Clinical severity is correlated with age at seizure onset and biophysical properties of recurrent gain of function variants associated with SCN8A-related epilepsy.

OBJECTIVE: Genetic variants in the SCN8A gene underlie a wide spectrum of neurodevelopmental phenotypes including several distinct seizure types and a host of comorbidities. One of the major challenges facing clinicians and researchers alike is to identify genotype-phenotype (G-P) correlations that may improve prognosis, guide treatment decisions, and lead to precision medicine approaches. METHODS: We investigated G-P correlations among 270 participants harboring gain-of-function (GOF) variants enrolled in the International SCN8A Registry, a patient-driven online database. We performed correlation analyses stratifying the cohort by clinical phenotypes to identify diagnostic features that differ among patients with varying levels of clinical severity, and that differ among patients with distinct GOF variants. RESULTS: Our analyses confirm positive correlations between age at seizure onset and developmental skills acquisition (developmental quotient), rate of seizure freedom, and percentage of cohort with developmental delays, and identify negative correlations with number of current and weaned antiseizure medications. This set of features is more detrimentally affected in individuals with a priori expectations of more severe clinical phenotypes. Our analyses also reveal a significant correlation between a severity index combining clinical features of individuals with a particular highly recurrent variant and an independent electrophysiological score assigned to each variant based on in vitro testing. SIGNIFICANCE: This is one of the first studies to identify statistically significant G-P correlations for individual SCN8A variants with GOF properties. The results suggest that individual GOF variants (1) are predictive of clinical severity for individuals carrying those variants and (2) may underlie distinct clinical phenotypes of SCN8A disease, thus helping to explain the wide SCN8A-related epilepsy disease spectrum. These results also suggest that certain features present at initial diagnosis are predictive of clinical severity, and with more informed treatment plans, may serve to improve prognosis for patients with SCN8A GOF variants.

Discrepancies of Implicit and Explicit Self-Esteem as Predictors of Attributional Bias and Paranoia.

OBJECTIVE: The current study aimed to examine the association of implicit self-esteem, explicit self-esteem and their interaction with paranoia and attributional bias. The relationship of the size and the direction of the discrepancy between implicit and explicit self-esteem with paranoia and attributional bias was examined. METHODS: A total of 128 female college students participated. We administered the Implicit Association Test to assess implicit self-esteem, and the Rosenberg Self-Esteem Scale to measure explicit self-esteem. Paranoia Scale was used, and the attributional bias was assessed using the Ambiguous Intentions Hostility Questionnaire. RESULTS: Results showed that explicit but not implicit self-esteem was negatively associated with paranoia, blame bias and hostility perception bias in ambiguous situations. The interaction of implicit and explicit self-esteem was associated with hostility perception in ambiguous situations. As for the discrepancy, the size of the discrepancy between implicit and explicit self-esteem was positively associated with hostility perception in ambiguous situations. Moreover, the direction of the discrepancy was specifically relevant: damaged self-esteem (high implicit and low explicit self-esteem) was associated with increased levels of paranoia, blame bias and hostility perception in ambiguous situations. CONCLUSION: These findings provide new insights into the role of the implicit and explicit self-esteem in attributional bias and paranoia and point to damaged self-esteem as a possible vulnerability marker for illogical attribution of blaming others and perceiving hostility in social situations.

Sequential Combination of Electro-Fenton and Electrochemical Chlorination Processes for the Treatment of Anaerobically-Digested Food Wastewater.

A two-stage sequential electro-Fenton (E-Fenton) oxidation followed by electrochemical chlorination (EC) was demonstrated to concomitantly treat high concentrations of organic carbon and ammonium nitrogen (NH4+-N) in real anaerobically digested food wastewater (ADFW). The anodic Fenton process caused the rapid mineralization of phenol as a model substrate through the production of hydroxyl radical as the main oxidant. The electrochemical oxidation of NH4+ by a dimensionally stable anode (DSA) resulted in temporal concentration profiles of combined and free chlorine species that were analogous to those during the conventional breakpoint chlorination of NH4+. Together with the minimal production of nitrate, this confirmed that the conversion of NH4+ to nitrogen gas was electrochemically achievable. The monitoring of treatment performance with varying key parameters (e.g., current density, H2O2 feeding rate, pH, NaCl loading, and DSA type) led to the optimization of two component systems. The comparative evaluation of two sequentially combined systems (i.e., the E-Fenton-EC system versus the EC-E-Fenton system) using the mixture of phenol and NH4+ under the predetermined optimal conditions suggested the superiority of the E-Fenton-EC system in terms of treatment efficiency and energy consumption. Finally, the sequential E-Fenton-EC process effectively mineralized organic carbon and decomposed NH4+-N in the real ADFW without external supply of NaCl.

Raoultella electrica sp. nov., isolated from anodic biofilms of a glucose-fed microbial fuel cell.

A Gram-stain-negative, non-spore-forming, rod-shaped bacterium, designated strain 1GB(T), was isolated from anodic biofilms of a glucose-fed microbial fuel cell. Strain 1GB(T) was facultatively anaerobic and chemo-organotrophic, having both a respiratory and a fermentative type of metabolism, and utilized a wide variety of sugars as carbon and energy sources. Cells grown aerobically contained Q-8 as the major quinone, but excreted Q-9 and a small amount of Q-10 when cultured with an electrode serving as the sole electron acceptor. The G+C content of the genomic DNA of 1GB(T) was 54.5 mol%. Multilocus sequence typing (MLST) analysis showed that strain 1GB(T) represented a distinct lineage within the genus Raoultella (98.5-99.4 % 16S rRNA gene sequence similarity and 94.0-96.5 % sequence similarity based on the three concatenated housekeeping genes gyrA, rpoB and parC. Strain 1GB(T) exhibited DNA-DNA hybridization relatedness of 7-43 % with type strains of all established species of the genus Raoultella. On the basis of these phenotypic, phylogenetic and genotypic data, the name Raoultella electrica sp. nov. is proposed for strain 1GB(T). The type strain is 1GB(T) ( = NBRC 109676(T) = KCTC 32430(T)).