Neuropsychological diagnostics and rehabilitation for patients with disorders of executive functions in brain diseases of various etiology

Background. Disorders of regulatory (control) functions are often observed in neuropsychological practice in brain lesions. This fact determines the high practical significance of timely neuropsychological diagnosis and rehabilitation for this category of patients. Daily functioning with impaired regulatory (control) functions is carried out in conditions of limited capabilities of the patient, which significantly worsens the quality of his/her life and the social well-being of the family. Realisation of the patient’s rehabilitation potential is impossible without taking into account psychological and behavioural features, as well as organising a partnership with the immediate social environment and with a multidisciplinary team of specialists. Objective. The article aims to analyse and generalise diagnostic and rehabilitation experience accumulated in neuropsychology, as well as to develop quality criteria for neuropsychological diagnostics and rehabilitation of patients with disorders of regulatory (control) functions arising from brain injuries. Results. The analysis of applied research and practical manuals was carried out. On this basis, recommendations on diagnostics of regulatory (control) function disorders were developed. The main methodical techniques of rehabilitation work, which demonstrated their effectiveness, were generalised. Conclusion. The criteria of neuropsychological assistance highlighted in the article can be recommended for use by a practicing clinical psychologist when working with patients with disorders of control functions resulting from brain damage

Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)[superscript +] macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE[superscript −/−] mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques

Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)+ macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE−/− mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques

Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease

Abstract Background Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative “shotgun” metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts—with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group. Results Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis—with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus—but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of functional potential, the patients showed different patterns of increase in functions related to alcohol metabolism and virulence factors, as well as pathways related to inflammation. Conclusions Multiple shifts in the community structure and metabolic potential suggest strong negative influence of alcohol dependence and associated liver dysfunction on gut microbiota. The identified differences in patterns of impact between these two factors are important for planning of personalized treatment and prevention of these pathologies via microbiota modulation. Particularly, the expansion of Bifidobacterium and Lactobacillus suggests that probiotic interventions for patients with alcohol-related disorders using representatives of the same taxa should be considered with caution. Taxonomic and functional analysis shows an increased propensity of the gut microbiota to synthesis of the toxic acetaldehyde, suggesting higher risk of colorectal cancer and other pathologies in alcoholics

Additional file 13: Table S11. of Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease

Associations between the levels of gut microbial genera and clinical factors. The table contains the coefficients of linear model obtained by applying MaAsLin method to the reference-mapping based taxonomic composition vectors (adjusted p-value < 0.05). Positive values denote direct association between the factor and the relative abundance of the respective taxon, while negative values denote reverse association. Each empty cell denotes that no significant association was detected between the respective factor and taxon. (XLSX 8 kb

Data on gut metagenomes of the patients with alcoholic dependence syndrome and alcoholic liver cirrhosis

Alcoholism is associated with significant changes in gut microbiota composition. Metagenomic sequencing allows to assess the altered abundance levels of bacterial taxa and genes in a culture-independent way. We collected 99 stool samples from the patients with alcoholic dependence syndrome (n=72) and alcoholic liver cirrhosis (n=27). Each of the samples was surveyed using “shotgun” (whole-genome) sequencing on SOLiD platform. The reads are deposited in the ENA (project ID: PRJEB18041)

Le Monde

06 septembre 18711871/09/06 (N117,A12).Appartient à l’ensemble documentaire : BbLevt

Additional file 7: Figure S1. of Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease

Heatmap displaying the relative abundance of the major microbial species for the gut metagenomes of ADS and ALC patients. Only the species with the abundance of >5% in at least one sample are shown. (PDF 115 kb

Additional file 6: Table S6. of Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease

Relative abundance of microbial species and viruses in the metagenomes (the percentage of overall abundance; obtained using MetaPhlAn2). (XLSX 185 kb