The CANNA-TICS Study Protocol: A Randomized Multi-Center Double-Blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders

Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS. Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders. Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments. Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication. Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders

Mef2b gene snp markers of meat productivity in Severokavkazskaya sheep breed

One of the new promising candidate genes defining productive qualities of sheep is MEF2B. Protein from the MEF2 group encoded by it affects the production of myostatin and the expression of the genes responsible for the growth of skeletal muscle fibers. Thus, the knowledge of the MEF2B gene structure is important for genomic selection. We have studied the structure of the MEF2B gene at sheep of Severokavkazskaya breed bred in Russia. To detect alleles we use NimbleGen sequencing technology by Roche (USA). As a result, it was revealed 14 single nucleotide polymorphisms (SNP) at the given breed. The discovered SNPare located in not coding areas. From them 7 polymorphisms are in the area of 5' upstream gene in loci: c.-1713, c.-1319, c.-839, c.-321, c.-246, c.-161, c.-3; 6 polymorphisms are in introns, loci: c.55-51, c.258+312, c.258+380, c.259-52, c.452+95, c.452+ 103, 1 SNP is in 3' downstream gene, c.*252. Two of the identified SNPs are significantly connected with high indices of meat productivity: c.55-51 and c.259-52. At the same time it was not possible to find out the impact on productivity of c.-1713 polymorphism. Our investigation is a base of next research of affection of different MEF2B gene alleles on meat quality and can be used to prepare PCR test-system for genomic selection

Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Russia.

In this report, we present new data on the diversity and geographical distribution of genetic variants in Crimean-Congo hemorrhagic fever virus (CCHFV) in Russia. Partial S, M, and L segment sequences of the CCHFV genome were obtained from 500 serum samples from CCHF patients and 103 pools of ticks collected in the south of the European region of Russia in 2007-2017. The investigated viral strains belonged to the lineages Europe 1 (596 samples), Africa 3 (1 sample) and a new genetic lineage, Europe 3 (6 samples). The Russian CCHFV strains of the Europe 1 lineage formed four subgroups (Va-Vd) correlated with the geographical site of virus isolation. Segment reassortment events between strains of different subgroups within lineage Europe 1 were revealed. The complete S, M and L genome segments of 18 CCHFV strains belonging to different subgroups of the Europe 1 lineage and the complete S segments of 3 strains of the Europe 3 lineage and 1 strain of the Africa 3 lineage were sequenced. The analysis of the geographical distribution of CCHFV genetic variants in southern Russia revealed local viral populations with partially overlapping boundaries

Correlation between gene expression profiles in muscle and live weight in dzhalginsky merino sheep

Summary Background: marker assisted selection methods of sheep require the identification of genes that positively and negatively affect meat quality. Genes with high expression levels could have the greatest impact on growth and structure of muscle fibers. Objective: this study evaluated the expression of genes in the loin muscle of Dzhalginsky Merino sheep. Methods: reverse transcription-quantitative real-time PCR (RT-qPCR) was used to investigate the expression of 48 genes in the loin muscle of Dzhalginsky Merino sheep bred in Russia. Results: genes GAPDH, PYGM, CAST, ATP5G1, CAPN3, SOD1, VEGFA, CALM2, YWHAZ, ASIP,MYOD1, CAPN1, GHR, OXTR, BEGAIN, SLC2A3, and SS18L2 showed the highest expression. The group of genes with a medium level of expression included ATOX1, BAMBI, TLR6, IGF2, FOS, FST, GGTA2P, C-MET, FGF5, ACVR2A, CAPN2, GH, DGAT1, and IGF1. Low levels of expression were identified for genes ABCG2, SPP2, PYGL, PPARG2, TGFB1, CXCR4, MSTN, CYP2J, LEPR, CDKN1A, IGFBP4, and SERT. Trace expression was detected in genes SST, TSHR, GDF9, FGF7 and BMP15. Significant correlation between expression level and live weight was observed for most of the investigated genes. Conclusion: our results demonstrate the feasibility of using these newly identified candidate genes as genetic markers in sheep.Resumo Antecedentes: métodos que utilizam marcadores de seleção assistida em ovelhas exigem a identificação de novos genes que afetam a qualidade da carne. Genes com maiores níveis de expressão podem ter maior impacto sobre o crescimento e a estrutura das fibras músculares. Objetivo: avaliar a expressão de genes no músculo lombar de ovinos da raça Merino Dzhalginsky. Métodos: foi utilizada a reação em cadeia da polimerase-transcriptase reversa e em tempo real (RT-qPCR) para investigar a expressão de 48 genes em músculo do lombo da raça de ovinos Merino Dzhalginsky, que foram criados na Rússia. Resultados: os genes GAPDH, PYGM, CAST, ATP5G1, CAPN3, SOD1, VEGFA, CALM2, YWHAZ, ASIP, MYOD1, CAPN1, GHR,OXTR, BEGAIN, SLC2A3 e SS18L2 apresentaram a maior expressão. O grupo de genes com um nível médio de expressão incluíram ATOX1, BAMBI, TLR6, IGF2, FOS, FST, GGTA2P, C-MET, FGF5, ACVR2A, CAPN2,GH, DGAT1 e IGF1. Foram identificados baixos níveis de expressão para os genes ABCG2, SPP2, PYGL, PPARG2, TGFB1, CXCR4, MSTN, CYP2J, LEPR, CDKN1A, IGFBP4 e SERT. Foi detectado rastreamento de expressão nos genes SST, TSHR, GDF9, FGF7 e BMP15. Para a maioria dos genes investigados, houve uma correlação significativa entre o nível de expressão e o peso vivo dos carneiros Dzhalginsky Merino. Conclusão: os resultados demonstram a viabilidade do uso desses genes candidatos recentemente identificados como marcadores genéticos no desenvolvimento de novas raças de ovinos.Resumen Antecedentes: los métodos de selección asistida de ovejas a través de marcadores requieren la identificación de los genes que afectan positiva o negativamente la calidad de la carne. Los genes con niveles más altos de expresión podrían tener mayor impacto en el crecimiento y estructura de las fibras musculares. Objetivo: evaluar la expresión de los genes en el músculo del lomo de carneros de la raza Dzhalginsky Merino. Métodos: se utilizó RT-PCR cuantitativa en tiempo real (RT-qPCR) para investigar la expresión de 48 genes en el músculo del lomo de ovejos raza Merino Dzhalginsky criados en Rusia. Resultados: los genes GAPDH, PYGM, CAST, ATP5G1, CAPN3, SOD1, VEGFa, CALM2, YWHAZ, ASIP, MYOD1, CAPN1, GHR, OXTR, BEGAIN,SLC2A3 y SS18L2 mostraron la más alta expresión. El grupo de genes con un nivel medio de expresión incluyó ATOX1, BAMBI, TLR6, IGF2, FOS, FST, GGTA2P, C-MET, FGF5, ACVR2A, CAPN2, GH, DGAT1 y IGF1. Se identificaron bajos niveles de expresión en los genes ABCG2, SPP2, PYGL, PPARG2, TGFB1, CXCR4, NTCR, CYP2J, LEPR, CDKN1A, IGFBP4 y SERT. Expresión traza fue detectada en los genes SST, TSHR, GDF9, FGF7 y BMP15. Para la mayoría de los genes investigados hubo una correlación significativa entre el nivel de expresión y el peso vivo de los carneros. Conclusión: los resultados demuestran la factibilidad del uso de estos genes candidatos identificados recientemente como marcadores genéticos en ovejas

Correlation between gene expression profiles in muscle and live weight in dzhalginsky merino sheep

Summary Background: marker assisted selection methods of sheep require the identification of genes that positively and negatively affect meat quality. Genes with high expression levels could have the greatest impact on growth and structure of muscle fibers. Objective: this study evaluated the expression of genes in the loin muscle of Dzhalginsky Merino sheep. Methods: reverse transcription-quantitative real-time PCR (RT-qPCR) was used to investigate the expression of 48 genes in the loin muscle of Dzhalginsky Merino sheep bred in Russia. Results: genes GAPDH, PYGM, CAST, ATP5G1, CAPN3, SOD1, VEGFA, CALM2, YWHAZ, ASIP,MYOD1, CAPN1, GHR, OXTR, BEGAIN, SLC2A3, and SS18L2 showed the highest expression. The group of genes with a medium level of expression included ATOX1, BAMBI, TLR6, IGF2, FOS, FST, GGTA2P, C-MET, FGF5, ACVR2A, CAPN2, GH, DGAT1, and IGF1. Low levels of expression were identified for genes ABCG2, SPP2, PYGL, PPARG2, TGFB1, CXCR4, MSTN, CYP2J, LEPR, CDKN1A, IGFBP4, and SERT. Trace expression was detected in genes SST, TSHR, GDF9, FGF7 and BMP15. Significant correlation between expression level and live weight was observed for most of the investigated genes. Conclusion: our results demonstrate the feasibility of using these newly identified candidate genes as genetic markers in sheep

Global evolution and phylogeography of Brucella melitensis strains

Abstract Background Brucellosis is a bacterial zoonotic disease. Annually in the world more than 500,000 new cases of brucellosis in humans are registered. In this study, we propose an evolutionary model of the historical distribution of B. melitensis based on the full-genomic SNP analysis of 98 strains. Results We performed an analysis of the SNP of the complete genomes of 98 B. melitensis strains isolated in different geographical regions of the world to obtain relevant information on the population structure, genetic diversity and the evolution history of the species. Using genomic sequences of 21 strains of B. melitensis isolated in Russia and WGS data from the NCBI database, it was possible to identify five main genotypes and 13 species genotypes for analysis. Data analysis based on the Bayesian Phylogenetics and Phylogeography method allowed to determine the regions of geographical origin and the expected pathways of distribution of the main lines (genotypes and subgenotypes) of the pathogen. Conclusions Within the framework of our study, the model of global evolution and phylogeography of B. melitensis strains isolated in various regions of the planet was proposed for the first time. The sets of unique specific SNPs described in our study, for all identified genotypes and subgenotypes, can be used to develop new bacterial typing and identification systems for B. melitensis

Table_1_Mass social media-induced illness presenting with Tourette-like behavior.docx

Currently, we are facing a new manifestation of functional neurological disorder presenting with functional Tourette-like behavior (FTB). This study aimed to show characteristics of this phenotype presenting as an outbreak of “mass social media-induced illness” (MSMI) and to explore predisposing factors. Between 5–9/2021, we prospectively investigated 32 patients (mean/median age: 20.1/18 years, range: 11–53 years, n = 16 females) with MSMI-FTB using a neuro-psychiatric examination, a comprehensive semi-structured interview and aspects of the Operationalized Psychodynamic Diagnostic System. In contrast to tics, numbers of complex movements and vocalizations were nine times greater than of “simple” symptoms, and of vocalizations one and a half times greater than of movements. In line with our hypothesis of MSMI, symptoms largely overlapped with those presented by German YouTuber Jan Zimmermann justifying his role as “virtual” index case in current outbreak. Typically, symptoms started abruptly at a mean age of 19 years and deteriorated gradually with no differences between males and females. In all patients, we identified timely-related psychological stressors, unconscious intrapsychic conflicts, and/or structural deficits. Nearly all patients (94%) suffered from further psychiatric symptoms including abnormalities in social behavior (81%), obsessive-compulsive behavior (OCB) (47%), Tourette syndrome (TS) (47%), anxiety (41%), and depression (31%), about half (47%) had experienced bullying, and 75% suffered from coexisting somatic diseases. Our data suggest that pre-existing abnormalities in social behavior and psychiatric symptoms (OCB, anxiety, and depression), but also TS in combination with timely-related psychological stressors, unconscious intrapsychic conflicts, and structural deficits predispose to contagion with MSMI-FTB.</p

Additional file 5: of Global evolution and phylogeography of Brucella melitensis strains

Table S5. Base of sites of nucleotide polymorphisms of Brucella strains. (XLSX 19468 kb

Additional file 4: of Global evolution and phylogeography of Brucella melitensis strains

Table S4. Antibiotic susceptibility testing. (DOCX 16 kb