Sea level anomalies affect the ocean circulation at abyssal depths.

Abyssal channels are the key points controlling bottom circulation of the World Ocean. They provide meridional transport of the coldest Antarctic Bottom Water between deep-water basins influencing the meridional overturning circulation and the climate on a global scale. Here we show that the synoptic variability of deep-water flows including blocking abyssal currents between deep ocean basins is related to sea level anomalies observed over the channels. Our results demonstrate that processes at the ocean surface have a more significant connection with the bottom circulation than it was considered earlier. This study opens a discussion of the importance of mesoscale eddies and air-sea interactions on water exchange between abyssal basins, meridional heat transport in the ocean, and possible responses of the ocean to the observed sea level rise in a changing climate.

[The significance of glymphatic pathway in the relationship between the sleep-wake cycle and neurodegenerative diseases]. / Rol' glimfaticheskogo klirensa v mekhanizmakh svyazi tsikla «son­bodrstvovanie¼ i razvitiya neirodegenerativnykh protsessov.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aß amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and scientific data of recent studies on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

[Changes in sleep patterns and the doom-scrolling (doom-surfing) phenomenon as modifiable risk factors for anxiety due to continuous stress of the COVID-19 pandemic]. / Izmeneniya rezhima sna i potreblenie informatsii s negativnym kontentom v internete («dumskrolling¼, «dumserfing¼) kak upravlyaemye faktory riska razvitiya trevogi v usloviyakh stressa pandemii COVID-19.

OBJECTIVE: To evaluate the modifiable daily behavior patterns associated with increased anxiety indicators in the general population in response to the COVID-19 pandemic. MATERIAL AND METHODS: The study examined the characteristics of the Russian population (n=7777) of the international multicenter project COMET-G. In particular, variables were targeted to describe deviations in the behavior of adults during the period of application of measures of social isolation in connection with the pandemic, and revealing a relationship with the total score on the Spielberger State Anxiety Scale (STAI-S). Among these variables, experts selected those that could potentially be subject to change in the short term, that is, act as manageable or modifiable risk factors for the development of anxiety. The selected variables were analyzed in a statistical PLS-model to identify indicators that make the most significant contribution to the increase in the total anxiety score. RESULTS: Our statistical model explained 48.4% of the variability in the STAI-S anxiety total scores related to changes in daily life habits. In particular, doom-scrolling/doom-surfing about the spread of the virus and the COVID-19 pandemic, changes in sleep patterns and usual daily life activities due to social isolation measures presented as factors significantly contributing to the increase of state anxiety. CONCLUSION: Given the manageable or modifiable risk factors that we have identified, public awareness and therapeutic recommendations, pointing to the need to (I) control the amount of time spent in the internet and monitor their internet-based content consumption, (II) regulate sleep-wake patterns, (III) maintain daily habits and household activities, may reduce the likelihood of developing anxiety disorders in the context of the impact of a global chronic stress due to the COVID-19 pandemic and associated social isolation measures.

[The significance of the glymphatic pathway in the relationship between the sleep-wake cycle and neurodegenerative diseases]. / Rol' glimfaticheskogo klirensa v mekhanizmakh vzaimosvyazi tsikla «son­bodrstvovanie¼ i razvitiya neirodegenerativnykh protsessov.

Selective and progressive death of neurons is a characteristic feature of the process of neurodegeneration and leads to corresponding neuronal dysfunctions. Neurodegenerative diseases represent a heterogeneous group of clinically distinct disorders with similar molecular mechanisms of pathogenesis. They are based on the processes of abnormal aggregation of proteins, the formation of fibrillary insoluble structures and their deposition in the form of histopathological inclusions in the tissues of the nervous system. Disturbance of homeostatic functions that regulate neuronal ion and energy metabolism, biosynthesis and degradation of proteins and nucleotides, chronic hypoxia and the penetration of toxic and inflammatory substances into the brain from the bloodstream not only cause metabolic changes associated with age and disorders in the sleep-wake cycle, but also contribute to the development of neurodegenerative diseases. In animal studies, clearance pathways have been identified in which solutes and specific tracers are excreted perivascular into the meningeal lymphatics. The glymphatic pathway promotes the removal of metabolites, including Aß amyloid and tau protein, from the parenchymal extracellular space of the brain. The glymphatic system is discussed to be more efficient during natural sleep, and fluid dynamics through this pathway exhibit daily fluctuations and are under circadian control. This review systematizes the key aspects and the data of recent research on the role of the glymphatic pathway and astroglial AQP-4 as its main determinant in maintaining homeostatic fluid circulation in the brain in normal and pathological conditions, in particular in relation to the regulatory role of the sleep-wake cycle and in development of neurodegeneration.

[Application of modern approaches in the screening and early diagnosis programs for the orphan diseases]. / Primenenie sovremennykh tekhnologii v programmakh rannei diagnostiki orfannykh boleznei v Rossii i za rubezhom.

Orphan diseases have a prevalence ranging one patient per 10.000 population in the Russian Federation to one per 1500-2000 individuals in Australia and the USA. Many orphan diseases lead to a severe decrease in quality of life and high mortality. In this article, we discuss the problem of early diagnosis in orphan diseases in the Russian Federation, which has lagged behind global trends towards improved recognition and treatment of orphan diseases. We identify the need for improved focus at the level of national healthcare, while discussing relevant issues arising from the international experience. We review national and regional health programs and healthcare practices of Australia, Germany, Denmark, China, Norway, Slovenia, UK, and the United States, with a focus on screening and diagnosis of orphan disease. We also present a review on the state of affairs in the Russian Federation. Orphan diseases are amenable to current molecular-genetic and other diagnostic technologies, including targeted, whole exome and whole genome sequencing (targeted NGS, WES, WGS) using next generation sequencing technologies (next generation sequencing, NGS) and tandem mass spectrometry (TMS, MS/MS). We conclude with a call for major measures aimed at improving the diagnosis of orphan diseases, in particular through the expansion of the neonatal screening program, the creation of a network of orphan disease referral centers, and centralized management of patients registers.

[Multi-centre clinical assessment of the Russian language version of the Diagnostic Interview for Psychoses]. / Mnogotsentrovoe klinicheskoe issledovanie russkoiazychnoi versii diagnosticheskogo interv'iu dlia psikhozov.

OBJECTIVES: The Diagnostic Interview for Psychoses (DIP) was developed to enhance the quality of diagnostic assessment of psychotic disorders. The aim of the study was the adaptation of the Russian language version and evaluation of its validity and reliability. MATERIAL AND METHODS: Ninety-eight patients with psychotic disorders (89 video recordings) were assessed by 12 interviewers using the Russian version of DIP at 7 clinical sites (in 6 cities of the Russian Federation). DIP ratings on 32 cases of a randomized case sample were made by 9 interviewers and the inter-rater reliability was compared with the researchers' DIP ratings. Overall pairwise agreement and Cohen's kappa were calculated. Diagnostic validity was evaluated on the basis of comparing the researchers' ratings using the Russian version of DIP with the 'gold standard' ratings of the same 62 clinical cases from the Western Australia Family Study Schizophrenia (WAFSS). RESULTS: The mean duration of the interview was 47±21 minutes. The Kappa statistic demonstrated a significant or almost perfect level of agreement on the majority of DIP items (84.54%) and a significant agreement for the ICD-10 diagnoses generated by the DIP computer diagnostic algorithm (κ=0.68; 95% CI 0.53,0.93). The level of agreement on the researchers' diagnoses was considerably lower (κ=0.31; 95% CI 0.06,0.56). The agreement on affective and positive psychotic symptoms was significantly higher than agreement on negative symptoms (F(2,44)=20.72, p<0.001, η2=0.485). The diagnostic validity of the Russian language version of DIP was confirmed by 73% (45/62) of the Russian DIP diagnoses matching the original WAFSS diagnoses. Among the mismatched diagnoses were 80 cases with a diagnosis of F20 Schizophrenia in the medical documentation compared to the researchers' F20 diagnoses in only 68 patients and in 62 of the DIP computerized diagnostic outputs. The reported level of subjective difficulties experienced when using the DIP was low to moderate. CONCLUSION: The results of the study confirm the validity and reliability of the Russian version of the DIP for evaluating psychotic disorders. DIP can be recommended for use in education and training, clinical practice and research as an important diagnostic resource.

[Peculiarities of the lower extremities perfusion in patients with complicated diabetic foot syndrome].

Analysis of the microcirculation indices in 246 patients, suffering diabetic foot syndrome (DFS), was presented. For a neuropathic form of DFS characteristic is lowering of the arterioles tone and enhancement of the blood volume in them, witnessed by raising of constant component of the blood flow. General worsening of perfusion is caused by lowering of endothelial secretion activation, and as well as neurogenic and myogenic control mechanisms. Occurrence of neurogenic regulation disorder is witnessed by the neurogenic oscillations lowering, the neurogenic and myogenic tone raising. In ischemic form of DFS there was noted the perfusion disorder, connected with reduction of the arterial inflow volume. The indices changes witness the disorder of sympathetic regulation of microcirculation and arteriole-venular reactions. The change of the perfusion indices, caused by a congestion processes in arterioles and venules, is characteristic for the mixed form of DFS. The perfusion control mechanisms was noted, as a consequence of the endothelial secretion lowering and the neurogenic and myogenic mechanisms activation of a control. The neurogenic and myogenic tone raising occurs depending on the sympathetic component activity, causing the arterioles diameter reduction.

[The attempt of clinical classification of the complicated diabetic foot syndrome].

The experience of surgical treatment of 1532 patients with the complicated forms of diabetic foot syndrome (DFS) was analyzed. The original clinical classification of the complicated DFS was suggested. The classification considered the clinical form (symbol "C"), anatomic localization (symbol "Z") and etiology (symbol "E"). The classification allows to define surgical tactics depending on concrete complications of the DFS, frames conditions for the unification and uniform registration of the form and severity of the disease and volume of the surgical treatment.