Diagnostic Specificity of Neurophysiological Endophenotypes in Schizophrenia and Bipolar Disorder

Background: The utility of an endophenotype depends on its ability to reduce complex disorders into stable, genetically linked phenotypes. P50 and P300 event-related potential (ERP) measures are endophenotype candidates for schizophrenia; however, their abnormalities are broadly observed across neuropsychiatric disorders. This study examined the diagnostic efficiency of P50 and P300 in schizophrenia as compared with healthy and bipolar disorder samples. Supplemental ERP measures and a multivariate classification approach were evaluated as methods to improve specificity. Methods: Diagnostic classification was first modeled in schizophrenia (SZ = 50) and healthy normal (HN = 50) samples using hierarchical logistic regression with predictors blocked by 4 levels of analysis: (1) P50 suppression, P300 amplitude, and P300 latency; (2) N100 amplitude; (3) evoked spectral power; and (4) P50 and P300 hemispheric asymmetry. The optimal model was cross-validated in a holdout sample (SZ = 34, HN = 31) and tested against a bipolar (BP = 50) sample. Results: P50 and P300 endophenotypes classified SZ from HN with 71% accuracy (sensitivity = .70, specificity = .72) but did not differentiate SZ from BP above chance level. N100 and spectral power measures improved classification accuracy of SZ vs HN to 79% (sensitivity = .78, specificity = .80) and SZ vs BP to 72% (sensitivity = .74, specificity = .70). Cross validation analyses supported the stability of these models. Conclusions: Although traditional P50 and P300 measures failed to differentiate schizophrenia from bipolar participants, N100 and evoked spectral power measures added unique variance to classification models and improved accuracy to nearly the same level achieved in comparison of schizophrenia to healthy individuals.Key words: event-related potential, P50, P300, N100, gamma frequency     

Identification of the SHREK Family of Proteins as Broad-Spectrum Host Antiviral Factors

Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123) that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudovirus. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.     

Online and Social Networking Interventions for the Treatment of Depression in Young People: A Systematic Review

Background

Major depression accounts for the greatest burden of all diseases globally. The peak onset of depression occurs between adolescence and young adulthood, and for many individuals, depression displays a relapse-remitting and increasingly severe course. Given this, the development of cost-effective, acceptable, and population-focused interventions for depression is critical. A number of online interventions (both prevention and acute phase) have been tested in young people with promising results. As these interventions differ in content, clinician input, and modality, it is important to identify key features (or unhelpful functions) associated with treatment outcomes.

Objective

A systematic review of the research literature was undertaken. The review was designed to focus on two aspects of online intervention: (1) standard approaches evaluating online intervention content in randomized controlled designs (Section 1), and (2) second-generation online interventions and services using social networking (eg, social networking sites and online support groups) in any type of research design (Section 2).

Methods

Two specific literature searches were undertaken. There was no date range specified. The Section 1 search, which focused on randomized controlled trials, included only young people (12-25 years) and yielded 101 study abstracts, of which 15 met the review inclusion criteria. The Section 2 search, which included all study design types and was not restricted in terms of age, yielded 358 abstracts, of which 22 studies met the inclusion criteria. Information about the studies and their findings were extracted and tabulated for review.

Results

The 15 studies identified in Section 1 described 10 trials testing eight different online interventions, all of which were based on a cognitive behavioral framework. All but one of the eight identified studies reported positive results; however, only five of the 15 studies used blinded interviewer administered outcomes with most trials using self-report data. Studies varied significantly in presentation of intervention content, treatment dose, and dropout. Only two studies included moderator or clinician input. Results for Section 2 were less consistent. None of the Section 2 studies reported controlled or randomized designs. With the exception of four studies, all included participants were younger than 25 years of age. Eight of the 16 social networking studies reported positive results for depression-related outcomes. The remaining studies were either mixed or negative. Findings for online support groups tended to be more positive; however, noteworthy risks were identified.

Conclusions

Online interventions with a broad cognitive behavioral focus appear to be promising in reducing depression symptomology in young people. Further research is required into the effectiveness of online interventions delivering cognitive behavioral subcomponents, such as problem-solving therapy. Evidence for the use of social networking is less compelling, although limited by a lack of well-designed studies and social networking interventions. A range of future social networking therapeutic opportunities are highlighted.     

Late stage (III and IV) non-small cell cancer of the lung: results of surgical resection at Inova Fairfax Hospital

One hundred forty-two patients underwent surgery and related treatment for advanced stage (III, IV) non-small cell cancer of the lung. One hundred seventeen patients underwent up-front surgery, with a hospital mortality rate of 1.7% (2/117). Kaplan-Meier 5-year survival in this group was 31% (+/- 5). Twenty-five patients underwent neoadjuvant therapy followed by surgical resection, with respective rates of hospital mortality, complete pathologic response, and major pathologic response of 0%, 16%, and 64%. Kaplan-Meier 5-year survival in this latter group was 34% (+/- 11). Of the 16 patients undergoing neoadjuvant therapy who had complete pathologic response or significant downstaging from stage III disease, Kaplan-Meier 5-year survival was 61% (+/- 15).Three clinical observations of interest emerged regarding survival. First, in those patients with postresection FEV1 < 1.0 L, hospital mortality rate was 20%, and there were no 5-year survivors (P < 0.0001). Second, where neoadjuvant therapy was associated with complete pathologic response or significant downstaging of disease, there was a trend for improved survival in the downstaged group, but it did not reach statistical significance (P = 0.14). Third, adjuvant therapy was associated with improved 5-year survival (P = 0.03), particularly for combination chemotherapy and radiotherapy (P = 0.02).     

Production and properties of Staphylococcus aureus (strain Newman D2C) with uniform clumping factor activity.

The most active CF+ $\text{Staphylococcus aureus}$ (strain Newman D₂C) cells were recovered during the exponential through the early resting phases of the growth cycle. Fermentation conditions are described for preparation of large quantities of those cells on BHI. Extractions with 70 per cent ethanol produced sterile particles with intact CF activity. Subsequent ethanol and acetone drying steps completed procedures for production of uniformly active, stable CF+ particles.Congo red stained the killed staphylococci without affecting CF activity, and the stained particles enhanced visualization of the agglutination end-points. Tris buffers (50 mM, pH 7.3) were excellent diluents for CF reagents, but only if freshly prepared or sterilized before storage.