Generation of two iPSC lines from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12.

We generated two human induced pluripotency stem cell (hiPSC) lines, RCMGi011-A and 11-B, from skin fibroblast from patient with Mucopolysaccharidosis IV B type and autosomal recessive non-syndromic hearing loss 12 using non-integrating, viral CytoTune™-iPS 2.0 Sendai Reprogramming Kit. We verified variant c.808 T > G and insertion in GLB1 gene, as well as two mutations, c.6992 T > C and c.805C > T, in CDH23 gene which lead to autosomal recessive hearing loss type 12. We have demonstrated normal karyotype of hiPSCs and capacity for cell differentiation into three germ layers.

Recombinant Adeno-associated Viral Vectors Serotypes 6 and 9 are Able to Transduce Human Tracheal Epithelial Cells but Not Human Induced Pluripotent Stem Cells.

Recombinant adeno-associated viruses (rAAVs) may be useful for the development of gene therapy for hereditary diseases. Patient-specific human induced pluripotent stem cells (hiPSCs) can be differentiated into a variety of cells which are difficult or impossible to obtain by biopsy. To date, few research on the efficiency of rAAV transduction of hiPSCs has been published, but the obtained data are very contradictory and do not answer the actual question: how effective are rAAVs for the delivery of transgenes into hiPSCs. In this work, we used rAAV serotypes 5, 6, and 9 carrying the GFP transgene. The transduction efficiency of rAAV2/9-GFP and rAAV2/6-GFP for the immortalized tracheal epithelial cell line derived from a patient with cystic fibrosis (CFTE29o-) was relatively high. At the same time, the efficiency of transduction of iPSCs from a healthy donor and a cystic fibrosis (CF) donor was extremely low. Thus, our results show that the efficiency of hiPSC transduction by rAAV serotypes 5, 6, and 9 is not suitable for the delivery of transgenes.

Diagnosis of Schizophrenia Based on the Data of Various Modalities: Biomarkers and Machine Learning Techniques (Review).

Schizophrenia is a socially significant mental disorder resulting frequently in severe forms of disability. Diagnosis, choice of treatment tactics, and rehabilitation in clinical psychiatry are mainly based on the assessment of behavioral patterns, socio-demographic data, and other investigations such as clinical observations and neuropsychological testing including examination of patients by the psychiatrist, self-reports, and questionnaires. In many respects, these data are subjective and therefore a large number of works have appeared in recent years devoted to the search for objective characteristics (indices, biomarkers) of the processes going on in the human body and reflected in the behavioral and psychoneurological patterns of patients. Such biomarkers are based on the results of instrumental and laboratory studies (neuroimaging, electro-physiological, biochemical, immunological, genetic, and others) and are successfully being used in neurosciences for understanding the mechanisms of the emergence and development of nervous system pathologies. Presently, with the advent of new effective neuroimaging, laboratory, and other methods of investigation and also with the development of modern methods of data analysis, machine learning, and artificial intelligence, a great number of scientific and clinical studies is being conducted devoted to the search for the markers which have diagnostic and prognostic value and may be used in clinical practice to objectivize the processes of establishing and clarifying the diagnosis, choosing and optimizing treatment and rehabilitation tactics, predicting the course and outcome of the disease. This review presents the analysis of the works which describe the correlates between the diagnosis of schizophrenia, established by health professionals, various manifestations of the psychiatric disorder (its subtype, variant of the course, severity degree, observed symptoms, etc.), and objectively measured characteristics/quantitative indicators (anatomical, functional, immunological, genetic, and others) obtained during instrumental and laboratory examinations of patients. A considerable part of these works has been devoted to correlates/biomarkers of schizophrenia based on the data of structural and functional (at rest and under cognitive load) MRI, EEG, tractography, and immunological data. The found correlates/biomarkers reflect anatomic disorders in the specific brain regions, impairment of functional activity of brain regions and their interconnections, specific microstructure of the brain white matter and the levels of connectivity between the tracts of various structures, alterations of electrical activity in various parts of the brain in different EEG spectral ranges, as well as changes in the innate and adaptive links of immunity. Current methods of data analysis and machine learning to search for schizophrenia biomarkers using the data of diverse modalities and their application during building and interpretation of predictive diagnostic models of schizophrenia have been considered in the present review.

[Regression of post-stroke aphasia and associated non-speech syndromes caused by a course of restorative treatment including intensive speech therapy]. / Regress postinsul'tnoi afazii i soputstvuiushchikh nerechevykh sindromov, obuslovlennyi kursom vosstanovitel'nogo lecheniia, vkliuchaiushchim intensivnuiu rechevuiu terapiiu.

AIM: To analyze clinical and fMRI indicators related with the therapeutic effectiveness of complex restorative treatment including intensive speech therapy in various clinical forms and severity of the aphasia syndrome. MATERIAL AND METHODS: The study included 40 right-handed patients with aphasia syndrome after the first hemispheric ischemic stroke. Patients were studied 3 month after disease onset. Patients were examined before and after rehabilitation treatment (4.7 weeks) including intensive speech therapy (15 hours of exercise per week). Evaluation of the effectiveness of treatment was carried out based on the dynamics of the results of neuropsychological, neurological and neuroimaging examinations of patients before and after treatment. The degree of recovery of speech and non-speech cognitive functions (based on the 10-point cognitive assessment, the dynamics of focal neurological deficit (NIHSS) and functional recovery of patients (Barthel index, modified Rankin scale) were assessed. Neuroimaging methods included structural MRI and two fMRI methods: fMRI resting state and fMRI equivalent of the evoked potentials of mismatch negativity (HP), using a sequence of standard and deviant sounds (Russian phonemes) to obtain the equivalent of HP. For statistical calculations, the program in Python version 3.6.0 was used. RESULTS: The maximum efficacy of restorative treatment (≥15% improvement in the scores of 10-point quantifying) was detected in 28 (70%) cases: 18 patients with initially severe and 10 patients with moderate aphasia, regardless of the clinical form of aphasia, and 11 patients with isolated sensory aphasia. Regression of speech and non-speech cognitive impairments in sensory aphasia was accompanied by a pronounced activation of intact speech homologues of the right hemisphere and the appearance of a small temporal and parietal region, which was small in volume and weak in intensity, similar in the localization to the norm. Regardless of the clinical form of aphasia, maximum therapeutic efficacy was accompanied by a reorganization of the speech neuronal rest network, which includes enhancement of both intra- and interhemispheric functional connectivity, with the predominance of amplification of the intra-hemispheric interactions of the posterior speech zones to the left while reducing their interhemispheric connectivity. Significant improvement in motor and sensory functions was detected in 9 (22%) patients with moderate contralateral spastic hemiparesis (p≤0.00) and did not correlate with the degree of regression of speech and non-speech focal cognitive impairments. A slight therapeutic effect was observed in 12 (30%) patients with mild to moderate speech and non-speech cognitive impairment. This effect was not correlated with a specific clinical form of aphasia. CONCLUSION: The maximum effectiveness of the 4.7 week restorative inpatient treatment, including intensive speech therapy (15 sessions per week), was obtained mainly with severe aphasia, and also with a specific clinical form - isolated sensory aphasia. According to the fMRI data, various compensatory reorganization of the neural speech network was detected, which probably reflects post stroke neuroplasticity associated with both the severity of aphasia and its specific clinical form.