Use of the Communication Checklist - Self Report (Cc-Sr) in Schizophrenia: Language Impairments Correlate with Poor Premorbid Social Adjustment.

BACKGROUND: The present study reports preliminary results from the multicentre project on the approbation of the Russian language version of the "The Communication Checklist-Self Report" (RL-CC-SR) and its first use in schizophrenia (SZ), aiming to evaluate the contribution of language disturbances in the pathogenesis of this heterogeneous disorder. SUBJECTS AND METHODS: The study evaluated patients' clinical state with the Diagnostic Interview for Psychoses (DIP), and assessed language and communication disturbances (LCD) with the RL-CC-SR in all participants (213 healthy controls (HC), 83 SZ patients, 31 SZ first-degree relatives). Data from the current sample of SZ (n=50), and HC (n=213) was analysed to calculate the relationships between LCD, social and clinical variables using descriptive statistics methods, T-test and Pearson's correlations (SPSS-26, 2019). RESULTS: The quotient scores (<6) and raw scores on all three CC-SR subscales demonstrated prominent LCD in SZ: (i) language structure (LS) (SZ:11.92±8.01, HC:7.54±5.91; p<0.001), (ii) pragmatic skills (PS) (SZ:11.30±10.07, HC:8.71±7.39; p=0.040), (iii) social engagement (SE) (SZ:31.94±11.76, HC:19.42±10.35; p<0.001). In SZ, Pearson correlations of LS scores were significant for the DIP-items Odd Speech (p=0.033), and Social Engagement - Blunted Affect (p=0.042). PS was related to early disease onset (p=0.027), poor premorbid work adjustment (p=0.003), along with LS (p=0.005), and was also linked to poor premorbid social adjustment (p=0.005). CONCLUSIONS: SZ patients are aware of their LCD at all levels of language structure, pragmatics, and nonverbal communication, but are unable to compensate. Disturbances of LS and PS in SZ patients relate to their poor social adjustment and functioning, and may prove to be associated with the primary negative symptoms domain of the disorder and its generally poor outcome.

Hypervariable domain of nonstructural protein nsP3 of Venezuelan equine encephalitis virus determines cell-specific mode of virus replication.

Venezuelan equine encephalitis virus (VEEV) is one of the most pathogenic members of the Alphavirus genus in the Togaviridae family. This genus is divided into the Old World and New World alphaviruses, which demonstrate profound differences in pathogenesis, replication, and virus-host interactions. VEEV is a representative member of the New World alphaviruses. The biology of this virus is still insufficiently understood, particularly the function of its nonstructural proteins in RNA replication and modification of the intracellular environment. One of these nonstructural proteins, nsP3, contains a hypervariable domain (HVD), which demonstrates very low overall similarity between different alphaviruses, suggesting the possibility of its function in virus adaptation to different hosts and vectors. The results of our study demonstrate the following. (i) Phosphorylation of the VEEV nsP3-specific HVD does not play a critical role in virus replication in cells of vertebrate origin but is important for virus replication in mosquito cells. (ii) The VEEV HVD is not required for viral RNA replication in the highly permissive BHK-21 cell line. In fact, it can be either completely deleted or replaced by a heterologous protein sequence. These variants require only one or two additional adaptive mutations in nsP3 and/or nsP2 proteins to achieve an efficiently replicating phenotype. (iii) However, the carboxy-terminal repeat in the VEEV HVD is indispensable for VEEV replication in the cell lines other than BHK-21 and plays a critical role in formation of VEEV-specific cytoplasmic protein complexes. Natural VEEV variants retain at least one of the repeated elements in their nsP3 HVDs.