Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age=46.2±12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72 h, and 7 days post treatment using the Montgomery–Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24 h following ketamine (t=2.3, p=0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators.     

A new solvothermal method for the synthesis of size-controlled YAG:Ce single-nanocrystals

Ce³⁺-doped Y₃Al₅O₁₂ (YAG:Ce) nanocrystals were synthesized by a unique solvothermal method, under sub-critical conditions. A home-made autoclave was used, operating in a larger pressure and temperature range than that with conventional commercial equipment and allowing direct in situ photoluminescence (PL) and X-ray absorption characterizations. The study of various synthesis conditions (pressure, temperature, precursor concentration, reaction time) allowed the best reaction conditions to be pinpointed to control YAG:Ce nanocrystal size, as well as crystal quality, and to get efficient optical properties. Without any post thermal treatment, we succeeded in obtaining well-crystallized YAG:Ce nanocrystals (30–200 nm), displaying typical PL properties of YAG:Ce with a maximal emission at 550 nm. The pristine 100 nm-sized YAG:Ce nanoparticles present an internal quantum yield of about 40 ± 5%. In situ X-ray absorption near edge spectroscopy demonstrates the presence of Ce⁴⁺ in nanocrystals elaborated at high temperature, resulting from the oxidation of Ce³⁺ during the crystallization process.

This modified solvothermal method, combined with in situ photoluminescence measurements, allows the synthesis of well-crystallized size-controlled YAG:Ce nanocrystals.     

New insights on IgA vasculitis with underlying solid tumor: a nationwide French study of 30 patients

Clinical Rheumatology - IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the...     

HIV Care Outcomes in Relation to Racial Redlining and Structural Factors Affecting Medical Care Access Among Black and White Persons with Diagnosed HIV—United States, 2017

AIDS and Behavior - Black/African American (Black) versus White persons are unequally burdened by human immunodeficiency virus (HIV) in the United States. Structural factors can influence social...     

Using Participatory Methods to Assess PrEP Interest and Uptake Among Young People Living in the Southeastern US: A Mixed Methods Assessment

AIDS and Behavior - Adolescents and young adults (AYA; 13–24 years-old) comprise 22% of new HIV infections in the United States (US), most of whom live in the South. We used the...     

The Role of Families in Adolescent and Young Adults’ PrEP Use

AIDS and Behavior - While pre-exposure prophylaxis (PrEP) is a key HIV prevention tool for adolescents and young adults (AYAs), its initiation and sustained use is shaped by AYAs’ unique...     

RANTES (CCL5) uses the proteoglycan CD44 as an auxiliary receptor to mediate cellular activation signals and HIV-1 enhancement

The CC-chemokine RANTES (regulated on activation normal T-cell expressed and secreted; CCL5) transduces multiple intracellular signals. Like all chemokines, it stimulates G protein-coupled receptor (GPCR) activity through interaction with its cognate chemokine receptor(s), but in addition also activates a GPCR-independent signaling pathway. Here, we show that the latter pathway is mediated by an interaction between RANTES and glycosaminoglycan chains of CD44. We provide evidence that this association, at both low, physiologically relevant, and higher, probably supraphysiologic concentrations of RANTES, induces the formation of a signaling complex composed of CD44, src kinases, and adapter molecules. This triggers the activation of the p44/42 mitogen-activated protein kinase (MAPK) pathway. By specifically reducing CD44 expression using RNA interference we were able to demonstrate that the p44/p42 MAPK activation by RANTES requires a high level of CD44 expression. As well as potently inhibiting the entry of CCR5 using HIV-1 strains, RANTES can enhance HIV-1 infectivity under certain experimental conditions. This enhancement process depends in part on the activation of p44/p42 MAPK. Here we show that silencing of CD44 in HeLa-CD4 cells prevents the activation of p44/p42 MAPK and leads to a substantial reduction in HIV-1 infectivity enhancement by RANTES.     

Prediction of neurological outcome after cardiopulmonary resuscitation by serial determination of serum neuron-specific enolase.

AIMS: Data on the diagnostic accuracy of neuron-specific enolase (NSE) as marker of hypoxic brain damage are conflicting. The purpose of this prospective observational cohort study was to explore the prognostic value of serum NSE after cardiopulmonary resuscitation (CPR) and to define the most sensitive cutoff value with a specificity of 100% for the prediction of persistent coma. METHODS AND RESULTS: Serum NSE concentrations were serially determined in 227 consecutive unconscious patients after CPR who were classified according to the best Glasgow-Pittsburgh cerebral performance categories (CPC, 1-4) achieved within 6 months follow-up. Sixteen patients were excluded due to incomplete NSE data and 34 due to death under analgesia sedation. The prevalence of poor neurological outcome (persistent coma, CPC 4) in our 177 analysed patients was 33%. At a specificity of 100%, a peak NSE concentration above 80 ng/mL predicted persistent coma with a sensitivity of 63%, a positive predictive value of 100%, a negative predictive value of 84%, and a predictive accuracy of 88%. CONCLUSION: A peak serum NSE concentration exceeding 80 ng/mL is a highly specific but only moderately sensitive marker for a poor neurological outcome after CPR.