Intranasal administration of a synthetic TLR4 agonist INI-2004 significantly reduces allergy symptoms following therapeutic administration in a murine model of allergic sensitization.

Introduction: Atopic diseases have been steadily increasing over the past decades and effective disease-modifying treatment options are urgently needed. These studies introduce a novel synthetic Toll-like receptor 4 (TLR4) agonist, INI-2004, with remarkable efficacy as a therapeutic intranasal treatment for seasonal allergic rhinitis.

Methods: Using a murine airway allergic sensitization model, the impact of INI-2004 on allergic responses was assessed.

Diamino Allose Phosphates: Novel, Potent, and Highly Stable Toll-like Receptor 4 Agonists.

Most known synthetic toll-like receptor 4 (TLR4) agonists are carbohydrate-based lipid-A mimetics containing several fatty acyl chains, including a labile 3--acyl chain linked to the C-3 position of the non-reducing sugar known to undergo cleavage impacting stability and resulting in loss of activity. To overcome this inherent instability, we rationally designed a new class of chemically more stable synthetic TLR4 ligands that elicit robust innate and adaptive immune responses. This new class utilized a diamino allose phosphate (DAP) scaffold containing a nonhydrolyzable 3-amide bond instead of the classical 3-ester.

Isolating the impact of antipsychotic medication on metabolic health: Secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first-episode psychosis (the STAGES study).

Background: Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids.

Efficacy of synchronous telepsychology interventions for people with anxiety, depression, posttraumatic stress disorder, and adjustment disorder: A rapid evidence assessment.

Telepsychology holds promise as a treatment delivery method that may increase access to services as well as reduce barriers to treatment accessibility. The aim of this rapid evidence assessment was to assess the evidence for synchronous telepsychology interventions for 4 common mental health conditions (depression, anxiety, posttraumatic stress disorder, and adjustment disorder). Randomized controlled trials published between 2005 and 2016 that investigated synchronous telepsychology (i.

Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ in Otherwise Healthy HIV-Infected Individuals.

Despite antiretroviral therapy (ART), respiratory infections increase mortality in individuals living with chronic human immunodeficiency virus (HIV) infection. In experimental and clinical studies of chronic HIV infection, alveolar macrophages (AMs) exhibit impaired phagocytosis and bacterial clearance. Peroxisome proliferator-activated receptor (PPAR)γ, NADPH oxidase (Nox) isoforms Nox1, Nox2, Nox4, and transforming growth factor-beta 1 (TGFβ) are critical mediators of AM oxidative stress and phagocytic dysfunction.

Comparison of Glutathione, Cysteine, and Their Redox Potentials in the Plasma of Critically Ill and Healthy Children.

Background: Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body's ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes.

Objective: To compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children.

Methods: We performed a prospective clinical observational study of children ages ≤18 years and weight ≥6 kg, who were hospitalized between January 2010 and April 2012 in a 30-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU).

Exhaled breath condensate in intubated neonates--a window into the lung's glutathione status.

Background: Analysis of exhaled breath condensates (EBC) is a non-invasive technique to evaluate biomarkers such as antioxidants in the pediatric population, but limited data exists of its use in intubated patients, particularly newborns. Currently, tracheal aspirate (TA) serves as the gold standard collection modality in critically ill newborns, but this method remains invasive. We tested the hypothesis that glutathione status would positively correlate between EBC and TA collections in intubated newborns in the Newborn Intensive Care Unit (NICU).

In utero nicotine exposure promotes M2 activation in neonatal mouse alveolar macrophages.

Background: Maternal smoking in utero has been associated with adverse health outcomes including lower respiratory tract infections in infants and children, but the mechanisms underlying these associations continue to be investigated. We hypothesized that nicotine plays a significant role in mediating the effects of maternal tobacco smoke on the function of the neonatal alveolar macrophage (AM), the resident immune cell in the neonatal lung.

Methods: Primary AMs were isolated at postnatal day 7 from a murine model of in utero nicotine exposure.

Characterisation of the prodrome to a first episode of psychotic mania: results of a retrospective study.

Background: Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative "high-risk" studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a sub-group of at-risk subjects.

Methods: Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses.

The proximal prodrome to first episode mania--a new target for early intervention.

Objective: Affective psychoses and bipolar disorders have been neglected in the development of early intervention strategies. This paper aims to gather current knowledge on the early phase of bipolar disorders in order to define new targets for early intervention.

Methods: Literature review based on the main computerized databases (MEDLINE, PUBMED and PSYCHLIT) and hand search of relevant literature.

Medium term follow-up of a randomized controlled trial of interventions for young people at ultra high risk of psychosis.

Valid criteria to identify young people who are believed to be at ultra high risk (UHR) of developing a psychotic episode were developed over the last decade. The first randomized controlled trial of treatment in a UHR cohort indicated that specific pharmacotherapy and psychotherapy delayed onset of disorder, and possibly reduced incidence. This paper reports results of follow-up of that trial.

The initial prodrome to bipolar affective disorder: prospective case studies.

Background: The initial prodrome to bipolar disorder has received very little attention to date, with most of the available data only addressing the prodrome to relapse. This study presents several prospective case studies of the initial prodrome to bipolar affective disorder.

Methods: Three patients are presented who developed bipolar disorder during their treatment at the Personal Assessment and Crisis Evaluation Clinic (PACE).