SUMMARY Definitive identification of Treponema pallidum (Tp) rare outer membrane proteins (OMPs) has long eluded researchers. TP0326, the sole protein in Tp with sequence homology to a Gram-negative OMP, belongs to the BamA family of proteins essential for OM biogenesis. Structural modeling predicted that five polypeptide transport-associated (POTRA) domains comprise the N-terminus of TP0326, while the C-terminus forms an 18-stranded amphipathic β-barrel. Circular dichroism, heat-modifiability by SDS-PAGE, Triton X-114 phase partitioning and liposome incorporation supported these topological predictions and confirmed that the β-barrel is responsible for the native protein's amphiphilicity. Expression analyses revealed that native TP0326 is expressed at low abundance, while a protease-surface accessibility assay confirmed surface exposure. Size-exclusion chromatography and blue native polyacrylamide gel electrophoresis revealed a modular Bam complex in Tp considerably larger than that of E. coli. Non-orthologous ancillary factors and self-association of TP0326 via its β-barrel may both contribute to the Bam complex. Tp-infected rabbits mount a vigorous antibody response to both POTRA and β-barrel portions of TP0326, whereas humans with secondary syphilis respond predominantly to POTRA. The syphilis spirochete appears to have devised a stratagem for harnessing the Bam pathway while satisfying its need to limit surface antigenicity.

The purposes of this paper were to complete factor and item analyses of the Toronto Alexithymia Scale (TAS) in a sample of mixed substance abusers and to examine the correlations between patients’ TAS scores and other variables. Results indicate that the TAS is a reliable, valid measure of alexithymia for substance abusers. The factor structure we found is congruent with the theoretical construct and is similar to those published in the normative studies; coefficient alpha reliability was 0.68. Additionally, a high percentage of the subjects (50.4%) scored in the alexithymic range while 24% had scores in the nonalexithymic range. Patients’ TAS scores were positively associated with Beck Depression Inventory scores, with a reported paternal history of alcoholism, and with attempted suicide; TAS scores were negatively associated with being Black.

BackgroundExon-targeted microarrays can detect small (<1000 bp) intragenic copy number variants (CNVs), including those that affect only a single exon. This genome-wide high-sensitivity approach increases the molecular diagnosis for conditions with known disease-associated genes, enables better genotype–phenotype correlations, and facilitates variant allele detection allowing novel disease gene discovery.MethodsWe retrospectively analyzed data from 63,127 patients referred for clinical chromosomal microarray analysis (CMA) at Baylor Genetics laboratories, including 46,755 individuals tested using exon-targeted arrays, from 2007 to 2017. Small CNVs harboring a single gene or two to five non-disease-associated genes were identified; the genes involved were evaluated for a potential disease association.ResultsIn this clinical population, among rare CNVs involving any single gene reported in 7200 patients (11%), we identified 145 de novo autosomal CNVs (117 losses and 28 intragenic gains), 257 X-linked deletion CNVs in males, and 1049 inherited autosomal CNVs (878 losses and 171 intragenic gains); 111 known disease genes were potentially disrupted by de novo autosomal or X-linked (in males) single-gene CNVs. Ninety-one genes, either recently proposed as candidate disease genes or not yet associated with diseases, were disrupted by 147 single-gene CNVs, including 37 de novo deletions and ten de novo intragenic duplications on autosomes and 100 X-linked CNVs in males. Clinical features in individuals with de novo or X-linked CNVs encompassing at most five genes (224 bp to 1.6 Mb in size) were compared to those in individuals with larger-sized deletions (up to 5 Mb in size) in the internal CMA database or loss-of-function single nucleotide variants (SNVs) detected by clinical or research whole-exome sequencing (WES). This enabled the identification of recently published genes (BPTF, NONO, PSMD12, TANGO2, and TRIP12), novel candidate disease genes (ARGLU1 and STK3), and further confirmation of disease association for two recently proposed disease genes (MEIS2 and PTCHD1). Notably, exon-targeted CMA detected several pathogenic single-exon CNVs missed by clinical WES analyses.ConclusionsTogether, these data document the efficacy of exon-targeted CMA for detection of genic and exonic CNVs, complementing and extending WES in clinical diagnostics, and the potential for discovery of novel disease genes by genome-wide assay.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0472-7) contains supplementary material, which is available to authorized users.

Here we provide comprehensive guidelines for the assessment and treatment of violence and aggression of various etiologies, including psychotic aggression and impulsive aggression due to schizophrenia, mood disorders, ADHD, or trauma, and predatory aggression due to psychopathy and other personality disorders. These guidelines have been developed from a collection of prescribing recommendations, clinical trial results, and years of clinical experience in treating patients who are persistently violent or aggressive in the California Department of State Hospital System. Many of the recommendations provided in these guidelines employ off-label prescribing practices; thus, sound clinical judgment based on individual patient needs and according to institution formularies must be considered when applying these guidelines in clinical practice.

The purpose of this investigation was to measure alexithymia in 90 newly abstinent alcoholism treatment candidates and to examine the relationship between alexithymia and depressive symptoms. Subjects completed the Schalling-Sifneos Personality Scale (SSPS) and the Beck Depression Inventory (BDI) at the time of application for care. The correlation between subjects’ SSPS scores and their BDI scores was statistically significant (r = ––0.398; p < 0.001). Study participants with high BDI scores tended to be ‘more alexithymic’ than were those with low BDI scores. The authors conclude that alexithymia may serve as a defensive operation for alcoholic patients denying painful affect.

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The purpose of this study was to determine the extent to which Toronto Alexithymia Scale (TAS) scores and derived subscale scores changed in a sample of newly abstinent alcoholic inpatients. Subjects completed the TAS and the Beck Depression Inventory (BDI) on the date of their application for care (Time 1) and at the end of their 3rd week in treatment (Time 2). Patients’ mean BDI scores dropped significantly from Time 1 to Time 2; however, the expected concomitant drop in mean TAS scores did not occur. TAS subscales analysis suggests that the subscale associated with the ability to identify one’s feelings and to distinguish them from bodily sensations may capture the alexithymia construct better by itself than when combined with the second 2 subscales, daydreaming and external thinking, to create the total TAS score.

Guidelines for treating various conditions can be helpful in setting practice standards, but the presence of several sets of guidelines from different countries, experts, and settings, written at different times, can also create confusion. Here we provide a "guideline of guidelines" for the treatment of schizophrenia, or "meta-guidelines, which not only reconcile the various existing standards but also update them to include the use of several newer agents, most of which were marketed following the publication of existing standards.