TINRO). Isotope composition of13С and15N is determined for tissues of 107 species of plankton, benthos, demersal fish, and cephalopods, which form a basis of pelagic and benthic communities. The carbon isotope content is significantly different between these groups: d13С ranges from -23.30 to -19.90 ‰ for zooplankton, from -18.90 to -13.33 ‰ for benthos, from -22.10 to -18.90 ‰ for fish (mean values), and from -20.08 to -15.75 ‰ for cephalopods. It depends mainly on proportion of pelagic and benthic food in their diet. Following to these values, 30 % of examined species of demersal fishes and cephalopods use resources of detritus food chain as the base of their diet. The range of d15N is from 6.79 ( Megayoldia thraciaeformis ), 6.88 ( Eucalanus bungii ) to 18.26 ‰ ( Molpadia roretzii ). Its highest level is observed for 4 species of benthic invertebrates and 8 species of demersal fishes on the continental slope characterized by high tropic level (≥5) and included to the bentho-pelagic food chain, that corresponds with their d13С values. Trophic relations in the deep-water Okhotsk Sea demonstrates high dependence between benthic and pelagiс communities, as far as many dominant species of pelagic and demersal nekton consume both benthic and pelagic food. Feeding about of 70 % of dominant species of demersal fishes and cephalopods is based on grazing rather than on detritus food

Новая мутация в гене TYMP: клинико-морфологическая характеристика пациента с синдромом MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G>T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.Синдром митохондриальной нейрогастроинтестинальной энцефаломиопатии – редкое (1–9:1000000, Orphanet, 2021) генетическое мультисистемное заболевание, обусловленное мутациями в ядерном гене TYMP, кодирующем фермент тимидинфосфорилазу.Представлены данные 13‑летнего наблюдения пациентки Д., 40 лет, с синдромом митохондриальной нейрогастроинтестинальной энцефаломиопатии, связанным с ранее не описанной миссенс‑заменой c.1301G>T (p.Gly434Val) в гене TYMP. Диагноз синдрома митохондриальной нейрогастроинтестинальной энцефаломиопатии был поставлен на основании клинических проявлений (дисфункция желудочно‑кишечного тракта, кахексия, блефароптоз, офтальмопарез, периферическая полинейропатия и лейкоэнцефалопатия), результатов электронейромиографии (демиелинизация с вторичной аксонопатией), а также повышения уровня дигидротимина в сыворотке крови при нормальных уровнях тимидина и дезоксиуридина. Патогистологическое исследование выявило атрофию продольного (наружного) мышечного слоя тонкой и толстой кишок и значимое уменьшение количества CD117+‑клеток (телоцитов), поражение скелетных мышц смешанного характера с преобладанием миогенного паттерна, а также деструкцию миелиновых оболочек периферических нервов. Исследование S100‑положительных вегетативных образований кишечной стенки не выявило патологических изменений. При гистохимическом исследовании не были обнаружены «рваные красные волокна», характерные для митохондриопатий. Трансмиссионная электронная микроскопия продемонстрировала наличие полиморфизма митохондрий кардиомиоцитов и мегаломитохондрий лейомиоцитов кишечника

Причины ложной диагностики полимиозита у пациентов с дисферлинопатией: клинический случай

Differential diagnosis of inflammatory myopathies with hereditary muscular dystrophies accompanied by a secondary inflammatory process is a time‑consuming clinical and pathomorphological task. In particular, false diagnosis of polymyositis in patients with dysferlinopathy reaches 25 % of cases.A 40‑year‑old female patient with a limb‑girdle phenotype of dysferlinopathy, initially diagnosed as polymyositis, is presented. The reasons that led to the erroneous diagnosis were: sporadic case; subacute onset; proximal muscle weakness; myalgia, which stopped on the glucocorticosteroid therapy; high levels of creatine phosphokinase (up to 17 times); the presence of lymphocytic‑macrophage infiltrate in the muscle biopsy and the absence of magnetic resonance imaging data in primary examination of the patient.The refractoriness of clinical and laboratory signs to complex immunosuppressive therapy was the reason for revising the muscle biopsy with typing of the inflammatory infiltrate. The predominantly unexpressed perivascular infiltrate was characterized by the predominance of macrophages and, to a lesser extent, CD4+, which indicated the secondary nature of the inflammation in the muscle observed in some hereditary muscular dystrophies. When conducting an immunohistochemical reaction, the absence of the dysferlin protein in the sarcoplasmic membrane was revealed.Whole‑exome sequencing (NGS) revealed a mutation in exon 39 of the DYSF gene (p.Gln1428Ter) in the heterozygous state, which leads to the appearance of a stop codon and premature termination of protein translation. MLPA method registered 3 copies of exons 18, 19, 20, 22, 24 of the DYSF gene.Thus, this clinical example reflects the main methodological errors and possible effects of immunosuppressive therapy in patients with dysferlinopathy.Дифференциальная диагностика воспалительных миопатий, сопровождающихся вторичным воспалительным процессом, с наследственными мышечными дистрофиями является сложной и трудоемкой клинико‑патоморфологической задачей. В частности, ложная диагностика полимиозита у пациентов с дисферлинопатией достигает 25 % случаев.Представлена пациентка 40 лет с поясно‑конечностным фенотипом дисферлинопатии, первично диагностированной как полимиозит. Причины, повлекшие ошибочную диагностику: спорадическое происхождение; подострый дебют; проксимальная мышечная слабость; миалгия, купировавшаяся на фоне глюкокортикостероидной терапии; повышение уровня креатинфосфокиназы (до 17 раз); наличие лимфоцитарно‑макрофагального инфильтрата в мышечном биоптате и отсутствие данных магнитно‑резонансной томографии при первичном обследовании.Рефрактерность клинико‑лабораторных признаков к комплексной иммуносупрессивной терапии послужила причиной пересмотра результатов биопсии мышцы с типированием воспалительного инфильтрата. Невыраженный, преимущественно периваскулярный инфильтрат характеризовался преобладанием макрофагов и, в меньшей степени, CD4+, что указывало на вторичный характер воспаления в мышечной ткани, наблюдаемого при некоторых наследственных мышечных дистрофиях. При проведении иммуногистохимической реакции выявлено отсутствие белка дисферлина в саркоплазматической мембране.В ходе полноэкзомного секвенирования (NGS) выявлена мутация в 39‑м экзоне гена DYSF (p.Gln1428Ter) в гетерозиготном состоянии, приводящая к появлению стоп‑кодона и преждевременной терминации трансляции белка. Методом MLPA зарегистрировано по 3 копии 18, 19, 20, 22, 24‑го экзонов гена DYSF. Клинический случай отражает основные ошибки оценки результатов обследования и эффективности иммуносупрессивной терапии у пациентов с дисферлинопатией

Anti-brane uplift instability from goldstino condensation

We investigate the possible appearance of composite states of the goldstino in models with four-dimensional non-linear supersymmetry and we provide a description of their dynamics in terms of a Kahler potential and a superpotential. Our analysis shows that the critical point corresponding to the Volkov-Akulov model is unstable. Similarly, we find that the uplifted stable de Sitter critical point of the KKLT model is shifted and acquires a tachyonic instability. Our findings indicate the existence of a potentially dangerous instability shared by all anti-brane uplifts